Antisolvent crystallization of a cardiotonic drug in ionic liquids: Effect of mixing on the crystal properties

NASA Astrophysics Data System (ADS)

de Azevedo Jacqueline, Resende; Fabienne, Espitalier; Jean-Jacques, Letourneau; Inês, Ré Maria

2017-08-01

LASSBio-294 (3,4-methylenedioxybenzoyl-2-thienylhydrazon) is a poorly soluble drug which has been proposed to have major advantages over other cardiotonic drugs. Poorly water soluble drugs present limited bioavailability due to their low solubility and dissolution rate. An antisolvent crystallization processing can improve the dissolution rate by decreasing the crystals particle size. However, LASSBio-294 is also poorly soluble in organic solvents and this operation is limited. In order to open new perspectives to improve dissolution rate, this work has investigated LASSBio-294 in terms of its antisolvent crystallization in 1-ethyl-3-methylimidazolium methyl phosphonate [emim][CH3O(H)PO2] as solvent and water as antisolvent. Two modes of mixing are tested in stirred vessel with different pre-mixers (Roughton or T-mixers) in order to investigate the mixing effect on the crystal properties (crystalline structure, particle size distribution, residual solvent and in vitro dissolution rate). Smaller drug particles with unchanged crystalline structure were obtained. Despite the decrease of the elementary particles size, the recrystallized particles did not achieve a better dissolution profile. However, this study was able to highlight a certain number of findings such as the impact of the hydrodynamic conditions on the crystals formation and the presence of a gel phase limiting the dissolution rate.

Pragmatic-mode mediation of sentence comprehension among aphasic bilinguals and hispanophones.

PubMed

Schnitzer, M L

1989-01-01

A test of sentence comprehension administered in four input-output modality combinations to a group of aphasic bilinguals and monolingual hispanophones provides evidence that aphasics tend to use pragmatic-mode (in the sense of Givón, 1979, On understanding-grammar, New York, Academic Press) strategies in approaching this task. When five factors were identified and dichotomized with respect to the pragmatic-mode-syntactic-mode dimension, the patients performed significantly better on items classified as pragmatic than on those classified as syntactic, in both languages. The results support a vertical/hierarchical view of aphasic language dissolution.

A dissolution-precipitation mechanism is at the origin of concrete creep in moist environments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pignatelli, Isabella; Kumar, Aditya; Alizadeh, Rouhollah

Long-term creep (i.e., deformation under sustained load) is a significant material response that needs to be accounted for in concrete structural design. However, the nature and origin of concrete creep remain poorly understood and controversial. Here, we propose that concrete creep at relative humidity ≥ 50%, but fixed moisture content (i.e., basic creep), arises from a dissolution-precipitation mechanism, active at nanoscale grain contacts, as has been extensively observed in a geological context, e.g., when rocks are exposed to sustained loads, in liquid-bearing environments. Based on micro-indentation and vertical scanning interferometry data and molecular dynamics simulations carried out on calcium–silicate–hydrate (C–S–H),more » the major binding phase in concrete, of different compositions, we show that creep rates are correlated with dissolution rates—an observation which suggests a dissolution-precipitation mechanism as being at the origin of concrete creep. C–S–H compositions featuring high resistance to dissolution, and, hence, creep are identified. Analyses of the atomic networks of such C–S–H compositions using topological constraint theory indicate that these compositions present limited relaxation modes on account of their optimally connected (i.e., constrained) atomic networks.« less

A dissolution-precipitation mechanism is at the origin of concrete creep in moist environments.

PubMed

Pignatelli, Isabella; Kumar, Aditya; Alizadeh, Rouhollah; Le Pape, Yann; Bauchy, Mathieu; Sant, Gaurav

2016-08-07

Long-term creep (i.e., deformation under sustained load) is a significant material response that needs to be accounted for in concrete structural design. However, the nature and origin of concrete creep remain poorly understood and controversial. Here, we propose that concrete creep at relative humidity ≥ 50%, but fixed moisture content (i.e., basic creep), arises from a dissolution-precipitation mechanism, active at nanoscale grain contacts, as has been extensively observed in a geological context, e.g., when rocks are exposed to sustained loads, in liquid-bearing environments. Based on micro-indentation and vertical scanning interferometry data and molecular dynamics simulations carried out on calcium-silicate-hydrate (C-S-H), the major binding phase in concrete, of different compositions, we show that creep rates are correlated with dissolution rates-an observation which suggests a dissolution-precipitation mechanism as being at the origin of concrete creep. C-S-H compositions featuring high resistance to dissolution, and, hence, creep are identified. Analyses of the atomic networks of such C-S-H compositions using topological constraint theory indicate that these compositions present limited relaxation modes on account of their optimally connected (i.e., constrained) atomic networks.

Detachment of particulate iron sulfide during shale-water interaction

NASA Astrophysics Data System (ADS)

Emmanuel, S.; Kreisserman, Y.

2017-12-01

Hydraulic fracturing, a commonly used technique to extract oil and gas from shales, is controversial in part because of the threat it poses to water resources. The technique involves the injection into the subsurface of large amounts of fluid, which can become contaminated by fluid-rock interaction. The dissolution of pyrite is thought to be a primary pathway for the contamination of fracturing fluids with toxic elements, such as arsenic and lead. In this study, we use direct observations with atomic force microscopy to show that the dissolution of carbonate minerals in Eagle Ford shale leads to the physical detachment of embedded pyrite grains. To simulate the way fluid interacts with a fractured shale surface, we also reacted rock samples in a flow-through cell, and used environmental scanning electron microscopy to compare the surfaces before and after interaction with water. Crucially, our results show that the flux of particulate iron sulfide into the fluid may be orders of magnitude higher than the flux of pyrite from chemical dissolution. This result suggests that mechanical detachment of pyrite grains could be the dominant mode by which arsenic and other inorganic elements are mobilized in the subsurface. Thus, during hydraulic fracturing operations and in groundwater systems containing pyrite, the transport of many toxic species may be controlled by the transport of colloidal iron sulfide particles.

Errors in reporting on dissolution research: methodological and statistical implications.

PubMed

Jasińska-Stroschein, Magdalena; Kurczewska, Urszula; Orszulak-Michalak, Daria

2017-02-01

In vitro dissolution testing provides useful information at clinical and preclinical stages of the drug development process. The study includes pharmaceutical papers on dissolution research published in Polish journals between 2010 and 2015. They were analyzed with regard to information provided by authors about chosen methods, performed validation, statistical reporting or assumptions used to properly compare release profiles considering the present guideline documents addressed to dissolution methodology and its validation. Of all the papers included in the study, 23.86% presented at least one set of validation parameters, 63.64% gave the results of the weight uniformity test, 55.68% content determination, 97.73% dissolution testing conditions, and 50% discussed a comparison of release profiles. The assumptions for methods used to compare dissolution profiles were discussed in 6.82% of papers. By means of example analyses, we demonstrate that the outcome can be influenced by the violation of several assumptions or selection of an improper method to compare dissolution profiles. A clearer description of the procedures would undoubtedly increase the quality of papers in this area.

Study on electrochemically deposited Mg metal

NASA Astrophysics Data System (ADS)

Matsui, Masaki

An electrodeposition process of magnesium metal from Grignard reagent based electrolyte was studied by comparing with lithium. The electrodeposition of magnesium was performed at various current densities. The obtained magnesium deposits did not show dendritic morphologies while all the lithium deposits showed dendritic products. Two different crystal growth modes in the electrodeposition process of magnesium metal were confirmed by an observation using scanning electron micro scope (SEM) and a crystallographic analysis using X-ray diffraction (XRD). An electrochemical study of the deposition/dissolution process of the magnesium showed a remarkable dependency of the overpotential of magnesium deposition on the electrolyte concentration compared with lithium. This result suggests that the dependency of the overpotential on the electrolyte concentration prevent the locally concentrated current resulting to form very uniform deposits.

Dissolution testing of isoniazid, rifampicin, pyrazinamide and ethambutol tablets using near-infrared spectroscopy (NIRS) and multivariate calibration.

PubMed

de Oliveira Neves, Ana Carolina; Soares, Gustavo Mesquita; de Morais, Stéphanie Cavalcante; da Costa, Fernanda Saadna Lopes; Porto, Dayanne Lopes; de Lima, Kássio Michell Gomes

2012-01-05

This work utilized the near-infrared spectroscopy (NIRS) and multivariate calibration to measure the percentage drug dissolution of four active pharmaceutical ingredients (APIs) (isoniazid, rifampicin, pyrazinamide and ethambutol) in finished pharmaceutical products produced in the Federal University of Rio Grande do Norte (Brazil). The conventional analytical method employed in quality control tests of the dissolution by the pharmaceutical industry is high-performance liquid chromatography (HPLC). The NIRS is a reliable method that offers important advantages for the large-scale production of tablets and for non-destructive analysis. NIR spectra of 38 samples (in triplicate) were measured using a Bomen FT-NIR 160 MB in the range 1100-2500nm. Each spectrum was the average of 50 scans obtained in the diffuse reflectance mode. The dissolution test, which was initially carried out in 900mL of 0.1N hydrochloric acid at 37±0.5°C, was used to determine the percentage a drug that dissolved from each tablet measured at the same time interval (45min) at pH 6.8. The measurement of the four API was performed by HPLC (Shimadzu, Japan) in the gradiente mode. The influence of various spectral pretreatments (Savitzky-Golay smoothing, Multiplicative Scatter Correction (MSC), and Savitzky-Golay derivatives) and multivariate analysis using the partial least squares (PLS) regression algorithm was calculated by the Unscrambler 9.8 (Camo) software. The correlation coefficient (R(2)) for the HPLC determination versus predicted values (NIRS) ranged from 0.88 to 0.98. The root-mean-square error of prediction (RMSEP) obtained from PLS models were 9.99%, 8.63%, 8.57% and 9.97% for isoniazid, rifampicin, ethambutol and pyrazinamide, respectively, indicating that the NIR method is an effective and non-destructive tool for measurement of drug dissolution from tablets. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

Evaluation of an Extended-Release, Abuse-Deterrent, Microsphere-in-Capsule Analgesic for the Management of Patients with Chronic Pain With Dysphagia (CPD).

PubMed

Fleming, Alison B; Carlson, Douglas R; Varanasi, Ravi K; Grima, Michael; Mayock, Stephen P; Saim, Said; Kopecky, Ernest A

2016-03-01

Patients who have chronic pain with dysphagia (difficulty swallowing) (CPD) often have difficulty taking oral medication and, as such, alter their medications by crushing or chewing in an attempt to make it easier to swallow. Such manipulation of currently marketed, extended-release (ER) opioid analgesics can significantly alter the pharmacokinetic (PK) properties of the formulations, resulting in poor treatment outcome or serious adverse events. There is an unmet medical need for oral ER opioid formulations suitable for patients with CPD. The primary objectives of this study were to conduct in vitro studies to evaluate alternate means of administration of a new, extended-release (ER), abuse-deterrent, microsphere-in-capsule formulation of oxycodone for patients with CPD. Specifically, these studies investigated the in vitro equivalence of drug release rates from Oxycodone DETERx® ER intact capsules (control condition) and administration via alternate modes-opening the capsule and sprinkling the microspheres onto soft foods or administration through enteral tubes. Secondary objectives were to compare alternate modes of administration of Oxycodone DETERx® to a commercially available ER-morphine product. Soft food study: Oxycodone DETERx® microspheres were sprinkled onto and mixed with several soft foods (ie, applesauce, vanilla pudding, strawberry jam, yogurt, and vanilla ice cream); the effect of drug contact time (0, 30, and 60 minutes) on drug release was studied. Enteral tube study: Oxycodone DETERx® microspheres were administered through varying sizes of nasogastric (10 and 12 Fr.) tubes and a 16 Fr. gastrostomy tube using 5 different delivery vehicles (ie, water, liquid nutritional feeds [Jevity®, Ensure®], and milk [whole milk and 2% milk]). Drug release rate was characterized using a standard in vitro dissolution methodology; dissolution of intact Oxycodone DETERx® capsules served as the control for both the soft food and enteral tube studies. Oxycodone concentration was measured using a standardized high-performance liquid chromatography (HPLC) assay. Similarity factor (f2) analysis was used to compare similarity of the dissolution profiles of test and control conditions. The mean dissolution profile of Oxycodone DETERx® microspheres sprinkled onto and mixed with each of the soft foods were similar (f2 > 50) to that of the control. Study drug-food contact time did not impact dissolution profiles. The dissolution data obtained from Oxycodone DETERx® microspheres passed through enteral feeding tubes of varying sizes were similar (f2 > 50) to that of the control. Unlike a marketed morphine sulfate ER pellet formulation, Oxycodone DETERx® did not clog any of the studied enteral tubes. A new ER, abuse-deterrent, microsphere-in-capsule formulation of oxycodone can be administered by sprinkling onto soft food without affecting the drug release profile of the formulation. The formulation can also be administered directly via enteral tubes without affecting drug release and without clogging enteral tubes. Oxycodone DETERx® may offer physicians and patients with CPD an alternate treatment option, especially in those patients who have dysphagia or an aversion to swallowing monolithic tablet/capsule formulations and for whom analgesic patches or other opioid formulations are not a viable therapeutic option. © 2015 World Institute of Pain.

In vitro acellular dissolution of mineral fibres: A comparative study.

PubMed

Gualtieri, Alessandro F; Pollastri, Simone; Bursi Gandolfi, Nicola; Gualtieri, Magdalena Lassinantti

2018-05-04

The study of the mechanisms by which mineral fibres promote adverse effects in both animals and humans is a hot topic of multidisciplinary research with many aspects that still need to be elucidated. Besides length and diameter, a key parameter that determines the toxicity/pathogenicity of a fibre is biopersistence, one component of which is biodurability. In this paper, biodurability of mineral fibres of social and economic importance (chrysotile, amphibole asbestos and fibrous erionite) has been determined for the first time in a systematic comparative way from in vitro acellular dissolution experiments. Dissolution was possible using the Gamble solution as simulated lung fluid (pH = 4 and at body temperature) so to reproduce the macrophage phagolysosome environment. The investigated mineral fibres display very different dissolution rates. For a 0.25 μm thick fibre, the calculated dissolution time of chrysotile is in the range 94-177 days, very short if compared to that of amphibole fibres (49-245 years), and fibrous erionite (181 years). Diffraction and SEM data on the dissolution products evidence that chrysotile rapidly undergoes amorphization with the formation of a nanophasic silica-rich fibrous metastable pseudomorph as first dissolution step whereas amphibole asbestos and fibrous erionite show minor signs of dissolution even after 9-12 months.

Dissolution-and-reduction CVD synthesis of few-layer graphene on ultra-thin nickel film lifted off for mode-locking fiber lasers

PubMed Central

Peng, Kaung-Jay; Lin, Yung-Hsiang; Wu, Chung-Lun; Lin, Sheng-Fong; Yang, Chun-Yu; Lin, Shih-Meng; Tsai, Din-Ping; Lin, Gong-Ru

2015-01-01

The in-situ dissolution-and-reduction CVD synthesized few-layer graphene on ultra-thin nickel catalyst film is demonstrated at temperature as low as 550 °C, which can be employed to form transmission-type or reflection-type saturable absorber (SA) for mode-locking the erbium-doped fiber lasers (EDFLs). With transmission-type graphene SA, the EDFL shortens its pulsewidth from 483 to 441 fs and broadens its spectral linewidth from 4.2 to 6.1 nm with enlarging the pumping current from 200 to 900 mA. In contrast, the reflection-type SA only compresses the pulsewidth from 875 to 796 fs with corresponding spectral linewidth broadened from 2.2 to 3.3 nm. The reflection-type graphene mode-locker increases twice of its equivalent layer number to cause more insertion loss than the transmission-type one. Nevertheless, the reflection-type based saturable absorber system can generate stabilized soliton-like pulse easier than that of transmission-type system, because the nonlinearity induced self-amplitude modulation depth is simultaneously enlarged when passing through the graphene twice under the retro-reflector design. PMID:26328535

Effects of glycine and current density on the mechanism of electrodeposition, composition and properties of Ni-Mn films prepared in ionic liquid

NASA Astrophysics Data System (ADS)

Guo, Jiacheng; Guo, Xingwu; Wang, Shaohua; Zhang, Zhicheng; Dong, Jie; Peng, Liming; Ding, Wenjiang

2016-03-01

The effects of glycine on the mechanism of electrodeposition of Ni-Mn alloy film prepared in ChCl-urea ionic liquid were studied in order to control the composition, microstructure and properties of the film. The cyclic voltammograms revealed that the presence of glycine in the ionic liquid can inhibit the reduction of Ni2+ ions but promote the reduction of Mn2+ ions in the cathodic scan. However, it promoted the dissolution of both Ni and Mn deposits in the ChCl-urea ionic liquids during the reverse scan. Glycine changed the mode of Ni-Mn film growth from Volmer-Weber mode into Stranski-Krastanov mode. The Mn content in the Ni-Mn film increased with the increase of concentration of glycine and current density. The Ni-Mn alloy film with 3.1 at.% Mn exhibited the lowest corrosion current density of 3 × 10-7 A/cm2 compared with other films prepared and exhibited better corrosion resistance than pure Ni film in 3.5 wt.% NaCl solution.

Multi-element analysis of water decoction of medicine food homology plants using inductively coupled plasma-tandem mass spectrometry

NASA Astrophysics Data System (ADS)

Fu, Liang; Shi, Shu-Yun; Chen, Xiao-Qing

2017-07-01

The concentration of twelve trace elements in the water decoction of medicine food homology plants (MFHP) was determined by inductively coupled plasma-tandem mass spectrometry (ICP-MS/MS). Water decoctions of MFHP were analyzed directly using the MS/MS mode after acidification by 1% (v/v) nitric acid. The polyatomic interferences were eliminated by oxygen mass shift, oxygen on-mass, and ammonia mass shift. The accuracy of the method was verified by analysis of standard reference materials. This method was utilized to investigate the water decoction composition of 16 common Chinese MFHPs. The trace elements in the water decoctions of different MFHPs presented significantly different dissolution ratios. The dissolution ratio of V was the lowest (4.21%-14.86%), whereas Zn showed the highest dissolution ratio (24.87%-86.80%). In addition, the dissolution ratio of heavy metallic elements in most MFHP was equal to or was lower than 30%. Therefore, consumption of MHFP decoction could decrease the heavy metal intake associated with MFHP use and reduce the risk of heavy metal poisoning.

Formation and dissolution of microbubbles on highly-ordered plasmonic nanopillar arrays

PubMed Central

Liu, Xiumei; Bao, Lei; Dipalo, Michele; De Angelis, Francesco; Zhang, Xuehua

2015-01-01

Bubble formation from plasmonic heating of nanostructures is of great interest in many applications. In this work, we study experimentally the intrinsic effects of the number of three-dimensional plasmonic nanostructures on the dynamics of microbubbles, largely decoupled from the effects of dissolved air. The formation and dissolution of microbubbles is observed on exciting groups of 1, 4, and 9 nanopillars. Our results show that the power threshold for the bubble formation depends on the number density of the nanopillars in highly-ordered arrays. In the degassed water, both the growth rate and the maximal radius of the plasmonic microbubbles increase with an increase of the illuminated pillar number, due to the heat balance between the heat loss across the bubble and the collective heating generated from the nanopillars. Interestingly, our results show that the bubble dissolution is affected by the spatial arrangement of the underlying nanopillars, due to the pinning effect on the bubble boundary. The bubbles on nanopillar arrays dissolve in a jumping mode with step-wise features on the dissolution curves, prior to a smooth dissolution phase for the bubble pinned by a single pillar. The insight from this work may facilitate the design of nanostructures for efficient energy conversion. PMID:26687143

The Kinetics of Dissolution Revisited

NASA Astrophysics Data System (ADS)

Antonel, Paula S.; Hoijemberg, Pablo A.; Maiante, Leandro M.; Lagorio, M. Gabriela

2003-09-01

An experiment analyzing the kinetics of dissolution of a solid with cylindrical geometry in water is presented. The dissolution process is followed by measuring the solid mass and its size parameters (thickness and diameter) as a function of time. It is verified that the dissolution rate follows the Nernst model. Data treatment is compared with the dissolution of a spherical solid previously described. Kinetics, diffusion concepts, and polynomial fitting of experimental data are combined in this simple experiment.

Toxoplasma gondii infection shifts dendritic cells into an amoeboid rapid migration mode encompassing podosome dissolution, secretion of TIMP-1, and reduced proteolysis of extracellular matrix.

PubMed

Ólafsson, Einar B; Varas-Godoy, Manuel; Barragan, Antonio

2018-03-01

Dendritic cells (DCs) infected by Toxoplasma gondii rapidly acquire a hypermigratory phenotype that promotes systemic parasite dissemination by a "Trojan horse" mechanism in mice. Recent paradigms of leukocyte migration have identified the amoeboid migration mode of DCs as particularly suited for rapid locomotion in extracellular matrix and tissues. Here, we have developed a microscopy-based high-throughput approach to assess motility and matrix degradation by Toxoplasma-challenged murine and human DCs. DCs challenged with T. gondii exhibited dependency on metalloproteinase activity for hypermotility and transmigration but, strikingly, also dramatically reduced pericellular proteolysis. Toxoplasma-challenged DCs up-regulated expression and secretion of tissue inhibitor of metalloproteinases-1 (TIMP-1) and their supernatants impaired matrix degradation by naïve DCs and by-stander DCs dose dependently. Gene silencing of TIMP-1 by short hairpin RNA restored matrix degradation activity in Toxoplasma-infected DCs. Additionally, dissolution of podosome structures in parasitised DCs coincided with abrogated matrix degradation. Toxoplasma lysates inhibited pericellular proteolysis in a MyD88-dependent fashion whereas abrogated proteolysis persevered in Toxoplasma-infected MyD88-deficient DCs. This indicated that both TLR/MyD88-dependent and TLR/MyD88-independent signalling pathways mediated podosome dissolution and the abrogated matrix degradation. We report that increased TIMP-1 secretion and cytoskeletal rearrangements encompassing podosome dissolution are features of Toxoplasma-induced hypermigration of DCs with an impact on matrix degradation. Jointly, the data highlight how an obligate intracellular parasite orchestrates key regulatory cellular processes consistent with non-proteolytic amoeboid migration of the vehicle cells that facilitate its dissemination. © 2017 John Wiley & Sons Ltd.

The effect of polymorphism on powder compaction and dissolution properties of chemically equivalent oxytetracycline hydrochloride powders.

PubMed

Liebenberg, W; de Villiers, M M; Wurster, D E; Swanepoel, E; Dekker, T G; Lötter, A P

1999-09-01

In South Africa, oxytetracycline is identified as an essential drug; many generic products are on the market, and many more are being developed. In this study, six oxytetracycline hydrochloride powders were obtained randomly from manufacturers, and suppliers were compared. It was found that compliance to a pharmacopoeial monograph was insufficient to ensure the optimum dissolution performance of a simple tablet formulation. Comparative physicochemical raw material analysis showed no major differences with regard to differential scanning calorimetry (DSC), infrared (IR) spectroscopy, powder dissolution, and particle size. However, the samples could be divided into two distinct types with respect to X-ray powder diffraction (XRD) and thus polymorphism. The two polymorphic forms had different dissolution properties in water or 0.1 N hydrochloride acid. This difference became substantial when the dissolution from tablets was compared. The powders containing form A were less soluble than that containing form B.

A new method for evaluating the dissolution of orodispersible films.

PubMed

Xia, Yiran; Chen, Fang; Zhang, Huiping; Luo, Chunlin

2015-05-01

The aim of this research was to develop and assess a new dissolution apparatus for orodispersible films (ODFs). The new apparatus was based on a flow-through cell design which requires only a limited amount of dissolution medium and can automatically collect samples in short-time intervals. Compared with the dissolution method in Chinese Pharmacopeia, our method simulated the flow condition of the oral cavity and resulted in reproducible dissolution data and remarkably discriminating capability. Therefore, we concluded that the proposed dissolution method was particularly suitable for evaluating the dissolution of ODFs and should also be applicable to other fast-dissolving solid dosage forms.

Different Material States of Pub1 Condensates Define Distinct Modes of Stress Adaptation and Recovery.

PubMed

Kroschwald, Sonja; Munder, Matthias C; Maharana, Shovamayee; Franzmann, Titus M; Richter, Doris; Ruer, Martine; Hyman, Anthony A; Alberti, Simon

2018-06-12

How cells adapt to varying environmental conditions is largely unknown. Here, we show that, in budding yeast, the RNA-binding and stress granule protein Pub1 has an intrinsic property to form condensates upon starvation or heat stress and that condensate formation is associated with cell-cycle arrest. Release from arrest coincides with condensate dissolution, which takes minutes (starvation) or hours (heat shock). In vitro reconstitution reveals that the different dissolution rates of starvation- and heat-induced condensates are due to their different material properties: starvation-induced Pub1 condensates form by liquid-liquid demixing and subsequently convert into reversible gel-like particles; heat-induced condensates are more solid-like and require chaperones for disaggregation. Our data suggest that different physiological stresses, as well as stress durations and intensities, induce condensates with distinct physical properties and thereby define different modes of stress adaptation and rates of recovery. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Evaluating bioequivalence of meloxicam tablets: is in-vitro dissolution test overdiscriminating?

PubMed

Jin, Chan; Zhao, Chenyao; Shen, Dachao; Dong, Wenxiang; Liu, Hongzhuo; He, Zhonggui

2018-02-01

The aim of the study was to assess the impact of the differences in dissolution profiles of meloxicam tablets on the in-vivo bioavailability parameters after oral administration. Compare in-vitro dissolution testing in the recommended media to evaluate in-vivo bioequivalence outcomes for the Biopharmaceutics Classification System Class II weak acidic drugs. Nine Beagle dogs received a single oral administration of each formulation (7.5 mg) in a three-way crossover design. The dissolution of meloxicam from both test products showed marked differences with that from the reference tablet in pH 1.0, 4.5 and 6.8 media at 50 or 75 rpm. Both formulations exhibiting slow or fast dissolution were then compared with the reference product for in-vivo bioequivalence study. Both products were bioequivalent with the reference tablet in either extent or rate of oral absorption. It indicated that the dissolution profiles which discriminated between the formulations in vitro did not accurately predict the in-vivo bioequivalence outcomes. Comparative dissolution profiles using similarity factor (f 2 ) in the recommended media should be relaxed to fulfil the requirements for the development, scale-up and postapproval changes to immediate release oral solid dosage forms of meloxicam. © 2017 Royal Pharmaceutical Society.

Investigation of the late summer Si-budget in the Sub-Antarctic and Polar Front Zones south of Tasmania (SAZ-SENSE)

NASA Astrophysics Data System (ADS)

Fripiat, F.; Leblanc, K.; Elskens, M.; Quéguiner, B.; Armand, L.; Cornet-Barthaux, V.; André, L.; Cardinal, D.

2009-04-01

In the surface ocean, the Si-biogeochemical budget can be estimated by the ratio between the integrated biogenic silica dissolution and production rates. However such data are scarce in the ocean mostly because of methodology limitation. This is especially true in the Sub-Antarctic Zone (SAZ) where only two profiles were measured so far, exhibiting large variation (dissolution: production ratio of 0.3 and 3.1 for spring and summer, respectively). Though, the SAZ plays a crucial role in the efficiency of the silicate pump and the fertility of the Sub-Antarctic Mode Waters which then replenish in nutrients the majority of the surface waters of the world ocean. Therefore, better constraining the dissolution: production ratios in this region will certainly improve our understanding of these processes. During the SAZ-SENSE cruise (Jan.-Feb. 2007), the Si-budget of three stations (two in the SAZ and one in the Polar Frontal Zone, PFZ, for a total of nine profiles) covering different biogeochemical properties (e.g., Fe enriched vs. depleted conditions, dominance of diatoms vs. other phytoplankton,…) was investigated. This was implemented in the framework of an exhaustive characterization of the Si-biogeochemical cycle using different parameters: PDMPO labelling, 32Si and 30Si spiked incubations, and, taxonomy. We have developed a new method for the determination of the production and dissolution rates from the 30Si isotopic dilution technique. We now measure the changes of the 30Si-abundances in particulate and liquid phases by High Resolution Sector Field Inductively Coupled Plasma Mass Spectrometer (HR-SF-ICP-MS). This method, which is faster, more sensitive and more precise than the traditional ones using an Isotope Ratio Mass Spectrometer (IRMS) or Thermal Ionization Mass Spectrometer (TIMS), will significantly aid in expanding the biogenic silica production-dissolution dataset in the ocean. The results obtained on Si budget indicate that the Si-regeneration (dissolution) dominates over Si-uptake (production) in the PFZ (1.9 ± 1.5), in contrast to SAZ where production is much larger than dissolution rate (0.08 ± 0.12). The efficiency of the Si-regeneration in late summer seems to be highly variable with significant variations at the same station on short timescale (days). These results will be compared with the other ones obtained from the unique toolbox implemented during SAZ-SENSE to study the Si cycle. They will be discussed to better assess the role of SAZ and PFZ in the global marine Si cycle.

Can crystal engineering be as beneficial as micronisation and overcome its pitfalls?: A case study with cilostazol.

PubMed

Sai Gouthami, Kodukula; Kumar, Dinesh; Thipparaboina, Rajesh; Chavan, Rahul B; Shastri, Nalini R

2015-08-01

Improvement in dissolution of the drugs having poor solubility is a challenge in pharmaceutical industry. Micronization is one technique, employed for dissolution enhancement of cilostazol, a BCS class II drug. However, the obtained micronized drug possesses poor flowability. The aim of this study was to improve the dissolution rate and flow properties of cilostazol by crystal engineering, using habit modification method and compare with micronized cilostazol bulk drug. Simulation studies were performed to predict the effect of solvents on cilostazol crystal habit. Cilostazol crystals with different habits were prepared by solvent:anti-solvent crystallization technique. SEM, FTIR, DSC, TGA and PXRD were used for solid state characterization. The results revealed that cilostazol re-crystallized from methanol-hexane system were hexagonal and ethanol-hexane system gave rods. Cilostazol engineered habits showed increased dissolution rate than unprocessed drug but similar dissolution rate when compared to micronized cilostazol. Micronized cilostazol showed a dissolution efficiency of 75.58% where as cilostazol recrystallized from methanol-hexane and ethanol-hexane systems resulted in a dissolution efficiency of 72.63% and 68.63%, respectively. In addition, crystal engineering resulted in improved flow properties of re-crystallized habits when compared to micronized form of the drug. In conclusion, crystal engineering by habit modification show potential for dissolution enhancement with an added advantage of improved flow properties over micronization technique, for poorly soluble drugs like cilostazol. Copyright © 2015 Elsevier B.V. All rights reserved.

Improving the dissolution properties of curcumin using dense gas antisolvent technology.

PubMed

Kurniawansyah, Firman; Quachie, Lisa; Mammucari, Raffaella; Foster, Neil R

2017-04-15

The dissolution properties of curcumin are notoriously poor and hinder its bioavailability. To improve its dissolution properties, curcumin has been formulated with methyl-β-cyclodextrin and polyvinylpyrrolidone by the atomized rapid injection solvent extraction (ARISE) system. The compounds were co-precipitated from organic solutions using carbon dioxide at 30°C and 95bar as the antisolvent. Curcumin formulations were also produced by physical mixing and freeze drying for comparative purposes. The morphology, crystallinity, solid state molecular interactions, apparent solubility and dissolution profiles of samples were observed. The results indicate that the ARISE process is effective in the preparation of curcumin micro-composites with enhanced dissolution profiles compared to unprocessed material and products from physical mixing and freeze drying. Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical structure influence on NAPL mixture nonideality evolution, rate-limited dissolution, and contaminant mass flux.

PubMed

Padgett, Mark C; Tick, Geoffrey R; Carroll, Kenneth C; Burke, William R

2017-03-01

The influence of chemical structure on NAPL mixture nonideality evolution, rate-limited dissolution, and contaminant mass flux was examined. The variability of measured and UNIFAC modeled NAPL activity coefficients as a function of mole fraction was compared for two NAPL mixtures containing structurally-different contaminants of concern including toluene (TOL) or trichloroethene (TCE) within a hexadecane (HEXDEC) matrix. The results showed that dissolution from the NAPL mixtures transitioned from ideality for mole fractions >0.05 to nonideality as mole fractions decreased. In particular, the TCE generally exhibited more ideal dissolution behavior except at lower mole fractions, and may indicate greater structural/polarity similarity between the two compounds. Raoult's Law and UNIFAC generally under-predicted the batch experiment results for TOL:HEXDEC mixtures especially for mole fractions ≤0.05. The dissolution rate coefficients were similar for both TOL and TCE over all mole fractions tested. Mass flux reduction (MFR) analysis showed that more efficient removal behavior occurred for TOL and TCE with larger mole fractions compared to the lower initial mole fraction mixtures (i.e. <0.2). However, compared to TOL, TCE generally exhibited more efficient removal behavior over all mole fractions tested and may have been the result of structural and molecular property differences between the compounds. Activity coefficient variability as a function of mole fraction was quantified through regression analysis and incorporated into dissolution modeling analyses for the dynamic flushing experiments. TOL elution concentrations were modeled (predicted) reasonable well using ideal and equilibrium assumptions, but the TCE elution concentrations could not be predicted using the ideal model. Rather, the dissolution modeling demonstrated that TCE elution was better described by the nonideal model whereby NAPL-phase activity coefficient varied as a function of COC mole fraction. For dynamic column flushing experiments, dissolution rate kinetics can vary significantly with changes in NAPL volume and surface area. However, under conditions whereby NAPL volume and area are not significantly altered during dissolution, mixture nonideality effects may have a greater relative control on dissolution (elution) and MFR behavior compared to kinetic rate limitations. Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical structure influence on NAPL mixture nonideality evolution, rate-limited dissolution, and contaminant mass flux

NASA Astrophysics Data System (ADS)

Padgett, Mark C.; Tick, Geoffrey R.; Carroll, Kenneth C.; Burke, William R.

2017-03-01

The influence of chemical structure on NAPL mixture nonideality evolution, rate-limited dissolution, and contaminant mass flux was examined. The variability of measured and UNIFAC modeled NAPL activity coefficients as a function of mole fraction was compared for two NAPL mixtures containing structurally-different contaminants of concern including toluene (TOL) or trichloroethene (TCE) within a hexadecane (HEXDEC) matrix. The results showed that dissolution from the NAPL mixtures transitioned from ideality for mole fractions > 0.05 to nonideality as mole fractions decreased. In particular, the TCE generally exhibited more ideal dissolution behavior except at lower mole fractions, and may indicate greater structural/polarity similarity between the two compounds. Raoult's Law and UNIFAC generally under-predicted the batch experiment results for TOL:HEXDEC mixtures especially for mole fractions ≤ 0.05. The dissolution rate coefficients were similar for both TOL and TCE over all mole fractions tested. Mass flux reduction (MFR) analysis showed that more efficient removal behavior occurred for TOL and TCE with larger mole fractions compared to the lower initial mole fraction mixtures (i.e. < 0.2). However, compared to TOL, TCE generally exhibited more efficient removal behavior over all mole fractions tested and may have been the result of structural and molecular property differences between the compounds. Activity coefficient variability as a function of mole fraction was quantified through regression analysis and incorporated into dissolution modeling analyses for the dynamic flushing experiments. TOL elution concentrations were modeled (predicted) reasonable well using ideal and equilibrium assumptions, but the TCE elution concentrations could not be predicted using the ideal model. Rather, the dissolution modeling demonstrated that TCE elution was better described by the nonideal model whereby NAPL-phase activity coefficient varied as a function of COC mole fraction. For dynamic column flushing experiments, dissolution rate kinetics can vary significantly with changes in NAPL volume and surface area. However, under conditions whereby NAPL volume and area are not significantly altered during dissolution, mixture nonideality effects may have a greater relative control on dissolution (elution) and MFR behavior compared to kinetic rate limitations.

High temperature dissolution of chromium substituted nickel ferrite in nitrilotriacetic acid medium

NASA Astrophysics Data System (ADS)

Sathyaseelan, V. S.; Chandramohan, P.; Velmurugan, S.

2016-12-01

High temperature (HT) dissolution of chromium substituted nickel ferrite was carried out with relevance to the decontamination of nuclear reactors by way of chemical dissolution of contaminated corrosion product oxides present on stainless steel coolant circuit surfaces. Chromium substituted nickel ferrites of composition, NiFe(2-x)CrxO4 (x ≤ 1), was synthetically prepared and characterized. HT dissolution of these oxides was carried out in nitrilotriacetic acid medium at 160 °C. Dissolution was remarkably increased at 160 °C when compared to at 85 °C in a reducing decontamination formulation. Complete dissolution could be achieved for the oxides with chromium content 0 and 0.2. Increasing the chromium content brought about a marked reduction in the dissolution rate. About 40 fold decrease in rate of dissolution was observed when chromium was increased from 0 to 1. The rate of dissolution was not very significantly reduced in the presence of N2H4. Dissolution of oxide was found to be stoichiometric.

Morphological changes produced by acid dissolution in Er:YAG laser irradiated dental enamel.

PubMed

Manuela Díaz-Monroy, Jennifer; Contreras-Bulnes, Rosalía; Fernando Olea-Mejía, Oscar; Emma Rodríguez-Vilchis, Laura; Sanchez-Flores, Ignacio

2014-06-01

Several scientific reports have shown the effects of Er:YAG laser irradiation on enamel morphology. However, there is lack of information regarding the morphological alterations produced by the acid attack on the irradiated surfaces. The aim of this study was to evaluate the morphological changes produced by acid dissolution in Er:YAG laser irradiated dental enamel. Forty-eight enamel samples were divided into four groups (n = 12). GI (control); Groups II, III, and IV were irradiated with Er:YAG at 100 mJ (12.7 J/cm(2) ), 200 mJ (25.5 J/cm(2) ), and 300 mJ (38.2 J/cm(2) ), respectively, at 10 Hz without water irrigation. Enamel morphology was evaluated before-irradiation, after-irradiation, and after-acid dissolution, by scanning electron microscopy (SEM). Sample coating was avoided and SEM analysis was performed in a low-vacuum mode. To facilitate the location of the assessment area, a reference point was marked. Morphological changes produced by acid dissolution of irradiated enamel were observed, specifically on laser-induced undesired effects. These morphological changes were from mild to severe, depending on the presence of after-irradiation undesired effects. © 2014 Wiley Periodicals, Inc.

Confirmation of filament dissolution behavior by analyzing electrical field effect during reset process in oxide-based RRAM

NASA Astrophysics Data System (ADS)

Pan, Chih-Hung; Chang, Ting-Chang; Tsai, Tsung-Ming; Chang, Kuan-Chang; Chu, Tian-Jian; Lin, Wen-Yan; Chen, Min-Chen; Sze, Simon M.

2016-09-01

In this letter, we demonstrate completely different characteristics with different operating modes and analyze the electrical field effect to confirm the filament dissolution behavior. The device exhibited a larger memory window when using a single voltage sweep method during reset process rather than the traditional double sweep method. The phenomenon was verified by using fast I-V measurement to simulate the two operating methods. A better high resistance state (HRS) will be obtained with a very short rising time pulse, but quite notably, lower power consumption was needed. We proposed the electrical field effect to explain the phenomenon and demonstrate distribution by COMSOL simulation.

The influence of co-formers on the dissolution rates of co-amorphous sulfamerazine/excipient systems.

PubMed

Gniado, Katarzyna; Löbmann, Korbinian; Rades, Thomas; Erxleben, Andrea

2016-05-17

A comprehensive study on the dissolution properties of three co-amorphous sulfamerazine/excipient systems, namely sulfamerazine/deoxycholic acid, sulfamerazine/citric acid and sulfamerazine/sodium taurocholate (SMZ/DA, SMZ/CA and SMZ/NaTC; 1:1 molar ratio), is reported. While all three co-formers stabilize the amorphous state during storage, only co-amorphization with NaTC provides a dissolution advantage over crystalline SMZ and the reasons for this were analyzed. In the case of SMZ/DA extensive gelation of DA protects the amorphous phase from crystallization upon contact with buffer, but at the same time prevents the release of SMZ into solution. Disk dissolution studies showed an improved dissolution behavior of SMZ/CA compared to crystalline SMZ. However, enhanced dissolution properties were not seen in powder dissolution testing due to poor dispersibility. Co-amorphization of SMZ and NaTC resulted in a significant increase in dissolution rate, both in powder and disk dissolution studies. Copyright © 2016. Published by Elsevier B.V.

Uranium carbide dissolution in nitric solution: Sonication vs. silent conditions

NASA Astrophysics Data System (ADS)

Virot, Matthieu; Szenknect, Stéphanie; Chave, Tony; Dacheux, Nicolas; Moisy, Philippe; Nikitenko, Sergey I.

2013-10-01

The dissolution of uranium carbide (UC) in nitric acid media is considered by means of power ultrasound (sonication) or magnetic stirring. The induction period required to initiate UC dissolution was found to be dramatically shortened when sonicating a 3 M nitric solution (Ar, 20 kHz, 18 W cm-2, 20 °C). At higher acidity, magnetic stirring offers faster dissolution kinetics compared to sonication. Ultrasound-assisted UC dissolution is found to be passivated after ∼60% dissolution and remains incomplete whatever the acidity which is confirmed by ICP-AES, LECO and SEM-EDX analyses. In general, the kinetics of UC dissolution is linked to the in situ generation of nitrous acid in agreement with the general mechanism of UC dissolution; the nitrous acid formation is reported to be faster under ultrasound at low acidity due to the nitric acid sonolysis. The carbon balance shared between the gaseous, liquid, and solid phases is strongly influenced by the applied dissolution procedure and HNO3 concentration.

Dissolution and coarsening of polydisperse, polymorph drug particles liberated from a disintegrating finished dosage form: Theoretical considerations.

PubMed

Horkovics-Kovats, Stefan

2016-08-25

In order to improve the bioavailability of substances with limited water-solubility, they are often formulated as nanoparticles. Nanoparticles show enhanced dissolution properties when compared to large particles. In this paper a dissolution theory is presented that comprehensively describes the dissolution properties of both large- and nanoparticles. It comprises non-sink conditions and arbitrary shaped isometrically dissolving particles, considering particle-size-independent dissolution layer thickness and several polymorphic drug forms. The known root-laws of dissolution kinetics happen to be special cases that depend on particle-size in relation to the diffusion layer thickness i.e. whether the particles are much larger, comparable, or much smaller than the diffusion layer thickness. The presented theory explains the improved dissolution properties of nanoparticles, such as their increased solubility, almost immediate dissolution, and the dissolution kinetics which is independent from hydrodynamic conditions. For polydisperse, polymorphic particles of arbitrary shapes that are liberated from a disintegrating finished dosage form, the Ostwald ripening (coarsening of particles and transition of metastable polymorphic forms into a more stable crystalline form) is described as water mediated mass transport. The presented theory points to certain limitations of the Ostwald-Freundlich equation for nanoparticles and provides their better characterization. This way it may contribute to a more specifically targeted development of finished dosage forms and may help to reduce the bias of toxicological and environmental assessments especially for drugs that are formed as nanoparticles. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparative evaluation of ibuprofen/beta-cyclodextrin complexes obtained by supercritical carbon dioxide and other conventional methods.

PubMed

Hussein, Khaled; Türk, Michael; Wahl, Martin A

2007-03-01

The preparation of drug/cyclodextrin complexes is a suitable method to improve the dissolution of poor soluble drugs. The efficacy of the Controlled Particle Deposition (CPD) as a new developed method to prepare these complexes in a single stage process using supercritical carbon dioxide is therefore compared with other conventional methods. Ibuprofen/beta-cyclodextrin complexes were prepared with different techniques and characterized using FTIR-ATR spectroscopy, powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). In addition, the influences of the processing technique on the drug content (HPLC) and the dissolution behavior were studied. Employing the CPD-process resulted in a drug content of 2.8+/-0.22 wt.% in the carrier. The material obtained by CPD showed an improved dissolution rate of ibuprofen at pH 5 compared with the pure drug and its physical mixture with beta-cyclodextrin. In addition CPD material displays the highest dissolution (93.5+/- 2.89% after 75 min) compared to material obtained by co-precipitation (61.3 +/-0.52%) or freeze-drying (90.6 +/-2.54%). This study presents the CPD-technique as a well suitable method to prepare a drug/beta-cyclodextrin complex with improved drug dissolution compared to the pure drug and materials obtained by other methods.

Multi-scale characterization of dissolution structures and porosity distribution in the upper part of the Biscayne aquifer using ground penetrating radar (GPR)

NASA Astrophysics Data System (ADS)

Mount, Gregory J.

The karst Biscayne aquifer is characterized by a heterogeneous spatial arrangement of porosity, making hydrogeological characterization difficult. In this dissertation, I investigate the use of ground penetrating radar (GPR), for understanding the spatial distribution of porosity variability in the Miami Limestone presented as a compilation of studies where scale of measurement is progressively increased to account for varying dimensions of dissolution features. In Chapter 2, GPR in zero offset acquisition mode is used to investigate the 2-D distribution of porosity and dielectric permittivity in a block of Miami Limestone at the laboratory scale (< 1.0 m). Petrophysical models based on fully saturated and unsaturated water conditions are used to estimate porosity and solid dielectric permittivity of the limestone. Results show a good correspondence between analytical and GPR-based porosity estimates and show variability between 22.0-66.0 %. In Chapter 3, GPR in common offset and common midpoint acquisition mode are used to estimate bulk porosity of the unsaturated Miami Limestone at the field scale (10.0-100.0 m). Estimates of porosity are based on the assumption that the directly measured water table reflector is flat and that any deviation is attributed to changes in velocity due to porosity variability. Results show sharp changes in porosity ranging between 33.2-60.9 % attributed to dissolution areas. In Chapter 4, GPR in common offset mode is used to characterize porosity variability in the saturated Biscayne aquifer at 100-1000 m field scales. The presence of numerous diffraction hyperbolae are used to estimate electromagnetic wave velocity and asses both horizontal and vertical changes in porosity after application of a petrophysical model. Results show porosity variability between 23.0-41.0 % and confirm the presence of isolated areas that could serve as enhanced infiltration or recharge. This research allows for the identification and delineation areas of macroporosity areas at 0.01 m lateral resolution and shows variability of porosity at different scales, reaching 37.0 % within 1.3 m, associated with areas of enhanced dissolution. Such improved resolution of porosity estimates can benefit water management efforts and transport modelling and help to better understand small scale relationships between ground water and surface water interactions.

Evaluation and selection of bio-relevant dissolution media for a poorly water-soluble new chemical entity.

PubMed

Tang, L; Khan, S U; Muhammad, N A

2001-11-01

The purpose of this work is to develop a bio-relevant dissolution method for formulation screening in order to select an enhanced bioavailable formulation for a poorly water-soluble drug. The methods used included a modified rotating disk apparatus for measuring intrinsic dissolution rate of the new chemical entity (NCE) and the USP dissolution method II for evaluating dissolution profiles of the drug in three different dosage forms. The in vitro dissolution results were compared with the in vivo bioavailability for selecting a bio-relevant medium. The results showed that the solubility of the NCE was proportional to the concentration of sodium lauryl sulfate (SLS) in the media. The apparent intrinsic dissolution rate of the NCE was linear to the rotational speed of the disk, which indicated that the dissolution of the drug is a diffusion-controlled mechanism. The apparent intrinsic dissolution rate was also linear to the surfactant concentration in the media, which was interpreted using the Noyes and Whitney Empirical Theory. Three formulations were studied in three different SLS media using the bulk drug as a reference. The dissolution results were compared with the corresponding bioavailability results in dogs. In the 1% SLS--sink conditions--the drug release from all the formulations was complete and the dissolution results were discriminative for the difference in particle size of the drug in the formulations. However, the data showed poor IVIV correlation. In the 0.5% SLS medium--non-sink conditions--the dissolution results showed the same rank order among the tested formulations as the bioavailability. The best IVIV correlation was obtained from the dissolution in 0.25% SLS medium, an over-saturated condition. The conclusions are: a surfactant medium increases the apparent intrinsic dissolution rate of the NCE linearly due to an increase in solubility. A low concentration of surfactant in the medium (0.25%) is more bio-relevant than higher concentrations of surfactant in the media for the poorly water-soluble drug. Creating sink conditions (based on bulk drug solubilities) by using a high concentration of a surfactant in the dissolution medium may not be a proper approach in developing a bio-relevant dissolution method for a poorly water-soluble drug.

Automated potentiometric procedure for studying dissolution kinetics acidic drugs under sink conditions.

PubMed

Underwood, F L; Cadwallader, D E

1978-08-01

An automated potentiometric procedure was used for studying in vitro dissolution kinetics of acidic drugs. Theoretical considerations indicated that the pH-stat method could be used to establish approximate sink conditions or, possibly, a perfect sink. Data obtained from dissolution studies using the pH-stat method were compared with data obtained from known sink and nonsink conditions. These comparisons indicated that the pH-stat method can be used to establish a sink condition for dissolution studies. The effective diffusion layer thicknesses for benzoic and salicylic acids dissolving in water were determined, and a theoretical dissolution rate was calculated utilizing these values. The close agreement between the experimental dissolution rates obtained under pH-stat conditions and theoretical dissolution rates indicated that perfect sink conditions were established under the experimental conditions used.

Biopharmaceutical characterisation of ciprofloxacin-metallic ion interactions: comparative study into the effect of aluminium, calcium, zinc and iron on drug solubility and dissolution.

PubMed

Stojković, Aleksandra; Tajber, Lidia; Paluch, Krzysztof J; Djurić, Zorica; Parojčić, Jelena; Corrigan, Owen I

2014-03-01

Ciprofloxacin bioavailability may be reduced when ciprofloxacin is co-administered with metallic ion containing preparations. In our previous study, physicochemical interaction between ciprofloxacin and ferrous sulphate was successfully simulated in vitro. In the present work, comparative in vitro ciprofloxacin solubility and dissolution studies were performed in the reactive media containing aluminium hydroxide, calcium carbonate or zinc sulphate. Solid phases collected from the dissolution vessel with aluminium hydroxide, calcium carbonate and zinc sulphate were investigated for their properties. The results obtained indicate that different types of adducts may form and retard ciprofloxacin solubility and dissolution. In the case of aluminium, no phase changes were observed. The solid phase generated in the presence of calcium carbonate was identified as hydrated ciprofloxacin base. Similarly to iron, a new complex consistent with Zn(SO4)2(Cl)2(ciprofloxacin)2 × nH2O stoichiometry was generated in the presence of relatively high concentrations of ciprofloxacin hydrochloride and zinc sulphate, indicating that small volume dissolution experiments can be useful for biorelevant dissolution tests.

Solubility and dissolution improvement of ketoprofen by emulsification ionic gelation

NASA Astrophysics Data System (ADS)

Rachmaniar, Revika; Tristiyanti, Deby; Hamdani, Syarif; Afifah

2018-02-01

Ketoprofen or [2-(3-benzoylphenyl) propionic acid] is non-steroidal anti-inflammatory (NSAID) and an analgesic which has high permeability and low solubility. The purpose of this work was to improve the solubility and dissolution of poorly water-soluble ketoprofen prepared by emulsification ionic gelation method and utilizing polymer (chitosan) and cross linker (tripolyphosphate, TPP) for particles formulation. The results show that increasing pH value of TPP, higher solubility and dissolution of as-prepared ketoprofen-chitosan was obtained. The solubility in water of ketoprofen-chitosan with pH 6 for TPP increased 2.71-fold compared to untreated ketoprofen. While the dissolution of ketoprofen-chitosan with pH 6 of TPP in simulated gastric fluid without enzyme (0.1 N HCl), pH 4.5 buffer and simulated intestinal fluid without enzyme (phosphate buffer pH 6.8) was increased 1.9-fold, 1.6-fold and 1.2-fold compared to untreated ketoprofen for dissolution time of 30 minutes, respectively. It could be concluded that chitosan and TPP in the emulsification ionic gelation method for ketoprofen preparation effectively increases solubility and dissolution of poorly water-soluble ketoprofen.

Statistical Considerations Concerning Dissimilar Regulatory Requirements for Dissolution Similarity Assessment. The Example of Immediate-Release Dosage Forms.

PubMed

Jasińska-Stroschein, Magdalena; Kurczewska, Urszula; Orszulak-Michalak, Daria

2017-05-01

When performing in vitro dissolution testing, especially in the area of biowaivers, it is necessary to follow regulatory guidelines to minimize the risk of an unsafe or ineffective product being approved. The present study examines model-independent and model-dependent methods of comparing dissolution profiles based on various compared and contrasted international guidelines. Dissolution profiles for immediate release solid oral dosage forms were generated. The test material comprised tablets containing several substances, with at least 85% of the labeled amount dissolved within 15 min, 20-30 min, or 45 min. Dissolution profile similarity can vary with regard to the following criteria: time point selection (including the last time point), coefficient of variation, and statistical method selection. Variation between regulatory guidance and statistical methods can raise methodological questions and result potentially in a different outcome when reporting dissolution profile testing. The harmonization of existing guidelines would address existing problems concerning the interpretation of regulatory recommendations and research findings. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Physical heterogeneity control on effective mineral dissolution rates

NASA Astrophysics Data System (ADS)

Jung, Heewon; Navarre-Sitchler, Alexis

2018-04-01

Hydrologic heterogeneity may be an important factor contributing to the discrepancy in laboratory and field measured dissolution rates, but the governing factors influencing mineral dissolution rates among various representations of physical heterogeneity remain poorly understood. Here, we present multiple reactive transport simulations of anorthite dissolution in 2D latticed random permeability fields and link the information from local grid scale (1 cm or 4 m) dissolution rates to domain-scale (1m or 400 m) effective dissolution rates measured by the flux-weighted average of an ensemble of flow paths. We compare results of homogeneous models to heterogeneous models with different structure and layered permeability distributions within the model domain. Chemistry is simplified to a single dissolving primary mineral (anorthite) distributed homogeneously throughout the domain and a single secondary mineral (kaolinite) that is allowed to dissolve or precipitate. Results show that increasing size in correlation structure (i.e. long integral scales) and high variance in permeability distribution are two important factors inducing a reduction in effective mineral dissolution rates compared to homogeneous permeability domains. Larger correlation structures produce larger zones of low permeability where diffusion is an important transport mechanism. Due to the increased residence time under slow diffusive transport, the saturation state of a solute with respect to a reacting mineral approaches equilibrium and reduces the reaction rate. High variance in permeability distribution favorably develops large low permeability zones that intensifies the reduction in mixing and effective dissolution rate. However, the degree of reduction in effective dissolution rate observed in 1 m × 1 m domains is too small (<1% reduction from the corresponding homogeneous case) to explain several orders of magnitude reduction observed in many field studies. When multimodality in permeability distribution is approximated by high permeability variance in 400 m × 400 m domains, the reduction in effective dissolution rate increases due to the effect of long diffusion length scales through zones with very slow reaction rates. The observed scale dependence becomes complicated when pH dependent kinetics are compared to the results from pH independent rate constants. In small domains where the entire domain is reactive, faster anorthite dissolution rates and slower kaolinite precipitation rates relative to pH independent rates at far-from-equilibrium conditions reduce the effective dissolution rate by increasing the saturation state. However, in large domains where less- or non-reactive zones develop, higher kaolinite precipitation rates in less reactive zones increase the effective anorthite dissolution rates relative to the rates observed in pH independent cases.

Evaluation of a biphasic in vitro dissolution test for estimating the bioavailability of carbamazepine polymorphic forms.

PubMed

Deng, Jia; Staufenbiel, Sven; Bodmeier, Roland

2017-07-15

The purpose of this study was to discriminate three crystal forms of carbamazepine (a BCS II drug) by in vitro dissolution testing and to correlate in vitro data with published in vivo data. A biphasic dissolution system (phosphate buffer pH6.8 and octanol) was used to evaluate the dissolution of the three polymorphic forms and to compare it with conventional single phase dissolution tests performed under sink and non-sink conditions. Similar dissolution profiles of three polymorphic forms were observed in the conventional dissolution test under sink conditions. Although a difference in dissolution was seen in the single phase dissolution test under non-sink conditions as well as in the aqueous phase of the biphasic test, little relevance for in vivo data was observed. In contrast, the biphasic dissolution system could discriminate between the different polymorphic forms in the octanol phase with a ranking of form III>form I>dihydrate form. This was in agreement with the in vivo performance. The dissolved drug available for oral absorption, which was dominated by dissolution and solution-mediated phase transformation, could be reflected in the biphasic dissolution test. Moreover, a good correlation was established between in vitro dissolution in the octanol phase of the biphasic test and in vivo pharmacokinetic data (R 2 =0.99). The biphasic dissolution method is a valuable tool to discriminate between different crystal forms in the formulations of poorly soluble drugs. Copyright © 2017. Published by Elsevier B.V.

Development and validation of a discriminating in vitro dissolution method for a poorly soluble drug, olmesartan medoxomil: comparison between commercial tablets.

PubMed

Bajerski, Lisiane; Rossi, Rochele Cassanta; Dias, Carolina Lupi; Bergold, Ana Maria; Fröehlich, Pedro Eduardo

2010-06-01

A dissolution test for tablets containing 40 mg of olmesartan medoxomil (OLM) was developed and validated using both LC-UV and UV methods. After evaluation of the sink condition, dissolution medium, and stability of the drug, the method was validated using USP apparatus 2, 50 rpm rotation speed, and 900 ml of deaerated H(2)O + 0.5% sodium lauryl sulfate (w/v) at pH 6.8 (adjusted with 18% phosphoric acid) as the dissolution medium. The model-independent method using difference factor (f(1)) and similarity factor (f(2)), model-dependent method, and dissolution efficiency were employed to compare dissolution profiles. The kinetic parameters of drug release were also investigated. The obtained results provided adequate dissolution profiles. The developed dissolution test was validated according to international guidelines. Since there is no monograph for this drug in tablets, the dissolution method presented here can be used as a quality control test for OLM in this dosage form, especially in a batch to batch evaluation.

Quartz dissolution. I - Negative crystal experiments and a rate law. II - Theory of rough and smooth surfaces

NASA Technical Reports Server (NTRS)

Gratz, Andrew J.; Bird, Peter

1993-01-01

The range of the measured quartz dissolution rates, as a function of temperature and pOH, extent of saturation, and ionic strength, is extended to cover a wider range of solution chemistries, using the negative crystal methodology of Gratz et al. (1990) to measure the dissolution rate. A simple rate law describing the quartz dissolution kinetics above the point of zero charge of quartz is derived for ionic strengths above 0.003 m. Measurements were performed on some defective crystals, and the mathematics of step motion was developed for quartz dissolution and was compared with rough-face behavior using two different models.

Dissolution of Biogenic and Synthetic UO2 under Varied Reducing Conditions

PubMed Central

ULRICH, KAI – UWE; SINGH, ABHAS; SCHOFIELD, ELEANOR J.; BARGAR, JOHN R.; VEERAMANI, HARISH; SHARP, JONATHAN O.; LATMANI, RIZLAN BERNIER -; GIAMMAR, DANIEL E.

2008-01-01

The chemical stability of biogenic UO2, a nanoparticulate product of environmental bioremediation, may be impacted by the particles’ surface free energy, structural defects, and compositional variability in analogy to abiotic UO2+x (0 ≤ x ≤ 0.25). This study quantifies and compares intrinsic solubility and dissolution rate constants of biogenic nano-UO2 and synthetic bulk UO2.00, taking molecular-scale structure into account. Rates were determined under anoxic conditions as a function of pH and dissolved inorganic carbon in continuous-flow experiments. The dissolution rates of biogenic and synthetic UO2 solids were lowest at near neutral pH and increased with decreasing pH. Similar surface area-normalized rates of biogenic and synthetic UO2 suggest comparable reactive surface site densities. This finding is consistent with the identified structural homology of biogenic UO2 and stoichiometric UO2.00. Compared to carbonate-free anoxic conditions, dissolved inorganic carbon accelerated the dissolution rate of biogenic UO2 by 3 orders of magnitude. This phenomenon suggests continuous surface oxidation of U(IV) to U(VI), with detachment of U(VI) as the rate-determining step in dissolution. Although reducing conditions were maintained throughout the experiments, the UO2 surface can be oxidized by water and radiogenic oxidants. Even in anoxic aquifers, UO2 dissolution may be controlled by surface U(VI) rather than U(IV) phases. PMID:18754482

Differential gene expression in Daphnia magna suggests distinct modes of action and bioavailability for ZnO nanoparticles and Zn ions

EPA Science Inventory

Zinc oxide nanoparticles (ZnO NPs) are being rapidly developed for use in consumer products, wastewater treatment and chemotherapy, providing several possible routes for ZnO NP exposure to humans and aquatic organisms. Recent studies have shown that ZnO NPs undergo rapid dissolut...

Iron dissolution of dust source materials during simulated acidic processing: the effect of sulfuric, acetic, and oxalic acids.

PubMed

Chen, Haihan; Grassian, Vicki H

2013-09-17

Atmospheric organic acids potentially display different capacities in iron (Fe) mobilization from atmospheric dust compared with inorganic acids, but few measurements have been made on this comparison. We report here a laboratory investigation of Fe mobilization of coal fly ash, a representative Fe-containing anthropogenic aerosol, and Arizona test dust, a reference source material for mineral dust, in pH 2 sulfuric acid, acetic acid, and oxalic acid, respectively. The effects of pH and solar radiation on Fe dissolution have also been explored. The relative capacities of these three acids in Fe dissolution are in the order of oxalic acid > sulfuric acid > acetic acid. Oxalate forms mononuclear bidentate ligand with surface Fe and promotes Fe dissolution to the greatest extent. Photolysis of Fe-oxalate complexes further enhances Fe dissolution with the concomitant degradation of oxalate. These results suggest that ligand-promoted dissolution of Fe may play a more significant role in mobilizing Fe from atmospheric dust compared with proton-assisted processing. The role of atmospheric organic acids should be taken into account in global-biogeochemical modeling to better access dissolved atmospheric Fe deposition flux at the ocean surface.

Make and break - Facile synthesis of cocrystals and comprehensive dissolution studies

NASA Astrophysics Data System (ADS)

Batzdorf, L.; Zientek, N.; Rump, D.; Fischer, F.; Maiwald, M.; Emmerling, F.

2017-04-01

Mechanochemistry is increasingly used as a 'green alternative' for synthesizing various materials including pharmaceutical cocrystals. Herein, we present the mechanochemical synthesis of three new cocrystals containing the API carbamazepine (cocrystals CBZ:Indometacin 1:1, CBZ:Benzamide 1:1, and CBZ:Nifedipine 1:1). The mechanochemical reaction was investigated in situ documenting a fast and complete reaction within one minute. Online NMR spectroscopy proved the direct influence of the dissolution behaviour of the coformers to the dissolution behaviour of the API carbamazepine. The dissolution behaviour of the organic cocrystals is compared to the behaviour of the pure drug indicating a general applicability of this approach for detailed cocrystal dissolution studies.

Dissolution Kinetics of Spheroidal-Shaped Precipitates in Age-Hardenable Aluminum Alloys

NASA Astrophysics Data System (ADS)

Anjabin, Nozar; Salehi, Majid Seyed

2018-05-01

As a first attempt, a mathematical model is proposed to predict the dissolution kinetics of non-spherical secondary phase precipitates during solution heat treatment of age-hardenable aluminum alloys. The model uses general spheroidal geometry to describe the dissolution process of the alloys containing needle/disc-shaped particles with different size distributions in a finite matrix. It is found that as the aspect ratio deviates from unity, the dissolution rate is accelerated. Also, the dissolution rate of the particles in the alloy containing the particle size distribution is lower than that of mono-sized particles system. The modeling results for dissolution of θ' precipitates in an Al-Cu alloy are compared with experiments, and a good agreement was found between the modeling and the experimental results. The proposed model can be applied to different isothermal and non-isothermal annealing conditions.

Glass fiber dissolution in simulated lung fluid and measures needed to improve consistency and correspondence to in vivo dissolution.

PubMed Central

Mattson, S M

1994-01-01

The dissolution of a range of glass fibers including commercial glass and mineral wools has been studied using a modification of Gamble's solution in a flow system at pH 7.4 and 37 degrees C. Dissolution has been followed by weight loss, effluent analysis, and morphology change of fibers and bulk glass. Flow per glass surface area can strongly affect both dissolution rate and morphology due to the effect of the dissolution process on the fluid. Effluent pH is shown to be a guide for choice of optimum flow/area conditions. These conditions provide measurable concentrations of dissolved glass in the effluent while maintaining their concentrations below the point at which they significantly affect the dissolution process. SiO2 and Al2O3 vary widely in the extent to which they are involved in the leaching process, which removes alkalis, alkaline earths, and B2O3. This makes analysis of a single component in the effluent unsuitable as a means of comparing the dissolution rates of a wide range of compositions. PMID:7882963

Corrosion study of AA2024-T3 by scanning Kelvin probe force microscopy and in situ atomic force microscopy scratching

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schmutz, P.; Frankel, G.S.

1998-07-01

The localized corrosion of AA2024-T3, and the behavior of intermetallic particles in particular, were studied using different capabilities of the atomic force microscope (AFM). The role of intermetallic particles in determining the locations and rates of localized corrosion was determined using scanning Kelvin probe force microscopy in air after exposure to chloride solutions. Al-Cu-Mg particles, which have a noble Volta potential in air because of an altered surface film, are actively dissolved in chloride solution after a certain induction time. Al-Cu(Fe, Mn) particles are heterogeneous in nature and exhibit nonuniform dissolution in chloride solution as well as trenching of themore » matrix around the particles. Light scratching of the surface by rastering with the AFM tip in contact mode in chloride solution results in accelerated dissolution of both pure Al and alloy 2024-T3. The abrasion associated with contact AFM in situ resulted in the immediate dissolution of the Al-Cu-Mg particles because of a destabilization of the surface film.« less

Microstructural disintegration in dense hydroxyapatite and hydroxyapatite-coated metal implants

NASA Astrophysics Data System (ADS)

Seo, Dong Seok; Lee, Jong Kook

2007-08-01

Hydroxyapatite (HA) has been widely used as a coating for orthopedic metal implants. An important concern regarding HA coating is its degradation of the biological milieu. In this study, the microstructure of a retrieved HA-coated acetabular cup implanted for four years after total hip arthroplasty (THA) was investigated by field emission scanning electron microscopy. In order to understand the underlying mechanism, of degradation and exfoliation of the HA coating, degradation of phase-pure and dense HA ceramics was also observed by in vitro and in vivo testing. The surface morphology and fracture surfaces of HA ceramics revealed that the dissolution starting at the surface extended inwards resulting in particle loosening and microstructural-level degradation. The dissolution features of HA ceramics were similar to the case of HA coating. It was found that extensive dissolution of the coating occurred and most of the coating disappeared. The majority of the remaining graints were fractured by the intergranular mode, suggesting that grain boundaries should be predominantly dissolved. These observations may explain the mechanism through which the biological stability of the HA coated layer becomes unexpectedly poor.

Influence of zeolite precipitation on borosilicate glass alteration under hyperalkaline conditions

NASA Astrophysics Data System (ADS)

Mercado-Depierre, S.; Fournier, M.; Gin, S.; Angeli, F.

2017-08-01

This study enables a better understanding of how nucleation-growth of zeolites affects glass dissolution kinetics in hyperalkaline solutions characteristic of cement waters. A 20-oxide borosilicate glass, an inactive surrogate of a typical intermediate level waste glass, was altered in static mode at 50 °C in a hyperalkaline solution rich in Na+, K+ and Ca2+ and at an initial pH50°C of 12.6. Experiments were performed at four glass-surface-area-to-solution-volume (S/V) ratios to investigate various reaction progresses. Two types of glass alteration kinetics were obtained: (i) at low S/V, a sharp alteration resumption occurred after a rate drop regime, (ii) at high S/V, a high dissolution rate was maintained throughout the test duration with a slight progressive slow-down. In all the experiments, zeolites precipitated but the time taken to form stable zeolite nuclei varied dramatically depending on the S/V. Resulting changes in pH affected zeolite composition, morphology, solubility and growth rate. A change in a critical parameter such as S/V affected all the processes controlling glass dissolution.

Limestone weathering rates accelerated by micron-scale grain detachment

NASA Astrophysics Data System (ADS)

Emmanuel, S.; Levenson, Y.

2014-12-01

The weathering rates of carbonate rocks is often thought to be controlled by chemical dissolution, although some studies have suggested that mechanical erosion could also play an important role. Quantifying the rates of the different processes has proved challenging due to the high degree of variability encountered in both field and lab settings. To determine the rates and mechanisms controlling long-term limestone weathering, we analyse a lidar scan of the Western Wall, a Roman period edifice located in Jerusalem. Weathering rates in fine-grained micritic limestone blocks are up to 2 orders of magnitude higher than the average rates estimated for coarse-grained limestone blocks at the same site. In addition, in experiments that use atomic force microscopy to image dissolving micritic limestone, we show that these higher reaction rates could be due to rapid dissolution along micron-scale grain boundaries, followed by mechanical detachment of tiny particles from the surface. Our analysis indicates that micron-scale grain detachment, rather than pure chemical dissolution, could be the dominant erosional mode for fine-grained rocks in many carbonate terrains.

Extreme limestone weathering rates due to micron-scale grain detachment

NASA Astrophysics Data System (ADS)

Emmanuel, Simon; Levenson, Yael

2014-05-01

Chemical dissolution is often assumed to control the weathering rates of carbonate rocks, although some studies have indicated that mechanical erosion could also play a significant role. Quantifying the rates of the different processes is challenging due to the high degree of variability encountered in both field and lab settings. To measure the rates and mechanisms controlling long-term limestone weathering, we analyse a lidar scan of the Western Wall, a Roman period edifice located in Jerusalem. Surface retreat rates in fine-grained micritic limestone blocks are found to be as much as 2 orders of magnitude higher than the average rates estimated for coarse-grained limestone blocks at the same site. In addition, in experiments that use atomic force microscopy to image dissolving micritic limestone, we show that these elevated reaction rates could be due to rapid dissolution along micron-scale grain boundaries, followed by mechanical detachment of tiny particles from the surface. Our analysis indicates that micron-scale grain detachment, rather than pure chemical dissolution, could be the dominant erosional mode for fine-grained carbonate rocks.

Dissolution Rates and Mineral Lifetimes of Phosphate Containing Minerals and Implications for Mars

NASA Astrophysics Data System (ADS)

Adcock, C. T.; Hausrath, E.

2011-12-01

The objectives of NASA's Mars Exploration Program include exploring the planet's habitability and the possibility of past, present, or future life. This includes investigating "possible supplies of bioessential elements" [1]. Phosphate is one such bioessential element for life as we understand it. Phosphate is also abundant on Mars [2], and the phosphate rich minerals chlorapatite, fluorapatite, and merrillite have been observed in Martian meteorites [3]. Surface rock analyses from the MER Spirit also show the loss of a phosphate rich mineral from the rocks Wishstone and Watchtower at Gusev Crater [4,5], implying mineral dissolution. Dissolution rates of phosphate containing minerals are therefore important for characterizing phosphate mobility and bioavailability on Mars. Previous studies have measured dissolution rates of fluorapatite [6-8]. However, chlorapatite and merrillite (a non-terrestrial mineral similar to whitlockite) are more common phosphate minerals found in Martian meteorites [3], and few dissolution data exist for these minerals. We have begun batch dissolution experiments on chlorapatite, synthesized using methods of [9], and whitlockite, synthesized using a method modified from [10]. Additionally, we are dissolving Durango fluorapatite to compare to dissolution rates in literature, and natural Palermo whitlockite to compare to dissolution rates of our synthesized whitlockite. Batch dissolution experiments were performed after [8], using a 0.01 molar KNO3 solution with 0.1500g-0.3000g mineral powders and starting solution volumes of 180ml in LDPE reaction vessels. HNO3 or KOH were used to adjust initial pH as required. Dissolution rates are calculated from the rate of change of elemental concentration in solution as a function of time, and normalized to the mineral surface area as measured by BET. Resulting rates will be used to calculate mineral lifetimes for the different phosphate minerals under potential Mars-like aqueous conditions, and in future reactive transport modeling.

Significance of a Shelf-wide Dissolution Event during the Paleocene-Eocene Thermal Maximum, Maryland and New Jersey, USA

NASA Astrophysics Data System (ADS)

Bralower, T. J.; Kump, L. R.; Robinson, M. M.; Self-Trail, J. M.; Zachos, J. C.

2016-12-01

Continental-shelf sediments of the US Atlantic margin experienced a brief episode of carbonate dissolution during the onset of the Paleocene-Eocene Thermal Maximum (PETM). Dissolution is represented by reduced percentages of carbonate, and calcareous microfossil distribution and preservation trends, in cores from Maryland and New Jersey. The base and the top of the dissolution zone are abrupt compared to the gradual nature of the onset of the carbon isotope excursion (CIE). The thickness of the dissolution zone varies from 9 cm in the Bass River core (outer paleoshelf) to 1.6 m in the CamDor core (middle paleoshelf). The decrease in %CaCO3 suggests dissolution locally removed 83 to 100% of the initial biogenic carbonate. Shelf-wide dissolution during the onset of the PETM may be a regional event, associated, for example, with eutrophication. Samples from across the paleoshelf contain abundant fine-grained framboidal pyrite, which suggests photic-zone euxinia occurred before, during, and after the dissolution event. Dissolution may also be associated with oxidation of this pyrite during later exposure to oxidizing groundwaters, although the restricted duration of the dissolution interval argues against this. Alternatively, the dissolution event may have global significance related to surface ocean-water acidification or shoaling of the calcite compensation depth (CCD) to shelf depths. The event began near the onset of the CIE on the shelf, whereas dissolution in deep-sea sections began later. Earlier shelf dissolution is consistent with surface ocean acidification while later deep-sea dissolution is thought to be associated with shoaling of the CCD. In our presentation, we weigh evidence for each of these possibilities and test them using the global dataset.

A novel dissolution media for testing drug release from a nanostructured polysaccharide-based colon specific drug delivery system: an approach to alternative colon media.

PubMed

Kotla, Niranjan G; Singh, Sima; Maddiboyina, Balaji; Sunnapu, Omprakash; Webster, Thomas J

2016-01-01

The aim of this study was to develop a novel microbially triggered and animal-sparing dissolution method for testing of nanorough polysaccharide-based micron granules for colonic drug delivery. In this method, probiotic cultures of bacteria present in the colonic region were prepared and added to the dissolution media and compared with the performance of conventional dissolution methodologies (such as media with rat cecal and human fecal media). In this study, the predominant species (such as Bacteroides, Bifidobacterium, Lactobacillus species, Eubacterium and Streptococcus) were cultured in 12% w/v skimmed milk powder and 5% w/v grade "A" honey. Approximately 10(10)-10(11) colony forming units m/L of probiotic culture was added to the dissolution media to test the drug release of polysaccharide-based formulations. A USP dissolution apparatus I/II using a gradient pH dissolution method was used to evaluate drug release from formulations meant for colonic drug delivery. Drug release of guar gum/Eudragit FS30D coated 5-fluorouracil granules was assessed under gastric and small intestine conditions within a simulated colonic environment involving fermentation testing with the probiotic culture. The results with the probiotic system were comparable to those obtained from the rat cecal and human fecal-based fermentation model, thereby suggesting that a probiotic dissolution method can be successfully applied for drug release testing of any polysaccharide-based oral formulation meant for colonic delivery. As such, this study significantly adds to the nanostructured biomaterials' community by elucidating an easier assay for colonic drug delivery.

Development of a discriminative biphasic in vitro dissolution test and correlation with in vivo pharmacokinetic studies for differently formulated racecadotril granules.

PubMed

Deng, Jia; Staufenbiel, Sven; Hao, Shilei; Wang, Bochu; Dashevskiy, Andriy; Bodmeier, Roland

2017-06-10

The purpose of this study was to discriminate the release behavior from three differently formulated racecadotril (BCS II) granules and to establish an in vitro-in vivo correlation. Three granule formulations of the lipophilic drug were prepared with equivalent composition but prepared with different manufacturing processes (dry granulation, wet granulation with or without binder). In vitro release of the three granules was investigated using a biphasic dissolution system (phosphate buffer pH6.8 and octanol) and compared to the conventional single phase USP II dissolution test performed under sink and non-sink conditions. In vivo studies with each granule formulation were performed in rats. Interestingly, the granule formulations exhibited pronouncedly different behavior in the different dissolution systems depending on different wetting and dissolution conditions. Single phase USP II dissolution tests lacked discrimination. In contrast, remarkable discrimination between the granule formulations was observed in the octanol phase of biphasic dissolution system with a rank order of release from granules prepared by wet granulation with binder>wet granulation without binder>dry granulation. This release order correlated well with the wettability of these granules. An excellent correlation was also established between in vitro release in the octanol phase of the biphasic test and in vivo data (R 2 =0.999). Compared to conventional dissolution methods, the biphasic method provides great potential to discriminate between only minor formulation and process changes within the same dosage form for poorly soluble drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

In Vivo Predictive Dissolution: Comparing the Effect of Bicarbonate and Phosphate Buffer on the Dissolution of Weak Acids and Weak Bases.

PubMed

Krieg, Brian J; Taghavi, Seyed Mohammad; Amidon, Gordon L; Amidon, Gregory E

2015-09-01

Bicarbonate is the main buffer in the small intestine and it is well known that buffer properties such as pKa can affect the dissolution rate of ionizable drugs. However, bicarbonate buffer is complicated to work with experimentally. Finding a suitable substitute for bicarbonate buffer may provide a way to perform more physiologically relevant dissolution tests. The dissolution of weak acid and weak base drugs was conducted in bicarbonate and phosphate buffer using rotating disk dissolution methodology. Experimental results were compared with the predicted results using the film model approach of (Mooney K, Mintun M, Himmelstein K, Stella V. 1981. J Pharm Sci 70(1):22-32) based on equilibrium assumptions as well as a model accounting for the slow hydration reaction, CO2 + H2 O → H2 CO3 . Assuming carbonic acid is irreversible in the dehydration direction: CO2 + H2 O ← H2 CO3 , the transport analysis can accurately predict rotating disk dissolution of weak acid and weak base drugs in bicarbonate buffer. The predictions show that matching the dissolution of weak acid and weak base drugs in phosphate and bicarbonate buffer is possible. The phosphate buffer concentration necessary to match physiologically relevant bicarbonate buffer [e.g., 10.5 mM (HCO3 (-) ), pH = 6.5] is typically in the range of 1-25 mM and is very dependent upon drug solubility and pKa . © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Enhancement of ibuprofen dissolution via wet granulation with beta-cyclodextrin.

PubMed

Ghorab, M K; Adeyeye, M C

2001-08-01

The purpose was to investigate the effect of wet granulation with beta-cyclodextrin (betaCD) on the enhancement of ibuprofen (IBU) dissolution. The effect of the granulation variables on the physical properties as well as the dissolution of tablets prepared from these granules was also examined. Granulation was performed using three granulating solvents: water, ethanol (95 vol%), and isopropanol. Granules were either oven-dried for 2 h or air-dried for 3 days. The granules or respective physical mixtures were compressed into tablets. Powder X-ray diffraction showed that oven-dried granulation resulted in less amorphous entities thatfacilitated IBU-betaCD complexation in solution and enhanced the dissolution of the corresponding tablets compared to the physical mixture with or without oven drying. In contrast, air-dried granulation did not cause any differences in the X-ray diffraction pattern (crystallinity) or the dissolution compared to the physical mixture without drying. Isopropanol and water, as granulating solvents, enhanced the dissolution of the oven-dried batches more than ethanol. The Differential scanning calorimetry (DSC) and Thermogravimetric analysis (TGA) data showed that tablets prepared from oven-dried granules, but not air-dried granules, had lower AH values and percent loss in weight, respectively, than those prepared from the physical mixture as a result of the expulsion of the water molecules from the betaCD cavity and enhancement of the complexation in solution. These results showed that oven-dried granulation of IBU and betaCD provided faster IBU dissolution than the physical mixture; air-dried granulation did not substantially affect the dissolution of IBU.

Modifying Surface Chemistry of Metal Oxides for Boosting Dissolution Kinetics in Water by Liquid Cell Electron Microscopy.

PubMed

Lu, Yue; Geng, Jiguo; Wang, Kuan; Zhang, Wei; Ding, Wenqiang; Zhang, Zhenhua; Xie, Shaohua; Dai, Hongxing; Chen, Fu-Rong; Sui, Manling

2017-08-22

Dissolution of metal oxides is fundamentally important for understanding mineral evolution and micromachining oxide functional materials. In general, dissolution of metal oxides is a slow and inefficient chemical reaction. Here, by introducing oxygen deficiencies to modify the surface chemistry of oxides, we can boost the dissolution kinetics of metal oxides in water, as in situ demonstrated in a liquid environmental transmission electron microscope (LETEM). The dissolution rate constant significantly increases by 16-19 orders of magnitude, equivalent to a reduction of 0.97-1.11 eV in activation energy, as compared with the normal dissolution in acid. It is evidenced from the high-resolution TEM imaging, electron energy loss spectra, and first-principle calculations where the dissolution route of metal oxides is dynamically changed by local interoperability between altered water chemistry and surface oxygen deficiencies via electron radiolysis. This discovery inspires the development of a highly efficient electron lithography method for metal oxide films in ecofriendly water, which offers an advanced technique for nanodevice fabrication.

Theoretical and Numerical Investigation of the Cavity Evolution in Gypsum Rock

NASA Astrophysics Data System (ADS)

Li, Wei; Einstein, Herbert H.

2017-11-01

When water flows through a preexisting cylindrical tube in gypsum rock, the nonuniform dissolution alters the tube into an enlarged tapered tube. A 2-D analytical model is developed to study the transport-controlled dissolution in an enlarged tapered tube, with explicit consideration of the tapered geometry and induced radial flow. The analytical model shows that the Graetz solution can be extended to model dissolution in the tapered tube. An alternative form of the governing equations is proposed to take advantage of the invariant quantities in the Graetz solution to facilitate modeling cavity evolution in gypsum rock. A 2-D finite volume model was developed to validate the extended Graetz solution. The time evolution of the transport-controlled and the reaction-controlled dissolution models for a single tube with time-invariant flow rate are compared. This comparison shows that for time-invariant flow rate, the reaction-controlled dissolution model produces a positive feedback between the tube enlargement and dissolution, while the transport-controlled dissolution does not.

Microfibrous Solid Dispersions of Poorly Water-Soluble Drugs Produced via Centrifugal Spinning: Unexpected Dissolution Behavior on Recrystallization.

PubMed

Marano, Stefania; Barker, Susan A; Raimi-Abraham, Bahijja T; Missaghi, Shahrzad; Rajabi-Siahboomi, Ali; Aliev, Abil E; Craig, Duncan Q M

2017-05-01

Temperature-controlled, solvent-free centrifugal spinning may be used as a means of rapid production of amorphous solid dispersions in the form of drug-loaded sucrose microfibers. However, due to the high content of amorphous sucrose in the formulations, such microfibers may be highly hygroscopic and unstable on storage. In this study, we explore both the effects of water uptake of the microfibers and the consequences of deliberate recrystallization for the associated dissolution profiles. The stability of sucrose microfibers loaded with three selected BCS class II model drugs (itraconazole (ITZ), olanzapine (OLZ), and piroxicam (PRX)) was investigated under four different relative humidity conditions (11, 33, 53, and 75% RH) at 25 °C for 8 months, particularly focusing on the effect of the highest level of moisture (75% RH) on the morphology, size, drug distribution, physical state, and dissolution performance of microfibers. While all samples were stable at 11% RH, at 33% RH the ITZ-sucrose system showed greater resistance against devitrification compared to the OLZ- and PRX-sucrose systems. For all three samples, the freshly prepared microfibers showed enhanced dissolution and supersaturation compared to the drug alone and physical mixes; surprisingly, the dissolution advantage was largely maintained or even enhanced (in the case of ITZ) following the moisture-induced recrystallization under 75% RH. Therefore, this study suggests that the moisture-induced recrystallization process may result in considerable dissolution enhancement compared to the drug alone, while overcoming the physical stability risks associated with the amorphous state.

In vitro dissolution of generic immediate-release solid oral dosage forms containing BCS class I drugs: comparative assessment of metronidazole, zidovudine, and amoxicillin versus relevant comparator pharmaceutical products in South Africa and India.

PubMed

Reddy, Nallagundla H S; Patnala, Srinivas; Löbenberg, Raimar; Kanfer, Isadore

2014-10-01

Biowaivers are recommended for immediate-release solid oral dosage forms using dissolution testing as a surrogate for in vivo bioequivalence studies. Several guidance are currently available (the World Health Organization (WHO), the US FDA, and the EMEA) where the conditions are described. In this study, definitions, criteria, and methodologies according to the WHO have been applied. The dissolution performances of immediate-release metronidazole, zidovudine, and amoxicillin products purchased in South African and Indian markets were compared to the relevant comparator pharmaceutical product (CPP)/reference product. The dissolution performances were studied using US Pharmacopeia (USP) apparatus 2 (paddle) set at 75 rpm in each of three dissolution media (pH1.2, 4.5, and 6.8). Concentrations of metronidazole, zidovudine, and amoxicillin in each dissolution media were determined by HPLC. Of the 11 metronidazole products tested, only 8 could be considered as very rapidly dissolving products as defined by the WHO, whereas 2 of those products could be considered as rapidly dissolving products but did not comply with the f 2 acceptance criteria in pH 6.8. All 11 zidovudine products were very rapidly dissolving, whereas in the case of the 14 amoxicillin products tested, none of those products met any of the WHO criteria. This study indicates that not all generic products containing the same biopharmaceutics classification system (BCS) I drug and in similar strength and dosage form are necessarily in vitro equivalent. Hence, there is a need for ongoing market surveillance to determine whether marketed generic products containing BCS I drugs meet the release requirements to confirm their in vitro bioequivalence to the respective reference product.

Aluminum Target Dissolution in Support of the Pu-238 Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

McFarlane, Joanna; Benker, Dennis; DePaoli, David W

2014-09-01

Selection of an aluminum alloy for target cladding affects post-irradiation target dissolution and separations. Recent tests with aluminum alloy 6061 yielded greater than expected precipitation in the caustic dissolution step, forming up to 10 wt.% solids of aluminum hydroxides and aluminosilicates. We present a study to maximize dissolution of aluminum metal alloy, along with silicon, magnesium, and copper impurities, through control of temperature, the rate of reagent addition, and incubation time. Aluminum phase transformations have been identified as a function of time and temperature, using X-ray diffraction. Solutions have been analyzed using wet chemical methods and X-ray fluorescence. These datamore » have been compared with published calculations of aluminum phase diagrams. Temperature logging during the transients has been investigated as a means to generate kinetic and mass transport data on the dissolution process. Approaches are given to enhance the dissolution of aluminum and aluminosilicate phases in caustic solution.« less

Differing disintegration and dissolution rates, pharmacokinetic profiles and gastrointestinal tolerability of over the counter ibuprofen formulations.

PubMed

Bjarnason, Ingvar; Sancak, Ozgur; Crossley, Anne; Penrose, Andrew; Lanas, Angel

2018-02-01

Formulations of over the counter (OTC) NSAIDs differ substantially, but information is lacking on whether this alters their gastrointestinal profiles. To assess disintegration and dissolution rates and pharmacokinetics of four preparations of OTC ibuprofen and relate these with spontaneously reported gastrointestinal adverse events. Disintegration and dissolution rates of ibuprofen tablets as (a) acid, (b) sodium salt, (c) lysine salt, and (d) as a liquid gelatine capsule were assessed. Pharmacokinetic data gastrointestinal and spontaneously reported adverse events arising from global sales were obtained from files from Reckitt Benckiser. Disintegration at low pH was progressively shorter for the preparations from a-to-d with formation of correspondingly smaller ibuprofen crystals, while dissolution was consistently poor. Dissolution at a neutral pH was least rapid for the liquid gelatine capsule. Pharmacokinetic data showed a shorter t max and a higher C max for preparations b-d as compared with ibuprofen acid. Spontaneously reported abdominal symptoms were rare with the liquid gelatine preparation. The formulations of OTC ibuprofen differ in their disintegration and dissolution properties, pharmacokinetic profiles and apparent gastrointestinal tolerability. Spontaneously reported abdominal symptoms were five times lower with the liquid gelatine capsule as compared with ibuprofen acid despite a 30% increase in C max . © 2017 Royal Pharmaceutical Society.

Abnormal grain growth in AISI 304L stainless steel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shirdel, M., E-mail: mshirdel1989@ut.ac.ir; Mirzadeh, H., E-mail: hmirzadeh@ut.ac.ir; Advanced Metalforming and Thermomechanical Processing Laboratory, School of Metallurgy and Materials Engineering, University of Tehran, Tehran

2014-11-15

The microstructural evolution during abnormal grain growth (secondary recrystallization) in 304L stainless steel was studied in a wide range of annealing temperatures and times. At relatively low temperatures, the grain growth mode was identified as normal. However, at homologous temperatures between 0.65 (850 °C) and 0.7 (900 °C), the observed transition in grain growth mode from normal to abnormal, which was also evident from the bimodality in grain size distribution histograms, was detected to be caused by the dissolution/coarsening of carbides. The microstructural features such as dispersed carbides were characterized by optical metallography, X-ray diffraction, scanning electron microscopy, energy dispersivemore » X-ray analysis, and microhardness. Continued annealing to a long time led to the completion of secondary recrystallization and the subsequent reappearance of normal growth mode. Another instance of abnormal grain growth was observed at homologous temperatures higher than 0.8, which may be attributed to the grain boundary faceting/defaceting phenomenon. It was also found that when the size of abnormal grains reached a critical value, their size will not change too much and the grain growth behavior becomes practically stagnant. - Highlights: • Abnormal grain growth (secondary recrystallization) in AISI 304L stainless steel • Exaggerated grain growth due to dissolution/coarsening of carbides • The enrichment of carbide particles by titanium • Abnormal grain growth due to grain boundary faceting at very high temperatures • The stagnancy of abnormal grain growth by annealing beyond a critical time.« less

Corrosion of Cu-xZn alloys in slightly alkaline chloride solutions studied by stripping voltammetry and microanalysis.

PubMed

Milosev, I; Minović, A

2001-01-01

The mechanism of corrosion of Cu-xZn alloys (x = 10-40 wt %) in slightly alkaline chloride solutions was investigated by analysing solid reaction products by energy dispersive X-ray analysis (EDS) and dissolved reaction products by differential anodic pulse stripping (DAPS) voltammetry. The corrosion process was studied under open circuit and under potentiostatic conditions at selected potentials. Pure metals were studied comparatively so that an interacting effect of particular metal components in the alloy could be determined. All four Cu-xZn alloys show an improved behaviour compared to pure metals. Under open-circuit condition both components dissolve simultaneously in the solution. With increasing immersion time the preferential, dissolution of zinc in the solution becomes pronounced. It is the highest for Cu-10Zn and the lowest for Cu-30Zn alloy. Under potentiostatic control the dissolution mechanism depends on the electrode potential and changes from exclusive dissolution of zinc to simultaneous dissolution of both components with preferential dissolution of zinc. The latter decreases, as the electrode potential becomes more positive.

Factors associated with relationship dissolution and post-dissolution adjustment among lesbian adoptive couples.

PubMed

Farr, Rachel H

2017-01-02

Same-sex adoptive couples are increasingly visible, yet few studies have addressed relationship stability and dissolution among these couples. In this study, using a theoretical framework based on Investment Models and Vulnerability-Stress-Adaptation Theory, factors associated with dissolution and post-dissolution adjustment among 27 lesbian adoptive couples were examined across two points. At Wave 1, all 27 couples were together; children were on average 3 years old. Results revealed that nearly one third broke up over 5 years (between Waves 1 and 2). Factors related to shorter relationship length and undermining coparenting at Wave 1 distinguished women who later broke up versus stayed together. Worse mental health at Wave 2 characterized women in dissolved rather than sustained relationships, even with comparable individual adjustment at Wave 1. Weaker parenting alliance and greater dissatisfaction with childcare divisions were reported by women no longer with their partners at Wave 2 as compared with those in enduring partnerships. This research has implications for understanding lesbian relationship dynamics and associations with individual adjustment.

Comparative Studies on the Dissolution Profiles of Oral Ibuprofen Suspension and Commercial Tablets using Biopharmaceutical Classification System Criteria

PubMed Central

Rivera-Leyva, J. C.; García-Flores, M.; Valladares-Méndez, A.; Orozco-Castellanos, L. M.; Martínez-Alfaro, M.

2012-01-01

In vitro dissolution studies for solid oral dosage forms have recently widened the scope to a variety of special dosage forms such as suspensions. For class II drugs, like Ibuprofen, it is very important to have discriminative methods for different formulations in physiological conditions of the gastrointestinal tract, which will identify different problems that compromise the drug bioavailability. In the present work, two agitation speeds have been performed in order to study ibuprofen suspension dissolution. The suspensions have been characterised relatively to particle size, density and solubility. The dissolution study was conducted using the following media: buffer pH 7.2, pH 6.8, 4.5 and 0.1 M HCl. For quantitative analysis, the UV/Vis spectrophotometry was used because this methodology had been adequately validated. The results show that 50 rpm was the adequate condition to discriminate the dissolution profile. The suspension kinetic release was found to be dependent on pH and was different compared to tablet release profile at the same experimental conditions. The ibuprofen release at pH 1.0 was the slowest. PMID:23626386

Effect of guest drug character encapsulated in the cavity and intermolecular spaces of γ-cyclodextrins on the dissolution property of ternary γ-cyclodextrin complex.

PubMed

Liu, Nan; Higashi, Kenjirou; Ueda, Keisuke; Moribe, Kunikazu

2017-10-15

Various ternary Guest 2/(Guest 1/γ-cyclodextrin (CD)) complexes were prepared using a cogrinding and subsequent heating method, wherein Guest 1 was incorporated in the cavity of γ-CD and Guest 2 was incorporated into the intermolecular spaces between γ-CD columns. Dissolution fluxes of Guest 1 and Guest 2 from all ternary complexes were almost identical. The dissolution flux of flurbiprofen (Guest 1) from the ternary complexes depended on the solubility of Guest 2 drugs (naproxen

Assessment of oral bioavailability enhancing approaches for SB-247083 using flow-through cell dissolution testing as one of the screens.

PubMed

Perng, Cherng-Yih; Kearney, Albert S; Palepu, Nagesh R; Smith, Brian R; Azzarano, Leonard M

2003-01-02

SB-247083 is a potent, nonpeptidic, orally active, ETA-selective, endothelin receptor antagonist. The diacid form and three salts (monoarginine, diarginine and disodium) of SB-247083 were evaluated during the pre-clinical phase of development. The developability attributes (i.e. hygroscopicity, thermal behavior, aqueous solubility, and drug-excipient compatibility) of these compounds were evaluated. In addition to these attributes, the flow-through cell (FTC) dissolution testing (using USP Apparatus 4) was used as a screening technique to evaluate several SB-247083 formulations of the diacid and its salts. FTC dissolution testing offers two distinct advantages over the more traditional static-condition dissolution testing: (1) maintenance of sink conditions; and (2) the ability to change the dissolution medium during a dissolution run. The former advantage is especially important for poorly aqueous soluble drugs having associated dissolution-rate-limitations, and the latter advantage allows one to more closely simulate the pH gradient associated with transit through the GI tract. Based on the comparative dissolution data, three formulations were chosen for oral dosing in dogs. The reasonable correlation found between the FTC dissolution results and the oral bioavailability data demonstrate that FTC dissolution testing can be a valuable tool for aiding in salt (solid-state form) and formulation selection in the early stages of development of drug candidates.

The effect of formulation additives on in vitro dissolution-absorption profile and in vivo bioavailability of telmisartan from brand and generic formulations.

PubMed

Borbás, Enikő; Nagy, Zsombor K; Nagy, Brigitta; Balogh, Attila; Farkas, Balázs; Tsinman, Oksana; Tsinman, Konstantin; Sinkó, Bálint

2018-03-01

In this study, brand and four generic formulations of telmisartan, an antihypertensive drug, were used in in vitro simultaneous dissolution-absorption, investigating the effect of different formulation additives on dissolution and on absorption through an artificial membrane. The in vitro test was found to be sensitive enough to show even small differences between brand and generic formulations caused by the use of different excipients. By only changing the type of filler from sorbitol to mannitol in the formulation, the flux through the membrane was reduced by approximately 10%. Changing the salt forming agent as well resulted in approximately 20% of flux reduction compared to the brand formulation. This significant difference was clearly shown in the published in vivo results as well. The use of additional lactose monohydrate in the formulation also leads to approximately 10% reduction in flux. The results show that by changing excipients, the dissolution of telmisartan was not altered significantly, but the flux through the membrane was found to be significantly changed. These results pointed out the limitations of traditional USP dissolution tests and emphasized the importance of simultaneously measuring dissolution and absorption, which allows the complex effect of formulation excipients on both processes to be measured. Moreover, the in vivo predictive power of the simultaneous dissolution-absorption test was demonstrated by comparing the in vitro fluxes to in vivo bioequivalence study results. Copyright © 2018 Elsevier B.V. All rights reserved.

Defining level A IVIVC dissolution specifications based on individual in vitro dissolution profiles of a controlled release formulation.

PubMed

González-García, I; García-Arieta, A; Merino-Sanjuan, M; Mangas-Sanjuan, V; Bermejo, M

2018-07-01

Regulatory guidelines recommend that, when a level A IVIVC is established, dissolution specification should be established using averaged data and the maximum difference between AUC and C max between the reference and test formulations cannot be greater than 20%. However, averaging data assumes a loss of information and may reflect a bias in the results. The objective of the current work is to present a new approach to establish dissolution specifications using a new methodology (individual approach) instead of average data (classical approach). Different scenarios were established based on the relationship between in vitro-in vivo dissolution rate coefficient using a level A IVIVC of a controlled release formulation. Then, in order to compare this new approach with the classical one, six additional batches were simulated. For each batch, 1000 simulations of a dissolution assay were run. C max ratios between the reference formulation and each batch were calculated showing that the individual approach was more sensitive and able to detect differences between the reference and the batch formulation compared to the classical approach. Additionally, the new methodology displays wider dissolution specification limits than the classical approach, ensuring that any tablet from the new batch would generate in vivo profiles which its AUC or C max ratio will be out of the 0.8-1.25 range, taking into account the in vitro and in vivo variability of the new batches developed. Copyright © 2018 Elsevier B.V. All rights reserved.

A comparison of the effect of temperature and moisture on the solid dispersions: aging and crystallization.

PubMed

Tian, Bin; Zhang, Ling; Pan, Zhendong; Gou, Jingxin; Zhang, Yu; Tang, Xing

2014-11-20

The purpose of this work was to compare the effect of temperature and relative humidity (RH) on the physical stability and dissolution of solid dispersions. Cinnarizine-Soluplus(®) solid dispersions (SDs) at three different drug loadings (10, 20 and 35 wt%) were prepared by hot melt extrusion and exposed to stress conditions: high temperatures (40 and 60 °C), high relative humidities (75% and 94% RH) and accelerated conditions (40 °C/75% RH) for 30 days, or stored at 25 °C for up to 5 months. Changes in solid state and dissolution of SDs were investigated by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and dissolution testing. For samples under stress conditions, the results showed a reduced dissolution and a recrystallization of the drug with an increased crystallinity in the order of 40 °C/75% RH, >60 °C/0% RH, >25 °C/94% RH, >40 °C/0% RH, >25 °C/75% RH. For samples stored at 25 °C, nonlinear physical aging was observed and the dissolution also decreased although the SDs were still amorphous. The results indicated that temperature and humidity seemed to have comparable effects on the crystallization of cinnarizine-Soluplus(®) SDs. It is not reasonable to regard recrystallization as a sign of reduced dissolution, and glass transition temperature (Tg) may be a good indicator of the changes in dissolution. Copyright © 2014 Elsevier B.V. All rights reserved.

A comparative pH-dissolution profile study of selected commercial levothyroxine products using inductively coupled plasma mass spectrometry.

PubMed

Pabla, Dimple; Akhlaghi, Fatemeh; Zia, Hossein

2009-05-01

Levothyroxine (T4) is a narrow therapeutic index drug with classic bioequivalence problem between various available products. Dissolution of a drug is a crucial step in its oral absorption and bioavailability. The dissolution of T4 from three commercial solid oral dosage forms: Synthroid (SYN), generic levothyroxine sodium by Sandoz Inc. (GEN) and Tirosint (TIR) was studied using a sensitive ICP-MS assay. All the three products showed variable and pH-dependent dissolution behaviors. The absence of surfactant from the dissolution media decreased the percent T4 dissolved for all the three products by 26-95% (at 30 min). SYN dissolution showed the most pH dependency, whereas GEN and TIR showed the fastest and highest dissolution, respectively. TIR was the most consistent one, and was minimally affected by pH and/or by the presence of surfactant. Furthermore, dissolution of T4 decreased considerably with increase in the pH, which suggests a possible physical interaction in patients concurrently on T4 and gastric pH altering drugs, such as proton pump inhibitors. Variable dissolution of T4 products can, therefore, impact the oral absorption and bioavailability of T4 and may result in bioequivalence problems between various available products.

Formulation and evaluation of a montelukast sodium orally disintegrating tablet with a similar dissolution profile as the marketed product.

PubMed

Chen, Yong; Feng, Tingting; Li, Yong; Du, Bin; Weng, Weiyu

2017-03-01

A major challenge of orally disintegrating tablet (ODT) development is predicting its bioequivalence to its corresponding marketed product. Therefore, comparing ODT dissolution profiles to those of the corresponding marketed product is very important. The objective of this study was to develop a 5.2-mg montelukast sodium (MS) ODT with a similar dissolution profile to that of the marketed chewable tablet. Dissolution profiles were examined in different media to screen each formulation. We found that MS dissolution from ODTs in acidic medium heavily depended on manufacturing methods. All MS ODTs prepared using direct compression rapidly disintegrated in acidic medium. However, dispersed MS powders aggregated into sticky masses, resulting in slow dissolution. In contrast, MS ODTs prepared using wet granulation had much faster dissolution rates in acidic medium with no obvious aggregation. Additionally, the optimized formulation, prepared using wet granulation, displayed similar dissolution profiles to the marketed reference in all four types of media examined (f 2  >   50). The in vitro disintegration time of the optimized ODT was 9.5 ± 2.4 s, which meets FDA requirements. In conclusion, the wet granulation preparation method of MS ODTs resulted in a product with equivalent dissolution profiles as those of the marketed product.

Impact of dissolution on the sedimentary record of the Paleocene-Eocene thermal maximum

NASA Astrophysics Data System (ADS)

Bralower, Timothy J.; Kelly, D. Clay; Gibbs, Samantha; Farley, Kenneth; Eccles, Laurie; Lindemann, T. Logan; Smith, Gregory J.

2014-09-01

The input of massive amounts of carbon to the atmosphere and ocean at the Paleocene-Eocene Thermal Maximum (PETM; ˜55.53 Ma) resulted in pervasive carbonate dissolution at the seafloor. At many sites this dissolution also penetrated into the underlying sediment column. The magnitude of dissolution at and below the seafloor, a process known as chemical erosion, and its effect on the stratigraphy of the PETM, are notoriously difficult to constrain. Here, we illuminate the impact of dissolution by analyzing the complete spectrum of sedimentological grain sizes across the PETM at three deep-sea sites characterized by a range of bottom water dissolution intensity. We show that the grain size spectrum provides a measure of the sediment fraction lost during dissolution. We compare these data with dissolution and other proxy records, electron micrograph observations of samples and lithology. The complete data set indicates that the two sites with slower carbonate accumulation, and less active bioturbation, are characterized by significant chemical erosion. At the third site, higher carbonate accumulation rates, more active bioturbation, and possibly winnowing have limited the impacts of dissolution. However, grain size data suggest that bioturbation and winnowing were not sufficiently intense to diminish the fidelity of isotopic and microfossil assemblage records.

Comparative study of the biodegradability of porous silicon films in simulated body fluid.

PubMed

Peckham, J; Andrews, G T

2015-01-01

The biodegradability of oxidized microporous, mesoporous and macroporous silicon films in a simulated body fluid with ion concentrations similar to those found in human blood plasma were studied using gravimetry. Film dissolution rates were determined by periodically weighing the samples after removal from the fluid. The dissolution rates for microporous silicon were found to be higher than those for mesoporous silicon of comparable porosity. The dissolution rate of macroporous silicon was much lower than that for either microporous or mesoporous silicon. This is attributed to the fact that its specific surface area is much lower than that of microporous and mesoporous silicon. Using an equation adapted from [Surf. Sci. Lett. 306 (1994), L550-L554], the dissolution rate of porous silicon in simulated body fluid can be estimated if the film thickness and specific surface area are known.

Evaluation of melt granulation and ultrasonic spray congealing as techniques to enhance the dissolution of praziquantel.

PubMed

Passerini, Nadia; Albertini, Beatrice; Perissutti, Beatrice; Rodriguez, Lorenzo

2006-08-02

Praziquantel (PZQ), an anthelminthic drug widely used in developing countries, is classified in Class II in the Biopharmaceutics Classification Systems; this means that PZQ has very low water solubility and high permeability, thus the dissolution is the absorption rate-limiting factor. The aim of this work was to evaluate the suitability of melt granulation and ultrasonic spray congealing as techniques for enhancing the dissolution rate of PZQ. Granules in high shear mixer were prepared by melt granulation, using polyethylene glycol 4000 or poloxamer 188 as meltable binders and alpha-lactose monohydrate as a filler. Quite regularly shaped granules having main size fraction in the range 200-500 microm were obtained using both formulations; however, only poloxamer 188 granules demonstrated a significant (P=0.05) increase of the PZQ dissolution rate compared to pure drug. To evaluate the potential of ultrasonic spray congealing, Gelucire 50/13 microparticles having different drug to carrier ratios (5, 10, 20 and 30%, w/w) were then prepared. The results showed that all the microparticles had a significant higher dissolution rate (P=0.05) respect to pure PZQ. The increase of the PZQ content considerably decreased the dissolution rate of the drug: 5 and 10% PZQ loaded systems evidenced dissolution significantly enhanced compared to 20 and 30% PZQ microparticles. The microparticle's characterisation, performed by Differential Scanning Calorimetry, Hot Stage Microscopy, X-ray powder diffraction and FT-Infrared analysis, evidenced the absence of both modifications of the solid state of PZQ and of significant interactions between the drug and the carrier. In conclusion, melt granulation and ultrasonic spray congealing could be proposed as solvent free, rapid and low expensive manufacturing methods to increase the in vitro dissolution rate of PZQ.

Dissolution patterns of biocompatible glasses in 2-amino-2-hydroxymethyl-propane-1,3-diol (Tris) buffer.

PubMed

Fagerlund, S; Hupa, L; Hupa, M

2013-02-01

A continuous flow measurement system with sensitive on-line ion analysis has been applied to study the initial dissolution behaviour of biocompatible glasses in Tris. Altogether 16 glasses with widely varying compositions were studied. The measurement system allowed for quantitative determination of the time-dependent rates of dissolution of sodium, potassium, calcium, magnesium, silicon and phosphorus during the first 10-15 min in contact with Tris solution. The dissolution rates of the different ions showed significant glass to glass variations, but all glasses studied showed one of four distinct dissolution patterns. The ion dissolution rates after an exposure of 1000 s, expressed as the normalized surface-specific mass loss rates, were compared with the in vitro and in vivo reactivity of the glasses as predicted by models in the literature. The results showed a clear correlation between the dissolution rates of the glasses in Tris and their reactivity as measured by other different methods. Consequently, the measured short-term dissolution patterns could be used to determine which glasses are suitable as bioactive, biodegradable, or inert biomaterials for medical devices. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Caffeine: a potential complexing agent for solubility and dissolution enhancement of celecoxib.

PubMed

Shakeel, Faiyaz; Faisal, Mohammed S

2010-01-01

Complexation of caffeine with the drug celecoxib was used to enhance its solubility as well as in vitro dissolution in the present investigation. Caffeine was extracted from tea leaves using the sublimation method. A molecular complex (1:1) of caffeine-celecoxib was prepared using the solubility method. The solubility of celecoxib in distilled water and the caffeine complex was determined using a HPLC method at a wavelength of 250 nm. Dissolution studies of pure celecoxib, a marketed capsule (Celebrex), and the complex were performed using USP dissolution apparatus I for pure celecoxib and the complex and apparatus II for the capsule in distilled water. The highest solubility (48.32 mg/mL) as well as percent dissolution (90.54%) of celecoxib was obtained with the caffeine-celecoxib complex. The results for solubility and dissolution were highly significant as compared to pure celecoxib and the marketed capsule (p < 0.01). These results suggest that caffeine is a promising complexing agent for solubility as well as dissolution enhancement of the poorly soluble drug celecoxib.

Synthetic coprecipitates of exopolysaccharides and ferrihydrite. Part II: Siderophore-promoted dissolution

NASA Astrophysics Data System (ADS)

Mikutta, Christian; Kretzschmar, Ruben

2008-02-01

Ferrihydrite (Fh) coprecipitated with exopolymers of plants and microbes may differ in its geochemical reactivity from its abiotic counterpart. We synthesized Fh in the presence and absence of acid polysaccharides (polygalacturonic acid (PGA), alginate, xanthan) and characterized the physical and structural properties of the precipitates formed [Mikutta C., Mikutta R., Bonneville S., Wagner F., Voegelin A., Christl I. and Kretzschmar R. (2008) Synthetic coprecipitates of exopolysaccharides and ferrihydrite. Part I: Characterization. Geochim. Cosmochim. Acta]. In this paper, we focus on the reactivity of PGA and alginate coprecipitates and pure Fh, and studied their interaction with the microbial siderophore desferrioxamine B (DFOB) in the presence and absence of low molecular weight organic (LMWO) acid anions (malate, citrate). Batch adsorption and dissolution experiments were performed in the dark at pH 7 in 10 mM NaClO 4 background electrolyte. In the dissolution experiments, different modes of ligand addition were applied (single, simultaneous, stepwise). With an estimated Langmuir sorption maximum of 15 mmol/mol Fe, a PGA coprecipitate with 11% C org sorbed about four times as much DFOB as pure Fh, and the amount of DFOB sorbed was ˜4-fold larger than estimated from the sum of DFOB sorption to pure Fh and PGA alone. The apparent initial dissolution rates, Rapp-initial, and pseudo-first order rate coefficients, k, of the coprecipitates exceeded those of pure Fh by up to two orders of magnitude. Citrate and malate exerted a strong synergistic effect on the DFOB-promoted dissolution of pure Fh, whereas synergistic effects of both anions were absent or negligible for the coprecipitates. Rapp-initial of the citrate and DFOB-promoted dissolution of PGA coprecipitates increased with increasing molar C/Fe ratio of the coprecipitates, independent of the charge of the LMWO ligand. Our results indicate that polyuronates stabilize Fh particles sterically and /or electrostatically, thus increasing the mineral surface area accessible to LMWO ligands. In contrast, pure Fh was coagulated at pH 7 (pH iep of Fh = 7.1), and hence only a small fraction of the Fh surface underwent dissolution. The increase in ligand-accessible surface area of Fh upon coprecipitation with acid polysaccharides seems to primarily control the kinetics of the ligand-promoted dissolution at neutral pH. In pH environments where the solubility of Fe(III) is very low, dissolution rates of Fe(III) (hydr)oxides in such coprecipitates may therefore exceed those of pure minerals by several orders of magnitude, despite a similar crystallinity of the minerals.

The effect of ion irradiation on the dissolution of UO 2 and UO 2 -based simulant fuel

DOE PAGES

Popel, Aleksej J.; Wietsma, Thomas W.; Engelhard, Mark H.; ...

2017-11-21

Our aim is to study the separate effect of fission fragment damage on the dissolution of simulant UK advanced gas-cooled reactor nuclear fuel in water. Plain UO 2 and UO 2 samples, doped with inactive fission products to simulate 43 GWd/tU of burn-up, were fabricated. A set of these samples were then irradiated with 92 MeV 129Xe 23+ ions to a fluence of 4.8 × 10 15 ions/cm 2 to simulate the fission damage that occurs within nuclear fuels. The primary effect of the irradiation on the UO 2 samples, observed by scanning electron microscopy, was to induce a smootheningmore » of the surface features and formation of hollow blisters, which was attributed to multiple overlap of ion tracks. Dissolution experiments were conducted in single-pass flow-through (SPFT) mode under anoxic conditions (<0.1 O 2 ppm in Ar) to study the effect of the induced irradiation damage on the dissolution of the UO 2 matrix with data collection capturing six minute intervals for several hours. These time-resolved data showed that the irradiated samples showed a higher initial release of uranium than unirradiated samples, but that the uranium concentrations converged towards ~10 -9 mol/l after a few hours. And apart from the initial spike in uranium concentration, attributed to irradiation induced surficial micro-structural changes, no noticeable difference in uranium chemistry as measured by X-ray electron spectroscopy or ‘effective solubility’ was observed between the irradiated, doped and undoped samples in this work. Some secondary phase formation was observed on the surface of UO 2 samples after the dissolution experiment.« less

The effect of ion irradiation on the dissolution of UO 2 and UO 2 -based simulant fuel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Popel, Aleksej J.; Wietsma, Thomas W.; Engelhard, Mark H.

Our aim is to study the separate effect of fission fragment damage on the dissolution of simulant UK advanced gas-cooled reactor nuclear fuel in water. Plain UO 2 and UO 2 samples, doped with inactive fission products to simulate 43 GWd/tU of burn-up, were fabricated. A set of these samples were then irradiated with 92 MeV 129Xe 23+ ions to a fluence of 4.8 × 10 15 ions/cm 2 to simulate the fission damage that occurs within nuclear fuels. The primary effect of the irradiation on the UO 2 samples, observed by scanning electron microscopy, was to induce a smootheningmore » of the surface features and formation of hollow blisters, which was attributed to multiple overlap of ion tracks. Dissolution experiments were conducted in single-pass flow-through (SPFT) mode under anoxic conditions (<0.1 O 2 ppm in Ar) to study the effect of the induced irradiation damage on the dissolution of the UO 2 matrix with data collection capturing six minute intervals for several hours. These time-resolved data showed that the irradiated samples showed a higher initial release of uranium than unirradiated samples, but that the uranium concentrations converged towards ~10 -9 mol/l after a few hours. And apart from the initial spike in uranium concentration, attributed to irradiation induced surficial micro-structural changes, no noticeable difference in uranium chemistry as measured by X-ray electron spectroscopy or ‘effective solubility’ was observed between the irradiated, doped and undoped samples in this work. Some secondary phase formation was observed on the surface of UO 2 samples after the dissolution experiment.« less

Geochemical evolution of groundwater in the Culebra dolomite near the Waste Isolation Pilot Plant, southeastern New Mexico, USA

USGS Publications Warehouse

Siegel, M.D.; Anderholm, S.

1994-01-01

The Culebra Dolomite Member of the Rustler Formation, a thin (10 m) fractured dolomite aquifer, lies approximately 450 m above the repository horizon of the Waste Isolation Pilot Plant (WIPP) in southeastern New Mexico, USA. Salinities of water in the Culebra range roughly from 10,000 to 200,000 mg/L within the WIPP site. A proposed model for the post-Pleistocene hydrochemical evolution of the Culebra tentatively identifies the major sources and sinks for many of the groundwater solutes. Reaction-path simulations with the PHRQPITZ code suggest that the Culebra dolomite is a partial chemical equilibrium system whose composition is controlled by an irreversible process (dissolution of evaporites) and equilibrium with gypsum and calcite. Net geochemical reactions along postulated modern flow paths, calculated with the NETPATH code, include dissolution of halite, carbonate and evaporite salts, and ion exchange. R-mode principal component analysis revealed correlations among the concentrations of Si, Mg, pH, Li, and B that are consistent with several clay-water reactions. The results of the geochemical calculations and mineralogical data are consistent with the following hydrochemical model: 1. (1) solutes are added to the Culebra by dissolution of evaporite minerals 2. (2) the solubilities of gypsum and calcite increase as the salinity increases; these minerals dissolve as chemical equilibrium is maintained between them and the groundwater 3. (3) equilibrium is not maintained between the waters and dolomite; sufficient Mg is added to the waters by dissolution of accessory carnallite or polyhalite such that the degree of dolomite supersaturation increases with ionic strength 4. (4) clays within the fractures and rock matrix exert some control on the distribution of Li, B, Mg, and Si via sorption, ion exchange, and dissolution. ?? 1994.

Ultrasound has synergistic effects in vitro with tirofiban and heparin for thrombus dissolution.

PubMed

Birnbaum, Y; Atar, S; Luo, H; Nagai, T; Siegel, R J

1999-12-15

Previous studies have shown synergism between ultrasound and thrombolytic agents or microbubbles on blood clot dissolution. It has not been investigated whether heparin or glycoprotein IIb/IIIa blockers enhance clot lysis by ultrasound. We compared the blood clot dissolution effect of saline, heparin, tissue plasminogen activator (tPA), tirofiban, and an echocardiographic contrast media (Optison) without and with ultrasound application. Human blood clots from four donors, 2 to 4 hours old, were cut into 200- to 400-mg sections, weighed, and immersed for 2 minutes in 1 L of normal saline 0.9% solution containing either heparin 1000 U, tirofiban 150 microg, tPA 20 mg, Optison 0.5 mL, or normal saline alone. Clots were randomized to 2 minutes ultrasound application or immersion alone without ultrasound. Ultrasound was applied with a 19.5 KHz catheter. After treatment, the clots were weighed, and the absolute and percent difference in weight was calculated. Immersion in heparin, tirofiban, and tPA without ultrasound did not augment clot disruption relative to normal saline alone. Immersion in Optison (p = 0.07) tended to result in less lysis than saline alone. Ultrasound enhanced clot dissolution compared to immersion alone with: saline (48.1+/-15.3% vs. 26.0+/-13.8%, p<0.0000002); heparin (60.8+/-17.5% vs. 30.8+/-15.1%, p = 0.000001); tirofiban (61.8+/-13.6% vs. 30.1+/-12.2%, p<0.0000001); tPA (53.1+/-15.3% vs. 30.2+/-11.5%, p<0.000002); and Optison (47.8+/-16.0% vs. 18.4+/-11.5%, p<0.0000001). The combination of tirofiban with ultrasound, as well as heparin with ultrasound, was associated with a significant augmentation of clot dissolution compared with the saline plus ultrasound group (p = 0.002, 0.013, respectively). Ultrasound with tPA or with Optison had no significant augmentation of clot dissolution over the ultrasound + saline effect. This in vitro study of catheter-delivered high-intensity low-frequency ultrasound demonstrates that: (1) tirofiban and heparin, as well as perfluorocarbon microbubbles, augment clot dissolution by ultrasound; (2) augmentation of clot dissolution is evident even after only brief exposure of ultrasound and the drug studied.

Biodurability of chrysotile and tremolite asbestos

NASA Astrophysics Data System (ADS)

Oze, C.; Solt, K.

2008-12-01

Chrysotile and tremolite asbestos represent two mineralogical categories of regulated asbestos commonly evaluated in epidemiological, toxicological, and pathological studies. Lung and digestive fluids are undersaturated with respect to chrysotile and tremolite asbestos (i.e. dissolution is thermodynamically favorable), where the dissolution kinetics control the durability of these minerals in respiratory and gastric systems. Here we examined the biodurability of chrysotile and tremolite asbestos in simulated body fluids (SBFs) as a function of mineral surface area over time. Batch experiments in simulated gastric fluid (SGF; HCl and NaCl solution at pH 1.2) and simulated lung fluid (SLF; a modified Gamble's solution at pH 7.4) were performed at 37°C over 720 hours. The rate-limiting step of Si release for both minerals was used to determine and compare dissolution rates. Chrysotile and tremolite asbestos are less biodurable in SGF compared to SLF. Based on equal suspension densities (surface area per volume of solution, m2 L- 1), chrysotile undergoes dissolution approximately 44 times faster than tremolite asbestos in SGF; however, amphibole asbestos dissolves approximately 6 times faster than chrysotile in SLF. Provided identical fiber dimensions, fiber dissolution models demonstrate that chrysotile is more biodurable in SLF and less biodurable in SGF compared to tremolite asbestos. Overall, the methodology employed here provides an alternative means to evaluate asbestos material fiber lifetimes based on mineral surface considerations.

An investigation into the mechanisms of drug release from taste-masking fatty acid microspheres.

PubMed

Qi, Sheng; Deutsch, David; Craig, Duncan Q M

2008-09-01

Fatty acid microspheres based on stearic and palmitic acids are known to form effective taste masking systems, although the mechanisms by which the drug is preferentially released in the lower gastrointestinal tract are not known. The objective of the present study was to identify the mechanisms involved, with a particular view to clarify the role of acid soap formation in the dissolution process. Microspheres were prepared by a spray chilling process. Using benzoic acid as a model drug and an alkaline dissolution medium, a faster drug release was observed in the mixed fatty acid formulation (50:50 stearic:palmitic acid (w/w)) compared to the single fatty acid component systems. Thermal and powder X-ray diffraction studies indicated a greater degree of acid soap formation for the mixed formulation in alkaline media compared to the single fatty acid systems. Particle size and porosity studies indicated a modest reduction in size for the mixed systems and an increase in porosity on immersion in the dissolution medium. It is proposed that the mixed fatty acid system form a mixed crystal system which in turn facilitates interaction with the dissolution medium, thereby leading to a greater propensity for acid soap formation which in turn forms a permeable liquid crystalline phase through which the drug may diffuse. The role of dissolution of palmitic acid into the dissolution medium is also discussed as a secondary mechanism.

Improving the dissolution rate of poorly water soluble drug by solid dispersion and solid solution: pros and cons.

PubMed

Chokshi, Rina J; Zia, Hossein; Sandhu, Harpreet K; Shah, Navnit H; Malick, Waseem A

2007-01-01

The solid dispersions with poloxamer 188 (P188) and solid solutions with polyvinylpyrrolidone K30 (PVPK30) were evaluated and compared in an effort to improve aqueous solubility and bioavailability of a model hydrophobic drug. All preparations were characterized by differential scanning calorimetry, powder X-ray diffraction, intrinsic dissolution rates, and contact angle measurements. Accelerated stability studies also were conducted to determine the effects of aging on the stability of various formulations. The selected solid dispersion and solid solution formulations were further evaluated in beagle dogs for in vivo testing. Solid dispersions were characterized to show that the drug retains its crystallinity and forms a two-phase system. Solid solutions were characterized to be an amorphous monophasic system with transition of crystalline drug to amorphous state. The evaluation of the intrinsic dissolution rates of various preparations indicated that the solid solutions have higher initial dissolution rates compared with solid dispersions. However, after storage at accelerated conditions, the dissolution rates of solid solutions were lower due to partial reversion to crystalline form. The drug in solid dispersion showed better bioavailability in comparison to solid solution. Therefore, considering physical stability and in vivo study results, the solid dispersion was the most suitable choice to improve dissolution rates and hence the bioavailability of the poorly water soluble drug.

Dissolution properties of co-amorphous drug-amino acid formulations in buffer and biorelevant media.

PubMed

Heikkinen, A T; DeClerck, L; Löbmann, K; Grohganz, H; Rades, T; Laitinen, R

2015-07-01

Co-amorphous formulations, particularly binary drug-amino acid mixtures, have been shown to provide enhanced dissolution for poorly-soluble drugs and improved physical stability of the amorphous state. However, to date the dissolution properties (mainly intrinsic dissolution rate) of the co-amorphous formulations have been tested only in buffers and their supersaturation ability remain unexplored. Consequently, dissolution studies in simulated intestinal fluids need to be conducted in order to better evaluate the potential of these systems in increasing the oral bioavailability of biopharmaceutics classification system class II drugs. In this study, solubility and dissolution properties of the co-amorphous simvastatin-lysine, gibenclamide-serine, glibenclamide-threonine and glibenclamide-serine-threonine were studied in phosphate buffer pH 7.2 and biorelevant media (fasted and fed state simulated intestinal fluids (FaSSIF and FeSSIF, respectively)). The co-amorphous formulations were found to provide a long-lasting supersaturation and improve the dissolution of the drugs compared to the crystalline and amorphous drugs alone in buffer. Similar improvement, but in lesser extent, was observed in biorelevant media suggesting that a dissolution advantage observed in aqueous buffers may overestimate the advantage in vivo. However, the results show that, in addition to stability advantage shown earlier, co-amorphous drug-amino acid formulations provide dissolution advantage over crystalline drugs in both aqueous and biorelevant conditions.

Citrate, not phosphate, can dissolve calcium oxalate monohydrate crystals and detach these crystals from renal tubular cells.

PubMed

Chutipongtanate, Somchai; Chaiyarit, Sakdithep; Thongboonkerd, Visith

2012-08-15

Dissolution therapy of calcium oxalate monohydrate (COM) kidney stone disease has not yet been implemented due to a lack of well characterized COM dissolution agents. The present study therefore aimed to identify potential COM crystal dissolution compounds. COM crystals were treated with deionized water (negative control), 5 mM EDTA (positive control), 5 mM sodium citrate, or 5mM sodium phosphate. COM crystal dissolution activities of these compounds were evaluated by phase-contrast and video-assisted microscopic examinations, semi-quantitative analysis of crystal size, number and total mass, and spectrophotometric oxalate-dissolution assay. In addition, effects of these compounds on detachment of COM crystals, which adhered tightly onto renal tubular cell surface, were also investigated. The results showed that citrate, not phosphate, had a significant dissolution effect on COM crystals as demonstrated by significant reduction of crystal size (approximately 37% decrease), crystal number (approximately 53% decrease) and total crystal mass (approximately 72% decrease) compared to blank and negative controls. Spectrophotometric oxalate-dissolution assay successfully confirmed the COM crystal dissolution property of citrate. Moreover, citrate could detach up to 85% of the adherent COM crystals from renal tubular cell surface. These data indicate that citrate is better than phosphate for dissolution and detachment of COM crystals. Copyright © 2012 Elsevier B.V. All rights reserved.

Enhancement of Loperamide Dissolution Rate by Liquisolid Compact Technique.

PubMed

Venkateswarlu, Kambham; Preethi, Jami Komala; Chandrasekhar, Kothapalli Bonnoth

2016-09-01

Purpose: The aim of present study was to improve the dissolution rate of poorly soluble drug Loperamide (LPM) by liquisolid compact technique. Methods: Liquisolid compacts of LPM were prepared using Propylene glycol (PG) as a solvent, Avicel pH 102 as carrier, Aerosil as coating material and Sodium Starch Glycolate (SSG) as superdisintegrant. Interactions between the drug and excipients were examined by Fourier Transform Infrared (FTIR) spectroscopy. The dissolution studies for LPM liquisolid formulation, marketed product and pure drug were carried out in pH 1.2 HCl buffer as dissolution media. Results: Results confirmed the absence of chemical interactions between the drug and excipients. From the solubility studies, it was observed the LPM was highly soluble in PG thereby it was selected as a solvent. The dissolution efficiency of LPM at 15 min was increased from 9.99 % for pure drug and 54.57% for marketed product to 86.81% for the tablets prepared by liquisolid compact technique. Stability studies showed no significant change in percent cumulative drug release, hardness, disintegration time, friability and drug content for 3 months. Conclusion: Formulation F2 showed significant increase in dissolution rate compared to the marketed product at pH 1.2 where LPM is largely absorbed. Around 90% of the drug was released from F2 in 30 min compared to the marketed product and it might be due to the increased wetting and surface area of the particles. Hence, the liquisolid compact technique appears to be a promising approach for improving the dissolution rate of poorly soluble drug.

Sonothrombolysis is effective with recombinant tissue-type plasminogen activator, but not with Abciximab. Results from an in vitro study with whole blood clots and platelet-rich clots.

PubMed

Eggers, Jürgen; Ossadnik, Stefan; Hütten, Heiko; Seidel, Günter

2009-12-01

Transcranial "diagnostic" ultrasound (US) has been shown to accelerate thrombolysis related to recombinant tissue-type plasminogen activator (rt-PA). In this in vitro study, we evaluated the potential of US to increase clot dissolution mediated by Abciximab (Abc) compared to rt-PA. The effect of 1.8-MHz pulsed wave (PW) Doppler US on dissolution of whole venous blood clots (WBC) and platelet-rich clots (PRC) treated with Abc and rt-PA was investigated in an in vitro model. Clot dissolution was measured by weight loss. Abc-related WBC dissolution was enhanced by additional US, but the effect was not any more detectable when the US was attenuated by a human temporal bone (US-tb). In PRC there was no additional effect of US on the Abc-related clot lysis. Rt-PA-related clot dissolution was increased by US in WBC and PRC as well, however, US-tb was only effective in WBC. The effect of insonation on WBC dissolution treated with the combination of Abc plus rt-PA was lower compared with those treated with rt-PA. In this in vitro experiment, the additional effect of "diagnostic" US in combination with Abc was only present in WBC and less strong than with rt-PA. The results do not support the use of Abc for sonothrombolysis targeting both, fibrin-rich and platelet-rich clots. In contrast, US when combined with rt-PA increases dissolution in both, WBC and PRC as well.

Low-viscosity hydroxypropylcellulose (HPC) grades SL and SSL: versatile pharmaceutical polymers for dissolution enhancement, controlled release, and pharmaceutical processing.

PubMed

Sarode, Ashish; Wang, Peng; Cote, Catherine; Worthen, David R

2013-03-01

Hydroxypropylcellulose (HPC)-SL and -SSL, low-viscosity hydroxypropylcellulose polymers, are versatile pharmaceutical excipients. The utility of HPC polymers was assessed for both dissolution enhancement and sustained release of pharmaceutical drugs using various processing techniques. The BCS class II drugs carbamazepine (CBZ), hydrochlorthiazide, and phenytoin (PHT) were hot melt mixed (HMM) with various polymers. PHT formulations produced by solvent evaporation (SE) and ball milling (BM) were prepared using HPC-SSL. HMM formulations of BCS class I chlorpheniramine maleate (CPM) were prepared using HPC-SL and -SSL. These solid dispersions (SDs) manufactured using different processes were evaluated for amorphous transformation and dissolution characteristics. Drug degradation because of HMM processing was also assessed. Amorphous conversion using HMM could be achieved only for relatively low-melting CBZ and CPM. SE and BM did not produce amorphous SDs of PHT using HPC-SSL. Chemical stability of all the drugs was maintained using HPC during the HMM process. Dissolution enhancement was observed in HPC-based HMMs and compared well to other polymers. The dissolution enhancement of PHT was in the order of SE>BM>HMM>physical mixtures, as compared to the pure drug, perhaps due to more intimate mixing that occurred during SE and BM than in HMM. Dissolution of CPM could be significantly sustained in simulated gastric and intestinal fluids using HPC polymers. These studies revealed that low-viscosity HPC-SL and -SSL can be employed to produce chemically stable SDs of poorly as well as highly water-soluble drugs using various pharmaceutical processes in order to control drug dissolution.

In vitro dissolution profile of two commercially available iron preparations.

PubMed

Patrício, José P H; Santos, Cristina; Cerdeira, Rui

2012-03-01

Current scientific evidence indicates that anemia in pregnancy, regardless of severity, is associated with an increased risk of maternal and fetal mortality. There is little published information about the bioavailability and bioequivalence of formulations containing both iron and folic acid. However, in vitro dissolution studies can provide important information on the likely relative bioavailability of various formulations. The objective of our study was to compare the in vitro dissolution of two similar commercially available formulations of iron- and folic acid-containing supplements, Folifer® (Bialport - Produtos Farmacêuticos, S.A., Portugal) and Ferroliver® (SM Pharma c.a., Venezuela), in order to determine the in vitro availability of their iron content. Folifer® and Ferroliver® were chosen because they contained similar amounts of elemental iron. The amount of iron released from each tablet was evaluated over a 4-hour period in three dissolution media replicating gastric or intestinal juices with pH values ranging from 1.5 to 6.9. The samples were then titrated with a solution of cerium ammonium sulfate in order to calculate the amount of iron released in each specific pH condition. The percentage of dissolved iron was calculated as a cumulative frequency, using the percentage of dissolved iron at all timepoints. The dissolution similarity between the two commercially available formulations was evaluated using the &U0192;(2) statistic formula. During a 4-hour dissolution test, Folifer® released 59.4 mg of iron compared with 48.5 mg released by Ferroliver®. The value obtained for the similarity factor, an indicator of likely bioequivalence, was 41. These data suggest that Folifer® releases more iron than Ferroliver®, and that the two formulations are not equivalent in vitro. The superior dissolution of ferrous sulfate with Folifer® compared with ferrous fumarate in Ferroliver® might be responsible for the observed difference.

Utilization of spray drying technique for improvement of dissolution and anti-inflammatory effect of Meloxicam.

PubMed

Shazly, Gamal; Badran, Mohamed; Zoheir, Khairy; Alomrani, Abdullah

2015-01-01

Meloxicam (MLX) is a poorly water-soluble non steroidal anti-inflammatory drug (NSAID). The main objective of the present work was to enhance the dissolution of MLX and thus its bioavailability by the aid of additives. The novelty of this work rises from the utilization of spray drying technology to produce micro particulates solid dispersion systems containing MLX in the presence of small amount of additives. Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), and Scan Electron Microscope (SEM) were used for studying the physico-chemical and morphological properties of MLX samples. The dissolution of MLX samples was investigated in two different pH media. The morphology of MLX solid dispersion micro-particles was spherical in shape according to SEM. FT-IR profiles indicated that a complex was formed between MLX and the additives. DSC patterns of the MLX micro-particles suggested a reduction in the crystallinity of MLX and probability of presence of an interaction between MLX and the additives. The rate of dissolution of the spray-dried MLX enhanced as compared with the unprocessed MLX in both acidic and neutral media. It was found that 100% of the added MLX released within 5 min in phosphate buffer dissolution medium (pH 7.4) compared to that of the unprocessed MLX (15% in 60 min). Such increase rate in the dissolution of the spray dried MLX could be attributed to the increase in wettability of MLX particles and the hydrophilic nature of the additives. The anti-inflammatory effect of the spray dried MLX was explored using formalin induced rat paw edema model. The spray-dried samples showed an increase in the anti-inflammatory activity of MLX as compared to the unprocessed MLX. This work reveals that the spray drying technique is suitable for preparation of micro-particles with improved dissolution and anti-inflammatory effect of MLX.

Role of Solvents in Improvement of Dissolution Rate of Drugs: Crystal Habit and Crystal Agglomeration

PubMed Central

Maghsoodi, Maryam

2015-01-01

Crystallization is often used for manufacturing drug substances. Advances of crystallization have achieved control over drug identity and purity, but control over the physical form remains poor. This review discusses the influence of solvents used in crystallization process on crystal habit and agglomeration of crystals with potential implication for dissolution. According to literature it has been known that habit modification of crystals by use of proper solvents may enhance the dissolution properties by changing the size, number and the nature of crystal faces exposed to the dissolution medium. Also, the faster dissolution rate of drug from the agglomerates of crystals compared with the single crystals may be related to porous structure of the agglomerates and consequently their better wettability. It is concluded from this review that in-depth understanding of role of the solvents in crystallization process can be applied to engineering of crystal habit or crystal agglomeration, and predictably dissolution improvement in poorly soluble drugs. PMID:25789214

Size-dependent reactivity of magnetite nanoparticles: a field-laboratory comparison

USGS Publications Warehouse

Swindle, Andrew L.; Elwood Madden, Andrew S.; Cozzarelli, Isabelle M.; Benamara, Mourad

2014-01-01

Logistic challenges make direct comparisons between laboratory- and field-based investigations into the size-dependent reactivity of nanomaterials difficult. This investigation sought to compare the size-dependent reactivity of nanoparticles in a field setting to a laboratory analog using the specific example of magnetite dissolution. Synthetic magnetite nanoparticles of three size intervals, ∼6 nm, ∼44 nm, and ∼90 nm were emplaced in the subsurface of the USGS research site at the Norman Landfill for up to 30 days using custom-made subsurface nanoparticle holders. Laboratory analog dissolution experiments were conducted using synthetic groundwater. Reaction products were analyzed via TEM and SEM and compared to initial particle characterizations. Field results indicated that an organic coating developed on the particle surfaces largely inhibiting reactivity. Limited dissolution occurred, with the amount of dissolution decreasing as particle size decreased. Conversely, the laboratory analogs without organics revealed greater dissolution of the smaller particles. These results showed that the presence of dissolved organics led to a nearly complete reversal in the size-dependent reactivity trends displayed between the field and laboratory experiments indicating that size-dependent trends observed in laboratory investigations may not be relevant in organic-rich natural systems.

Systematic review: Coca-Cola can effectively dissolve gastric phytobezoars as a first-line treatment.

PubMed

Ladas, S D; Kamberoglou, D; Karamanolis, G; Vlachogiannakos, J; Zouboulis-Vafiadis, I

2013-01-01

Gastric phytobezoars represent the most common bezoars in patients with poor gastric motility. A variety of dissolution therapies and endoscopic fragmentation techniques have been evaluated as conservative treatment so as to avoid surgery. To investigate the effectiveness of Coca-Cola for gastric phytobezoars dissolution. We performed a systematic search to identify publications on gastric phytobezoars to assess the efficacy of Coca-Cola as a dissolution therapy. Diospyrobezoars, formed after persimmon ingestion, are a distinct type of phytobezoars characterized by their hard consistency. Thus, these two subgroups of bezoars were compared in terms of successful dissolution. Over a 10-year period (2002-2012), 24 papers including 46 patients have been published. In 91.3% of the cases, phytobezoar resolution with Coca-Cola administration was successful, either as a single treatment (50%) or combined with further endoscopic techniques, whereas only 4 patients underwent surgery. Phytobezoars were more likely to dissolve after initial attempt with Coca-Cola compared with diospyrobezoars (60.6% vs. 23%, P = 0.022). Coca-Cola alone is effective in gastric phytobezoar dissolution in half of the cases and, combined with additional endoscopic methods, is successful in more than 90% of them. © 2012 Blackwell Publishing Ltd.

Pharmaceutical Equivalence of Clarithromycin Oral Dosage Forms Marketed in Nairobi County, Kenya

PubMed Central

Manani, Rebecca O.; Abuga, Kennedy O.; Chepkwony, Hezekiah K.

2017-01-01

Clarithromycin is a broad-spectrum semi-synthetic macrolide indicated for treatment of pneumonias, Helicobacter pylori, and chlamydial and skin infections. The object of this study was to evaluate the pharmaceutical equivalence of 14 generic clarithromycin products marketed in Nairobi County, Kenya, to the innovator products, using in vitro dissolution profiles and similarity factors (f2). Further, dissolution profiles of four innovator formulations manufactured in different sites were compared. Fourteen clarithromycin tablets/capsules and four suspensions were subjected to assay and comparative dissolution runs at pH 1.2, 4.5 and 6.8, for 60 and 90 min, respectively. All products complied with pharmacopoeial assay specifications. However, significant differences were observed in their dissolution profiles. The non-compliance rates for tablets/capsules were 50% at pH 1.2, 33% at pH 4.5 and 50% at pH 6.8, while none of the four suspensions were compliant. Overall, only four (25%) products complied with the specifications for similarity factor. The results obtained indicate that a significant percentage of generic clarithromycin products are pharmaceutically non-equivalent to the innovator products, and that assay and single-point dissolution tests are insufficient demonstration of equivalence between the generic and innovator products. PMID:28445444

Freshwater biodissolution rates of limestone in the temperate climate of the Dinaric karst in Slovenia

NASA Astrophysics Data System (ADS)

Mulec, J.; Prelovšek, M.

2015-01-01

Dissolution rates in two freshwater karst systems were determined by using tablets of dense micrite-biopelmicrite Cretaceous limestone. Submerged limestone tablets in riverbeds were subjected to a natural gradient from complete darkness to direct sunlight. Higher light rates significantly (p < 0.05) increased the epilithic biomass of phototrophs and the overall dissolution rates, which were highest at the Unica spring (- 49.2 μm a- 1), but the exact portion of light-dependent dissolution remains elusive. In the karst river Unica, with its big fluctuations in environmental parameters (e.g., discharge), light rates can be used in estimating the dissolution rates enhanced by phototrophs. Natural biofilms in aquatic systems have important implications for landform evolution, and the impact on limestone dissolution rates is comparable with rates of debris falling from steep slopes.

Rates and mechanisms of uranyl oxyhydroxide mineral dissolution

NASA Astrophysics Data System (ADS)

Reinoso-Maset, Estela; Steefel, Carl I.; Um, Wooyong; Chorover, Jon; O'Day, Peggy A.

2017-06-01

Uranyl oxyhydroxide minerals are important weathering products in uranium-contaminated surface and subsurface environments that regulate dissolved uranium (U) concentrations. However, dissolution rates for this class of minerals and associated dissolution mechanisms have not been previously reported for circumneutral pH conditions, particularly for the case of flow through porous media. In this work, the dissolution rates of K- and Na-compreignacite (K2(UO2)6O4(OH)6·8H2O and Na2(UO2)6O4(OH)6·8H2O, respectively) were measured using flow-through columns reacted with two simulated background porewater (BPW) solutions of low and high dissolved carbonate concentration (ca. 0.2 and 2.8 mmol L-1). Column materials were characterized before and after reaction with electron microscopy, bulk chemistry, and EXAFS to identify structural and chemical changes during dissolution and to obtain insight into molecular-scale processes. The reactive transport code CrunchFlow was used to calculate overall dissolution rates while accounting for fluid transport and changes in mineral volume and reactive surface area, and results were compared to steady-state dissolution rate calculations. In low carbonate BPW systems, interlayer K and Na were initially leached from both minerals, and in Na-compreignacite, K and minor divalent cations from the input solution were incorporated into the mineral structure. Results of characterization analyses suggested that after reaction both K- and Na-compreignacite resembled a disordered K-compreignacite with altered surfaces. A 10-fold increase in dissolved carbonate concentration and corresponding increase in pH (from 6.65 to 8.40) resulted in a net removal of 58-87% of total U mass from the columns, compared to <1% net loss in low carbonate BPW systems. Steady-state release of dissolved U was not observed with high carbonate solutions and post-reaction characterizations indicated a lack of development of leached or altered surfaces. Dissolution rates (normalized to specific surface area) were 2.5-3 orders-of-magnitude faster in high versus low carbonate BPW systems, with Na-compreignacite dissolving more rapidly than K-compreignacite under both BPW conditions, possibly due to greater ion exchange (1.57 · 10-10 vs. 1.28 · 10-13 mol m-2 s-1 [log R = -9.81 and -12.89] and 5.79 · 10-10 vs. 3.71 · 10-13 mol m-2 s-1 [log R = -9.24 and -12.43] for K- and Na-compreignacite, respectively). Experimental and spectroscopic results suggest that the dissolution rate is controlled by bond breaking of a uranyl group and detachment from polyhedral layers of the mineral structure. With higher dissolved carbonate concentrations, this rate-determining step is accelerated by the formation of Ca-uranyl carbonate complexes (dominant species under these conditions), which resulted in an increase of the dissolution rates. Optimization of both dissolution rate and mineral volume fraction in the reactive transport model to account for U mass removal during dissolution more accurately reproduced effluent data in high carbonate systems, and resulted in faster overall rates compared with a steady-state dissolution assumption. This study highlights the importance of coupling reaction and transport processes during the quantification of mineral dissolution rates to accurately predict the fate of contaminants such as U in porous geomedia.

Rates and mechanisms of uranyl oxyhydroxide mineral dissolution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reinoso-Maset, Estela; Steefel, Carl I.; Um, Wooyong

Uranyl oxyhydroxide minerals are important weathering products in uranium-contaminated surface and subsurface environments that regulate dissolved uranium concentrations. However, dissolution rates for this class of minerals and associated dissolution mechanisms have not been previously reported for circumneutral pH conditions, particularly for the case of flow through porous media. In this paper, the dissolution rates of K- and Na-compreignacite (K 2(UO 2) 6O 4(OH) 6·8H 2O and Na 2(UO 2) 6O 4(OH) 6·8H 2O respectively) were measured using flow-through columns reacted with two simulated background porewater (BPW) solutions of low and high dissolved total carbonate content (ca. 0.2 and 2.8 mmolmore » L -1). Column materials were characterized before and after reaction with electron microscopy, bulk chemistry, and EXAFS to identify structural and chemical changes during dissolution and to obtain insight into molecular-scale processes. The reactive transport code CrunchFlow was used to calculate overall dissolution rates while accounting for fluid transport and changes in mineral volume and reactive surface area and results were compared to steady-state dissolution rate calculations. In low carbonate BPW systems, interlayer K and Na were initially leached from both minerals, and in Na-compreignacite, K and minor divalent cations from the input solution were incorporated into the mineral structure. Results of characterization analyses suggested that after reaction both K- and Na-compreignacite resembled a disordered K-compreignacite with altered surfaces. A 10-fold increase in dissolved carbonate concentration and corresponding increase in pH (from 6.65 to 8.40) resulted in a net removal of 58-87% of total uranium mass from the columns, compared to <1% net loss in low carbonate BPW systems. Steady-state release of dissolved uranium was not observed with high carbonate solutions and post-reaction characterizations indicated a lack of development of leached or altered surfaces. Dissolution rates (normalized to specific surface area) were about 2.5-3 orders-of-magnitude faster in high versus low carbonate BPW systems, with Na-compreignacite dissolving more rapidly than K-compreignacite under both BPW conditions, possibly due to greater ion exchange (1.57·10 -10 vs. 1.28·10 -13 mol m -2 s -1 [log R = -9.81 and -12.89] and 5.79·10 -10 vs. 3.71·10 -13 mol m -2 s -1 [log R = -9.24 and -12.43] for K- and Na-compreignacite respectively). Experimental and spectroscopic results suggest that the dissolution rate is controlled by bond breaking of a uranyl group and detachment from polyhedral layers of the mineral structure. With higher dissolved carbonate concentrations, this rate-determining step is accelerated by the formation of Ca-uranyl carbonate complexes (dominant species under these conditions), which resulted in an increase of the dissolution rates. Optimization of both dissolution rate and mineral volume fraction in the reactive transport model to account for uranium mass removal during dissolution more accurately reproduced effluent data in high carbonate systems, and resulted in faster overall rates compared with a steady-state dissolution assumption. Finally, this study highlights the importance of coupling reaction and transport processes during the quantification of mineral dissolution rates to accurately predict the fate of contaminants such as uranium in porous geomedia.« less

Rates and mechanisms of uranyl oxyhydroxide mineral dissolution

DOE PAGES

Reinoso-Maset, Estela; Steefel, Carl I.; Um, Wooyong; ...

2017-06-01

Uranyl oxyhydroxide minerals are important weathering products in uranium-contaminated surface and subsurface environments that regulate dissolved uranium concentrations. However, dissolution rates for this class of minerals and associated dissolution mechanisms have not been previously reported for circumneutral pH conditions, particularly for the case of flow through porous media. In this paper, the dissolution rates of K- and Na-compreignacite (K 2(UO 2) 6O 4(OH) 6·8H 2O and Na 2(UO 2) 6O 4(OH) 6·8H 2O respectively) were measured using flow-through columns reacted with two simulated background porewater (BPW) solutions of low and high dissolved total carbonate content (ca. 0.2 and 2.8 mmolmore » L -1). Column materials were characterized before and after reaction with electron microscopy, bulk chemistry, and EXAFS to identify structural and chemical changes during dissolution and to obtain insight into molecular-scale processes. The reactive transport code CrunchFlow was used to calculate overall dissolution rates while accounting for fluid transport and changes in mineral volume and reactive surface area and results were compared to steady-state dissolution rate calculations. In low carbonate BPW systems, interlayer K and Na were initially leached from both minerals, and in Na-compreignacite, K and minor divalent cations from the input solution were incorporated into the mineral structure. Results of characterization analyses suggested that after reaction both K- and Na-compreignacite resembled a disordered K-compreignacite with altered surfaces. A 10-fold increase in dissolved carbonate concentration and corresponding increase in pH (from 6.65 to 8.40) resulted in a net removal of 58-87% of total uranium mass from the columns, compared to <1% net loss in low carbonate BPW systems. Steady-state release of dissolved uranium was not observed with high carbonate solutions and post-reaction characterizations indicated a lack of development of leached or altered surfaces. Dissolution rates (normalized to specific surface area) were about 2.5-3 orders-of-magnitude faster in high versus low carbonate BPW systems, with Na-compreignacite dissolving more rapidly than K-compreignacite under both BPW conditions, possibly due to greater ion exchange (1.57·10 -10 vs. 1.28·10 -13 mol m -2 s -1 [log R = -9.81 and -12.89] and 5.79·10 -10 vs. 3.71·10 -13 mol m -2 s -1 [log R = -9.24 and -12.43] for K- and Na-compreignacite respectively). Experimental and spectroscopic results suggest that the dissolution rate is controlled by bond breaking of a uranyl group and detachment from polyhedral layers of the mineral structure. With higher dissolved carbonate concentrations, this rate-determining step is accelerated by the formation of Ca-uranyl carbonate complexes (dominant species under these conditions), which resulted in an increase of the dissolution rates. Optimization of both dissolution rate and mineral volume fraction in the reactive transport model to account for uranium mass removal during dissolution more accurately reproduced effluent data in high carbonate systems, and resulted in faster overall rates compared with a steady-state dissolution assumption. Finally, this study highlights the importance of coupling reaction and transport processes during the quantification of mineral dissolution rates to accurately predict the fate of contaminants such as uranium in porous geomedia.« less

Rapid analysis of drug dissolution by paper spray ionization mass spectrometry.

PubMed

Liu, Yang; Liu, Ning; Zhou, Ya-Nan; Lin, Lan; He, Lan

2017-03-20

With a great quantity of solid dosage tested by dissolution technology, developing a rapid and sensitive method to access the content of drug within dissolution media is highly desired by analysts and scientists. Traditionally, dissolution media is not compatible with mass spectrometry since the inorganic salts in the media might damage the mass spectrometer. Here, paper spray ionization mass spectrometry (PSI-MS), one of the ambient mass spectrometry technologies, is developed to characterize the content of drugs in dissolution media. The porous structure of paper can effectively retain salts from entering mass spectrometer. This makes the measurement of drug content within dissolution media by mass spectrometer possible. After the experimental parameters were optimized, calibration curves of model drugs - enalapril, quinapril and benazepril were established by using corresponding deuterated internal standards. PSI-MS was then deployed to characterize the content of enalapril from the dissolution testing of enalapril tablets. The results from PSI-MS are comparable to those from HPLC characterization. More importantly, the analysis time of 6 samples is shortened from 90min to 6min. Detection limit of enalapril maleate tablets by PSI-MS is 1/300 of LC. PSI-MS is rapid, sensitive and accurate in analyzing drug content from dissolution tests. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of natural organic matter properties on the dissolution kinetics of zinc oxide nanoparticles

USGS Publications Warehouse

Jiang, Chuanjia; Aiken, George R.; Hsu-Kim, Heileen

2015-01-01

The dissolution of zinc oxide (ZnO) nanoparticles (NPs) is a key step of controlling their environmental fate, bioavailability, and toxicity. Rates of dissolution often depend upon factors such as interactions of NPs with natural organic matter (NOM). We examined the effects of 16 different NOM isolates on the dissolution kinetics of ZnO NPs in buffered potassium chloride solution using anodic stripping voltammetry to directly measure dissolved zinc concentrations. The observed dissolution rate constants (kobs) and dissolved zinc concentrations at equilibrium increased linearly with NOM concentration (from 0 to 40 mg C L–1) for Suwannee River humic and fulvic acids and Pony Lake fulvic acid. When dissolution rates were compared for the 16 NOM isolates, kobs was positively correlated with certain properties of NOM, including specific ultraviolet absorbance (SUVA), aromatic and carbonyl carbon contents, and molecular weight. Dissolution rate constants were negatively correlated to hydrogen/carbon ratio and aliphatic carbon content. The observed correlations indicate that aromatic carbon content is a key factor in determining the rate of NOM-promoted dissolution of ZnO NPs. The findings of this study facilitate a better understanding of the fate of ZnO NPs in organic-rich aquatic environments and highlight SUVA as a facile and useful indicator of NOM interactions with metal-based nanoparticles.

Mechanistic Basis of Cocrystal Dissolution Advantage.

PubMed

Cao, Fengjuan; Amidon, Gordon L; Rodríguez-Hornedo, Naír; Amidon, Gregory E

2018-01-01

Current interest in cocrystal development resides in the advantages that the cocrystal may have in solubility and dissolution compared with the parent drug. This work provides a mechanistic analysis and comparison of the dissolution behavior of carbamazepine (CBZ) and its 2 cocrystals, carbamazepine-saccharin (CBZ-SAC) and carbamazepine-salicylic acid (CBZ-SLC) under the influence of pH and micellar solubilization. A simple mathematical equation is derived based on the mass transport analyses to describe the dissolution advantage of cocrystals. The dissolution advantage is the ratio of the cocrystal flux to drug flux and is defined as the solubility advantage (cocrystal to drug solubility ratio) times the diffusivity advantage (cocrystal to drug diffusivity ratio). In this work, the effective diffusivity of CBZ in the presence of surfactant was determined to be different and less than those of the cocrystals. The higher effective diffusivity of drug from the dissolved cocrystals, the diffusivity advantage, can impart a dissolution advantage to cocrystals with lower solubility than the parent drug while still maintaining thermodynamic stability. Dissolution conditions where cocrystals can display both thermodynamic stability and a dissolution advantage can be obtained from the mass transport models, and this information is useful for both cocrystal selection and formulation development. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Interactions between a poorly soluble cationic drug and sodium dodecyl sulfate in dissolution medium and their impact on in vitro dissolution behavior.

PubMed

Huang, Zongyun; Parikh, Shuchi; Fish, William P

2018-01-15

In the pharmaceutical industry, in vitro dissolution testing ofsolid oral dosage forms is a very important tool for drug development and quality control. However, ion-pairing interaction between the ionic drugand surfactants in dissolution medium often occurs, resulting in inconsistent and incomplete drug release. The aim of this study is toevaluate the effects ofsodium dodecyl sulfate (SDS) mediated medium onthe dissolution behaviors of a poorly soluble cationic drug (Drug B). The study was carried out by measuring solubility of Drug B substance and dissolution rate of Drug B product in media containing SDS.Desolubilization of Drug B substance was observed at pH 4.5 in the presence of SDS at concentrations below critical micelle concentration (CMC) which is attributed to the formation of an insoluble di-dodecyl sulfate salt between SDS and Drug B. This ion-pairing effect is less significant with increasing medium pH where Drug B is less ionized and CMC of SDS is lower. In medium at pH 4.5, dissolution of Drug B product was found incomplete with SDS concentration below CMC due to the desolubilization of Drug B substance. In media with SDS level above CMC, the dissolution rate is rather slower with higher inter-vessel variations compared to that obtained in pH 4.5 medium without SDS. The dissolution results demonstrate that the presence of SDS in medium generates unexpected irregular dissolution profiles for Drug B which are attributed to incompatible dissolution medium for this particular drug. Therefore, non-ionic surfactant was selected for Drug B product dissolution method and ion-pairing effect in SDS mediated medium should be evaluated when developing a dissolution method for any poorly soluble cationic drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

A three step supercritical process to improve the dissolution rate of eflucimibe.

PubMed

Rodier, Elisabeth; Lochard, Hubert; Sauceau, Martial; Letourneau, Jean-Jacques; Freiss, Bernard; Fages, Jacques

2005-10-01

The aim of this study is to improve the dissolution properties of a poorly-soluble active substance, Eflucimibe by associating it with gamma-cyclodextrin. To achieve this objective, a new three-step process based on supercritical fluid technology has been proposed. First, Eflucimibe and cyclodextrin are co-crystallized using an anti-solvent process, dimethylsulfoxide being the solvent and supercritical carbon dioxide being the anti-solvent. Second, the co-crystallized powder is held in a static mode under supercritical conditions for several hours. This is the maturing step. Third, in a final stripping step, supercritical CO(2) is flowed through the matured powder to extract the residual solvent. The coupling of the first two steps brings about a significant synergistic effect to improve the dissolution rate of the drug. The nature of the entity obtained at the end of each step is discussed and some suggestions are made as to what happens in these operations. It is shown the co-crystallization ensures a good dispersion of both compounds and is rather insensitive to the operating parameters tested. The maturing step allows some dissolution-recrystallization to occur thus intensifying the intimate contact between the two compounds. Addition of water is necessary to make maturing effective as this is governed by the transfer properties of the medium. The stripping step allows extraction of the residual solvent but also removes some of the Eflucimibe which is the main drawback of this final stage.

Oral bioavailability enhancement of β-lapachone, a poorly soluble fast crystallizer, by cocrystal, amorphous solid dispersion, and crystalline solid dispersion.

PubMed

Liu, Chengyu; Liu, Zhengsheng; Chen, Yuejie; Chen, Zhen; Chen, Huijun; Pui, Yipshu; Qian, Feng

2018-03-01

The aim of this paper was to compare the in vitro dissolution and in vivo bioavailability of three solubility enhancement technologies for β-lapachone (LPC), a poorly water soluble compound with extremely high crystallization propensity. LPC cocrystal was prepared by co-grinding LPC with resorcinol. LPC crystalline and amorphous solid dispersions (CSD and ASD) were obtained by spray drying with Poloxamer 188 and HPMC-AS, respectively. The cocrystal structure was solved by single crystal x-ray diffraction. All formulations were characterized by WAXRD, DSC, POM and SEM. USP II and intrinsic dissolution studies were used to compare the in vitro dissolution of these formulations, and a crossover dog pharmacokinetic study was used to compare their in vivo bioavailability. An 1:1 LPC-resorcinol cocrystal with higher solubility and faster dissolution rate was obtained, yet it converted to LPC crystal rapidly in solution. LPC/HPMC-AS ASD was confirmed to be amorphous and uniform, while the crystal and crystallite sizes of LPC in CSD were found to be ∼1-3 μm and around 40 nm, respectively. These formulations performed similarly during USP II dissolution, while demonstrated dramatically different oral bioavailability of ∼32%, ∼5%, and ∼1% in dogs, for CSD, co-crystal, and ASD, respectively. CSD showed the fastest intrinsic dissolution rate among the three. The three formulations showed poor IVIVC which could be due to rapid and unpredictable crystallization kinetics. Considering all the reasons, we conclude that for molecules with extremely high crystallization tendency that cannot be inhibited by any pharmaceutical excipients, size-reduction technologies such as CSD could be advantageous for oral bioavailability enhancement in vivo than technologies only generating transient but not sustained supersaturation. Copyright © 2018 Elsevier B.V. All rights reserved.

Study of Electromigration-Induced Failures on Cu Pillar Bumps Joined to OSP and ENEPIG Substrates

NASA Astrophysics Data System (ADS)

Hsiao, Yu-Hsiang; Lin, Kwang-Lung; Lee, Chiu-Wen; Shao, Yu-Hsiu; Lai, Yi-Shao

2012-12-01

This work studies electromigration (EM)-induced failures on Cu pillar bumps joined to organic solderability preservative (OSP) on Cu substrates (OSP-bumps) and electroless Ni(P)/electroless Pd/immersion Au (ENEPIG) under bump metallurgy (UBM) on Cu substrates (ENEPIG-bumps). Two failure modes (Cu pad consumption and gap formation) were found with OSP-bumps, but only one failure mode (gap formation) was found with ENEPIG-bumps. The main interfacial compound layer was the Cu6Sn5 compound, which suffered significant EM-induced dissolution, eventually resulting in severe Cu pad consumption at the cathode side for OSP-bumps. A (Cu,Ni)6Sn5 layer with strong resistance to EM-induced dissolution exists at the joint interface when a nickel barrier layer is incorporated at the cathode side (Ni or ENEPIG), and these imbalanced atomic fluxes result in the voids and gap formation. OSP-bumps showed better lifetime results than ENEPIG-bumps for several current stressing conditions. The inverse Cu atomic flux ( J Cu,chem) which diffuses from the Cu pad to cathode side retards the formation of voids. The driving force for J Cu,chem comes from the difference in chemical potential between the (Cu,Ni)6Sn5 and Cu6Sn5 phases.

Diatom species abundance and morphologically-based dissolution proxies in coastal Southern Ocean assemblages

NASA Astrophysics Data System (ADS)

Warnock, Jonathan P.; Scherer, Reed P.

2015-07-01

Taphonomic processes alter diatom assemblages in sediments, thus potentially negatively impacting paleoclimate records at various rates across space, time, and taxa. However, quantitative taphonomic data is rarely included in diatom-based paleoenvironmental reconstructions and no objective standard exists for comparing diatom dissolution in sediments recovered from marine depositional settings, including the Southern Ocean's opal belt. Furthermore, identifying changes to diatom dissolution through time can provide insight into the efficiency of both upper water column nutrient recycling and the biological pump. This is significant in that reactive metal proxies (e.g. Al, Ti) in the sediments only account for post-depositional dissolution, not the water column where the majority of dissolution occurs. In order to assess the range of variability of responses to dissolution in a typical Southern Ocean diatom community and provide a quantitative guideline for assessing taphonomic variability in diatoms recovered from core material, a sediment trap sample was subjected to controlled, serial dissolution. By evaluating dissolution-induced changes to diatom species' relative abundance, three preservational categories of diatoms have been identified: gracile, intermediate, and robust. The relative abundances of these categories can be used to establish a preservation grade for diatom assemblages. However, changes to the relative abundances of diatom species in sediment samples may reflect taphonomic or ecological factors. In order to address this complication, relative abundance changes have been tied to dissolution-induced morphological change to the areolae of Fragilariopsis curta, a significant sea-ice indicator in Southern Ocean sediments. This correlation allows differentiation between gracile species loss to dissolution versus ecological factors or sediment winnowing. These results mirror a similar morphological dissolution index from a parallel study utilizing Fragilariopsis kerguelensis, suggesting that results are applicable to a broad spectrum of diatoms typically preserved in the sediments.

Dissolution of cinnabar (HgS) in the presence of natural organic matter

USGS Publications Warehouse

Waples, J.S.; Nagy, K.L.; Aiken, G.R.; Ryan, J.N.

2005-01-01

Cinnabar (HgS) dissolution rates were measured in the presence of 12 different natural dissolved organic matter (DOM) isolates including humic, fulvic, and hydrophobic acid fractions. Initial dissolution rates varied by 1.3 orders of magnitude, from 2.31 ?? 10-13 to 7.16 ?? 10-12 mol Hg (mg C)-1 m-2 s-1. Rates correlate positively with three DOM characteristics: specific ultraviolet absorbance (R2 = 0.88), aromaticity (R2 = 0.80), and molecular weight (R2 = 0.76). Three experimental observations demonstrate that dissolution was controlled by the interaction of DOM with the cinnabar surface: (1) linear rates of Hg release with time, (2) significantly reduced rates when DOM was physically separated from the surface by dialysis membranes, and (3) rates that approached constant values at a specific ratio of DOM concentration to cinnabar surface area, suggesting a maximum surface coverage by dissolution-reactive DOM. Dissolution rates for the hydrophobic acid fractions correlate negatively with sorbed DOM concentrations, indicating the presence of a DOM component that reduced the surface area of cinnabar that can be dissolved. When two hydrophobic acid isolates that enhanced dissolution to different extents were mixed equally, a 20% reduction in rate occurred compared to the rate with the more dissolution-enhancing isolate alone. Rates in the presence of the more dissolution-enhancing isolate were reduced by as much as 60% when cinnabar was prereacted with the isolate that enhanced dissolution to a lesser extent. The data, taken together, imply that the property of DOM that enhances cinnabar dissolution is distinct from the property that causes it to sorb irreversibly to the cinnabar surface. Copyright ?? 2005 Elsevier Ltd.

A mathematical analysis of drug dissolution in the USP flow through apparatus

NASA Astrophysics Data System (ADS)

McDonnell, David; D'Arcy, D. M.; Crane, L. J.; Redmond, Brendan

2018-03-01

This paper applies boundary layer theory to the process of drug dissolution in the USP (United States Pharmacopeia) Flow Through Apparatus. The mass transfer rate from the vertical planar surface of a compact within the device is examined. The theoretical results obtained are then compared with those of experiment. The paper also examines the effect on the dissolution process caused by the interaction between natural and forced convection within the apparatus and the introduction of additional boundaries.

Bio resorbability of the modified hydroxyapatite in Tris-HCL buffer

NASA Astrophysics Data System (ADS)

Golovanova, O. A.; Izmailov, R. R.; Ghyngazov, S. A.

2016-02-01

The solubility of carbonated hydroxyapatite powders and granulated carbonated hydroxyapatite produced from the synovial biofluid model solution has been studied. The kinetic characteristics of dissolution were determined. It was found that the solubility of carbonated hydroxyapatite is higher as compared to that of hydroxyapatite. The impact of the organic matrix on the rate of sample dissolution was revealed. For HA-gelatin composites, as the gelatin concentration grows, the dissolution rate becomes greater, and a sample of 6.0 g / L concentration has higher resorbability. The results of the research can be used to study the kinetics of dissolution and the biocompatibility of ceramic materials for medicine, namely for reconstructive surgery, dentistry, and development of drug delivery systems.

An abuse-deterrent, microsphere-in-capsule formulation of extended-release oxycodone: alternative modes of administration to facilitate pain management in patients with dysphagia.

PubMed

McCarberg, Bill H; Kopecky, Ernest A; O'Connor, Melinda; Marseilles, Ann; Varanasi, Ravi K; Thompson, Christy; Fleming, Alison B

2016-12-01

Patients with chronic pain may experience difficulty swallowing, in part due to worsening disease, comorbid conditions, iatrogenic etiology, or age. Patients or caregivers may manipulate extended-release (ER) opioid formulations to facilitate oral dosing due to a lack of therapeutic options that allow for sprinkle or enteral feeding tube administration. If crushed or broken, current oral ER opioids can be associated with adverse sequelae, including risk of potentially fatal overdose. To review the safety, in vitro dissolution data, and in vivo pharmacokinetic data that support alternative modes of administration of oxycodone DETERx (Xtampza ER) via sprinkling onto soft foods for oral ingestion or via enteral feeding tubes. A review of oxycodone DETERx data from in vitro and in vivo studies was conducted to demonstrate support for alternative routes and modes of administration. There was no difference in the dissolution profile when administered with various soft foods or when mixed with various liquid vehicles and administered via nasogastric (NG) or gastrostomy (G) tubes, based on in vitro studies. When sprinkled onto applesauce and administered orally, the microspheres were bioequivalent to the intact oxycodone capsules. When crushed or chewed, the formulation maintained its pharmacokinetic profile; no bolus dose of opioid was released. The sprinkle-dose study was limited by the single-dose study design, as well as the small sample size. Oxycodone DETERx is the first ER oxycodone formulation that can be administered either intact, sprinkled onto soft foods, or via NG/G tubes, thereby providing options for treating pain in patients who have difficulty swallowing.

Dissolution curve comparisons through the F(2) parameter, a Bayesian extension of the f(2) statistic.

PubMed

Novick, Steven; Shen, Yan; Yang, Harry; Peterson, John; LeBlond, Dave; Altan, Stan

2015-01-01

Dissolution (or in vitro release) studies constitute an important aspect of pharmaceutical drug development. One important use of such studies is for justifying a biowaiver for post-approval changes which requires establishing equivalence between the new and old product. We propose a statistically rigorous modeling approach for this purpose based on the estimation of what we refer to as the F2 parameter, an extension of the commonly used f2 statistic. A Bayesian test procedure is proposed in relation to a set of composite hypotheses that capture the similarity requirement on the absolute mean differences between test and reference dissolution profiles. Several examples are provided to illustrate the application. Results of our simulation study comparing the performance of f2 and the proposed method show that our Bayesian approach is comparable to or in many cases superior to the f2 statistic as a decision rule. Further useful extensions of the method, such as the use of continuous-time dissolution modeling, are considered.

The dissolution of quartz in dilute aqueous solutions of organic acids at 25°C

USGS Publications Warehouse

Bennett, P.C.; Melcer, M.E.; Siegel, D.I.; Hassett, J.P.

1988-01-01

The dissolution of quartz in dilute aqueous solutions of organic acids at 25° and standard pressure was investigated by the batch dissolution method. The bulk dissolution rate of quartz in 20 mmole/Kg citrate solutions at pH 7 was 8 to 10 times faster than that in pure water. After 1750 hours the concentration of dissolved silica in the citrate solution was 167 μmole/Kg compared to 50 μmole/Kg in water and a 20 mmole/Kg solution of acetate at pH 7. Solutions of salicylic, oxalic, and humic acids also accelerated the dissolution of quartz in aqueous solution at pH 7. The rate of dissolution in organic acids decreased sharply with decreasing pH.The possibility of a silica-organic acid complex was investigated using UV-difference spectroscopy. Results suggest that dissolved silica is complexed by citrate, oxalate and pyruvate at pH 7 by an electron-donor acceptor complex, whereas no complexation occurs between silica and acetate, lactate, malonate, or succinate. Three models are proposed for the solution and surface complexation of silica by organic acid anions which result in the accelerated dissolution and increased solubility of quartz in organic rich water.

Dissolution comparisons using a Multivariate Statistical Distance (MSD) test and a comparison of various approaches for calculating the measurements of dissolution profile comparison.

PubMed

Cardot, J-M; Roudier, B; Schütz, H

2017-07-01

The f 2 test is generally used for comparing dissolution profiles. In cases of high variability, the f 2 test is not applicable, and the Multivariate Statistical Distance (MSD) test is frequently proposed as an alternative by the FDA and EMA. The guidelines provide only general recommendations. MSD tests can be performed either on raw data with or without time as a variable or on parameters of models. In addition, data can be limited-as in the case of the f 2 test-to dissolutions of up to 85% or to all available data. In the context of the present paper, the recommended calculation included all raw dissolution data up to the first point greater than 85% as a variable-without the various times as parameters. The proposed MSD overcomes several drawbacks found in other methods.

Dissolution and Separation of Aluminum and Aluminosilicates

DOE PAGES

McFarlane, Joanna; Benker, Dennis; DePaoli, David W.; ...

2015-12-19

The selection of an aluminum alloy for target irradiation affects post-irradiation target dissolution and separations. Recent tests with aluminum alloy 6061 yielded greater than expected precipitation in the dissolver, forming up to 10 wt.% solids of aluminum hydroxides and aluminosilicates. Aluminosilicate dissolution presents challenges in a number of different areas, metals extraction from minerals, flyash treatment, and separations from aluminum alloys. We present experimental work that attempts to maximize dissolution of aluminum metal, along with silicon, magnesium, and copper impurities, through control of temperature, the rate of reagent addition, and incubation time. Aluminum phase transformations have been identified as amore » function of time and temperature, using X-ray diffraction. Solutions have been analyzed using wet chemical methods and X-ray fluorescence. Our data have been compared with published calculations of aluminum phase diagrams. Approaches are given to enhance the dissolution of aluminum and aluminosilicate phases in caustic solution.« less

Influence of enzymes and surfactants on the disintegration behavior of cross-linked hard gelatin capsules during dissolution.

PubMed

Pennings, F H; Kwee, B L S; Vromans, H

2006-01-01

Gelatin exhibits cross-linking upon storage at stress conditions. Capsules stored at these conditions fail to show appropriate in vitro dissolution. The aim of this study is to show the effect of surfactants in the medium on the disintegration of the gelatin capsule. This is demonstrated in the presence and absence of the enzymes pancreatin and pepsin, the function of which is to improve the dissolution. Sodium lauryl sulfate (SLS) and Tween 80 are tested as surfactants. When SLS is used in the medium, dissolution is significantly hampered due to the formation of a less soluble precipitate of gelatin. Compared to SLS, Tween 80 shows far better disintegration and solubility results in dissolution media with neutral or low pH. Therefore, it is concluded in this study that Tween 80 is preferred when a surfactant is necessary to comply with sink condition requirements.

Comparative Application of PLS and PCR Methods to Simultaneous Quantitative Estimation and Simultaneous Dissolution Test of Zidovudine - Lamivudine Tablets.

PubMed

Üstündağ, Özgür; Dinç, Erdal; Özdemir, Nurten; Tilkan, M Günseli

2015-01-01

In the development strategies of new drug products and generic drug products, the simultaneous in-vitro dissolution behavior of oral dosage formulations is the most important indication for the quantitative estimation of efficiency and biopharmaceutical characteristics of drug substances. This is to force the related field's scientists to improve very powerful analytical methods to get more reliable, precise and accurate results in the quantitative analysis and dissolution testing of drug formulations. In this context, two new chemometric tools, partial least squares (PLS) and principal component regression (PCR) were improved for the simultaneous quantitative estimation and dissolution testing of zidovudine (ZID) and lamivudine (LAM) in a tablet dosage form. The results obtained in this study strongly encourage us to use them for the quality control, the routine analysis and the dissolution test of the marketing tablets containing ZID and LAM drugs.

Influence of dissolution media pH and USP1 basket speed on erosion and disintegration characteristics of immediate release metformin hydrochloride tablets.

PubMed

Desai, Divyakant; Wong, Benjamin; Huang, Yande; Tang, Dan; Hemenway, Jeffrey; Paruchuri, Srinivasa; Guo, Hang; Hsieh, Daniel; Timmins, Peter

2015-01-01

To investigate the influence of the pH of the dissolution medium on immediate release 850 mg metformin hydrochloride tablets. A traditional wet granulation method was used to manufacture metformin hydrochloride tablets with or without a disintegrant. Tablet dissolution was conducted using the USP apparatus I at 100 rpm. In spite of its pH-independent high solubility, metformin hydrochloride tablets dissolved significantly slower in 0.1 N HCl (pH 1.2) and 50 mM pH 4.5 acetate buffer compared with 50 mM pH 6.8 phosphate buffer, the dissolution medium in the USP. Metformin hydrochloride API compressed into a round 1200 mg disk showed a similar trend. When basket rotation speed was increased from 100 to 250 rpm, the dissolution of metformin hydrochloride tablets was similar in all three media. Incorporation of 2% w/w crospovidone in the tablet formulation improved the dissolution although the pH-dependent trend was still evident, but incorporation of 2% w/w croscarmellose sodium resulted in rapid pH-independent tablet dissolution. In absence of a disintegrant in the tablet formulation, the dissolution was governed by the erosion-diffusion process. Even for a highly soluble drug, a super-disintegrant was needed in the formulation to overcome the diffusion layer limitation and change the dissolution mechanism from erosion-diffusion to disintegration.

The differences between the branded and generic medicines using solid dosage forms: In-vitro dissolution testing

PubMed Central

Al Ameri, Mubarak Nasser; Nayuni, Nanda; Anil Kumar, K.G.; Perrett, David; Tucker, Arthur; Johnston, Atholl

2011-01-01

Introduction Dissolution is the amount of substance that goes into solution per unit time under standardised conditions of liquid/solid interface, solvent composition and temperature. Dissolution is one of the most important tools to predict the in-vivo bioavailability and in some cases to determine bioequivalence and assure interchangeability. Aim To compare the differences in dissolution behaviour of solid dosage forms between innovators (reference products) and their generic counterparts (tested products). Methods Four replicates for each batch of 37 tested medicines was carried out using A PT-DT70 dissolution tester from Pharma Test. A total of 13 branded medicines and 24 generic counterparts were obtained locally and internationally to detect any differences in their dissolution behaviour. They were tested according to the British Pharmacopeia, European Pharmacopeia and the US Pharmacopeia with the rate of dissolution determined by ultra-violet Spectrophotometery. Results Most tested medicines complied with the pharmacopoeial specifications and achieved 85% dissolution in 60 min. However, some generic medicines showed significant differences in dissolution rate at 60 and 120 min. Many generic medicines showed a slower dissolution rate than their branded counterparts such as the generic forms of omeprazole 20 mg. Some showed an incomplete dissolution such as the generic form of nifedipine 10 mg. Other generics showed faster dissolution rate than their branded counterpart such as the generic forms of meloxicam 15 mg. Moreover, some generics from different batches of the same manufacturer showed significant differences in their dissolution rate such as the generic forms of meloxicam 7.5 mg. Nevertheless, some generic medicines violated the EMA and the FDA guidelines for industry when they failed to achieve 85% dissolution at 60 min, such as the generic form of diclofenac sodium 50 mg. Conclusion Most medicines in this study complied with the pharmacopeial limits. However, some generics dissolved differently than their branded counterparts. This can clearly question the interchangeability between the branded and its generic counterpart or even among generics. PMID:25755988

An investigation into the influence of experimental conditions on in vitro drug release from immediate-release tablets of levothyroxine sodium and its relation to oral bioavailability.

PubMed

Kocic, Ivana; Homsek, Irena; Dacevic, Mirjana; Parojcic, Jelena; Miljkovic, Branislava

2011-09-01

The aim of this study was to investigate the influence of experimental conditions on levothyroxine sodium release from two immediate-release tablet formulations which narrowly passed the standard requirements for bioequivalence studies. The in vivo study was conducted as randomised, single-dose, two-way cross-over pharmacokinetic study in 24 healthy subjects. The in vitro study was performed using various dissolution media, and obtained dissolution profiles were compared using the similarity factor value. Drug solubility in different media was also determined. The in vivo results showed narrowly passing bioequivalence. Considering that levothyroxine sodium is classified as Class III drug according to the Biopharmaceutics Classification System, drug bioavailability will be less sensitive to the variation in its dissolution characteristics and it can be assumed that the differences observed in vitro in some of investigated media probably do not have significant influence on the absorption process, as long as rapid and complete dissolution exists. The study results indicate that the current regulatory criteria for the value of similarity factor in comparative dissolution testing, as well as request for very rapid dissolution (more than 85% of drug dissolved in 15 min), are very restricted for immediate-release dosage forms containing highly soluble drug substance and need further investigation. The obtained results also add to the existing debate on the appropriateness of the current bioequivalence standards for levothyroxine sodium products.

Enhanced dissolution and stability of adefovir dipivoxil by cocrystal formation.

PubMed

Gao, Yuan; Zu, Hui; Zhang, Jianjun

2011-04-01

The objectives of this study were to prepare and characterize the novel adefovir dipivoxil-saccharin cocrystal and to demonstrate the enhanced dissolution and stability of adefovir dipivoxil by cocrystal formation. Adefovir dipivoxil-saccharin cocrystal was prepared using a novel solution crystallization approach and scaled up to 30 g for subsequent studies. DSC, IR and XRPD were used to characterize the novel solid form. The stoichiometry of the cocrystal was analysed by HPLC. Dissolution and chemical stability were assessed and compared with marketed adefovir dipivoxil (form 1) used in marketed Hepsera Tablets. A new solid adefovir dipivoxil-saccharin cocrystal with unique melting point, DSC, FTIR and XRPD data was obtained. The molar ratio of adefovir dipivoxil and saccharin in the cocrystal was determined to be 1 : 1. The cocrystal had a pH-independent dissolution profile and showed a two-fold increase in the dissolution efficiency in water and phosphate buffer (pH 6.8) compared with adefovir dipivoxil. The cocrystal was kinetically much more stable than form 1. Form 1 degraded almost completely at 60°C in 18 days, while adefovir dipivoxil-saccharin cocrystal remained unchanged for 47 days at 60°C. This study demonstrated that the dissolution and stability of adefovir dipivoxil could be significantly enhanced by its cocrystal formation with saccharin. The use of cocrystals could be a feasible and valuable approach for improving the physicochemical properties of adefovir dipivoxil. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

A comparative study of spray-dried and freeze-dried hydrocortisone/polyvinyl pyrrolidone solid dispersions.

PubMed

Dontireddy, Rakesh; Crean, Abina M

2011-10-01

Poor water solubility of new chemical entities (NCEs) is one of the major challenges the pharmaceutical industry currently faces. The purpose of this study was to investigate the feasibility of freeze-drying as an alternative technique to spray-drying to produce solid dispersions of poorly water-soluble drugs. Also investigated was the use of aqueous solvent mixtures in place of pure solvent for the production of solid dispersions. Aqueous solvent systems would reduce the environmental impact of pure organic solvent systems. Spray-dried and freeze-dried hydrocortisone/polyvinyl pyrrolidone solid dispersions exhibited differences in dissolution behavior. Freeze-dried dispersions exhibited faster dissolution rates than the corresponding spray-dried dispersions. Spray-dried systems prepared using both solvent systems (20% v/v and 96% v/v ethanol) displayed similar dissolution performance despite displaying differences in glass transition temperatures (T(g)) and surface areas. All dispersions showed drug/polymer interactions indicated by positive deviations in T(g) from the predicted values calculated using the Couchman-Karasz equation. Fourier transform infrared (FTIR) spectroscopic results confirmed the conversion of crystalline drug to the amorphous in the dispersions. Stability studies were preformed at 40°C and 75% relative humidity to investigate the physical stability of prepared dispersions. Recrystallization was observed after a month and the resultant dispersions were tested for their dissolution performance to compare with the dissolution performance of the dispersions prior to the stability study. The dissolution rate of the freeze-dried dispersions remained higher than both spray-dried dispersions after storage.

Understanding the generation and maintenance of supersaturation during the dissolution of amorphous solid dispersions using modulated DSC and 1H NMR.

PubMed

Baghel, Shrawan; Cathcart, Helen; O'Reilly, Niall J

2018-01-30

In this study, the dissolution behaviour of dipyridamole (DPM) and cinnarizine (CNZ) spray-dried amorphous solid dispersions (ASDs) using polyvinyl pyrrolidone (PVP) and polyacrylic acid (PAA) as a carrier matrix were evaluated and compared. The drug concentrations achieved from the dissolution of PVP and PAA solid dispersions were significantly greater than the equilibrium solubility of crystalline DPM and CNZ in phosphate buffer pH 6.8 (PBS 6.8). The maximum drug concentration achieved by dissolution of PVP and PAA solid dispersions did not exceed the theoretically calculated apparent solubility of amorphous DPM and CNZ. However, the degree of supersaturation of DPM and CNZ increased considerably as the polymer weight fraction within the solid dispersion increased. In addition, the supersaturation profile of DPM and CNZ were studied in the presence and absence of the polymers. PAA was found to maintain a higher level of supersaturation compared to PVP. The enhanced drug solution concentration following dissolution of ASDs can be attributed to the reduced crystal growth rates of DPM and CNZ at an equivalent supersaturation. We have also shown that, for drugs having high crystallization tendency and weak drug-polymer interaction, the feasible way to increase dissolution might be increase the polymer weight fraction in the ASD. Solution 1 H NMR spectra were used to understand dissolution mechanism and to identify drug-polymer interaction. The change in electron densities of proton attached to different groups in DPM and CNZ suggested drug-polymer interaction in solution. The relative intensities of peak shift and nature of interaction between drug and polymer in different systems are different. These different effects suggest that DPM and CNZ interacts in a different way with PVP and PAA in solution which goes some way towards explaining the different polymeric effect, particularly in terms of inhibition of drug recrystallization and dissolution of DPM and CNZ ASDs. These results established that the different drug/polymer interactions in the solid state and in solution give rise to the variation in dissolution profile observed for different systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Testing lyoequivalency for three commercially sustained-release tablets containing diltiazem hydrochloride.

PubMed

Maswadeh, Hamzah A; Al-Hanbali, Othman A; Kanaan, Reem A; Shakya, Ashok K; Maraqa, Anwar

2010-01-01

In vitro release kinetics of three commercially available sustained release tablets (SR) diltiazem hydrochloride were studied at pH 1.1 for 2 h and for another 6 h at pH 6.8 using the USP dissolution apparatus with the paddle assemble. The kinetics of the dissolution process was studied by analyzing the dissolution data using five kinetic equations: the zero-order equation, the first-order equation, the Higuchi square root equation, the Hixson-Crowell cube root law and the Peppas equation. Analyses of the dissolution kinetic data for diltiazem hydrochloride commercial SR tablets showed that both Dilzacard and Dilzem SR tablets released drug by Non-Fickian (Anomalous transport) release with release exponent (n) equal to 0.59 and 0.54, respectively, which indicate the summation of both diffusion and dissolution controlled drug release. Bi-Tildiem SR tablets released drug by super case II (n = 1.29) which indicate zero-order release due to the dissolution of polymeric matrix and relaxation of the polymer chain. This finding was also in agreement with results obtained from application of zero-order and Hixson-Crowell equations. A dissolution profile comparative study was done to test the lyoequivelancy of the three products by using the mean dissolution time (MDT), dissimilarity factor f1 and similarity factor f2. Results showed that the three products are different and not lyoequivalent.

Preparation, characterization and in vitro evaluation of solid dispersions containing docetaxel.

PubMed

Chen, Jie; Qiu, Liyan; Hu, Minxin; Jin, Yi; Han, Jieru

2008-06-01

Solid dispersions using water-soluble carriers were studied for improving the dissolution of docetaxel, a poorly soluble compound. In order to obtain the most optimized formulation, we prepared many solid dispersions with different carriers, different solvents, or at a series of drug-to-carrier ratios, and compared their dissolution. The accumulative dissolution of docetaxel from poloxamer 188 was more excellent than that from PVP(k30) and glyceryl monostearate, and the dissolution of docetaxel from solid dispersion was markedly higher than that of pure docetaxel; meanwhile the increased dissolution was partly dependent on the ratios of docetaxel and poloxamer 188. The ethanol used to prepare solid dispersion is of more significant effect on the dissolution of docetaxel than that of acetone. The docetaxel/poloxamer 188 system was characterized by differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and environmental scanning electron microscope (ESEM). The results of DSC, XRD, and ESEM analyses of docetaxel/poloxamer 188 system showed that there are intermolecular interactions between docetaxel and poloxamer, and the crystallinity of docetaxel disappeared. These results show that solid dispersion is a promising approach of developing docetaxel drug formulates.

A functional relation for field-scale nonaqueous phase liquid dissolution developed using a pore network model

USGS Publications Warehouse

Dillard, L.A.; Essaid, H.I.; Blunt, M.J.

2001-01-01

A pore network model with cubic chambers and rectangular tubes was used to estimate the nonaqueous phase liquid (NAPL) dissolution rate coefficient, Kdissai, and NAPL/water total specific interfacial area, ai. Kdissai was computed as a function of modified Peclet number (Pe???) for various NAPL saturations (SN) and ai during drainage and imbibition and during dissolution without displacement. The largest contributor to ai was the interfacial area in the water-filled corners of chambers and tubes containing NAPL. When Kdissai was divided by ai, the resulting curves of dissolution coefficient, Kdiss versus Pe??? suggested that an approximate value of Kdiss could be obtained as a weak function of hysteresis or SN. Spatially and temporally variable maps of Kdissai calculated using the network model were used in field-scale simulations of NAPL dissolution. These simulations were compared to simulations using a constant value of Kdissai and the empirical correlation of Powers et al. [Water Resour. Res. 30(2) (1994b) 321]. Overall, a methodology was developed for incorporating pore-scale processes into field-scale prediction of NAPL dissolution. Copyright ?? 2001 .

NUMERICAL TECHNIQUES TO SOLVE CONDENSATIONAL AND DISSOLUTIONAL GROWTH EQUATIONS WHEN GROWTH IS COUPLED TO REVERSIBLE REACTIONS (R823186)

EPA Science Inventory

Noniterative, unconditionally stable numerical techniques for solving condensational and
dissolutional growth equations are given. Growth solutions are compared to Gear-code solutions for
three cases when growth is coupled to reversible equilibrium chemistry. In all cases, ...

To evaluate the change in release from solid dispersion using sodium lauryl sulfate and model drug sulfathiazole.

PubMed

Dave, Rutesh H; Patel, Hardikkumar H; Donahue, Edward; Patel, Ashwinkumar D

2013-10-01

The solubility of drugs remains one of the most challenging aspects of formulation development. There are numerous ways to improve the solubility of drugs amongst which the most promising strategy is solid dispersion. Different ratios of sulfathiazole: PVP-K29/32: sodium lauryl sulfate (SLS) were prepared (1:1:0.1, 1:1:0.5, 1:1:1) and various methods were employed to characterize the prepared solid dispersions, namely modulated differential scanning calorimeter, X-ray powder diffraction, Fourier Transformed Infrared Spectroscopy and dissolution studies. Lack of crystallinity was observed in internal and external systems suggesting a loss of crystallinity, whereas the physical mixtures showed a characteristic peak of sulfathiazole. In vitro dissolution results clearly showed that the incorporation of a relatively small amount of surfactants (5, 20 or 33% w/w) into a solid dispersion can improve its dissolution rates compared to binary solid dispersion (SD) alone and pure sulfathiazole. In all ratios solid dispersion internal shows a higher dissolution rate compared to a physical mixture and solid dispersion external which suggests that the way that the surfactant is incorporated into the solid dispersion plays an important role in changing the solubility of a drug. The solubilization mechanism is mainly responsible for this higher dissolution rate when we incorporate the SLS in SD.

Dissolution and solubility behavior of fenofibrate in sodium lauryl sulfate solutions.

PubMed

Granero, Gladys E; Ramachandran, Chandrasekharan; Amidon, Gordon L

2005-10-01

The solubility of fenofibrate in pH 6.8 McIlvaine buffers containing varying concentrations of sodium lauryl sulfate was determined. The dissolution behavior of fenofibrate was also examined in the same solutions with rotating disk experiments. It was observed that the enhancement in intrinsic dissolution rate was approximately 500-fold and the enhancement in solubility was approximately 2000-fold in a pH 6.8 buffer containing 2% (w/v) sodium lauryl sulfate compared to that in buffer alone. The micellar solubilization equilibrium coefficient (k*) was estimated from the solubility data and found to be 30884+/-213 L/mol. The diffusivity for the free solute, 7.15x10(-6) cm2/s, was calculated using Schroeder's additive molal volume estimates and Hayduk-Laurie correlation. The diffusivity of the drug-loaded micelle, estimated from the experimental solubility and dissolution data and the calculated value for free solute diffusivity, was 0.86x10(-6) cm2/s. Thus, the much lower enhancement in dissolution of fenofibrate compared to its enhancement in solubility in surfactant solutions appears to be consistent with the contribution to the total transport due to enhanced micellar solubilization as well as a large decrease (approximately 8-fold) in the diffusivity of the drug-loaded micelle.

Reprint of: Effects of solution degassing on solubility, crystal growth and dissolution-Case study: Salicylic acid in methanol

NASA Astrophysics Data System (ADS)

Seidel, J.; Ulrich, J.

2017-07-01

The influence of dissolved gases on the crystallization parameter solubility, MZW, growth and dissolution rates was investigated experimentally using degassed and non-degassed (air-saturated) solutions. The results of this study show that degassing has no effect on the solubility curve of the used model substance salicylic acid (SA) in methanol (MeOH). This reveals in the assumption that a thermodynamic effect of dissolved gases can be excluded. Growth rates were measured by means of a desupersaturation method and the results indicate that the growth rates of SA are not affected by degassing. The results of the dissolution rate measurements reveal a distinct decrease in dissolution rates for non-degassed solutions compared to degassed solutions, especially, at low temperature (10 °C). To explain this phenomenon the gas solubility, represented by oxygen, in MeOH in dependence on the SA concentration was estimated by means of Hansen Solubility Parameters (HSP) [1]. It was found that the oxygen solubility decreases with increasing SA content which explains the inhibition of crystal dissolution in non-degassed solution compared to degassed solution. Moreover, this kind of 'drowing-out' mechanism would not appear in growth rate measurements, where indeed no effect of degassing could be observed.

Influence of the oral dissolution time on the absorption rate of locally administered solid formulations for oromucosal use: the flurbiprofen lozenges paradigm.

PubMed

Imberti, Roberto; De Gregori, Simona; Lisi, Lucia; Navarra, Pierluigi

2014-01-01

Flurbiprofen is a nonsteroidal anti-inflammatory agent preferentially used for local oromucosal treatment of painful and/or inflammatory conditions of the oropharynx such as gingivitis, stomatitis, periodontitis, pharyngitis and laryngitis. In this study, we have investigated the bioavailability of a new generic formulation of flurbiprofen lozenges developed by Epifarma Srl, compared to the originator Benactiv Gola® taken as reference. Within the framework of a formal bioequivalence study, we investigated in particular the putative influence of oral dissolution time (i.e. the time spent suckling the lozenge from its intake to complete dissolution) on the absorption rate, and the contribution of this factor to the total variability of plasma flurbiprofen during absorption. We found that the amount of flurbiprofen absorbed into the systemic circulation is not significantly higher for the test drug compared to that of the reference product. We observed that the length of oral dissolution time is inversely correlated to 10-min flurbiprofen plasma levels in the test but not in the reference formulation. We estimated that oral dissolution time accounts for about 14% of overall variability in flurbiprofen plasma 10 min after test drug administration. © 2014 S. Karger AG, Basel.

Effects of solution degassing on solubility, crystal growth and dissolution-Case study: Salicylic acid in methanol

NASA Astrophysics Data System (ADS)

Seidel, J.; Ulrich, J.

2017-02-01

The influence of dissolved gases on the crystallization parameter solubility, MZW, growth and dissolution rates was investigated experimentally using degassed and non-degassed (air-saturated) solutions. The results of this study show that degassing has no effect on the solubility curve of the used model substance salicylic acid (SA) in methanol (MeOH). This reveals in the assumption that a thermodynamic effect of dissolved gases can be excluded. Growth rates were measured by means of a desupersaturation method and the results indicate that the growth rates of SA are not affected by degassing. The results of the dissolution rate measurements reveal a distinct decrease in dissolution rates for non-degassed solutions compared to degassed solutions, especially, at low temperature (10 °C). To explain this phenomenon the gas solubility, represented by oxygen, in MeOH in dependence on the SA concentration was estimated by means of Hansen Solubility Parameters (HSP) [1]. It was found that the oxygen solubility decreases with increasing SA content which explains the inhibition of crystal dissolution in non-degassed solution compared to degassed solution. Moreover, this kind of 'drowing-out' mechanism would not appear in growth rate measurements, where indeed no effect of degassing could be observed.

Chemoinformetrical evaluation of dissolution property of indomethacin tablets by near-infrared spectroscopy.

PubMed

Otsuka, Makoto; Tanabe, Hideaki; Osaki, Kazuo; Otsuka, Kuniko; Ozaki, Yukihiro

2007-04-01

The purpose of this study was to use near-infrared spectrometry (NIR) with chemoinformetrics to predict the change of dissolution properties in indomethacin (IMC) tablets during the manufacturing process. A comparative evaluation of the dissolution properties of the tablets was performed by the diffused reflectance (DRNIR) and transmittance (TNIR) NIR spectroscopic methods. Various kinds of IMC tablets (200 mg) were obtained from a powder (20 mg of IMC, 18 mg of microcrystalline cellulose, 160 mg of lactose, and 2 mg of magnesium stearate) under various compression pressures (60-398 MPa). Dissolution tests were performed in phosphate buffer, and the time required for 75% dissolution (T75) and mean dissolution time (MDT) were calculated. DRNIR and TNIR spectra were recorded, and the both NIR spectra used to establish a calibration model for predicting the dissolution properties by principal component regression analysis (PCR). The T75 and MDT increased as the compression pressure increased, since tablet porosity decreased with increasing pressure. Intensity of the DRNIR spectra of the compressed tablets decreased as the compression pressure increased. However, the intensity of TNIR spectra increased along with the pressure. The calibration models used to evaluate the dissolution properties of tablets were established by using PCR based on both DRNIR and TNIR spectra of the tablets. The multiple correlation coefficients of the relationship between the actual and predictive T75 by the DRNIR and TNIR methods were 0.831 and 0.962, respectively. It is possible to predict the dissolution properties of pharmaceutical preparations using both DRNIR and TNIR chemoinformetric methods. The TNIR method was more accurate for predictions of the dissolution behavior of tablets than the DRNIR method. (c) 2007 Wiley-Liss, Inc.

Clinopyroxene dissolution in basaltic melt

NASA Astrophysics Data System (ADS)

Chen, Yang; Zhang, Youxue

2009-10-01

The history of magmatic systems may be inferred from reactions between mantle xenoliths and host basalt if the thermodynamics and kinetics of the reactions are quantified. To study diffusive and convective clinopyroxene dissolution in silicate melts, diffusive clinopyroxene dissolution experiments were conducted at 0.47-1.90 GPa and 1509-1790 K in a piston-cylinder apparatus. Clinopyroxene saturation is found to be roughly determined by MgO and CaO content. The effective binary diffusivities, DMgO and DCaO, and the interface melt saturation condition, C0MgO×C0CaO, are extracted from the experiments. DMgO and DCaO show Arrhenian dependence on temperature. The pressure dependence is small and not resolved within 0.47-1.90 GPa. C0MgO×C0CaO in the interface melt increases with increasing temperature, but decreases with increasing pressure. Convective clinopyroxene dissolution, where the convection is driven by the density difference between the crystal and melt, is modeled using the diffusivities and interface melt saturation condition. Previous studies showed that the convective dissolution rate depends on the thermodynamics, kinetics and fluid dynamics of the system. Comparing our results for clinopyroxene dissolution to results from a previous study on convective olivine dissolution shows that the kinetic and fluid dynamic aspects of the two minerals are quite similar. However, the thermodynamics of clinopyroxene dissolution depends more strongly on the degree of superheating and composition of the host melt than that of olivine dissolution. The models for clinopyroxene and olivine dissolution are tested against literature experiments on mineral-melt interaction. They are then applied to previously proposed reactions between Hawaii basalts and mantle minerals, mid-ocean ridge basalts and mantle minerals, and xenoliths digestion in a basalt at Kuandian, Northeast China.

Investigation of the Dissolution Profile of Gliclazide Modified-Release Tablets Using Different Apparatuses and Dissolution Conditions.

PubMed

Skripnik, K K S; Riekes, M K; Pezzini, B R; Cardoso, S G; Stulzer, H K

2017-07-01

In the absence of an official dissolution method for modified-release tablets of gliclazide, dissolution parameters, such as apparatuses (1, 2, and 3), rotation speeds, pH, and composition of the dissolution medium were investigated. The results show that although the drug presents a pH-mediated solubility (pH 7.0 > 6.8 > 6.4 > 6.0 > 5.5 > 4.5), the in vitro release of the studied tablets was not dependent on this parameter, despite of the apparatus tested. On the other hand, the rotation speed demonstrated a greater influence (100 rpm >50 rpm). Using similar hydrodynamic conditions, the three different apparatuses were compared in pH 6.8 and provided the following trend: apparatus 1 at 100 rpm >2 at 50 rpm ≈3 at 10 dpm. As a complete, but slow release is expected from modified-release formulations, apparatus 2, in phosphate buffer pH 6.8 and 100 rpm, were selected as the optimized dissolution method. In comparison to apparatus 1 under the same conditions, the paddle avoids the stickiness of formulation excipients at the mesh of the basket, which could prejudice the release of gliclazide. Results obtained with biorelevant medium through the developed dissolution method were similar to the buffer solution pH 6.8. The application of the optimized method as a quality control test between two different brands of gliclazide modified-release tablets showed that both dissolution profiles were considered similar by the similarity factor (f2 = 51.8). The investigation of these dissolution profiles indicated a dissolution kinetic following first-order model.

The impact of calcium carbonate as pore forming agent and drug entrapment method towards drug dissolution mechanism of amoxicillin trihydrate encapsulated by chitosan-methyl cellulose semi-IPN hydrogel for floating drug delivery system

NASA Astrophysics Data System (ADS)

Dewantara, Fauzi; Budianto, Emil

2018-04-01

Chitosan-methyl cellulose semi-IPN hydrogel is used as floating drug delivery system, and calcium carbonate also added as pore forming agent. The hydrogel network arranged by not only using biopolymer chitosan and methyl cellulose, but also the crosslink agent that is glutaraldehyde. Amoxicillin trihydrate entrapped into the polymer network with two different method, in situ loading and post loading. Furthermore both method has been tested for drug entrapment efficiency along with drug dissolution test, and the result for drug entrapment efficiency is in situ loading method has highest value of 100%, compared to post loading method which has value only 71%. Moreover, at the final time of drug dissolution test shows in situ loading method has value of 96% for total accumulative of drug dissolution, meanwhile post loading method has 72%. The value of drug dissolution test from both method is used for analyzing drug dissolution mechanism of amoxicillin trihydrate from hydrogel network with four mathematical drug mechanism models as parameter. The polymer network encounter destructive degradation causes by acid solution which used as dissolution medium, and the level of degradation is observed with optical microscope. However the result shows that degradation of the polymer network doesn't affect drug dissolution mechanism directly. Although the pore forming agent causes the pore inside the hydrogel network create interconnection and it was quite influential to drug dissolution mechanism. Interconnected pore is observed with Scanning Electron Microscope (SEM) and shows that the amount and area of interconnected pore inside the hydrogel network is increasing as drug dissolution goes on.

Optimization of the dissolution of molybdenum disks. FY-16 results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tkac, Peter; Rotsch, David A.; Chemerisov, Sergey D.

2016-09-01

Argonne National Laboratory is providing technical development assistance to NorthStar Medical Technologies LLC in its pursuit of two pathways for production of molybdenum-99: the 98Mo(n,γ) 99Mo reaction and the photonuclear reaction, 100Mo(γ,n) 99Mo. Processing of irradiated targets, from either production mode, requires dissolution of the target material in H 2O 2 followed by a concentration step, addition of ferric ion to precipitate impurities, and conversion of the final solution to 5M potassium hydroxide solution of potassium molybdate. Currently, NorthStar is using pressed and sintered Mo disks as targets. Several options are being considered for the design of Mo targets formore » the production of 99Mo using the (γ,n) reaction. In the current design, the target holder contains a series of sintered Mo disks lined up perpendicular to two incident electron beams, one entering from each side of the target stack. In this configuration, the front-most disks absorb most of the heat from the electron beam and need to be thinner to allow for better cooling, while the middle of the target can be thicker. Distribution of the total mass of Mo allows for larger masses of Mo material and thus larger production batches of 99Mo. A limitation of the sintering approach is the production of very thin disks. Recent advances in 3D printing allow for much thinner target components can be achieved than when the traditional press-and-sinter approach is used. We have demonstrated that several factors can play important roles in dissolution behavior: particle size of Mo metal used for production of targets, sintering conditions, degree of open porosity, and thickness of the sintered Mo targets. Here we report experimental results from studies of small-scale dissolution of sintered Mo disks fabricated from various recycled and commercial Mo materials, and dissolution of 3D-printed Mo disks that were fabricated by Oak Ridge National Laboratory (ORNL). We also report on large-scale dissolution studies with 600 g batches of sintered Mo disks.« less

Dissolution process analysis using model-free Noyes-Whitney integral equation.

PubMed

Hattori, Yusuke; Haruna, Yoshimasa; Otsuka, Makoto

2013-02-01

Drug dissolution process of solid dosages is theoretically described by Noyes-Whitney-Nernst equation. However, the analysis of the process is demonstrated assuming some models. Normally, the model-dependent methods are idealized and require some limitations. In this study, Noyes-Whitney integral equation was proposed and applied to represent the drug dissolution profiles of a solid formulation via the non-linear least squares (NLLS) method. The integral equation is a model-free formula involving the dissolution rate constant as a parameter. In the present study, several solid formulations were prepared via changing the blending time of magnesium stearate (MgSt) with theophylline monohydrate, α-lactose monohydrate, and crystalline cellulose. The formula could excellently represent the dissolution profile, and thereby the rate constant and specific surface area could be obtained by NLLS method. Since the long time blending coated the particle surface with MgSt, it was found that the water permeation was disturbed by its layer dissociating into disintegrant particles. In the end, the solid formulations were not disintegrated; however, the specific surface area gradually increased during the process of dissolution. The X-ray CT observation supported this result and demonstrated that the rough surface was dominant as compared to dissolution, and thus, specific surface area of the solid formulation gradually increased. Copyright © 2012 Elsevier B.V. All rights reserved.

Preparation, characterization and in vivo evaluation of amorphous atorvastatin calcium nanoparticles using supercritical antisolvent (SAS) process.

PubMed

Kim, Min-Soo; Jin, Shun-Ji; Kim, Jeong-Soo; Park, Hee Jun; Song, Ha-Seung; Neubert, Reinhard H H; Hwang, Sung-Joo

2008-06-01

In this work, amorphous atorvastatin calcium nanoparticles were successfully prepared using the supercritical antisolvent (SAS) process. The effect of process variables on particle size and distribution of atorvastatin calcium during particle formation was investigated. Solid state characterization, solubility, intrinsic dissolution, powder dissolution studies and pharmacokinetic study in rats were performed. Spherical particles with mean particle size ranging between 152 and 863 nm were obtained by varying process parameters such as precipitation vessel pressure and temperature, drug solution concentration and feed rate ratio of CO2/drug solution. XRD, TGA, FT-IR, FT-Raman, NMR and HPLC analysis indicated that atorvastatin calcium existed as anhydrous amorphous form and no degradation occurred after SAS process. When compared with crystalline form (unprocessed drug), amorphous atorvastatin calcium nanoparticles were of better performance in solubility and intrinsic dissolution rate, resulting in higher solubility and faster dissolution rate. In addition, intrinsic dissolution rate showed a good correlation with the solubility. The dissolution rates of amorphous atorvastatin calcium nanoparticles were highly increased in comparison with unprocessed drug by the enhancement of intrinsic dissolution rate and the reduction of particle size resulting in an increased specific surface area. The absorption of atorvastatin calcium after oral administration of amorphous atorvastatin calcium nanoparticles to rats was markedly increased.

Dissolution of a new explosive formulation containing TNT and HMX: comparison with octol.

PubMed

Monteil-Rivera, Fanny; Deschamps, Stéphane; Ampleman, Guy; Thiboutot, Sonia; Hawari, Jalal

2010-02-15

GIM (Greener Insensitive Material) is a new explosive formulation made of HMX (51.5%), TNT (40.7%), and a binder, ETPE (7.8%), which is currently investigated by the Canadian Department of National Defense for a wider use by the Army. In the present study, dissolution of GIM in water was measured and compared to the dissolution of octol (HMX/TNT: 70/30). Although the presence of ETPE did not prevent completely TNT and HMX from dissolving, GIM appeared to dissolve more slowly than octol. The ETPE was shown to prevent the formulation particles from collapsing and to retard the dissolution of both TNT and HMX by limiting their exposure to water. In both octol and GIM, the dissolution rate of the particles was governed by the compound(s) that are slower to dissolve, i.e. HMX in octol, and HMX and ETPE in GIM. A model based on Fick's diffusion law allowed fitting well the dissolution data of octol but was less appropriate to fit the data of GIM likely due to a physical rearrangement of the solid upon dissolution. The present findings demonstrate that ETPE in GIM decreases the risks of explosives leakage from particles of the new formulation and should facilitate the collecting of non-exploded GIM particles in training sites.

The effect of fuel chemistry on UO2 dissolution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Casella, Amanda; Hanson, Brady; Miller, William

2016-08-01

The dissolution rate of both unirradiated UO2 and used nuclear fuel has been studied by numerous countries as part of the performance assessment of proposed geologic repositories. In the scenario of waste package failure and groundwater infiltration into the fuel, the effects of variables such as temperature, dissolved oxygen, and water and fuel chemistry on the dissolution rates of the fuel are necessary to provide a quantitative estimate of the potential release over geologic time frames. The primary objective of this research was to determine the influence these parameters have on the dissolution rate of unirradiated UO2 under repository conditionsmore » and compare them to the rates predicted by current dissolution models. Both unirradiated UO2 and UO2 doped with varying concentrations of Gd2O3, to simulate used fuel composition after long time periods where radiolysis has minor contributions to dissolution, were examined. In general, a rise in temperature increased the dissolution rate of UO2 and had a larger effect on pure UO2 than on those doped with Gd2O3. Oxygen dependence was observed in the UO2 samples with no dopant and increased as the temperature rose; in the doped fuels less dependence was observed. The addition of gadolinia into the UO2 matrix showed a significant decrease in the dissolution rate. The matrix stabilization effect resulting from the dopant proved even more beneficial in lowering the dissolution rate at higher temperatures and dissolved O2 concentrations in the leachate where the rates would typically be elevated.« less

Development and Evaluation of Mouth Dissolving Films of Amlodipine Besylate for Enhanced Therapeutic Efficacy

PubMed Central

Maheswari, K. M.; Devineni, Pavan Kumar; Deekonda, Sravanthi; Shaik, Salma; Uppala, Naga Pravallika; Nalluri, Buchi N.

2014-01-01

The present investigation was undertaken with an objective of formulating mouth dissolving films (MDFs) of Amlodipine Besylate (AMLO) to enhance convenience and compliance of the elderly and pediatric patients for better therapeutic efficacy. Film formers like hydroxy propyl methyl cellulose (HPMC) and methyl cellulose (MC) along with film modifiers like poly vinyl pyrrolidone K30 (PVP K30), and sodium lauryl sulphate (SLS) as solubilizing agents were evaluated. The prepared MDFs were evaluated for in vitro dissolution characteristics, in vitro disintegration time, and their physicomechanical properties. All the prepared MDFs showed good mechanical properties like tensile strength, folding endurance, and % elongation. MDFs were evaluated by means of FTIR, SEM, and X-RD studies. MDFs with 7.5% (w/w) of HPMC E3 gave better dissolution properties when compared to HPMC E5, HPMC E15, and MC. MDFs with PVP K30 and SLS gave superior dissolution properties when compared to MDFs without PVP K30 and SLS. The dissolution properties of MDFs with PVP K30 were superior when compared to MDFs with SLS. In the case of F3 containing 7.5% of HPMC E3 and 0.04% of PVP K30, complete and faster release was observed within 60 sec when compared to other formulations. Release kinetics data reveals diffusion is the release mechanism. PMID:26556197

Development and Evaluation of Mouth Dissolving Films of Amlodipine Besylate for Enhanced Therapeutic Efficacy.

PubMed

Maheswari, K M; Devineni, Pavan Kumar; Deekonda, Sravanthi; Shaik, Salma; Uppala, Naga Pravallika; Nalluri, Buchi N

2014-01-01

The present investigation was undertaken with an objective of formulating mouth dissolving films (MDFs) of Amlodipine Besylate (AMLO) to enhance convenience and compliance of the elderly and pediatric patients for better therapeutic efficacy. Film formers like hydroxy propyl methyl cellulose (HPMC) and methyl cellulose (MC) along with film modifiers like poly vinyl pyrrolidone K30 (PVP K30), and sodium lauryl sulphate (SLS) as solubilizing agents were evaluated. The prepared MDFs were evaluated for in vitro dissolution characteristics, in vitro disintegration time, and their physicomechanical properties. All the prepared MDFs showed good mechanical properties like tensile strength, folding endurance, and % elongation. MDFs were evaluated by means of FTIR, SEM, and X-RD studies. MDFs with 7.5% (w/w) of HPMC E3 gave better dissolution properties when compared to HPMC E5, HPMC E15, and MC. MDFs with PVP K30 and SLS gave superior dissolution properties when compared to MDFs without PVP K30 and SLS. The dissolution properties of MDFs with PVP K30 were superior when compared to MDFs with SLS. In the case of F3 containing 7.5% of HPMC E3 and 0.04% of PVP K30, complete and faster release was observed within 60 sec when compared to other formulations. Release kinetics data reveals diffusion is the release mechanism.

Effects of solid dispersion and self-emulsifying formulations on the solubility, dissolution, permeability and pharmacokinetics of isorhamnetin, quercetin and kaempferol in total flavones of Hippophae rhamnoides L.

PubMed

Zhao, Guoying; Duan, Jingze; Xie, Yan; Lin, Guobei; Luo, Huilin; Li, Guowen; Yuan, Xiurong

2013-07-01

The aim of this study was to investigate the effects of solid dispersions (SD) and self-emulsifying (SE) formulations on the solubility and absorption properties of active components in total flavones of Hippophae rhamnoides L. (TFH). The solubility, dissolution rate, permeability and pharmacokinetics of isorhamnetin, quercetin and kaempferol in TFH SD/SE formulations and TFH were compared. The results showed that the solubility and dissolution rate of isorhamnetin, quercetin and kaempferol in SD/SE formulations were significantly enhanced compared to those in TFH, however, their intestinal permeability was comparable. The bioavailability of isorhamnetin, quercetin and kaempferol in rats remarkably increased after oral administration of TFH SD formulations compared to TFH, but there was no significant increase after oral administration of TFH SE formulations. The results of this study indicated the SD formulations on the improvement of pharmacokinetic properties of isorhamnetin, quercetin and kaempferol in TFH were much better than those of SE formulations. The improvement of pharmacokinetic properties of isorhamnetin, quercetin and kaempferol in TFH by SD formulations was probably ascribed to the enhancement of the solubility and dissolution of the three components, but was not relevant to the intestinal permeability. Therefore, as for herb extracts containing multiple components, especially for their major components with poor water solubility, solid dispersion formulations might have the better potential to enhance their bioavailability.

Investigation of Cyclodextrin-Based Nanosponges for Solubility and Bioavailability Enhancement of Rilpivirine.

PubMed

Rao, Monica R P; Chaudhari, Jagruti; Trotta, Francesco; Caldera, Fabrizio

2018-06-04

Rilpivrine is BCS class II drug used for treatment of HIV infection. The drug has low aqueous solubility (0.0166 mg/ml) and dissolution rate leading to low bioavailability (32%). Aim of this work was to enhance solubility and dissolution of rilpivirine using beta-cyclodextrin-based nanosponges. These nanosponges are biocompatible nanoporous particles having high loading capacity to form supramolecular inclusion and non-inclusion complexes with hydrophilic and lipophilic drugs for solubility enhancement. Beta-cyclodextrin was crosslinked with carbonyl diimidazole and pyromellitic dianhydride to prepare nanosponges. The nanosponges were loaded with rilpivirine by solvent evaporation method. Binary and ternary complexes of drug with β-CD, HP-β-CD, nanosponges, and tocopherol polyethylene glycol succinate were prepared and characterized by phase solubility, saturation solubility in different media, in vitro dissolution, and in vivo pharmacokinetics. Spectral analysis by Fourier transform infrared spectroscopy, powder X-ray diffraction, and differential scanning calorimetry was performed. Results obtained from spectral characterization confirmed inclusion complexation. Phase solubility studies indicated stable complex formation. Saturation solubility was found to be 10-13-folds higher with ternary complexes in distilled water and 12-14-fold higher in 0.1 N HCl. Solubility enhancement was evident in biorelevant media. Molecular modeling studies revealed possible mode of entrapment of rilpivirine within β-CD cavities. A 3-fold increase in dissolution with ternary complexes was observed. Animal studies revealed nearly 2-fold increase in oral bioavailability of rilpivirine. It was inferred that electronic interactions, hydrogen bonding, and van der Waals forces are involved in the supramolecular interactions.

Crushed tablets: does the administration of food vehicles and thickened fluids to aid medication swallowing alter drug release?

PubMed

Manrique, Yady J; Lee, Danielle J; Islam, Faiza; Nissen, Lisa M; Cichero, Julie A Y; Stokes, Jason R; Steadman, Kathryn J

2014-01-01

To evaluate the influence of co-administered vehicles on in vitro dissolution in simulated gastric fluid of crushed immediate release tablets as an indicator for potential drug bioavailability compromise. Release and dissolution of crushed amlodipine, atenolol, carbamazepine and warfarin tablets were tested with six foods and drinks that are frequently used in the clinical setting as mixers for crushed medications (water, orange juice, honey, yoghurt, strawberry jam and water thickened with Easythick powder) in comparison to whole tablets. Five commercial thickening agents (Easythick Advanced, Janbak F, Karicare, Nutilis, Viscaid) at three thickness levels were tested for their effect on the dissolution of crushed atenolol tablets. Atenolol dissolution was unaffected by mixing crushed tablets with thin fluids or food mixers in comparison to whole tablets or crushed tablets in water, but amlodipine was delayed by mixing with jam. Mixing crushed warfarin and carbamazepine tablets with honey, jam or yoghurt caused them to resemble the slow dissolution of whole tablets rather than the faster dissolution of crushed tablets in water or orange juice. Crushing and mixing any of the four medications with thickened water caused a significant delay in dissolution. When tested with atenolol, all types of thickening agents at the greatest thickness significantly restricted dissolution, and products that are primarily based on xanthan gum also delayed dissolution at the intermediate thickness level. Dissolution testing, while simplistic, is a widely used and accepted method for comparing drug release from different formulations as an indicator for in vivo bioavailability. Thickened fluids have the potential to retard drug dissolution when used at the thickest levels. These findings highlight potential clinical implications of the addition of these agents to medications for the purpose of dose delivery and indicate that further investigation of thickened fluids and their potential to influence therapeutic outcomes is warranted.

Adsorption onto Mesoporous Silica Using Supercritical Fluid Technology Improves Dissolution Rate of Carbamazepine-a Poorly Soluble Compound.

PubMed

Gandhi, Aditya V; Thipsay, Priyanka; Kirthivasan, Bharat; Squillante, Emilio

2017-11-01

The purpose of this research was to design and characterize an immediate-release formulation of carbamazepine (CBZ), a poorly soluble anti-epileptic drug, using a porous silica carrier. Carbon dioxide in its supercritical state (2000 psi, 30-35°C) was used as an anti-solvent to precipitate CBZ onto two particle size variants of silica. Adsorption isotherms were used as a pre-formulation strategy to select optimum ratios of silica and CBZ. The obtained drug-silica formulations were characterized by dissolution studies, differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). This formulation strategy resulted in a 2.4-fold improvement in dissolution rate when compared to pure drug after 30 min of dissolution testing. PXRD and DSC confirmed the amorphous nature of CBZ in the formulations as well as the differences in polymorphic forms of commercial and supercritical fluid-processed CBZ. Additionally, solid-state NMR spectroscopy showed that the spin-lattice relaxation time for bulk drug (without silica) was ∼7.5 times greater than that for silica-confined CBZ, implying that when CBZ was adsorbed onto mesoporous silica, it is structurally disordered and had higher structural mobility, a characteristic of amorphous solids. The mesoporous silica matrix prevented CBZ crystal growth by imposing spatial constraint on CBZ nuclei and hence resulted in faster dissolution compared to bulk solid drug. Adsorption onto mesoporous silica using supercritical fluid technology may be used as a novel formulation strategy for amorphization of poorly soluble compounds, in turn improving their dissolution rate.

Simultaneous determination of uranium carbide dissolution products by capillary zone electrophoresis.

PubMed

Sladkov, Vladimir; Fourest, Blandine

2009-03-20

Separation and simultaneous determination of a number of organic acid anions (oxalate, mellitate, trimellitate and benzoate) and U(VI) with direct UV detection is developed for analysis of uranium carbide (UC) dissolution products by capillary zone electrophoresis (CZE). Reverse polarity mode is used. It is found that complex formation of U(VI) with carbonate, used as a carrier electrolyte, allows U(VI) to be determined, as negatively charged species, in a single run with organic acid anions. Some parameters such as pH value, composition of electrolyte and detection wavelength are optimized. Under the chosen conditions (carbonate buffer (ionic strength of 100 mM), pH 9.8, 0.15 mM tetradecyltrimethylammonium bromide (TTAB)) a complete separation is achieved. Calibration plots are linear in two ranges of concentration for U(VI) ( approximately 1 x 10(-5) to 1 x 10(-3)), mellitate and trimellitate ( approximately 5 x 10(-6) to 5 x 10(-4)), and about one range ( approximately 1 x 10(-4) to 5 x 10(-3)) for oxalate and benzoate. Accuracy of the procedure is checked by the "added-found" method in standard mixture solutions. Relative standard deviation is within the range of 2-10% and the recovery is in the range of 90-110%. This method is applied for the analysis of real UC dissolution samples.

Impact of chitosan as a disintegrant on the bioavailability of furosemide tablets: in vitro evaluation and in vivo simulation of novel formulations.

PubMed

Rasool, Bazigha Kadhim Abdul; Fahmy, Sahar Abdelsattar; Galeel, Omar Waleed Abdul

2012-10-01

To determine the effect of chitosan, starch powder, polyvinylpyrrolidone (PVP), Avicel PH 101 powder, Avicel PH 102 granules as a function of different concentrations on the solubility, disintegration and hence dissolution of furosemide from immediate release tablet dosage forms. The tablets were prepared by the wet granulation method and evaluated for hardness, friability, disintegration and in vitro dissolution. Chitosan 7% w/w showed the fastest disintegration of furosemide tablets among the other disintegrants studied. This was attributed to its highest swelling properties and velocity constant of water uptake. The step of adding chitosan during tablet preparation had a great effect on the physical properties and dissolution profiles of the prepared tablets with external addition of chitosan showed best results compared to best results comparing to internal-external or internal addition. The most appropriate force of compression was 4ton/cm(2). The selected formula F15 containing 7% w/w chitosan was successful and showed a high significant (p<0.001) enhancement in disintegration and dissolution behaviors of furosemide tablets in comparison with the commercially available Furosemide ® tablets. These results were supported by the simulated data where F15 formula showed the highest plasma concentration C-max 1.89mcg/mL after 0.5 hr compared to C-max 1.05mcg/mL after 1hr for the reference. The present study demonstrated that chitosan is a very good candidate to be used as a tablet disintegrant and was able to enhance the dissolution of poorly absorbable drugs.

Molecular-level elucidation of saccharin-assisted rapid dissolution and high supersaturation level of drug from Eudragit® E solid dispersion.

PubMed

Ueda, Keisuke; Kanaya, Harunobu; Higashi, Kenjirou; Yamamoto, Keiji; Moribe, Kunikazu

2018-03-01

In this work, the effect of saccharin (SAC) addition on the dissolution and supersaturation level of phenytoin (PHT)/Eudragit® E (EUD-E) solid dispersion (SD) at neutral pH was examined. The PHT/EUD-E SD showed a much slower dissolution of PHT compared to the PHT/EUD-E/SAC SD. EUD-E formed a gel layer after the dispersion of the PHT/EUD-E SD into an aqueous medium, resulting in a slow dissolution of PHT. Pre-dissolving SAC in the aqueous medium significantly improved the dissolution of the PHT/EUD-E SD. Solid-state 13 C NMR measurements showed an ionic interaction between the tertiary amino group of EUD-E and the amide group of SAC in the EUD-E gel layer. Consequently, the ionized EUD-E could easily dissolve from the gel layer, promoting PHT dissolution. Solution-state 1 H NMR measurements revealed the presence of ionic interactions between SAC and the amino group of EUD-E in the PHT/EUD-E/SAC solution. In contrast, interactions between PHT and the hydrophobic group of EUD-E strongly inhibited the crystallization of the former from its supersaturated solution. The PHT supersaturated solution was formed from the PHT/EUD-E/SAC SD by the fast dissolution of PHT and the strong crystallization inhibition effect of EUD-E after aqueous dissolution. Copyright © 2018 Elsevier B.V. All rights reserved.

Can dosage form-dependent food effects be predicted using biorelevant dissolution tests? Case example extended release nifedipine.

PubMed

Andreas, Cord J; Tomaszewska, Irena; Muenster, Uwe; van der Mey, Dorina; Mueck, Wolfgang; Dressman, Jennifer B

2016-08-01

Food intake is known to have various effects on gastrointestinal luminal conditions in terms of transit times, hydrodynamic forces and/or luminal fluid composition and can therefore affect the dissolution behavior of solid oral dosage forms. The aim of this study was to investigate and detect the dosage form-dependent food effect that has been observed for two extended-release formulations of nifedipine using in vitro dissolution tests. Two monolithic extended release formulations, the osmotic pump Adalat® XL 60mg and matrix-type Adalat® Eins 30mg formulation, were investigated with biorelevant dissolution methods using the USP apparatus III and IV under both simulated prandial states, and their corresponding quality control dissolution method. In vitro data were compared to published and unpublished in vivo data using deconvolution-based in vitro - in vivo correlation (IVIVC) approaches. Quality control dissolution methods tended to overestimate the dissolution rate due to the excessive solubilizing capabilities of the sodium dodecyl sulfate (SDS)-containing dissolution media. Using Level II biorelevant media the dosage form dependent food effect for nifedipine was described well when studied with the USP apparatus III, whereas the USP apparatus IV failed to detect the positive food effect for the matrix-type dosage form. It was demonstrated that biorelevant methods can serve as a useful tool during formulation development as they were able to qualitatively reflect the in vivo data. Copyright © 2016 Elsevier B.V. All rights reserved.

IDENTIFICATION OF PHARMACEUTICAL EXCIPIENT BEHAVIOR OF CHICKPEA (CICER ARIETINUM) STARCH IN GLICLAZIDE IMMEDIATE RELEASE TABLETS.

PubMed

Meka, Venkata Srikanth; Yee, Phung; Sheshala, Ravi

2016-01-01

In the past few years, there are number of researchers carrying out their research on the excipients derived from polysaccharides and some of these researches show that natural excipients are comparable and can serve as an alternative to the synthetic excipients. Hence, the objectives of this research are to characterize the naturally sourced chickpea starch powder and to study the pharmaceutical excipient behavior of chickpea starch in gliclazide immediate release (IR) tablets. In this research, the binding properties of chickpea starch were compared to that of povidone, whereas the disintegrant properties of chickpea starch were compared to those of crospovidone, croscarmellose sodium and sodium starch glycolate. Flow property of chickpea starch was assessed with the measurement of bulk density, tapped density, compressibility index and angle of repose. Calibration curve for gliclazide in phosphate buffer pH 7.4 was developed. Gliclazide IR tablets were then produced with direct compression method. Physicochemical characteristics of the tablets, including thickness, tablet weight uniformity, hardness, disintegration time and friability were evaluated. Then, in vitro dissolution studies were performed by following United States Pharmacopeia (USP) dissolution method. The dissolution results were analyzed and compared with t30, t50, dissolution efficiency (DE). Lastly, drug-excipient compatibility studies, including Fourier transform infrared (FTIR) spectroscopic analysis and differential scanning calorimetric (DSC) analysis were carried out. Fair flow property was observed in the chickpea starch powder. Furthermore, the tablets produced passed all the tests in physicochemical characteristics evaluation except hardness and disintegration test. Additionally, in vitro dissolution studies show that chickpea starch acted as a disintegrant instead of a binder in gliclazide IR tablets and its disintegrant properties were comparable to those of crospovidone, croscarmellose sodium and sodium starch glycolate. Besides that, gliclazide was also compatible with the excipients used. Chickpea starch acted as a disintegrant in gliclazide IR tablets, instead of a binder. Therefore, chickpea starch can be a promising disintegrant in gliclazide IR tablets.

Thermodynamics of Silica Dissolution From In-situ Raman +Spectroscopy

NASA Astrophysics Data System (ADS)

Davis, M. K.; Fumagalli, P.; Stixrude, L. P.

2001-12-01

Solubilities of cations, such as silicon, in water strongly effect both the physical and thermodynamical properties of supercritical metamorphic fluids. Modeling the thermodynamics of fluid-rock interactions requires therefore a profound understanding of cation dissolution and aqueous speciation. In-situ Raman experiments of the silica-water system were performed in an externally heated Bassett-type diamond-anvil cell at the Department of Geological Sciences, University of Michigan. Natural quartz samples (from Owl Creek Mountains, Wyoming) were loaded in the sample chamber with de-ionized or spectrographic water. All experiments used doubly polished rhenium gaskets with a thickness of 200 μ m, diameter of 1.0 mm, and a 500 μ m drillhole for the sample chamber. Temperature was measured using K-type thermocouples wrapped around both the upper and lower diamond anvils. Pressures are obtained on the basis of the shift of the 464 cm-1 Raman mode of quartz. In-situ Raman spectra were collected from 250-1200 cm-1, focusing on the vibrational modes of aqueous silica species at temperatures up to 700 ° C and pressures up to 14 kbar. We observed Si-O stretching modes attributable to dimer (H6Si2O7, 965 cm-1) and monomer (H4SiO4, 771 cm-1) aqueous silica species. The relative intensities of these two bands as a function of isochoric heating place constraints on the energetics of the polymerization reaction, if we assume that the intensity ratio is linearly related to concentration ratio. We have been able to perform experiments along two different isochores (0.9 and 0.75 g/cm3, respectively) from which we are able to derive the enthalpy of reaction.

Improved oral bioavailability of probucol by dry media-milling.

PubMed

Li, Jia; Yang, Yan; Zhao, Meihui; Xu, Hui; Ma, Junyuan; Wang, Shaoning

2017-09-01

The polymer/probucol co-milled mixtures were prepared to improve drug dissolution rate and oral bioavailability. Probucol, a BCS II drug, was co-milled together with Copovidone (Kollidon VA64, VA64), Soluplus, or MCC using the dry media-milling process with planetary ball-milling equipment. The properties of the milled mixtures including morphology, crystal form, vitro drug dissolution and in vivo oral bioavailability in rats were evaluated. Probucol existed as an amorphous in the matrix of the co-milled mixtures containing VA64, which helped to enhance drug dissolution. The ternary mixture composed of VA64, RH40, and probucol showed increased dissolution rates in both sink and non-sink conditions. It also had a higher oral bioavailability compared to the reference formulation. Dry-media milling of binary or ternary mixtures composed of drug, polymer and surfactant possibly have wide applications to improve dissolution rate and oral bioavailability of water-insoluble drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Preparation and in vitro/in vivo Evaluation of Lacidipine by Adsorption onto Fumed Silica Using Supercritical Carbon Dioxide.

PubMed

Geng, Yajie; Fu, Qiang; Guo, Bei; Li, Yun; Zhang, Xiangrong; Wang, Xianglin; Zhang, Tianhong

2016-01-01

The aim of this study was to design a silica-supported solid dispersion of lacidipine (LCDP) to enhance the dissolution rate and oral absorption using supercritical CO2 (scCO2) as a solvent. The formulation was characterized using differential scanning calorimetry, powder X-ray diffraction, scanning electron microscopy and fourier transformed infrared spectroscopy. In the dissolution test, LCDP-scCO2 formulation showed a significantly enhanced dissolution compared with LCDPsilica physical mixture and a faster dissolution rate than Lacipil® under different dissolution conditions. In an in vivo test, the area under concentration-time curve and Cmax of LCDP-scCO2 formulation was 9.23 and 23.78 fold greater than LCDP-silica physical mixture (1:15, w/w), respectively, whereas the corresponding values were 1.92 and 2.80 fold greater than Lacipil®, respectively. Our results showed that the solid dispersion prepared by supercritical fluids technology is a feasible method to enhance the oral bioavailability of LCDP.

Melts of Octaacetyl Sucrose as Oral-Modified Release Dosage Forms for Delivery of Poorly Soluble Compound in Stable Amorphous Form.

PubMed

Haznar-Garbacz, Dorota; Kaminska, Ewa; Zakowiecki, Daniel; Lachmann, Marek; Kaminski, Kamil; Garbacz, Grzegorz; Dorożyński, Przemysław; Kulinowski, Piotr

2018-02-01

The presented work describes the formulation and characterization of modified release glassy solid dosage forms (GSDFs) containing an amorphous nifedipine, as a model BCS (Biopharmaceutical Classification System) class II drug. The GSDFs were prepared by melting nifedipine together with octaacetyl sucrose. Dissolution profiles, measured under standard and biorelevant conditions, were compared to those obtained from commercially available formulations containing nifedipine such as modified release (MR) tablets and osmotic release oral system (OROS). The results indicate that the dissolution profiles of the GSDFs with nifedipine are neither affected by the pH of the dissolution media, type and concentration of surfactants, nor by simulated mechanical stress of biorelevant intensity. Furthermore, it was found that the dissolution profiles of the novel dosage forms were similar to the profiles obtained from the nifedipine OROS. The formulation of GSDFs is relatively simple, and the dosage forms were found to have favorable dissolution characteristics.

DNAPL remediation with in situ chemical oxidation using potassium permanganate - Part I. Mineralogy of Mn oxide and its dissolution in organic acids

NASA Astrophysics Data System (ADS)

Li, X. David; Schwartz, Franklin W.

2004-01-01

Previous studies on in situ chemical oxidation of trichloroethylene (TCE) with potassium permanganate indicated that the solid reaction product, Mn oxide, could reduce the permeability of the porous medium and impact the success of dense non-aqueous phase liquid (DNAPL) removal. In order to address the issue of permeability reduction caused by precipitation, this study investigated the mineralogy of Mn oxides and the possibilities of removing the solid precipitates by dissolution. The solid reaction product from the oxidation of TCE by permanganate is semi-amorphous potassium-rich birnessite, which has a layered mineral structure with an interlayer spacing of 7.3 Å. The chemical formula is K 0.854Mn 1.786O 4·1.55H 2O. It has a relatively small specific surface area at 23.6±0.82 m 2/g. Its point of zero charge (pzc) was measured as 3.7±0.4. This birnessite is a relatively active species and could participate in various reactions with existing organic and inorganic matter. The dissolution kinetics of Mn oxide was evaluated in batch experiments using solutions of citric acid, oxalic acid, and ethylenediaminetetraacetic acid (EDTA). Initial dissolution rates were determined to be 0.126 mM/m 2/h for citric acid, 1.35 mM/m 2/h for oxalic acid, and 5.176 mM/m 2/h for EDTA. These rates compare with 0.0025 mM/m 2/h for nitric acid at pH=2. Organic acids dissolve Mn oxide quickly. Reaction rates increase with acid concentration, as tested with citric acid. The dissolution mechanism likely involves proton and ligand-promoted dissolution and reductive dissolution. Citric and oxalic acid can induce ligand-promoted dissolution, while EDTA can induce ligand-promoted and reductive dissolutions. At low pH, proton-promoted dissolution seems to occur with all the acids tested, but this process is not dominant. Reductive dissolution appears to be the most effective process in dissolving the solid, followed by ligand-promoted dissolution. These experiments indicate the significant potential in using these organic acids to remove precipitates formed during the oxidation reaction.

Dynamic leaching studies of 48 MWd/kgU UO2 commercial spent nuclear fuel under oxic conditions

NASA Astrophysics Data System (ADS)

Serrano-Purroy, D.; Casas, I.; González-Robles, E.; Glatz, J. P.; Wegen, D. H.; Clarens, F.; Giménez, J.; de Pablo, J.; Martínez-Esparza, A.

2013-03-01

The leaching of a high-burn-up spent nuclear fuel (48 MWd/KgU) has been studied in a carbonate-containing solution and under oxic conditions using a Continuously Stirred Tank Flow-Through Reactor (CSTR). Two samples of the fuel, one prepared from the centre of the pellet (labelled CORE) and another one from the fuel pellet periphery, enriched with the so-called High Burn-Up Structure (HBS, labelled OUT) have been used.For uranium and actinides, the results showed that U, Np, Am and Cm gave very similar normalized dissolution rates, while Pu showed slower dissolution rates for both samples. In addition, dissolution rates were consistently two to four times lower for OUT sample compared to CORE sample.Considering the fission products release the main results are that Y, Tc, La and Nd dissolved very similar to uranium; while Cs, Sr, Mo and Rb have up to 10 times higher dissolution rates. Rh, Ru and Zr seemed to have lower dissolution rates than uranium. The lowest dissolution rates were found for OUT sample.Three different contributions were detected on uranium release, modelled and attributed to oxidation layer, fines and matrix release.

Dissolution of coccolithophorid calcite by microzooplankton and copepod grazing

NASA Astrophysics Data System (ADS)

Antia, A. N.; Suffrian, K.; Holste, L.; Müller, M. N.; Nejstgaard, J. C.; Simonelli, P.; Carotenuto, Y.; Putzeys, S.

2008-01-01

Independent of the ongoing acidification of surface seawater, the majority of the calcium carbonate produced in the pelagial is dissolved by natural processes above the lysocline. We investigate to what extent grazing and passage of coccolithophorids through the guts of copepods and the food vacuoles of microzooplankton contribute to calcite dissolution. In laboratory experiments where the coccolithophorid Emiliania huxleyi was fed to the rotifer Brachionus plicatilis, the heterotrophic flagellate Oxyrrhis marina and the copepod Acartia tonsa, calcite dissolution rates of 45-55%, 37-53% and 5-22% of ingested calcite were found. We ascribe higher loss rates in microzooplankton food vacuoles as compared to copepod guts to the strongly acidic digestion and the individual packaging of algal cells. In further experiments, specific rates of calcification and calcite dissolution were also measured in natural populations during the PeECE III mesocosm study under differing ambient pCO2 concentrations. Microzooplankton grazing accounted for between 27 and 70% of the dynamic calcite stock being lost per day, with no measurable effect of CO2 treatment. These measured calcite dissolution rates indicate that dissolution of calcite in the guts of microzooplankton and copepods can account for the calcite losses calculated for the global ocean using budget and model estimates.

Liquigroud technique: a new concept for enhancing dissolution rate of glibenclamide by combination of liquisolid and co-grinding technologies.

PubMed

Azharshekoufeh, Leila; Shokri, Javad; Barzegar-Jalali, Mohammad; Javadzadeh, Yousef

2017-01-01

Introduction: The potential of combining liquisolid and co-grinding technologies (liquiground technique) was investigated to improve the dissolution rate of a water-insoluble agent (glibenclamide) with formulation-dependent bioavailability. Methods: To this end, different formulations of liquisolid tablets with a wide variety of non-volatile solvents contained varied ratios of drug: solvent and dissimilar carriers were prepared, and then their release profiles were evaluated. Furthermore, the effect of size reduction by ball milling on the dissolution behavior of glibenclamide from liquisolid tablets was investigated. Any interaction between the drug and the excipient or crystallinity changes during formulation procedure was also examined using X-ray diffraction (XRD) and differential scanning calorimetry (DSC). Results: The present study revealed that classic liquisolid technique did not significantly affect the drug dissolution profile as compared to the conventional tablets. Size reduction obtained by co-grinding of liquid medication was more effective than the implementation of liquisolid technique in enhancing the dissolution rate of glibenclamide. The XRD and DSC data displayed no formation of complex or any crystallinity changes in both formulations. Conclusion: An enhanced dissolution rate of glibenclamide is achievable through the combination of liquisolid and co-grinding technologies.

Geometry of modified release formulations during dissolution--influence on performance of dosage forms with diclofenac sodium.

PubMed

Dorożyński, Przemysław; Kulinowski, Piotr; Jamróz, Witold; Juszczyk, Ewelina

2014-12-30

The objectives of the work included: presentation of magnetic resonance imaging (MRI) and fractal analysis based approach to comparison of dosage forms of different composition, structure, and assessment of the influence of the compositional factors i.e., matrix type, excipients etc., on properties and performance of the dosage form during drug dissolution. The work presents the first attempt to compare MRI data obtained for tablet formulations of different composition and characterized by distinct differences in hydration and drug dissolution mechanisms. The main difficulty, in such a case stems from differences in hydration behavior and tablet's geometry i.e., swelling, cracking, capping etc. A novel approach to characterization of matrix systems i.e., quantification of changes of geometrical complexity of the matrix shape during drug dissolution has been developed. Using three chosen commercial modified release tablet formulations with diclofenac sodium we present the method of parameterization of their geometrical complexity on the base of fractal analysis. The main result of the study is the correlation between the hydrating tablet behavior and drug dissolution - the increase of geometrical complexity expressed as fractal dimension relates to the increased variability of drug dissolution results. Copyright © 2014 Elsevier B.V. All rights reserved.

Piroxicam cocrystals with phenolic coformers: preparation, characterization, and dissolution properties.

PubMed

Emami, Shahram; Adibkia, Khosro; Barzegar-Jalali, Mohammad; Siahi-Shadbad, Mohammadreza

2018-04-04

This study explores the preparation and investigation of dissolution properties of piroxicam cocrystals. Differential scanning calorimetry (DSC) was used to determine the capability of resorcinol (RES), methylparaben (MPB), and vanillin (VAN) to form cocrystals with piroxicam (PRX). Generation of cocrystals was attempted by liquid assisted grinding and slurry methods. Cocrystals were characterized by thermal methods, powder X-ray diffraction, and Fourier-transform infrared spectroscopy. Apparent solubility, intrinsic dissolution rate (IDR), and powder dissolution profile of cocrystals were compared with anhydrous piroxicam, piroxicam monohydrate (PRXMH), and previously reported piroxicam-succinic acid cocrystal. Contact angles and particle sizes of the studied solids were also measured. Based on the DSC screening results, we prepared and characterized PRX-RES and PRX-MPB cocrystals. Interestingly, the cocrystals not only failed to improve apparent solubility and IDR of PRX but also showed lower values than PRX that were attributed to induction of phase transformation of PRX to PRXMH. In contrary, cocrystals performed better than PRX in powder dissolution studies. The higher dissolution rates of cocrystals were explained by improved wettability and reduced sizes. This study has highlighted the complexity of solid state properties of cocrystals and has provided new evidence for the in-solution stability issues of cocrystals.

Improved Dissolution and Oral Bioavailability of Celecoxib by a Dry Elixir System.

PubMed

Cho, Kwan Hyung; Jee, Jun-Pil; Yang, Da A; Kim, Sung Tae; Kang, Dongjin; Kim, Dae-Young; Sim, Taeyong; Park, Sang Yeob; Kim, Kyeongsoon; Jang, Dong-Jin

2018-02-01

The purpose of this study was to develop and evaluate a dry elixir (DE) system for enhancing the dissolution rate and oral bioavailability of celecoxib. DE system has been used for improving solubility, oral bioavailability of poorly water-soluble drugs. The encapsulated drugs or solubilized drugs in the matrix are rapidly dissolved due to the co-solvent effect, resting in both an enhanced dissolution and bioavailability. DEs containing celecoxib were prepared by spray-drying method and characterized by morphology, drug/ethanol content, drug crystallinity, dissolution rate and oral bioavailability. The ethanol content and drug content in DE system could be easily altered by controlling the spraydrying conditions. The dissolution profile of celecoxib from DE proved to be much higher than that of celecoxib powder due to the nano-structured matrix, amorphous state and encapsulated ethanol. The bioavailability of celecoxib from DEs was compared with celecoxib powder alone and commercial product (Celebrex®) in rats. In particular, blood concentrations of celecoxib form DE formulation were much greater than those of native celecoxib and market product. The data demonstrate that the DE system could provide an useful solid dosage form to enhance the solubility, dissolution rate and oral bioavailability of celecoxib.

Evaluation of various dissolution media for predicting in vivo performance of class I and II drugs.

PubMed

Galia, E; Nicolaides, E; Hörter, D; Löbenberg, R; Reppas, C; Dressman, J B

1998-05-01

In this paper we seek to verify the differences in dissolution behavior between class I and class II drugs and to evaluate the suitability of two new physiologically based media, of Simulated Gastric Fluid (SGF) and of milk for their ability to forecast trends in the in vivo performance of class II compounds and their formulations. Dissolution behavior of two class I drugs, i.e. acetaminophen and metoprolol, and of three class II drugs, i.e. danazol, mefenamic acid and ketoconazole, was studied with USP Apparatus 2 in water, SGF, milk, Simulated Intestinal Fluid without pancreatin (SIFsp) and in two media simulating the small intestinal contents in the fed (FeSSIF) and fasted (FaSSIF) states, respectively. Class I powders dissolved rapidly in all media tested. Acetaminophen dissolution in milk was slow from one tablet formulation, in all other cases dissolution was more than 85% complete in 15 minutes. The dissolution rate of metoprolol was shown to be dependent on formulation and manufacturing method, and one of the three tablet formulations did not meet compendial specifications (80%/30 minutes). Dissolution behavior of class II drugs was greatly affected by choice of medium. Dissolution from a capsule formulation of danazol proved to be dependent on the concentration of solubilizing agents, with a the 30-fold increase in percentage dissolved within 90 minutes upon changing from aqueous media without surfactants to FaSSIF. Use of FeSSIF or milk as the dissolution medium resulted in an even greater increase in percentage dissolved, 100 and 180-fold respectively. Dissolution of the weak acid mefenamic acid from a capsule formulation is dependent on both pH and bile salt concentration, which leads to an offset between increased bile salt concentration and lower pH in the fed state compared to the fasted state medium. The weak base ketoconazole showed complete dissolution from a tablet formulation in Simulated Gastric Fluid without pepsin (SGFsp) within 30 minutes, 70% dissolution in 2 hours under fed state simulated upper jejunal conditions but only 6% dissolution in 2 hours under fasted state conditions. As predicted, dissolution of class II drugs proved to be in general much more dependent on the medium than class I drugs. With the array of compendial and physiological media available, it should be possible to design a suitable set of tests to predict the in vivo dissolution of both class I and II drugs from immediate release formulations.

Comparative release studies on suppositories using the basket, paddle, dialysis tubing and flow-through cell methods I. Acetaminophen in a lipophilic base suppository.

PubMed

Hori, Seiichi; Kawada, Tsubasa; Kogure, Sanae; Yabu, Shinako; Mori, Kenji; Akimoto, Masayuki

2017-02-01

The release characteristics of lipophilic suppositories containing acetaminophen (AAP) were examined using four types of dissolution methods: the basket, paddle, dialysis tubing (DT) and flow-through cell (FTC) methods. The suitability of each apparatus for quality control in AAP compounded suppositories was evaluated using statistical procedures. More than 80% of the drug was released over 60 min in all the release methods studied, with the exception of the basket method. Reproducible and faster release was achieved using the paddle method at 100 and 200 rpm, whereas poor release occurred with the basket method. The mean dissolution time (MDT), maximum dissolved quantity of AAP at the end of the sampling time (Q) and dissolution efficiency (DE) were calculated by model-independent methods. The FTC method with a single chamber used in this study was also appreciable for AAP suppositories (Q of 100%, MDT of 71-91 min and DE of 75-80%). The DT apparatus is considered similar to the FTC apparatus from a quality control perspective for judging the release properties of lipophilic base suppositories containing AAP. However, even the single chamber FTC used in this study has potential as an in vitro drug release test for suppositories. The comparative dissolution method is expected to become one of the valuable tools for selecting an adequate dissolution test.

Synergistic Effect of Hydrotrope and Surfactant on Solubility and Dissolution of Atorvastatin Calcium: Screening Factorial Design Followed by Ratio Optimization

PubMed Central

Patel, V. F.; Sarai, J.

2014-01-01

The present study was aimed at investigating the effect of hydrotrope and surfactant on poor solubility of atorvastatin calcium. Excipients screening followed by factorial design was performed to study effect of excipients and manufacturing methods on solubility of drug. Three independent factors (carrier, surfactant and manufacturing method) were evaluated at two levels using solubility as a dependant variable. Solid-state characterisation was performed using Fourier transform infrared spectroscopy and differential scanning calorimetry. Optimised complex were incorporated into orally disintegrating micro tablets and in vitro dissolution test was performed. Nicotinamide, Plasdone and sodium dodecyl sulphate were emerged as promising excipients from excipient screening. General regression analysis revealed only the type of carrier has significantly enhanced (P<0.05) the solubility of drug while other factors were found to be nonsignificant. Ratio optimisation trial revealed that drug to nicotinamide ratio is more critical in enhancing the solubility of drug (40 fold increases in solubility compared to pure drug) in comparison to drug-surfactant ratio; however the presence of surfactant deemed essential. Significantly higher rate and extent of dissolution was observed from solid dispersion complex and tablets compared to dissolution of pure drug (P<0.05). Study revealed hydrotrope and surfactant have synergistic effect on solubility and dissolution of atorvastatin calcium and this can be explored further. PMID:25593381

Design and optimization of self-nanoemulsifying drug delivery systems (SNEDDS) for enhanced dissolution of gemfibrozil.

PubMed

Villar, Ana Maria Sierra; Naveros, Beatriz Clares; Campmany, Ana Cristina Calpena; Trenchs, Monserrat Aróztegui; Rocabert, Coloma Barbé; Bellowa, Lyda Halbaut

2012-07-15

Self-nanoemulsifying drug delivery systems of gemfibrozil were developed under Quality by Design approach for improvement of dissolution and oral absorption. Preliminary screening was performed to select proper components combination. Box-Behnken experimental design was employed as statistical tool to optimize the formulation variables, X(1) (Cremophor(®) EL), X(2) (Capmul(®) MCM-C8), and X(3) (lemon essential oil). Systems were assessed for visual characteristics (emulsification efficacy), turbidity, droplet size, polydispersity index and drug release. Different pH media were also assayed for optimization. Following optimization, the values of formulation components (X(1), X(2), and X(3)) were 32.43%, 29.73% and 21.62%, respectively (16.22% of gemfibrozil). Transmission electron microscopy demonstrated spherical droplet morphology. SNEEDS release study was compared to commercial tablets. Optimized SNEDDS formulation of gemfibrozil showed a significant increase in dissolution rate compared to conventional tablets. Both formulations followed Weibull mathematical model release with a significant difference in t(d) parameter in favor of the SNEDDS. Equally amodelistic parameters were calculated being the dissolution efficiency significantly higher for SNEDDS, confirming that the developed SNEDDS formulation was superior to commercial formulation with respect to in vitro dissolution profile. This paper provides an overview of the SNEDDS of the gemfibrozil as a promising alternative to improve oral absorption. Copyright © 2012 Elsevier B.V. All rights reserved.

Dissolution kinetics of a lunar glass simulant at 25 degrees C: the effect of pH and organic acids

NASA Technical Reports Server (NTRS)

Eick, M. J.; Grossl, P. R.; Golden, D. C.; Sparks, D. L.; Ming, D. W.

1996-01-01

The dissolution kinetics of a simulated lunar glass were examined at pH 3, 5, and 7. Additionally, the pH 7 experiments were conducted in the presence of citric and oxalic acid at concentrations of 2 and 20 mM. The organic acids were buffered at pH 7 to examine the effect of each molecule in their dissociated form. At pH 3, 5, and 7, the dissolution of the synthetic lunar glass was observed to proceed via a two-stage process. The first stage involved the parabolic release of Ca, Mg, Al, and Fe, and the linear release of Si. Dissolution was incongruent, creating a leached layer rich in Si and Ti which was verified by transmission electron microscopy (TEM). During the second stage the release of Ca, Mg, Al, and Fe was linear. A coupled diffusion/surface dissolution model was proposed for dissolution of the simulated lunar glass at pH 3, 5, and 7. During the first stage the initial release of mobile cations (i.e., Ca, Mg, Al, Fe) was limited by diffusion through the surface leached layer of the glass (parabolic release), while Si release was controlled by the hydrolysis of the Si-O-Al bonds at the glass surface (linear release). As dissolution continued, the mobile cations diffused from greater depths within the glass surface. A steady-state was then reached where the diffusion rate across the increased path lengths equalled the Si release rate from the surface. In the presence of the organic acids, the dissolution of the synthetic lunar glass proceeded by a one stage process. The release of Ca, Mg, Al, and Fe followed a parabolic relationship, while the release of Si was linear. The relative reactivity of the organic acids used in the experiments was citrate > oxalate. A thinner leached layer rich in Si/Ti, as compared to the pH experiments, was observed using TEM. Rate data suggest that the chemisorption of the organic anion to the surface silanol groups was responsible for enhanced dissolution in the presence of the organic acids. It is proposed that the increased rate of Si release is responsible for the one stage parabolic release of mobile cations and the relatively thin leached layer compared to experiments at pH 3 and 5.

Students' Understanding of Salt Dissolution: Visualizing Animation in the Chemistry Classroom

NASA Astrophysics Data System (ADS)

Malkoc, Ummuhan

The present study explored the effect of animation implementation in learning a chemistry topic. 135 high school students taking chemistry class were selected for this study (quasi-experimental groups = 67 and control groups = 68). Independent samples t-tests were run to compare animation and control groups between and within the schools. The over-arching finding of this research indicated that when science teachers used animations while teaching salt dissolution phenomena, students will benefit the application of animations. In addition, the findings informed the TPACK framework on the idea that visual tools are important in students' understanding of salt dissolution concepts.

Utilization of supercritical carbon dioxide for complex formation of ibuprofen and methyl-beta-cyclodextrin.

PubMed

Charoenchaitrakool, M; Dehghani, F; Foster, N R

2002-06-04

The dissolution rate of a drug into the biological environment can be enhanced by forming complexes with cyclodextrins and their derivatives. In this study, ibuprofen-methyl-beta-cyclodextrin complexes were prepared successfully by passing ibuprofen-laden CO(2) through a methyl-beta-cyclodextrin packed bed. The maximum drug loading obtained in this work was 10.8 wt.%, which was comparable to that of a 1:1 complex (13.6 wt.% of ibuprofen). The complex exhibited instantaneous dissolution profiles in water solution. The enhanced dissolution rate was attributed to the amorphous character and improved wettability of the product.

A novel microdialysis-dissolution/permeation system for testing oral dosage forms: A proof-of-concept study.

PubMed

Fong, Sophia Yui Kau; Poulsen, Jessie; Brandl, Martin; Bauer-Brandl, Annette

2017-01-01

A novel microdialysis-dissolution/permeation (M-D/P) system was developed for the biopharmaceutical assessment of oral drug formulations. This system consists of a side-by-side diffusion chamber, a microdialysis unit fixed within the dissolution chamber for continuous sampling, and a biomimetic Permeapad® as the intestinal barrier. In the M-D/P system, the concentration of the molecularly dissolved drug (with MWCO <20kDa) was measured over time in the dissolution compartment (representing the gastrointestinal tract) while the concentration of the permeated drug was measured in the acceptor compartment (representing the blood). The kinetics of both the dissolution process and the permeation process were simultaneously quantified under circumstances that mimic physiological conditions. For the current proof-of-concept study, hydrocortisone (HCS) in the form of slowly dissolving solvate crystals and buffer and the biorelevant fasted state simulated intestinal fluids (FaSSIF), were employed as the model drug and dissolution media, respectively. The applicability of the M-D/P system to dissolution and permeation profiling of HCS in buffer and in FaSSIF has been successfully demonstrated. Compared to the conventional direct sampling method (using filter of 0.1-0.45μm), sampling by the M-D/P system exhibited distinct advantages, including (1) showing minimal disturbance of the permeation process, (2) differentiating "molecularly" dissolved drugs from "apparently" dissolved drugs during dissolution of HCS in FaSSIF, and (3) being less laborious and having better sampling temporal resolution. M-D/P system appeared to be a promising, simple and routine tool that allows for the researchers' intensive comprehension of the interplay of dissolution and permeation thus helping for better oral formulation screening and as an ultimate goal, for better dosage forms assessment. Copyright © 2016. Published by Elsevier B.V.

Phagosomal pH and glass fiber dissolution in cultured nasal epithelial cells and alveolar macrophages: a preliminary study.

PubMed Central

Johnson, N F

1994-01-01

The dissolution rate of glass fibers has been shown to be pH sensitive using in vitro lung fluid simulant models. The current study investigated whether there is a difference in phagosomal pH (ppH) between rat alveolar macrophages (AM) and rat nasal epithelial cells (RNEC) and whether such a difference would influence the dissolution of glass fibers. The ppH was measured in cultured AM and RNEC using flow cytometric, fluorescence-emission rationing techniques with fluorescein-labeled, amorphous silica particles. Glass fiber dissolution was determined in AM and RNEC cultured for 3 weeks with fast dissolving glass fibers (GF-A) or slow dissolving ones (GF-B). The mean diameters of GF-A were 2.7 microns and of GF-B, 2.6 microns, the average length of both fibers was approximately 22 to 25 microns. Dissolution was monitored by measuring the length and diameter of intracellular fibers and estimating the volume, assuming a cylindrical morphology. The ppH of AM was 5.2 to 5.8, and the ppH of RNEC was 7.0 to 7.5. The GF-A dissolved more slowly in RNEC than in AM, and no dissolution was evident in either cell type with GF-B. The volume loss with GF-A after a 3-week culture with AM was 66% compared to 45% for cultured RNEC. These results are different from those obtained using in vitro lung fluid-simulant models where dissolution is faster at higher pH. This difference suggests that dissolution rates of glass fibers in AM should not be applied to the dissolution of fibers in epithelial cells. Images Figure 1. a Figure 1. b Figure 2. a Figure 2. b Figure 3. a Figure 3. b PMID:7882965

Dissolution enhancement of Deflazacort using hollow crystals prepared by antisolvent crystallization process.

PubMed

Paulino, A S; Rauber, G; Campos, C E M; Maurício, M H P; de Avillez, R R; Capobianco, G; Cardoso, S G; Cuffini, S L

2013-05-13

Deflazacort (DFZ), a derivate of prednisolone, is a poorly soluble drug which has been proposed to have major advantages over other corticosteroids. Poorly soluble drugs present limited bioavailability due to their low solubility and dissolution rate and several strategies have been developed in order to find ways to improve them. In general, pharmaceutical laboratories use a micronized process to reduce the particle size in order to increase the dissolution of the drugs. However, this process causes changes such as polymorphic transitions, particle agglomeration and a reduction in fluidity and wettability. These solid-state properties affect the dissolution behavior and stability performance of drugs. Crystallization techniques are widely used in the pharmaceutical industry and antisolvent crystallization has been used to obtain ultrafine particles. In this study, DFZ was investigated in terms of its antisolvent crystallization in different solvents and under various preparation conditions (methanol/water ratio, stirring and evaporation rate, etc.), in order to compare the physicochemical properties between crystallized samples and raw materials available on the Brazilian market with and without micronization. Crystalline structure, morphology, and particle size, and their correlation with the Intrinsic Dissolution Rate (IDR) and dissolution profile as relevant biopharmaceutical properties were studied. Crystallization conditions were achieved which provided crystalline samples of hollow-shaped crystals with internal channels, which increased the dissolution rate of DFZ. The antisolvent crystallization process allowed the formation of hollow crystals, which demonstrated a better dissolution profile than the raw material (crystalline and micronized), making this a promising technique as a crystallization strategy for improving the dissolution and thus the bioavailability of poorly soluble drugs. Copyright © 2013 Elsevier B.V. All rights reserved.

Deep geothermal: The ‘Moon Landing’ mission in the unconventional energy and minerals space

DOE PAGES

Regenauer-Lieb, Klaus; Bunger, Andrew; Chua, Hui Tong; ...

2015-01-30

Deep geothermal from the hot crystalline basement has remained an unsolved frontier for the geothermal industry for the past 30 years. This poses the challenge for developing a new unconventional geomechanics approach to stimulate such reservoirs. While a number of new unconventional brittle techniques are still available to improve stimulation on short time scales, the astonishing richness of failure modes of longer time scales in hot rocks has so far been overlooked. These failure modes represent a series of microscopic processes: brittle microfracturing prevails at low temperatures and fairly high deviatoric stresses, while upon increasing temperature and decreasing applied stressmore » or longer time scales, the failure modes switch to transgranular and intergranular creep fractures. Accordingly, fluids play an active role and create their own pathways through facilitating shear localization by a process of time-dependent dissolution and precipitation creep, rather than being a passive constituent by simply following brittle fractures that are generated inside a shear zone caused by other localization mechanisms. We lay out a new paradigm for reservoir stimulation by reactivating pre-existing faults at reservoir scale in a reservoir scale aseismic, ductile manner. A side effect of the new “soft” stimulation method is that owing to the design specification of a macroscopic ductile response, the proposed method offers the potential of a safer control over the stimulation process compared to conventional stimulation protocols such as currently employed in shale gas reservoirs.« less

The Dissolution Behavior of Borosilicate Glasses in Far-From Equilibrium Conditions

DOE PAGES

Neeway, James J.; Rieke, Peter C.; Parruzot, Benjamin P.; ...

2018-02-10

An area of agreement in the waste glass corrosion community is that, at far-from-equilibrium conditions, the dissolution of borosilicate glasses used to immobilize nuclear waste is known to be a function of both temperature and pH. The aim of this work is to study the effects of temperature and pH on the dissolution rate of three model nuclear waste glasses (SON68, ISG, AFCI). The dissolution rate data are then used to parameterize a kinetic rate model based on Transition State Theory that has been developed to model glass corrosion behavior in dilute conditions. To do this, experiments were conducted atmore » temperatures of 23, 40, 70, and 90 °C and pH(22 °C) values of 9, 10, 11, and 12 with the single-pass flow-through (SPFT) test method. Both the absolute dissolution rates and the rate model parameters are compared with previous results. Rate model parameters for the three glasses studied here are nearly equivalent within error and in relative agreement with previous studies though quantifiable differences exist. The glass dissolution rates were analyzed with a linear multivariate regression (LMR) and a nonlinear multivariate regression performed with the use of the Glass Corrosion Modeling Tool (GCMT), with which a robust uncertainty analysis is performed. This robust analysis highlights the high degree of correlation of various parameters in the kinetic rate model. As more data are obtained on borosilicate glasses with varying compositions, a mathematical description of the effect of glass composition on the rate parameter values should be possible. This would allow for the possibility of calculating the forward dissolution rate of glass based solely on composition. In addition, the method of determination of parameter uncertainty and correlation provides a framework for other rate models that describe the dissolution rates of other amorphous and crystalline materials in a wide range of chemical conditions. As a result, the higher level of uncertainty analysis would provide a basis for comparison of different rate models and allow for a better means of quantifiably comparing the various models.« less

The dissolution behavior of borosilicate glasses in far-from equilibrium conditions

NASA Astrophysics Data System (ADS)

Neeway, James J.; Rieke, Peter C.; Parruzot, Benjamin P.; Ryan, Joseph V.; Asmussen, R. Matthew

2018-04-01

An area of agreement in the waste glass corrosion community is that, at far-from-equilibrium conditions, the dissolution of borosilicate glasses used to immobilize nuclear waste is known to be a function of both temperature and pH. The aim of this work is to study the effects of temperature and pH on the dissolution rate of three model nuclear waste glasses (SON68, ISG, AFCI). The dissolution rate data are then used to parameterize a kinetic rate model based on Transition State Theory that has been developed to model glass corrosion behavior in dilute conditions. To do this, experiments were conducted at temperatures of 23, 40, 70, and 90 °C and pH (22 °C) values of 9, 10, 11, and 12 with the single-pass flow-through (SPFT) test method. Both the absolute dissolution rates and the rate model parameters are compared with previous results. Rate model parameters for the three glasses studied here are nearly equivalent within error and in relative agreement with previous studies though quantifiable differences exist. The glass dissolution rates were analyzed with a linear multivariate regression (LMR) and a nonlinear multivariate regression performed with the use of the Glass Corrosion Modeling Tool (GCMT), with which a robust uncertainty analysis is performed. This robust analysis highlights the high degree of correlation of various parameters in the kinetic rate model. As more data are obtained on borosilicate glasses with varying compositions, a mathematical description of the effect of glass composition on the rate parameter values should be possible. This would allow for the possibility of calculating the forward dissolution rate of glass based solely on composition. In addition, the method of determination of parameter uncertainty and correlation provides a framework for other rate models that describe the dissolution rates of other amorphous and crystalline materials in a wide range of chemical conditions. The higher level of uncertainty analysis would provide a basis for comparison of different rate models and allow for a better means of quantifiably comparing the various models.

The Dissolution Behavior of Borosilicate Glasses in Far-From Equilibrium Conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neeway, James J.; Rieke, Peter C.; Parruzot, Benjamin P.

An area of agreement in the waste glass corrosion community is that, at far-from-equilibrium conditions, the dissolution of borosilicate glasses used to immobilize nuclear waste is known to be a function of both temperature and pH. The aim of this work is to study the effects of temperature and pH on the dissolution rate of three model nuclear waste glasses (SON68, ISG, AFCI). The dissolution rate data are then used to parameterize a kinetic rate model based on Transition State Theory that has been developed to model glass corrosion behavior in dilute conditions. To do this, experiments were conducted atmore » temperatures of 23, 40, 70, and 90 °C and pH(22 °C) values of 9, 10, 11, and 12 with the single-pass flow-through (SPFT) test method. Both the absolute dissolution rates and the rate model parameters are compared with previous results. Rate model parameters for the three glasses studied here are nearly equivalent within error and in relative agreement with previous studies though quantifiable differences exist. The glass dissolution rates were analyzed with a linear multivariate regression (LMR) and a nonlinear multivariate regression performed with the use of the Glass Corrosion Modeling Tool (GCMT), with which a robust uncertainty analysis is performed. This robust analysis highlights the high degree of correlation of various parameters in the kinetic rate model. As more data are obtained on borosilicate glasses with varying compositions, a mathematical description of the effect of glass composition on the rate parameter values should be possible. This would allow for the possibility of calculating the forward dissolution rate of glass based solely on composition. In addition, the method of determination of parameter uncertainty and correlation provides a framework for other rate models that describe the dissolution rates of other amorphous and crystalline materials in a wide range of chemical conditions. As a result, the higher level of uncertainty analysis would provide a basis for comparison of different rate models and allow for a better means of quantifiably comparing the various models.« less

Freezing-Enhanced Dissolution of Iron Oxides: Effects of Inorganic Acid Anions.

PubMed

Jeong, Daun; Kim, Kitae; Min, Dae Wi; Choi, Wonyong

2015-11-03

Dissolution of iron from mineral dust particles greatly depends upon the type and amount of copresent inorganic anions. In this study, we investigated the roles of sulfate, chloride, nitrate, and perchlorate on the dissolution of maghemite and lepidocrocite in ice under both dark and UV irradiation and compared the results with those of their aqueous counterparts. After 96 h of reaction, the total dissolved iron in ice (pH 3 before freezing) was higher than that in the aqueous phase (pH 3) by 6-28 times and 10-20 times under dark and UV irradiation, respectively. Sulfuric acid was the most efficient in producing labile iron under dark condition, whereas hydrochloric acid induced the most dissolution of the total and ferrous iron in the presence of light. This ice-induced dissolution result was also confirmed with Arizona Test Dust (AZTD). In the freeze-thaw cycling test, the iron oxide samples containing chloride, nitrate, or perchlorate showed a similar extent of total dissolved iron after each cycling while the sulfate-containing sample rapidly lost its dissolution activity with repeating the cycle. This unique phenomenon observed in ice might be related to the freeze concentration of protons, iron oxides, and inorganic anions in the liquid-like ice grain boundary region. These results suggest that the ice-enhanced dissolution of iron oxides can be a potential source of bioavailable iron, and the acid anions critically influence this process.

Comprehensive validation scheme for in situ fiber optics dissolution method for pharmaceutical drug product testing.

PubMed

Mirza, Tahseen; Liu, Qian Julie; Vivilecchia, Richard; Joshi, Yatindra

2009-03-01

There has been a growing interest during the past decade in the use of fiber optics dissolution testing. Use of this novel technology is mainly confined to research and development laboratories. It has not yet emerged as a tool for end product release testing despite its ability to generate in situ results and efficiency improvement. One potential reason may be the lack of clear validation guidelines that can be applied for the assessment of suitability of fiber optics. This article describes a comprehensive validation scheme and development of a reliable, robust, reproducible and cost-effective dissolution test using fiber optics technology. The test was successfully applied for characterizing the dissolution behavior of a 40-mg immediate-release tablet dosage form that is under development at Novartis Pharmaceuticals, East Hanover, New Jersey. The method was validated for the following parameters: linearity, precision, accuracy, specificity, and robustness. In particular, robustness was evaluated in terms of probe sampling depth and probe orientation. The in situ fiber optic method was found to be comparable to the existing manual sampling dissolution method. Finally, the fiber optic dissolution test was successfully performed by different operators on different days, to further enhance the validity of the method. The results demonstrate that the fiber optics technology can be successfully validated for end product dissolution/release testing. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association

The Influence of Drug Physical State on the Dissolution Enhancement of Solid Dispersions Prepared Via Hot-Melt Extrusion: A Case Study Using Olanzapine

PubMed Central

Pina, Maria Fátima; Zhao, Min; Pinto, João F; Sousa, João J; Craig, Duncan Q M

2014-01-01

In this study, we examine the relationship between the physical structure and dissolution behavior of olanzapine (OLZ) prepared via hot-melt extrusion in three polymers [polyvinylpyrrolidone (PVP) K30, polyvinylpyrrolidone-co-vinyl acetate (PVPVA) 6:4, and Soluplus® (SLP)]. In particular, we examine whether full amorphicity is necessary to achieve a favorable dissolution profile. Drug–polymer miscibility was estimated using melting point depression and Hansen solubility parameters. Solid dispersions were characterized using differential scanning calorimetry, X-ray powder diffraction, and scanning electron microscopy. All the polymers were found to be miscible with OLZ in a decreasing order of PVP>PVPVA>SLP. At a lower extrusion temperature (160°C), PVP generated fully amorphous dispersions with OLZ, whereas the formulations with PVPVA and SLP contained 14%–16% crystalline OLZ. Increasing the extrusion temperature to 180°C allowed the preparation of fully amorphous systems with PVPVA and SLP. Despite these differences, the dissolution rates of these preparations were comparable, with PVP showing a lower release rate despite being fully amorphous. These findings suggested that, at least in the particular case of OLZ, the absence of crystalline material may not be critical to the dissolution performance. We suggest alternative key factors determining dissolution, particularly the dissolution behavior of the polymers themselves. PMID:24765654

Investigating the effect of moisture protection on solid-state stability and dissolution of fenofibrate and ketoconazole solid dispersions using PXRD, HSDSC and Raman microscopy.

PubMed

Kanaujia, Parijat; Lau, Grace; Ng, Wai Kiong; Widjaja, Effendi; Schreyer, Martin; Hanefeld, Andrea; Fischbach, Matthias; Saal, Christoph; Maio, Mario; Tan, Reginald B H

2011-09-01

Enhanced dissolution of poorly soluble active pharmaceutical ingredients (APIs) in amorphous solid dispersions often diminishes during storage due to moisture-induced re-crystallization. This study aims to investigate the influence of moisture protection on solid-state stability and dissolution profiles of melt-extruded fenofibrate (FF) and ketoconazole (KC) solid dispersions. Samples were kept in open, closed and Activ-vials(®) to control the moisture uptake under accelerated conditions. During 13-week storage, changes in API crystallinity were quantified using powder X-ray diffraction (PXRD) (Rietveld analysis) and high sensitivity differential scanning calorimetry (HSDSC) and compared with any change in dissolution profiles. Trace crystallinity was observed by Raman microscopy, which otherwise was undetected by PXRD and HSDSC. Results showed that while moisture protection was ineffective in preventing the re-crystallization of amorphous FF, KC remained X-ray amorphous despite 5% moisture uptake. Regardless of the degree of crystallinity increase in FF, the enhanced dissolution properties were similarly diminished. Moisture uptake above 10% in KC samples also led to re-crystallization and significant decrease in dissolution rates. In conclusion, eliminating moisture sorption may not be sufficient in ensuring the stability of solid dispersions. Analytical quantification of API crystallinity is crucial in detecting subtle increase in crystallinity that can diminish the enhanced dissolution properties of solid dispersions.

Dissolution of glass wool, rock wool and alkaline earth silicate wool: morphological and chemical changes in fibers.

PubMed

Campopiano, Antonella; Cannizzaro, Annapaola; Angelosanto, Federica; Astolfi, Maria Luisa; Ramires, Deborah; Olori, Angelo; Canepari, Silvia; Iavicoli, Sergio

2014-10-01

The behavior of alkaline earth silicate (AES) wool and of other biosoluble wools in saline solution simulating physiological fluids was compared with that of a traditional wool belonging to synthetic vitreous fibers. Morphological and size changes of fibers were studied by scanning electron microscopy (SEM). The elements extracted from fibers were analyzed by inductively coupled plasma atomic emission spectrometry. SEM analysis showed a larger reduction of length-weighted geometric mean fiber diameter at 4.5 pH than at 7.4 pH. At the 7.4 pH, AES wool showed a higher dissolution rate and a dissolution time less than a few days. Their dissolution was highly non-congruent with rapid leaching of calcium. Unlike rock wool, glass wool dissolved more rapidly at physiological pH than at acid pH. Dissolution of AES and biosoluble rock wool is accompanied by a noticeable change in morphology while by no change for glass wool. Biosoluble rock wool developed a leached surface with porous honeycomb structure. SEM analysis showed the dissolution for glass wool is mainly due to breakage transverse of fiber at pH 7.4. AES dissolution constant (Kdis) was the highest at pH 7.4, while at pH 4.5 only biosoluble rockwool 1 showed a higher Kdis. Copyright © 2014 Elsevier Inc. All rights reserved.

Sucralose as co-crystal co-former for hydrochlorothiazide: development of oral disintegrating tablets.

PubMed

Arafa, Mona F; El-Gizawy, Sanaa A; Osman, Mohamed A; El Maghraby, Gamal M

2016-08-01

Development of oral disintegrating tablets requires enhancement of drug dissolution and selection of sweetener. Co-crystallization of drugs with inert co-former is an emerging technique for enhancing dissolution rate. The benefit of this technique will become even greater if one of the sweeteners can act as co-crystal co-former to enhance dissolution and mask the taste. Accordingly, the objective of this work was to investigate the efficacy of sucralose as a potential co-crystal co-former for enhancing the dissolution rate of hydrochlorothiazide. This was extended to prepare oral disintegrating tablets. Co-crystallization was achieved after dissolving hydrochlorothiazide with increasing molar ratios of sucralose in the least amount of acetone. The co-crystallization products were characterized using Fourier transform infrared spectroscopy, differential thermal analysis and powder X-ray diffraction. These measurements indicated that co-crystallization process started at a drug sucralose molar ratio of 1:1 and completed at 1:2. The developed co-crystals exhibited faster drug dissolution compared with the control, with co-crystal containing the drug with sucralose at 1:2 molar ratio being optimum. The later was used to prepare fast disintegrating tablets. These tablets had acceptable physical characteristics and showed fast disintegration with subsequent rapid dissolution. The study introduced sucralose as co-crystal co-former for enhanced dissolution and masking the taste.

[Comparison in dissolution behavior of ethical and over-the counter scopolamine butylbromide].

PubMed

Suzuki, Ichie; Miyazaki, Yasunori; Uchino, Tomonobu; Kagawa, Yoshiyuki

2011-01-01

Marketing authorization holders do not disclose any information on the pharmaceutical properties of over-the-counter drugs (OTC). When a drug is switched from a prescription drug to OTC, pharmacists can acquire that information from the corresponding ethical drug (ED) through the package insert, interview form, and so on. However, the pharmaceutical equivalence between ED and OTC is unclear. In this study, we examined the drug dissolution behavior of both ED and OTCs containing scopolamine butylbromide. Dissolution tests were performed by the paddle method using Japanese Pharmacopeia (JP) XV test fluids at pH 1.2, 4.0 and 6.8 and water based on the guidelines for bioequivalence studies of generic products. The dissolution profiles of OTCs differed significantly from ED showing a similarity factor (f2) value ranging from 8.9 to 42.9. Time until 85% dissolution ranged from 23 to 95 min and from 17 to 174 min at pH 1.2 and pH 6.8, respectively. Then JP XV disintegration tests were conducted to investigate differences in the disintegration process. The disintegration time of preparations showing delayed dissolution was prolonged compared to that of others, suggesting that the disintegration of the tablet or capsule is one of the important factors affecting the drug dissolution. These differences in the disintegration and drug dissolution might cause differences in the bioavailability of the drug. For patient safety, more detailed product information of OTCs should be supplied by the manufacturer, and not be assumed from that of corresponding ED.

Dissolution Kinetics of Meta-Torbernite under Circum-neutral to Alkaline Conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wellman, Dawn M.; McNamara, Bruce K.; Bacon, Diana H.

2009-12-21

Autunite group minerals have been identified in contaminated sediments as the long-term controlling phase of uranium. Meta-torbernite, has been identified in subsurface environments which were subjected to co-contaminant disposal practices from past nuclear weapons and fuel operations. Under these conditions the mobility of uranium in subsurface pore waters is limited by the rate of meta-torbernite dissolution; however, there are no known investigations which report the dissolution behavior of meta-torbernite. The purpose of this investigation was to conduct a series of single-pass flow-through (SPFT) tests to 1) quantify the effect of temperature (23 - 90oC) and pH (6 -10) on meta-torbernitemore » dissolution, 2) compare the dissolution of meta-torbernite to other autunite-group minerals, and 3) evaluate the effect of aqueous phosphate on the dissolution kinetics of meta-torbernite. Results presented here illustrate meta-torbernite dissolution rates increase by ~100X over the pH interval of 6 to 10 (eta = 0.59 ± 0.07), irrespective of temperature. The power law coefficient for meta-torbernite, eta = 0.59 ± 0.07, is greater than that quantified for Ca-meta-autunite, eta = 0.42 ± 0.12. This suggests the stability of meta-torbernite is greater than that of meta-autunite, which is reflected in the predicted stability constants. The rate equation for the dissolution of meta-torbernite as a function of aqueous phosphate concentration is log rdissol (mol m-2 sec-1) = -4.7 x 10-13 + 4.1 x 10-10 [PO43-].« less

Predictors of supportive coparenting after relationship dissolution among at-risk parents.

PubMed

Kamp Dush, Claire M; Kotila, Letitia E; Schoppe-Sullivan, Sarah J

2011-06-01

Supportive coparenting after relationship dissolution is associated with increased father involvement which can buffer against the negative effects of parental relationship dissolution. Low-income, at-risk families are much more likely to experience relationship dissolutions; hence, supportive coparenting after dissolution is particularly important in these families. We examined whether relationship (commitment and quality) and child (difficult temperament and gender) characteristics predicted initial levels of, and change in, supportive coparenting after relationship dissolution in the Fragile Families and Child Wellbeing Study (N = 1,603). We used structural equation modeling of latent growth curves to examine four time points collected at the focal child's birth and first, third, and fifth birthdays. Ninety-percent of the mothers had nonmarital births, and about three-quarters had a high school diploma or less education. Overall, supportive coparenting decreased over time. Mothers in more committed relationships prior to the dissolution initially had significantly lower supportive coparenting. But over time, mothers who had been in more committed relationships increased in supportive coparenting. Mothers who had been in higher quality relationships prior to dissolution initially reported more supportive coparenting. At each time point, if a mother was romantically involved with a new partner, she reported significantly lower supportive coparenting compared to mothers who were single. With regard to child characteristics, mothers who reported their child as more difficult had significantly lower initial supportive coparenting. Similar results for fathers are discussed. Overall, the relationship characteristics of parents were important predictors of supportive coparenting both initially and over time. 2011 APA, all rights reserved

Improved dissolution and absorption of ketoconazole in the presence of organic acids as pH-modifiers.

PubMed

Adachi, Masashi; Hinatsu, Yuta; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Nakatani, Manabu; Wada, Koichi; Yamamoto, Akira

2015-08-30

Formulation development of poorly water-soluble compounds can be challenging because of incomplete dissolution that causes low and variable bioavailability. Enhancing compound solubility is important and many techniques have been investigated to that end, but they require specific materials and machinery. This study investigates the incorporation of a pH-modifier as a method to increase compound solubility and uses ketoconazole (KZ), which is weakly basic (pKa: 6.5), as a model compound. Organic acids are effective pH-modifiers and are generally used in pharmaceutical industries. We successfully obtained granules containing variable organic acids (KZ/acid granule) using a high-shear mixer. Dissolution tests of the KZ/acid granule resulted in highly enhanced solubility under non-sink conditions. Adding water-soluble acids, such as citric acid (CA) and tartaric acid, resulted in more than 8-fold higher dissolution at pH 6.0 compared to that of KZ only. The granules containing citric acid (KZ/CA granule) improved the dissolution of KZ after oral administration to rats under low gastric acid conditions, where the bioavailability of the KZ/CA granules at elevated gastric pH was comparable with that of KZ only at gastric acidic pH. The incorporation of organic acids would result in effective therapeutic outcomes independent of gastric pH in patients. In addition, higher bioavailability of KZ was observed after oral administration of KZ/CA granules under gastric acidic pH conditions than that of KZ alone. Thus, CA improved the dissolution and absorption rate of KZ after oral administration. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of Tool Offset and Tool Rotational Speed on Enhancing Mechanical Property of Al/Mg Dissimilar FSW Joints

NASA Astrophysics Data System (ADS)

Liang, Zhiyuan; Chen, Ke; Wang, Xiaona; Yao, Junshan; Yang, Qi; Zhang, Lanting; Shan, Aidang

2013-08-01

Friction stir welding (FSW) is a promising solid-state joining technique for producing effective welds between Al alloy and Mg alloy. However, previously reported Al/Mg dissimilar FSW joints generally have limited strength or barely any ductility with relatively high strength, which was blamed on the brittle intermetallics formed during welding. In this study, effective joints with comparably high strength (163 MPa) and large elongation (~6 pct) were obtained. Three crucial/weak zones were identified in the welds: (1) Al/Mg bottom interface (BI) zone that resulted from the insufficient materials' intermixing and interdiffusion; (2) banded structure (BS) zone which contains intermetallic particles possibly formed by constitutional liquation; and (3) softened Al alloy to the retreating side (SAA-RS) zone due to the dissolution and coarsening of the strengthening precipitates. Three fracture modes observed in the tensile specimens perpendicular to the weld seam were found closely related to these zones. Their microstructure evolution with the change of tool rotational speed and tool offset was characterized and the consequent effect on the fracture mode alteration was studied. It turned out that enhancing the strengths of all these zones, but keeping the strength of the SAA lowest, is an effective way for enhancing ductility while keeping comparatively high strength in Al/Mg FSW joints. Also, suggestions for further improving the mechanical property of the Al/Mg dissimilar FSW joints were made accordingly for practical applications.

Computational and theoretical approaches for studies of a lipid recognition protein on biological membranes

PubMed Central

Yamamoto, Eiji

2017-01-01

Many cellular functions, including cell signaling and related events, are regulated by the association of peripheral membrane proteins (PMPs) with biological membranes containing anionic lipids, e.g., phosphatidylinositol phosphate (PIP). This association is often mediated by lipid recognition modules present in many PMPs. Here, I summarize computational and theoretical approaches to investigate the molecular details of the interactions and dynamics of a lipid recognition module, the pleckstrin homology (PH) domain, on biological membranes. Multiscale molecular dynamics simulations using combinations of atomistic and coarse-grained models yielded results comparable to those of actual experiments and could be used to elucidate the molecular mechanisms of the formation of protein/lipid complexes on membrane surfaces, which are often difficult to obtain using experimental techniques. Simulations revealed some modes of membrane localization and interactions of PH domains with membranes in addition to the canonical binding mode. In the last part of this review, I address the dynamics of PH domains on the membrane surface. Local PIP clusters formed around the proteins exhibit anomalous fluctuations. This dynamic change in protein-lipid interactions cause temporally fluctuating diffusivity of proteins, i.e., the short-term diffusivity of the bound protein changes substantially with time, and may in turn contribute to the formation/dissolution of protein complexes in membranes. PMID:29159013

Solubility Enhancement of Raloxifene Using Inclusion Complexes and Cogrinding Method

PubMed Central

Patil, Payal H.; Belgamwar, Veena S.; Patil, Pratibha R.; Surana, Sanjay J.

2013-01-01

The objective of the present work was to enhance the solubility and dissolution of practically water-insoluble drug raloxifene HCl (RLX), for the same two approaches that were used. In the first approach, drug was kneaded with hydroxypropyl-β-cyclodextrin (HPβCD), and in the second one drug was cogrinded with modified guar gum (MGG). The drug-cyclodextrin complex and drug-MGG cogrind mixtures were characterized by differential scanning calorimetry, X-ray diffraction studies, scanning electron microscopy, and Fourier transform infrared spectroscopy. The solubility and dissolution study reveals that solubility and dissolution rate of RLX remarkably increased in both methods. It was concluded that the prepared inclusion complex showed a remarkable increase in solubility and dissolution of poorly water-soluble drug raloxifene. In the cogrinding mixture, a natural modified gum is used as a surfactant and enhances the solubility and dissolution of RLX without requiring addition of organic solvent or high temperature for its preparation; thus, process is less cumbersome and cost effective. But when both methods were compared; HPβCD complexation method showed significant enhancement of drug solubility. PMID:26555984

Solar Radiation Management and Olivine Dissolution Methods in Climate Engineering

NASA Astrophysics Data System (ADS)

Kone, S.

2014-12-01

An overview of solar radiation management and olivine dissolution methods allows to discuss, comparatively, the benefits and consequences of these two geoengineering techniques. The combination of those two techniques allows to concomitantly act on the two main agents intervening in global warming: solar radiation and carbon dioxide. The earth surface temperature increases due mainly to carbon dioxide (a greenhouse gas) that keeps the solar radiation and causes the global warming. Two complementary methods to mitigate climate change are overviewed: SRM method, which uses injected aerosols, aims to reduce the amount of the inbound solar radiation in atmosphere; and olivine dissolution in water, a key chemical reaction envisaged in climate engineering , aiming to reduce the amount of the carbon dioxide in extracting it from atmosphere. The SRM method works on scenarios of solar radiation decrease and the olivine dissolution method works as a carbon dioxide sequestration method. Olivine dissolution in water impacts negatively on the pH of rivers but positively in counteracting ocean acidification and in transporting the silica in ocean, which has benefits for diatom shell formation.

Model calculation of Cr dissolution behavior of ODS ferritic steel in high-temperature flowing sodium environment

NASA Astrophysics Data System (ADS)

Ohtsuka, Satoshi; Tanno, Takashi; Oka, Hiroshi; Yano, Yasuhide; Kato, Shoichi; Furukawa, Tomohiro; Kaito, Takeji

2018-07-01

A calculation model was constructed to systematically study the effects of environmental conditions (i.e. Cr concentration in sodium, test temperature, axial temperature gradient of fuel pin, and sodium flow velocity) on Cr dissolution behavior. Chromium dissolution was largely influenced by small changes in Cr concentration (i.e. chemical potential of Cr) in liquid sodium in the model calculation. Chromium concentration in sodium coolant, therefore, should be recognized as a critical parameter for the prediction and management of Cr dissolution behavior in the sodium-cooled fast reactor (SFR) core. Because the fuel column length showed no impact on dissolution behavior in the model calculation, no significant downstream effects possibly take place in the SFR fuel cladding tube due to the much shorter length compared with sodium loops in the SFR plant and the large axial temperature gradient. The calculated profile of Cr concentration along the wall-thickness direction was consistent with that measured in BOR-60 irradiation test where Cr concentration in inlet sodium bulk flow was set at 0.07 wt ppm in the calculation.

Fenofibrate Nanocrystals Embedded in Oral Strip-Films for Bioavailability Enhancement

PubMed Central

Barvaliya, Manish; Zhang, Lu; Anovadiya, Ashish; Brahmbhatt, Harshad; Paul, Parimal; Tripathi, Chandrabhanu

2018-01-01

The aim of the present study was to make a fenofibrate (FNB) nanocrystal (NC) by wet media milling, characterizations and formulates into oral strip-films (OSFs). Mechanical properties, redispersion study, and solid-state characterizations results suggested that reduction of drug crystal size at nanoscale and incorporation into OSFs does not affect the solid-state properties of the drug. In vitro dissolution kinetics showed enhanced dissolution rate was easily manipulated by changing the thickness of the OSF. In situ UV-imaging was used to monitor drug dissolution qualitatively and quantitatively in real time. Results confirm that the intrinsic dissolution rates and surface drug concentration measured with this device were in agreement with the USP-IV dissolution profiles. In vivo pharmacokinetics in rabbits showed a significant difference in the pharmacokinetics parameter (1.4 fold increase bioavailability) of FNB NC-loaded OSFs as compared to the marketed formulation “Tricor” and as-received (pristine) drug. This approach of drug nanocrystallization and incorporation into OSFs may have significant applications in cost-effective tools for bioavailability enhancement of FNB. PMID:29438297

Preparation and Optimization of Amorphous Ursodeoxycholic Acid Nano-suspensions by Nanoprecipitation based on Acid-base Neutralization for Enhanced Dissolution.

PubMed

Xie, Yike; Chen, Zhongjian; Su, Rui; Li, Ye; Qi, Jianping; Wu, Wei; Lu, Yi

2017-01-01

Ursodeoxycholic acid, usually used to dissolve cholesterol gallstones in clinic, is a typical hydrophobic drug with poor oral bioavailability due to dissolution rate-limited performance. The objective of this study was to increase the dissolution of ursodeoxycholic acid by amorphous nanosuspensions. Nanoprecipitation based on acid-base neutralization was used to prepare the nanosuspensions with central composite design to optimize the formula. The nanosuspensions were characterized by particle size, morphology, crystallology and dissolution. The ursodeoxycholic acid nanosuspensions showed mean particle size around 380 nm with polydispersion index value about 0.25. Scanning electron microscope observed high coverage of HPMC-E50 onto the surface of the nanosuspensions. Differential scanning calorimetry and powder X-ray diffractometry revealed amorphous structure of the ursodeoxycholic acid nanosuspensions. A significant increase of dissolution in acidic media was achieved by the amorphous nanosuspensions compared with the physical mixture. It can be predicted that the amorphous nanosuspensions show great potential in improving the oral bioavailability of ursodeoxycholic acid. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The effect of fission-energy Xe ion irradiation on the structural integrity and dissolution of the CeO2 matrix

NASA Astrophysics Data System (ADS)

Popel, A. J.; Le Solliec, S.; Lampronti, G. I.; Day, J.; Petrov, P. K.; Farnan, I.

2017-02-01

This work considers the effect of fission fragment damage on the structural integrity and dissolution of the CeO2 matrix in water, as a simulant for the UO2 matrix of spent nuclear fuel. For this purpose, thin films of CeO2 on Si substrates were produced and irradiated by 92 MeV 129Xe23+ ions to a fluence of 4.8 × 1015 ions/cm2 to simulate fission damage that occurs within nuclear fuels along with bulk CeO2 samples. The irradiated and unirradiated samples were characterised and a static batch dissolution experiment was conducted to study the effect of the induced irradiation damage on dissolution of the CeO2 matrix. Complex restructuring took place in the irradiated films and the irradiated samples showed an increase in the amount of dissolved cerium, as compared to the corresponding unirradiated samples. Secondary phases were also observed on the surface of the irradiated CeO2 films after the dissolution experiment.

Application of the BCS biowaiver approach to assessing bioequivalence of orally disintegrating tablets with immediate release formulations.

PubMed

Ono, Asami; Sugano, Kiyohiko

2014-11-20

The aim of this study was to compare the dissolution profiles of oral disintegrating tablets (ODTs) and immediate release (IR) formulations in order to experimentally validate the regulatory biowaiver scheme (BWS) for biopharmaceutical classification system (BCS) class III drugs. We examined six drugs that show clinical bioequivalence between the ODTs and IR formulations: taltirelin, olopatadine, droxidopa, famotidine, fexofenadine, and hydrochlorothiazide. The dissolution profiles of these drugs were evaluated using the compendium paddle apparatus at pH 1.2 and 6.8. Taltirelin and olopatadine showed very rapid dissolution and met the dissolution criteria in the BWS, whereas droxidopa, famotidine, fexofenadine, and hydrochlorothiazide did not. Furthermore, in the case of famotidine, fexofenadine, and hydrochlorothiazide, the ODTs and IR formulations showed dissimilar dissolution profiles. The dose-to-solubility ratio (D:S) of these drugs was larger than that of the other drugs. The results of this study suggest that extension of the BCS-BWS to ODTs and IR formulations of BCS class III drugs is appropriate. Furthermore, for BCS class III drugs with relatively high D:S, clinical bioequivalence would be achievable even when two formulations showed different dissolution profiles in vitro. Copyright © 2014 Elsevier B.V. All rights reserved.

Mesoporous silica-based dosage forms improve bioavailability of poorly soluble drugs in pigs: case example fenofibrate.

PubMed

O'Shea, Joseph P; Nagarsekar, Kalpa; Wieber, Alena; Witt, Vanessa; Herbert, Elisabeth; O'Driscoll, Caitriona M; Saal, Christoph; Lubda, Dieter; Griffin, Brendan T; Dressman, Jennifer B

2017-10-01

Mesoporous silicas (SLC) have demonstrated considerable potential to improve bioavailability of poorly soluble drugs by facilitating rapid dissolution and generating supersaturation. The addition of certain polymers can further enhance the dissolution of these formulations by preventing drug precipitation. This study uses fenofibrate as a model drug to investigate the performance of an SLC-based formulation, delivered with hydroxypropyl methylcellulose acetate succinate (HPMCAS) as a precipitation inhibitor, in pigs. The ability of biorelevant dissolution testing to predict the in vivo performance was also assessed. Fenofibrate-loaded mesoporous silica (FF-SLC), together with HPMCAS, displayed significant improvements in biorelevant dissolution tests relative to a reference formulation consisting of a physical mixture of crystalline fenofibrate with HPMCAS. In vivo assessment in fasted pigs demonstrated bioavailabilities of 86.69 ± 35.37% with combination of FF-SLC and HPMCAS in capsule form and 75.47 ± 14.58% as a suspension, compared to 19.92 ± 9.89% with the reference formulation. A positive correlation was identified between bioavailability and dissolution efficiency. The substantial improvements in bioavailability of fenofibrate from the SLC-based formulations confirm the ability of this formulation strategy to overcome the dissolution and solubility limitations, further raising the prospects of a future commercially available SLC-based formulation. © 2017 Royal Pharmaceutical Society.

Inventory of oral anticancer agents: Pharmaceutical formulation aspects with focus on the solid dispersion technique.

PubMed

Sawicki, E; Schellens, J H M; Beijnen, J H; Nuijen, B

2016-11-01

Dissolution from the pharmaceutical formulation is a prerequisite for complete and consistent absorption of any orally administered drug, including anticancer agents (oncolytics). Poor dissolution of an oncolytic can result in low oral bioavailability, high variability in blood concentrations and with that suboptimal or even failing therapy. This review discusses pharmaceutical formulation aspects and absorption pharmacokinetics of currently licensed orally administered oncolytics. In nearly half of orally dosed oncolytics poor dissolution is likely to play a major role in low and unpredictable absorption. Dissolution-limited drug absorption can be improved with a solid dispersion which is a formulation method that induces super-saturated drug dissolution and with that it enhances in vivo absorption. This review discusses formulation principles with focus on the solid dispersion technology and how it works to enhance drug absorption. There are currently three licensed orally dosed oncolytics formulated as a solid dispersion (everolimus, vemurafenib and regorafenib) and these formulations result in remarkably improved dissolution and absorption compared to what can be achieved with conventional formulations of the respective oncolytics. Because of the successful implementation of these three solid dispersion formulations, we encourage the application of this formulation method for poorly soluble oral oncolytics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Passivating film artificially built on LiNi0.5Mn1.5O4 by molecular layer deposition of (pentafluorophenylpropyl)trimethoxysilane

NASA Astrophysics Data System (ADS)

Chae, Seulki; Soon, Jiyong; Jeong, Hyejeong; Lee, Tae jin; Ryu, Ji Heon; Oh, Seung M.

2018-07-01

In this study, (pentafluorophenylpropyl)trimethoxysilane (PFPPS) is grafted on a nickel-doped manganese spinel (LiNi0.5Mn1.5O4, LNMO) surface to suppress the failure modes in the 5-V positive electrode; electrolyte oxidation/film deposition, acid generation, and metal (Ni and Mn) dissolution. Vapor-phase molecular layer deposition is used to deposit a uniformly covered PFPPS layer on the LNMO surface. When the Li/LNMO cell is cycled at 3.5-4.9 V (vs. Li/Li+), the PFPPS moiety on the LNMO surface remains intact (not oxidized) under the highly oxidizing condition. Several beneficial features are observed with the PFPPS grafting. The oxidative electrolyte decomposition is mitigated, which increases the Coulombic efficiency of the Li/LNMO cell. Consequently, the surface film deposition and cell polarization are reduced, improving the capacity retention. Moreover, the acid generation and metal dissolution are also mitigated.

Kinetics of dissolution of thorium and uranium doped britholite ceramics

NASA Astrophysics Data System (ADS)

Dacheux, N.; Du Fou de Kerdaniel, E.; Clavier, N.; Podor, R.; Aupiais, J.; Szenknect, S.

2010-09-01

In the field of immobilization of actinides in phosphate-based ceramics, several thorium and uranium doped britholite samples were submitted to leaching tests. The normalized dissolution rates determined for several pH values, temperatures and acidic media from the calcium release range from 4.7 × 10 -2 g m -2 d -1 to 21.6 g m -2 d -1. Their comparison with that determined for phosphorus, thorium and uranium revealed that the dissolution is clearly incongruent for all the conditions examined. Whatever the leaching solution considered, calcium and phosphorus elements were always released with higher RL values than the other elements (Nd, Th, U). Simultaneously, thorium was found to quickly precipitate as alteration product, leading to diffusion phenomena for uranium. For all the media considered, the uranium release is higher than that of thorium, probably due to its oxidation from tetravalent oxidation state to uranyl. Moreover, the evaluation of the partial order related to proton concentration and the apparent energy of activation suggest that the reaction of dissolution is probably controlled by surface chemical reactions occurring at the solid/liquid interface. Finally, comparative leaching tests performed in sulphuric acid solutions revealed a significant influence of such media on the chemical durability of the leached pellets, leading to higher normalized dissolution rates for all the elements considered. On the basis of the results of chemical speciation, this difference was mainly explained in the light of higher complexion constants by sulfate ions compared to nitrate, chloride and phosphate.

Development of novel fast-dissolving tacrolimus solid dispersion-loaded prolonged release tablet.

PubMed

Cho, Jung Hyun; Kim, Yong-Il; Kim, Dong-Wuk; Yousaf, Abid Mehmood; Kim, Jong Oh; Woo, Jong Soo; Yong, Chul Soon; Choi, Han-Gon

2014-04-11

The goal of this research was to develop a novel prolonged release tablet bioequivalent to the commercial sustained release capsule. A number of tacrolimus-loaded fast-dissolving solid dispersions containing various amounts of DOSS were prepared using the spray drying technique. Their solubility, dissolution and pharmacokinetics in rats were studied. DOSS increased drug solubility and dissolution in the solid dispersions. Compared with the drug powder, the solubility, dissolution and bioavailability of tacrolimus with the fast-dissolving solid dispersion containing tacrolimus/HP-β-CD/DOSS in the weight ratio of 5:40:4 were boosted by approximately 700-, 30- and 2-fold, respectively. Several tablet formulations were accomplished with this solid dispersion in combination with various ratios of HPMC/ethylcellulose. The release behaviour and pharmacokinetic studies in beagle dogs were assessed compared with the commercial prolonged release capsule. A decrease in HPMC/ethylcellulose ratios reduced the dissolution of tacrolimus from the tablets. Particularly, the tacrolimus-loaded prolonged release tablet consisting of fast-dissolving tacrolimus solid dispersion, HPMC, ethylcellulose and talc at the weight ratio of 20:66:112:2 exhibited a dissolution profile similar to that produced by the commercial prolonged release capsule. Furthermore, there were no significant differences in the AUC, Cmax, Tmax and MRT values between them in beagle dogs. Consequently, this tacrolimus-loaded prolonged release tablet might be bioequivalent to the tacrolimus-loaded commercial capsule. Copyright © 2013 Elsevier B.V. All rights reserved.

Ego-Dissolution and Psychedelics: Validation of the Ego-Dissolution Inventory (EDI).

PubMed

Nour, Matthew M; Evans, Lisa; Nutt, David; Carhart-Harris, Robin L

2016-01-01

The experience of a compromised sense of "self", termed ego-dissolution, is a key feature of the psychedelic experience. This study aimed to validate the Ego-Dissolution Inventory (EDI), a new 8-item self-report scale designed to measure ego-dissolution. Additionally, we aimed to investigate the specificity of the relationship between psychedelics and ego-dissolution. Sixteen items relating to altered ego-consciousness were included in an internet questionnaire; eight relating to the experience of ego-dissolution (comprising the EDI), and eight relating to the antithetical experience of increased self-assuredness, termed ego-inflation. Items were rated using a visual analog scale. Participants answered the questionnaire for experiences with classical psychedelic drugs, cocaine and/or alcohol. They also answered the seven questions from the Mystical Experiences Questionnaire (MEQ) relating to the experience of unity with one's surroundings. Six hundred and ninety-one participants completed the questionnaire, providing data for 1828 drug experiences (1043 psychedelics, 377 cocaine, 408 alcohol). Exploratory factor analysis demonstrated that the eight EDI items loaded exclusively onto a single common factor, which was orthogonal to a second factor comprised of the items relating to ego-inflation (rho = -0.110), demonstrating discriminant validity. The EDI correlated strongly with the MEQ-derived measure of unitive experience (rho = 0.735), demonstrating convergent validity. EDI internal consistency was excellent (Cronbach's alpha 0.93). Three analyses confirmed the specificity of ego-dissolution for experiences occasioned by psychedelic drugs. Firstly, EDI score correlated with drug-dose for psychedelic drugs (rho = 0.371), but not for cocaine (rho = 0.115) or alcohol (rho = -0.055). Secondly, the linear regression line relating the subjective intensity of the experience to ego-dissolution was significantly steeper for psychedelics (unstandardized regression coefficient = 0.701) compared with cocaine (0.135) or alcohol (0.144). Ego-inflation, by contrast, was specifically associated with cocaine experiences. Finally, a binary Support Vector Machine classifier identified experiences occasioned by psychedelic drugs vs. cocaine or alcohol with over 85% accuracy using ratings of ego-dissolution and ego-inflation alone. Our results demonstrate the psychometric structure, internal consistency and construct validity of the EDI. Moreover, we demonstrate the close relationship between ego-dissolution and the psychedelic experience. The EDI will facilitate the study of the neuronal correlates of ego-dissolution, which is relevant for psychedelic-assisted psychotherapy and our understanding of psychosis.

Characterization of Thin Film Dissolution in Water with in Situ Monitoring of Film Thickness Using Reflectometry.

PubMed

Yersak, Alexander S; Lewis, Ryan J; Tran, Jenny; Lee, Yung C

2016-07-13

Reflectometry was implemented as an in situ thickness measurement technique for rapid characterization of the dissolution dynamics of thin film protective barriers in elevated water temperatures above 100 °C. Using this technique, multiple types of coatings were simultaneously evaluated in days rather than years. This technique enabled the uninterrupted characterization of dissolution rates for different coating deposition temperatures, postdeposition annealing conditions, and locations on the coating surfaces. Atomic layer deposition (ALD) SiO2 and wet thermally grown SiO2 (wtg-SiO2) thin films were demonstrated to be dissolution-predictable barriers for the protection of metals such as copper. A ∼49% reduction in dissolution rate was achieved for ALD SiO2 films by increasing the deposition temperatures from 150 to 300 °C. ALD SiO2 deposited at 300 °C and followed by annealing in an inert N2 environment at 1065 °C resulted in a further ∼51% reduction in dissolution rate compared with the nonannealed sample. ALD SiO2 dissolution rates were thus lowered to values of wtg-SiO2 in water by the combination of increasing the deposition temperature and postdeposition annealing. Thin metal films, such as copper, without a SiO2 barrier corroded at an expected ∼1-2 nm/day rate when immersed in room temperature water. This measurement technique can be applied to any optically transparent coating.

Experimental investigation of the dissolution of fractures. From early stage instability to phase diagram

NASA Astrophysics Data System (ADS)

Osselin, Florian; Budek, Agnieszka; Cybulski, Olgierd; Kondratiuk, Pawel; Garstecki, Piotr; Szymczak, Piotr

2016-04-01

Dissolution of natural rocks is a fundamental geological process and a key part of landscape formation and weathering processes. Moreover, in current hot topics like Carbon Capture and Storage or Enhanced Oil Recovery, mastering dissolution of the host rock is fundamental for the efficiency and the security of the operation. The basic principles of dissolution are well-known and the theory of the reactive infiltration instability has been extensively studied. However, the experimental aspect has proved very challenging because of the strong dependence of the outcome with pore network, chemical composition, flow rate... In this study we are trying to tackle this issue by using a very simple and efficient device consisting of a chip of pure gypsum inserted between two polycarbonate plates and subjected to a constant flow rate of pure water. Thanks to this device, we are able to control all parameters such as flow rate, fracture aperture, roughness of the walls... but also to observe in situ the progression of the dissolution thanks to the transparency of the polycarbonate which is impossible with 3D rocks. We have been using this experimental set-up to explore and investigate all aspects of the dissolution in a fracture, such as initial instability and phase diagram of different dissolution patterns, and to compare it with theory and simulations, yielding very good agreement and interesting feedbacks on the coupling between flow and chemistry in geological media

Degradation characteristics of polylactide in thermophilic anaerobic digestion with hyperthermophilic solubilization condition.

PubMed

Wang, F; Hidaka, T; Oishi, T; Osumi, S; Tsubota, J; Tsuno, H

2011-01-01

To test whether hyperthermophilic treatment promotes polylactide (PLA) dissolution and methane conversion under anaerobic digestion conditions, a single thermophilic control reactor (55 °C) and a two-phase system consisting of a hyperthermophilic reactor (80 °C) and a thermophilic reactor (55 °C) were continuously fed with a mixture of PLA and artificial kitchen garbage. In Runs 1 and 2, the PLA dissolution ratios in the two-phase system were 79.2 ± 6.5% and 85.2 ± 7.0%, respectively, higher than those of the control. Batch experimental results indicated that hyperthermophilic treatment could promote PLA dissolution to a greater degree as compared with single thermophilic treatment and that ammonia addition also had a promotional effect on PLA dissolution. In the two-phase system, after hyperthermophilic treatment, dissolved PLA was converted to methane gas under the subsequent thermophilic condition.

Porous aerosil loading probucol using supercritical carbon dioxide: preparation, in vitro and in vivo characteristics.

PubMed

Chu, Chunxia; Liu, Muhua; Wang, Dongmei; Guan, Jibin; Cai, Cuifang; Sun, Yuanpeng; Zhang, Tianhong

2014-06-01

The aim of this study was to enhance the dissolution rate and oral bioavailability of probucol. Probucol was adsorbed onto aerosils via supercritical carbon dioxide (ScCO2) and the physicochemistry properties of probucol-aerosil powder were evaluated by differential scanning calorimetry, X-ray diffraction, infrared spectroscopy and scanning electron microscopy. Tablets of the probucol-aerosil powder were prepared by direct compression method. In the dissolution test, the probucol-aerosil tablets showed a significant enhanced dissolution rate compared with commercial tablets. Bioavailability study was carried out in beagle dogs. Probucol-aerosil tablets exhibited higher AUC and Cmax than commercial tablets. The improved dissolution and bioavailability of probucol-aerosil tablets were attributed to the amorphous state and good dispersion of probucol. It is a feasible method to enhance the oral bioavailability by adsorbing probucol onto aerosils via ScCO2.

Enthalpy characteristics of the dissolution of L-valine in water/formamide mixtures at 298.15 K

NASA Astrophysics Data System (ADS)

Smirnov, V. I.; Badelin, V. G.

2016-11-01

The thermochemical dissolution of L-valine in solvent mixtures H2O + (formamide, N-methylformamide, and N, N-dimethylformamide) is studied at an organic component concentration of x 2 = 0-0.35 molar fractions and a temperature of 298.15 K. The experimental data are used to calculate standard enthalpies of dissolution, the transferring of L-valine from water to a mixed solvent, and the enthalpy coefficients of pairwise interactions ( h xy ) with organic solvent molecules. The correlation between the enthalpy characteristics of the dissolution of L-valine with the composition of aqueous organic mixtures and the nature of the organic solvent (its physicochemical properties) is determined. A comparative analysis of the values of h xy of a number of aliphatic L-amino acids in similar solvent mixtures with the hydrophobicity parameters of their side chains is performed.

In-line ATR-UV and Raman Spectroscopy for Monitoring API Dissolution Process During Liquid-Filled Soft-Gelatin Capsule Manufacturing.

PubMed

Wan, Boyong; Zordan, Christopher A; Lu, Xujin; McGeorge, Gary

2016-10-01

Complete dissolution of the active pharmaceutical ingredient (API) is critical in the manufacturing of liquid-filled soft-gelatin capsules (SGC). Attenuated total reflectance UV spectroscopy (ATR-UV) and Raman spectroscopy have been investigated for in-line monitoring of API dissolution during manufacturing of an SGC product. Calibration models have been developed with both techniques for in-line determination of API potency. Performance of both techniques was evaluated and compared. The ATR-UV methodology was found to be able to monitor the dissolution process and determine the endpoint, but was sensitive to temperature variations. The Raman technique was also capable of effectively monitoring the process and was more robust to the temperature variation and process perturbations by using an excipient peak for internal correction. Different data preprocessing methodologies were explored in an attempt to improve method performance.

Characterization of pH-fractionated humic acids with respect to their dissociation behaviour.

PubMed

Klučáková, Martina

2016-04-01

Humic acids were divided into several fractions using buffer solutions as extraction agents with different pH values. Two methods of fractionation were used. The first one was subsequent dissolution of bulk humic acids in buffers adjusted to different pH. The second one was sequential dissolution in buffers with increasing pH values. Experimental data were compared with hypothesis of partial solubility of humic acids in aqueous solutions. Behaviour of humic fractions obtained by sequential dissolution, original bulk sample and residual fractions obtained by subsequent dissolution at pH 10 and 12 agrees with the hypothesis. Results demonstrated that regardless the common mechanism, solubility and dissociation degree of various humic fractions may be very different and can be estimated using parameters of the model based on the proposed mechanism. Presented results suggest that dissolving of solid humic acids in water environment is more complex than conventional solubility behaviour of sparingly soluble solids.

Solution-mediated phase transformation of haloperidol mesylate in the presence of sodium lauryl sulfate.

PubMed

Greco, Kristyn; Bogner, Robin

2011-09-01

Forming a salt is a common way to increase the solubility of a poorly soluble compound. However, the solubility enhancement gained by salt formation may be lost due to solution-mediated phase transformation (SMPT) during dissolution. The SMPT of a salt can occur due to a supersaturated solution near the dissolving surface caused by pH or other solution conditions. In addition to changes in pH, surfactants are also known to affect SMPT. In this study, SMPT of a highly soluble salt, haloperidol mesylate, at pH 7 in the presence of a commonly used surfactant, sodium lauryl sulfate (SLS), was investigated. Dissolution experiments were performed using a flow-through dissolution apparatus with solutions containing various concentrations of SLS. Compacts of haloperidol mesylate were observed during dissolution in the flow-through apparatus using a stereomicroscope. Raman microscopy was used to characterize solids. The dissolution of haloperidol mesylate was significantly influenced by the addition of sodium lauryl sulfate. In conditions where SMPT was expected, the addition of SLS at low concentrations (0.1-0.2 mM) reduced the dissolution of haloperidol mesylate. In solutions containing concentrations of SLS above the critical micelle concentration (CMC) (10-15 mM), the dissolution of haloperidol mesylate increased compared to below the CMC. The solids recovered from solubility experiments of haloperidol mesylate indicated that haloperidol free base precipitated at all concentrations of SLS. Above 5 mM of SLS, Raman microscopy suggested a new form, perhaps the estolate salt. The addition of surfactant in solids that undergo solution-mediated phase transformation can add complexity to the dissolution profiles and conversion.

Influence of pH, particle size and crystal form on dissolution behaviour of engineered nanomaterials.

PubMed

Avramescu, M-L; Rasmussen, P E; Chénier, M; Gardner, H D

2017-01-01

Solubility is a critical component of physicochemical characterisation of engineered nanomaterials (ENMs) and an important parameter in their risk assessments. Standard testing methodologies are needed to estimate the dissolution behaviour and biodurability (half-life) of ENMs in biological fluids. The effect of pH, particle size and crystal form on dissolution behaviour of zinc metal, ZnO and TiO 2 was investigated using a simple 2 h solubility assay at body temperature (37 °C) and two pH conditions (1.5 and 7) to approximately frame the pH range found in human body fluids. Time series dissolution experiments were then conducted to determine rate constants and half-lives. Dissolution characteristics of investigated ENMs were compared with those of their bulk analogues for both pH conditions. Two crystal forms of TiO 2 were considered: anatase and rutile. For all compounds studied, and at both pH conditions, the short solubility assays and the time series experiments consistently showed that biodurability of the bulk analogues was equal to or greater than biodurability of the corresponding nanomaterials. The results showed that particle size and crystal form of inorganic ENMs were important properties that influenced dissolution behaviour and biodurability. All ENMs and bulk analogues displayed significantly higher solubility at low pH than at neutral pH. In the context of classification and read-across approaches, the pH of the dissolution medium was the key parameter. The main implication is that pH and temperature should be specified in solubility testing when evaluating ENM dissolution in human body fluids, even for preliminary (tier 1) screening.

Dissolution Rates of Biogenic Carbonate Sediments from the Bermuda Platform

NASA Astrophysics Data System (ADS)

Finlay, A. J.; Andersson, A. J.

2016-02-01

The contribution of biogenic carbonate sediment dissolution rates to overall net reef accretion/erosion (under both present and future oceanic pCO2 levels) has been strikingly neglected, despite experimental results indicating that sediment dissolution might be more sensitive to ocean acidification (OA) than calcification. Dissolution of carbonate sediments could impact net reef accretion rates as well as the formation and preservation of valuable marine and terrestrial ecosystems. Bulk sediment dissolution rates of samples from the Bermuda carbonate platform were measured in natural seawater at pCO2 values ranging from approximately 3500 μatm to 9000 μatm. This range of pCO2 levels incorporates values currently observed in porewaters on the Bermuda carbonate platform as well as a potential future increase in porewater pCO2 levels due to OA. Sediment samples from two different stations on the reef platform were analyzed for grain size and mineralogy. Dissolution rates of sediments in the dominant grain size fraction of the platform (500-1000 μm) from both stations ranged between 16.25 and 47.19 (± 0.27 to 0.79) μmoles g-1 hr-1 and are comparable to rates previously obtained from laboratory experiments on other natural carbonate sediments. At a pCO2 of 3500 μatm, rates from both samples were similar, despite their differing mineralogy. However, at pCO2 levels above 3500 μatm, the sediment sample with a greater weight percent of Mg-calcite had slightly higher dissolution rates. Despite many laboratory studies on biogenic carbonate dissolution, a significant disparity still exists between laboratory measurements and field observations. Performing additional controlled, laboratory experiments on natural sediment may help to elucidate the reasons for this disparity.

In silico prediction of drug dissolution and absorption with variation in intestinal pH for BCS class II weak acid drugs: ibuprofen and ketoprofen.

PubMed

Tsume, Yasuhiro; Langguth, Peter; Garcia-Arieta, Alfredo; Amidon, Gordon L

2012-10-01

The FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS class III and BCS class II have been proposed, in particular, BCS class II weak acids. However, a discrepancy between the in vivo BE results and in vitro dissolution results for BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient for in vitro bioequivalence studies of ibuprofen and ketoprofen as models of carboxylic acid drugs. The oral absorption of these BCS class II acids from the gastrointestinal tract was predicted by GastroPlus™. Ibuprofen did not satisfy the bioequivalence criteria at lower settings of intestinal pH of 6.0. Further the experimental dissolution of ibuprofen tablets in a low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol l (-1) /pH) was dramatically reduced compared with the dissolution in SIF (the average buffer capacity 12.6 mmol l (-1) /pH). Thus these predictions for the oral absorption of BCS class II acids indicate that the absorption patterns depend largely on the intestinal pH and buffer strength and must be considered carefully for a bioequivalence test. Simulation software may be a very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard. Copyright © 2012 John Wiley & Sons, Ltd.

In Silico Prediction of Drug Dissolution and Absorption with variation in Intestinal pH for BCS Class II Weak Acid Drugs: Ibuprofen and Ketoprofen§

PubMed Central

Tsume, Yasuhiro; Langguth, Peter; Garcia-Arieta, Alfredo; Amidon, Gordon L.

2012-01-01

The FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS Class III and BCS class II have been proposed, particularly, BCS class II weak acids. However, a discrepancy between the in vivo- BE results and in vitro- dissolution results for a BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient for in vitro bioequivalence studies of ibuprofen and ketoprofen as models of carboxylic acid drugs. The oral absorption of these BCS class II acids from the gastrointestinal tract was predicted by GastroPlus™. Ibuprofen did not satisfy the bioequivalence criteria at lower settings of intestinal pH=6.0. Further the experimental dissolution of ibuprofen tablets in the low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol L-1/pH) was dramatically reduced compared to the dissolution in SIF (the average buffer capacity 12.6 mmol L -1/pH). Thus these predictions for oral absorption of BCS class II acids indicate that the absorption patterns largely depend on the intestinal pH and buffer strength and must be carefully considered for a bioequivalence test. Simulation software may be very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard. PMID:22815122

Evaluating the reliability of equilibrium dissolution assumption from residual gasoline in contact with water saturated sands

NASA Astrophysics Data System (ADS)

Lekmine, Greg; Sookhak Lari, Kaveh; Johnston, Colin D.; Bastow, Trevor P.; Rayner, John L.; Davis, Greg B.

2017-01-01

Understanding dissolution dynamics of hazardous compounds from complex gasoline mixtures is a key to long-term predictions of groundwater risks. The aim of this study was to investigate if the local equilibrium assumption for BTEX and TMBs (trimethylbenzenes) dissolution was valid under variable saturation in two dimensional flow conditions and evaluate the impact of local heterogeneities when equilibrium is verified at the scale of investigation. An initial residual gasoline saturation was established over the upper two-thirds of a water saturated sand pack. A constant horizontal pore velocity was maintained and water samples were recovered across 38 sampling ports over 141 days. Inside the residual NAPL zone, BTEX and TMBs dissolution curves were in agreement with the TMVOC model based on the local equilibrium assumption. Results compared to previous numerical studies suggest the presence of small scale dissolution fingering created perpendicular to the horizontal dissolution front, mainly triggered by heterogeneities in the medium structure and the local NAPL residual saturation. In the transition zone, TMVOC was able to represent a range of behaviours exhibited by the data, confirming equilibrium or near-equilibrium dissolution at the scale of investigation. The model locally showed discrepancies with the most soluble compounds, i.e. benzene and toluene, due to local heterogeneities exhibiting that at lower scale flow bypassing and channelling may have occurred. In these conditions mass transfer rates were still high enough to fall under the equilibrium assumption in TMVOC at the scale of investigation. Comparisons with other models involving upscaled mass transfer rates demonstrated that such approximations with TMVOC could lead to overestimate BTEX dissolution rates and underestimate the total remediation time.

Evaluating the reliability of equilibrium dissolution assumption from residual gasoline in contact with water saturated sands.

PubMed

Lekmine, Greg; Sookhak Lari, Kaveh; Johnston, Colin D; Bastow, Trevor P; Rayner, John L; Davis, Greg B

2017-01-01

Understanding dissolution dynamics of hazardous compounds from complex gasoline mixtures is a key to long-term predictions of groundwater risks. The aim of this study was to investigate if the local equilibrium assumption for BTEX and TMBs (trimethylbenzenes) dissolution was valid under variable saturation in two dimensional flow conditions and evaluate the impact of local heterogeneities when equilibrium is verified at the scale of investigation. An initial residual gasoline saturation was established over the upper two-thirds of a water saturated sand pack. A constant horizontal pore velocity was maintained and water samples were recovered across 38 sampling ports over 141days. Inside the residual NAPL zone, BTEX and TMBs dissolution curves were in agreement with the TMVOC model based on the local equilibrium assumption. Results compared to previous numerical studies suggest the presence of small scale dissolution fingering created perpendicular to the horizontal dissolution front, mainly triggered by heterogeneities in the medium structure and the local NAPL residual saturation. In the transition zone, TMVOC was able to represent a range of behaviours exhibited by the data, confirming equilibrium or near-equilibrium dissolution at the scale of investigation. The model locally showed discrepancies with the most soluble compounds, i.e. benzene and toluene, due to local heterogeneities exhibiting that at lower scale flow bypassing and channelling may have occurred. In these conditions mass transfer rates were still high enough to fall under the equilibrium assumption in TMVOC at the scale of investigation. Comparisons with other models involving upscaled mass transfer rates demonstrated that such approximations with TMVOC could lead to overestimate BTEX dissolution rates and underestimate the total remediation time. Copyright © 2016. Published by Elsevier B.V.

Field-scale Prediction of Enhanced DNAPL Dissolution Using Partitioning Tracers and Flow Pattern Effects

NASA Astrophysics Data System (ADS)

Wang, F.; Annable, M. D.; Jawitz, J. W.

2012-12-01

The equilibrium streamtube model (EST) has demonstrated the ability to accurately predict dense nonaqueous phase liquid (DNAPL) dissolution in laboratory experiments and numerical simulations. Here the model is applied to predict DNAPL dissolution at a PCE-contaminated dry cleaner site, located in Jacksonville, Florida. The EST is an analytical solution with field-measurable input parameters. Here, measured data from a field-scale partitioning tracer test were used to parameterize the EST model and the predicted PCE dissolution was compared to measured data from an in-situ alcohol (ethanol) flood. In addition, a simulated partitioning tracer test from a calibrated spatially explicit multiphase flow model (UTCHEM) was also used to parameterize the EST analytical solution. The ethanol prediction based on both the field partitioning tracer test and the UTCHEM tracer test simulation closely matched the field data. The PCE EST prediction showed a peak shift to an earlier arrival time that was concluded to be caused by well screen interval differences between the field tracer test and alcohol flood. This observation was based on a modeling assessment of potential factors that may influence predictions by using UTCHEM simulations. The imposed injection and pumping flow pattern at this site for both the partitioning tracer test and alcohol flood was more complex than the natural gradient flow pattern (NGFP). Both the EST model and UTCHEM were also used to predict PCE dissolution under natural gradient conditions, with much simpler flow patterns than the forced-gradient double five spot of the alcohol flood. The NGFP predictions based on parameters determined from tracer tests conducted with complex flow patterns underestimated PCE concentrations and total mass removal. This suggests that the flow patterns influence aqueous dissolution and that the aqueous dissolution under the NGFP is more efficient than dissolution under complex flow patterns.

Improvement of the dissolution rate of artemisinin by means of supercritical fluid technology and solid dispersions.

PubMed

Van Nijlen, T; Brennan, K; Van den Mooter, G; Blaton, N; Kinget, R; Augustijns, P

2003-03-26

The purpose of this study was to enhance the dissolution rate of artemisinin in order to improve the intestinal absorption characteristics. The effect of: (1) micronisation and (2) formation of solid dispersions with PVPK25 was assessed in an in vitro dissolution system [dissolution medium: water (90%), ethanol (10%) and sodium lauryl sulphate (0.1%)]. Coulter counter analysis was used to measure particle size. X-ray diffraction and DSC were used to analyse the physical state of the powders. Micronisation by means of a jet mill and supercritical fluid technology resulted in a significant decrease in particle size as compared to untreated artemisinin. All powders appeared to be crystalline. The dissolution rate of the micronised forms improved in comparison to the untreated form, but showed no difference in comparison to mechanically ground artemisinin. Solid dispersions of artemisinin with PVPK25 as a carrier were prepared by the solvent method. Both X-ray diffraction and DSC showed that the amorphous state was reached when the amount of PVPK25 was increased to 67%. The dissolution rate of solid dispersions with at least 67% of PVPK25 was significantly improved in comparison to untreated and mechanically ground artemisinin. Modulation of the dissolution rate of artemisinin was obtained by both particle size reduction and formation of solid dispersions. The effect of particle size reduction on the dissolution rate was limited. Solid dispersions could be prepared by using a relatively small amount of PVPK25. The formation of solid dispersions with PVPK25 as a carrier appears to be a promising method to improve the intestinal absorption characteristics of artemisinin. Copyright 2003 Elsevier Science B.V.

Facilitating Conceptual Understanding of Gas-Liquid Mass Transfer Coefficient through a Simple Experiment Involving Dissolution of Carbon Dioxide in Water in a Surface Aeration Reactor

ERIC Educational Resources Information Center

Utgikar, Vivek P.; MacPherson, David

2016-01-01

Students in the undergraduate "transport phenomena" courses typically have a greater difficulty in understanding the theoretical concepts underlying the mass transport phenomena as compared to the concepts of momentum and energy transport. An experiment based on dissolution of carbon dioxide in water was added to the course syllabus to…

CuO Nanoparticle Dissolution and Toxicity to Wheat ( Triticum aestivum) in Rhizosphere Soil.

PubMed

Gao, Xiaoyu; Avellan, Astrid; Laughton, Stephanie; Vaidya, Rucha; Rodrigues, Sónia M; Casman, Elizabeth A; Lowry, Gregory V

2018-03-06

It has been suggested, but not previously measured, that dissolution kinetics of soluble nanoparticles such as CuO nanoparticles (NPs) in soil affect their phytotoxicity. An added complexity is that such dissolution is also affected by the presence of plant roots. Here, we measured the rate of dissolution of CuO NPs in bulk soil, and in soil in which wheat plants ( Triticum aestivum) were grown under two soil NP dosing conditions: (a) freshly added CuO NPs (500 mg Cu/kg soil) and (b) CuO NPs aged for 28 d before planting. At the end of the plant growth period (14 d), available Cu was measured in three different soil compartments: bulk (not associated with roots), loosely attached to roots, and rhizosphere (soil firmly attached to roots). The labile Cu fraction increased from 17 mg/kg to 223 mg/kg in fresh treatments and from 283 mg/kg to 305 mg/kg in aged treatments over the growth period due to dissolution. Aging CuO NPs increased the toxicity to Triticum aestivum (reduction in root maximal length). The presence of roots in the soil had opposite and somewhat compensatory effects on NP dissolution, as measured in rhizosphere soil. pH increased 0.4 pH units for fresh NP treatments and 0.6 pH units for aged NPs. This lowered CuO NP dissolution in rhizosphere soil. Exudates from T. aestivum roots also increased soluble Cu in pore water. CaCl 2 extractable Cu concentrations increaed in rhizosphere soil compared to bulk soil, from 1.8 mg/kg to 6.2 mg/kg in fresh treatment and from 3.4 mg/kg to 5.4 mg/kg in aged treatments. Our study correlated CuO NP dissolution and the resulting Cu ion exposure profile to phytotoxicity, and showed that plant-induced changes in rhizosphere conditions should be considered when measuring the dissolution of CuO NPs near roots.

Dissolution Dominating Calcification Process in Polar Pteropods Close to the Point of Aragonite Undersaturation

PubMed Central

Bednaršek, Nina; Tarling, Geraint A.; Bakker, Dorothee C. E.; Fielding, Sophie; Feely, Richard A.

2014-01-01

Thecosome pteropods are abundant upper-ocean zooplankton that build aragonite shells. Ocean acidification results in the lowering of aragonite saturation levels in the surface layers, and several incubation studies have shown that rates of calcification in these organisms decrease as a result. This study provides a weight-specific net calcification rate function for thecosome pteropods that includes both rates of dissolution and calcification over a range of plausible future aragonite saturation states (Ωar). We measured gross dissolution in the pteropod Limacina helicina antarctica in the Scotia Sea (Southern Ocean) by incubating living specimens across a range of aragonite saturation states for a maximum of 14 days. Specimens started dissolving almost immediately upon exposure to undersaturated conditions (Ωar∼0.8), losing 1.4% of shell mass per day. The observed rate of gross dissolution was different from that predicted by rate law kinetics of aragonite dissolution, in being higher at Ωar levels slightly above 1 and lower at Ωar levels of between 1 and 0.8. This indicates that shell mass is affected by even transitional levels of saturation, but there is, nevertheless, some partial means of protection for shells when in undersaturated conditions. A function for gross dissolution against Ωar derived from the present observations was compared to a function for gross calcification derived by a different study, and showed that dissolution became the dominating process even at Ωar levels close to 1, with net shell growth ceasing at an Ωar of 1.03. Gross dissolution increasingly dominated net change in shell mass as saturation levels decreased below 1. As well as influencing their viability, such dissolution of pteropod shells in the surface layers will result in slower sinking velocities and decreased carbon and carbonate fluxes to the deep ocean. PMID:25285916

Vulnerability of the paper Nautilus (Argonauta nodosa) shell to a climate-change ocean: potential for extinction by dissolution.

PubMed

Wolfe, Kennedy; Smith, Abigail M; Trimby, Patrick; Byrne, Maria

2012-10-01

Shell calcification in argonauts is unique. Only females of these cephalopods construct the paper nautilus shell, which is used as a brood chamber for developing embryos in the pelagic realm. As one of the thinnest (225 μm) known adult mollusc shells, and lacking an outer protective periostracum-like cover, this shell may be susceptible to dissolution as the ocean warms and decreases in pH. Vulnerability of the A. nodosa shell was investigated through immersion of shell fragments in multifactorial experiments of control (19 °C/pH 8.1; pCO(2) 419; Ω(Ca) = 4.23) and near-future conditions (24 °C/pH 7.8-7.6; pCO(2) 932-1525; Ω(Ca) = 2.72-1.55) for 14 days. More extreme pH treatments (pH 7.4-7.2; pCO(2) 2454-3882; Ω(Ca) = 1.20-0.67) were used to assess tipping points in shell dissolution. X-ray diffractometry revealed no change in mineralogy between untreated and treated shells. Reduced shell weight due to dissolution was evident in shells incubated at pH 7.8 (projected for 2070) after 14 days at control temperature, with increased dissolution in warmer and lower pH treatments. The greatest dissolution was recorded at 24 °C (projected for local waters by 2100) compared to control temperature across all low-pH treatments. Scanning electron microscopy revealed dissolution and etching of shell mineral in experimental treatments. In the absence of compensatory mineralization, the uncovered female brood chamber will be susceptible to dissolution as ocean pH decreases. Since the shell was a crucial adaptation for the evolution of the argonauts' holopelagic existence, persistence of A. nodosa may be compromised by shell dissolution in an ocean-change world.

Dissolution dominating calcification process in polar pteropods close to the point of aragonite undersaturation.

PubMed

Bednaršek, Nina; Tarling, Geraint A; Bakker, Dorothee C E; Fielding, Sophie; Feely, Richard A

2014-01-01

Thecosome pteropods are abundant upper-ocean zooplankton that build aragonite shells. Ocean acidification results in the lowering of aragonite saturation levels in the surface layers, and several incubation studies have shown that rates of calcification in these organisms decrease as a result. This study provides a weight-specific net calcification rate function for thecosome pteropods that includes both rates of dissolution and calcification over a range of plausible future aragonite saturation states (Ω(ar)). We measured gross dissolution in the pteropod Limacina helicina antarctica in the Scotia Sea (Southern Ocean) by incubating living specimens across a range of aragonite saturation states for a maximum of 14 days. Specimens started dissolving almost immediately upon exposure to undersaturated conditions (Ω(ar) ∼ 0.8), losing 1.4% of shell mass per day. The observed rate of gross dissolution was different from that predicted by rate law kinetics of aragonite dissolution, in being higher at Ω(ar) levels slightly above 1 and lower at Ω(ar) levels of between 1 and 0.8. This indicates that shell mass is affected by even transitional levels of saturation, but there is, nevertheless, some partial means of protection for shells when in undersaturated conditions. A function for gross dissolution against Ω(ar) derived from the present observations was compared to a function for gross calcification derived by a different study, and showed that dissolution became the dominating process even at Ω(ar) levels close to 1, with net shell growth ceasing at an Ω(ar) of 1.03. Gross dissolution increasingly dominated net change in shell mass as saturation levels decreased below 1. As well as influencing their viability, such dissolution of pteropod shells in the surface layers will result in slower sinking velocities and decreased carbon and carbonate fluxes to the deep ocean.

Loading amorphous Asarone in mesoporous silica SBA-15 through supercritical carbon dioxide technology to enhance dissolution and bioavailability.

PubMed

Zhang, Zhengzan; Quan, Guilan; Wu, Qiaoli; Zhou, Chan; Li, Feng; Bai, Xuequn; Li, Ge; Pan, Xin; Wu, Chuanbin

2015-05-01

The aim of this study was to load amorphous hydrophobic drug into ordered mesoporous silica (SBA-15) by supercritical carbon dioxide technology in order to improve the dissolution and bioavailability of the drug. Asarone was selected as a model drug due to its lipophilic character and poor bioavailability. In vitro dissolution and in vivo bioavailability of the obtained Asarone-SBA-15 were significantly improved as compared to the micronized crystalline drug. This study offers an effective, safe, and environmentally benign means of solving the problems relating to the solubility and bioavailability of hydrophobic molecules. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of a Physiologically Relevant Population Pharmacokinetic in Vitro-in Vivo Correlation Approach for Designing Extended-Release Oral Dosage Formulation.

PubMed

Kim, Tae Hwan; Shin, Soyoung; Bulitta, Jürgen B; Youn, Yu Seok; Yoo, Sun Dong; Shin, Beom Soo

2017-01-03

Establishing a level A in vitro-in vivo correlation (IVIVC) for a drug with complex absorption kinetics is challenging. The objective of the present study was to develop an IVIVC approach based on population pharmacokinetic (POP-PK) modeling that incorporated physiologically relevant absorption kinetics. To prepare three extended release (ER) tablets of loxoprofen, three types of hydroxypropyl methylcellulose (HPMC 100, 4000, and 15000 cps) were used as drug release modifiers, while lactose and magnesium stearate were used as the diluent and lubricant, respectively. An in vitro dissolution test in various pH conditions showed that loxoprofen dissolution was faster at higher pH. The in vivo pharmacokinetics of loxoprofen was assessed following oral administration of the different loxoprofen formulations to Beagle dogs (n = 22 in total). Secondary peaks or shoulders were observed in many of the individual plasma concentration vs time profiles after ER tablet administration, which may result from secondary absorption in the intestine due to a dissolution rate increase under intestinal pH compared to that observed at stomach pH. In addition, in vivo oral bioavailability was found to decrease with prolonged drug dissolution, indicating site-specific absorption. Based on the in vitro dissolution and in vivo absorption data, a POP-PK IVIVC model was developed using S-ADAPT software. pH-dependent biphasic dissolution kinetics, described using modified Michaelis-Menten kinetics with varying V max , and site-specific absorption, modeled using a changeable absorbed fraction parameter, were applied to the POP-PK IVIVC model. To experimentally determine the biphasic dissolution profiles of the ER tablets, another in vitro dissolution test was conducted by switching dissolution medium pH based on an in vivo estimate of gastric emptying time. The model estimated, using linear regression, that in vivo initial maximum dissolution rate (V max (0) in vivo ) was highly correlated (r 2 > 0.998) with in vitro (V max (0) in vitro ), indicating that in vivo dissolution profiles obtained from POP-PK modeling could be converted to in vitro dissolution profiles and vice versa. Monte Carlo simulations were performed for model validation, and prediction errors for C max and AUC were all within the acceptable range (90 to 110%) according to the FDA guidelines. The developed model was successfully applied for the prediction of in vivo pharmacokinetics of a loxoprofen double-layered tablet using the in vitro dissolution profile. In conclusion, a level A IVIVC approach was developed and validated using population modeling that accounted for pH-dependent dissolution and site-specific absorption. Excellent correlations were observed between in vitro and in vivo dissolution profiles. This new approach holds great promise for the establishment of IVIVCs for drug and formulation development where absorption kinetics strongly depend on complex physiologically absorption processes.

Stability and compatibility of tegaserod from crushed tablets mixed in beverages and foods.

PubMed

Carrier, Marie-Noëlle; Garinot, Olivier; Vitzling, Christian

2004-06-01

The stability and compatibility of tegaserod from crushed tablets in selected beverages and foods were studied. Suspensions of tegaserod maleate tablets containing 6 mg of the drug base were prepared by crushing the tablets and mixing the powder with tap water, apple juice, orange juice, milk, applesauce, yogurt, and chocolate-hazelnut spread. Drug stability, drug comparability, suspension homogeneity, and completeness of a dose were measured by high-performance liquid chromatography at intervals up to three days at 20-25 degrees C and 5 degrees C. In vitro dissolution profiles were determined for crushed tegaserod tablets in water, apple juice, orange juice, and applesauce. Tegaserod from crushed tablets was stable in and compatible with water, apple juice, orange juice, and applesauce, and the suspensions were homogeneous. The complete dose was delivered with these media. The dissolution profiles of crushed tegaserod tablets in water and in apple juice were comparable to those of intact tablets; the dissolution profiles in orange juice and applesauce were not comparable with those of intact tablets. The results with milk, yogurt, and chocolate-hazelnut spread as vehicles were inconclusive. The suspension in milk was not homogeneous, and the dose was incomplete. Tegaserod from crushed tablets was stable in and compatible with water, apple juice, orange juice, and applesauce, but the dissolution profile in orange juice or applesauce was not acceptable. Apple juice may be the preferred vehicle because it masks the drug's taste.

Fabrication, characterization and in vitro evaluation of silibinin nanoparticles: an attempt to enhance its oral bioavailability

PubMed Central

Sahibzada, Muhammad Umar Khayam; Sadiq, Abdul; Khan, Shahzeb; Faidah, Hani S; Naseemullah; Khurram, Muhammad; Amin, Muhammad Usman; Haseeb, Abdul

2017-01-01

Background Silibinin has gained in importance in the past few decades as a hepatoprotector and is used widely as oral therapy for toxic liver damage, liver cirrhosis, and chronic inflammatory liver diseases, as well as for the treatment of different types of cancers. Unfortunately, it has low aqueous solubility and inadequate dissolution, which results in low oral bioavailability. Materials and methods In this study, nanoparticles (NPs) of silibinin, which is a hydrophobic drug, were manufactured using two cost-effective methods. Antisolvent precipitation with a syringe pump (APSP) and evaporative precipitation of nanosuspension (EPN) were used. The prepared NPs were characterized using different analytical techniques such as scanning electron microscopy (SEM), fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray powder diffractometry (XRD) and were sifted for their bioavailability through in vitro dissolution and solubility studies. Moreover, the prepared NPs were evaluated for antimicrobial activity against a battery of bacteria and yeast. Results DSC and XRD studies indicated that the prepared NPs were amorphous in nature, with more solubility and dissolution compared to the crystalline form of this drug. NPs prepared through the EPN method had better results than those prepared using the APSP method. Antimicrobial activities of the NPs were improved compared to the unprocessed drugs, while having comparable activities to standard antimicrobial drugs. Conclusion Results indicate that the NPs have significantly increased solubility, dissolution rate, and antimicrobial activities due to the conversion of crystalline structure into amorphous form. PMID:28553075

Coral reef sediment dissolution: Insights from chamber incubations around the globe

NASA Astrophysics Data System (ADS)

Cyronak, T.; Andersson, A. J.; Eyre, B.

2016-02-01

Ocean acidification (OA) is expected to negatively affect the calcium carbonate (CaCO3) budget of coral reefs by decreasing calcification and increasing CaCO3 dissolution rates. Sediments represent the largest reservoir of CaCO3 in coral reefs and form important habitats above and below the hide tide mark. Results from in situ benthic incubations at different coral reef locations around the world (Australia, Tahiti, Bermuda, Cook Islands, and Hawaii) reveal that there is a general trend between bulk seawater aragonite saturation state (Ωar) and net CaCO3 sediment dissolution rates. Experimental incubations also indicate that the ratio of production to respiration (P/R) in the sediments plays a significant role in CaCO3 dissolution, with high P/R ratios potentially offsetting the effects of human induced OA. This is most likely due to benthic microalgae photosynthesizing and consuming CO2, which produces conditions more favourable for CaCO3 precipitation in sediment pore waters. Despite any interactions with benthic organic metabolism, sediment dissolution could be an order of magnitude more sensitive to OA compared to the process of biogenic calcification. Increases in CaCO3 sediment dissolution under predicted CO2 emissions could shift the net ecosystem calcification (NEC) of coral reefs from net CaCO3 precipitating to net dissolving by the end of this century.

How good is cola for dissolution of gastric phytobezoars?

PubMed

Lee, Beom-Jae; Park, Jong-Jae; Chun, Hoon-Jai; Kim, Ji-Hoon; Yeon, Jong-Eun; Jeen, Yoon-Tae; Kim, Jae-Seon; Byun, Kwan-Soo; Lee, Sang-Woo; Choi, Jae-Hyun; Kim, Chang-Duck; Ryu, Ho-Sang; Bak, Young-Tae

2009-05-14

To evaluate the efficacy of cola treatment for gastric phytobezoars, including diospyrobezoars. A total of 17 patients (range: 48 to 78 years) with symptomatic gastric phytobezoars treated with cola and adjuvant endoscopic therapy were reviewed. Three liters of cola lavage (10 cases) or drink (7 cases) were initially used, and then endoscopic fragmentation was done for the remnant bezoars by using a lithotripsy basket or a polypectomy snare. The overall success of dissolving a gastric phytobezoars with using three liters of cola and the clinical and endoscopic findings were compared retrospectively between four cases of complete dissolution by using only cola and 13 cases of partial dissolution with cola. After 3 L of cola lavage or drinking, a complete dissolution of bezoars was achieved in four patients (23.5%), while 13 cases (76.5%) were only partially dissolved. Phytobezoars (4 of 6 cases) were observed more frequently than diospyrobezoars (0 of 11) in the group that underwent complete dissolution (P = 0.006). Gender, symptom duration, size of bezoar and method of cola administration were not significantly different between the two groups. Twelve of 13 patients with residual bezoars were completely treated with a combination of cola and endoscopic fragmentation. The rate of complete dissolution with three liters of cola was 23.5%, but no case of diospyrobezoar was completely dissolved using this method. However, pretreatment with cola may be helpful and facilitate endoscopic fragmentation of gastric phytobezoars.

Dissolution of cerium(IV)-lanthanide(III) oxides: Comparative effect of chemical composition, temperature, and acidity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Horlait, D.; Clavier, N.; Szenknect, S.

2012-03-15

The dissolution of Ce{sub 1-x}Ln{sub x}O{sub 2-x/2} solid solutions was undertaken in various acid media in order to evaluate the effects of several physicochemical parameters such as chemical composition, temperature, and acidity on the reaction kinetics. The normalized dissolution rates (R{sub L,0}) were found to be strongly modified by the trivalent lanthanide incorporation rate, due to the presence of oxygen vacancies decreasing the samples cohesion. Conversely, the nature of the trivalent cation considered only weakly impacted the R{sub L,0} values. The dependence of the normalized dissolution rates on the temperature then appeared to be of the same order of magnitudemore » than that of chemical composition. Moreover, it allowed determining the corresponding activation energy (E{sub A} ≅ 60-85 kJ.mol{sup -1}) which accounts for a dissolution driven by surface-controlled reactions. A similar conclusion was made regarding the acidity of the solution: the partial order related to (H{sub 3}O{sup +}) reaching about 0.7. Finally, the prevailing effect of the incorporation of aliovalent cations in the fluorite-type CeO{sub 2} matrix on the dissolution kinetics precluded the observation of slight effects such as those linked to the complexing agents or to the crystal structure of the samples. (authors)« less

Computational hydrodynamic comparison of a mini vessel and a USP 2 dissolution testing system to predict the dynamic operating conditions for similarity of dissolution performance.

PubMed

Wang, Bing; Bredael, Gerard; Armenante, Piero M

2018-03-25

The hydrodynamic characteristics of a mini vessel and a USP 2 dissolution testing system were obtained and compared to predict the tablet-liquid mass transfer coefficient from velocity distributions near the tablet and establish the dynamic operating conditions under which dissolution in mini vessels could be conducted to generate concentration profiles similar to those in the USP 2. Velocity profiles were obtained experimentally using Particle Image Velocimetry (PIV). Computational Fluid Dynamics (CFD) was used to predict the velocity distribution and strain rate around a model tablet. A CFD-based mass transfer model was also developed. When plotted against strain rate, the predicted tablet-liquid mass transfer coefficient was found to be independent of the system where it was obtained, implying that a tablet would dissolve at the same rate in both systems provided that the concentration gradient between the tablet surface and the bulk is the same, the tablet surface area per unit liquid volume is identical, and the two systems are operated at the appropriate agitation speeds specified in this work. The results of this work will help dissolution scientists operate mini vessels so as to predict the dissolution profiles in the USP 2, especially during the early stages of drug development. Copyright © 2018 Elsevier B.V. All rights reserved.

Validation of Dissolution Testing with Biorelevant Media: An OrBiTo Study.

PubMed

Mann, James; Dressman, Jennifer; Rosenblatt, Karin; Ashworth, Lee; Muenster, Uwe; Frank, Kerstin; Hutchins, Paul; Williams, James; Klumpp, Lukas; Wielockx, Kristina; Berben, Philippe; Augustijns, Patrick; Holm, Rene; Hofmann, Michael; Patel, Sanjaykumar; Beato, Stefania; Ojala, Krista; Tomaszewska, Irena; Bruel, Jean-Luc; Butler, James

2017-12-04

Dissolution testing with biorelevant media has become widespread in the pharmaceutical industry as a means of better understanding how drugs and formulations behave in the gastrointestinal tract. Until now, however, there have been few attempts to gauge the reproducibility of results obtained with these methods. The aim of this study was to determine the interlaboratory reproducibility of biorelevant dissolution testing, using the paddle apparatus (USP 2). Thirteen industrial and three academic laboratories participated in this study. All laboratories were provided with standard protocols for running the tests: dissolution in FaSSGF to simulate release in the stomach, dissolution in a single intestinal medium, FaSSIF, to simulate release in the small intestine, and a "transfer" (two-stage) protocol to simulate the concentration profile when conditions are changed from the gastric to the intestinal environment. The test products chosen were commercially available ibuprofen tablets and zafirlukast tablets. The biorelevant dissolution tests showed a high degree of reproducibility among the participating laboratories, even though several different batches of the commercially available medium preparation powder were used. Likewise, results were almost identicalbetween the commercial biorelevant media and those produced in-house. Comparing results to previous ring studies, including those performed with USP calibrator tablets or commercially available pharmaceutical products in a single medium, the results for the biorelevant studies were highly reproducible on an interlaboratory basis. Interlaboratory reproducibility with the two-stage test was also acceptable, although the variability was somewhat greater than with the single medium tests. Biorelevant dissolution testing is highly reproducible among laboratories and can be relied upon for cross-laboratory comparisons.

A mechanistic understanding of plagioclase dissolution based on Al occupancy and T-O bond length: from geologic carbon sequestration to ambient conditions.

PubMed

Yang, Yi; Min, Yujia; Jun, Young-Shin

2013-11-14

A quantitative description of how the bulk properties of aluminosilicates affect their dissolution kinetics is important in helping people understand the regulation of atmospheric CO2 concentration by silicate weathering and predict the fate and transport of geologically sequestered CO2 through brine-rock interactions. In this study, we employed a structure model based on the C1 space group to illustrate how differences in crystallographic properties of aluminosilicates, such as T-O (Tetrahedral site-Oxygen) bond length and Al/Si ordering, can result in quantifiable variations in mineral dissolution rates. The dissolution rates of plagioclases were measured under representative geologic carbon sequestration (GCS) conditions (90 °C, 100 atm of CO2, 1.0 M NaCl, and pH ∼ 3.1), and used to validate the model. We found that the logarithm of the characteristic time of the breakdown of Al-O-Si linkages in plagioclases follows a good linear relation with the mineral's aluminum content (nAl). The Si release rates of plagioclases can be calculated based on an assumption of dissolution congruency or on the regularity of Al/Si distribution in the constituent tetrahedra of the mineral. We further extended the application of our approach to scenarios where dissolution incongruency arises because of different linkage reactivities in the solid matrix, and compared the model predictions with published data. The application of our results enables a significant reduction of experimental work for determining the dissolution rates of structurally related aluminosilicates, given a reaction environment.

Aripiprazole-Cyclodextrin Binary Systems for Dissolution Enhancement: Effect of Preparation Technique, Cyclodextrin Type and Molar Ratio

PubMed Central

M. Badr-Eldin, Shaimaa; A. Ahmed, Tarek; R Ismail, Hatem

2013-01-01

Objective(s): The aim of this work was to investigate the effect of the natural and the chemically modified form of cyclodextrins namely; β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) respectively on the solubility and dissolution rate of aripiprazole; an antipsychotic medication showing poor aqueous solubility. Materials and Methods: Phase solubility of aripiprazole with the studied CDs and the complexation efficiency values (CE) which reflect the solubilizing power of the CDs towards the drug was performed. Solid binary systems of aripiprazole with CDs were prepared by kneading, microwave irradiation and freeze-drying techniques at 1:1 and 1:2 (drug to CD) molar ratios. Drug-CD physical mixtures were also prepared in the same molar ratios for comparison. The dissolution of aripiprazole-binary systems was carried out to select the most appropriate CD type, molar ratio and preparation technique. Results: Phase solubility study indicated formation of higher order complexes and the complexation efficiency values was higher for HP-β-CD compared to β-CD. Drug dissolution study revealed that aripiprazole dissolution was increased upon increasing the CD molar ratio and, the freeze-drying technique was superior to the other studied methods especially when combined with the HP-β-CD. The cyclodextrin type, preparation technique and molar ratio exhibited statistically significant effect on the drug dissolution at P≤ 0.05. Conclusion: The freeze-dried system prepared at molar ratio 1:2 (drug: CD) can be considered as efficient tool for enhancing aripiprazole dissolution with the possibility of improving its bioavailability. PMID:24570827

Influence of drug load on dissolution behavior of tablets containing a poorly water-soluble drug: estimation of the percolation threshold.

PubMed

Wenzel, Tim; Stillhart, Cordula; Kleinebudde, Peter; Szepes, Anikó

2017-08-01

Drug load plays an important role in the development of solid dosage forms, since it can significantly influence both processability and final product properties. The percolation threshold of the active pharmaceutical ingredient (API) corresponds to a critical concentration, above which an abrupt change in drug product characteristics can occur. The objective of this study was to identify the percolation threshold of a poorly water-soluble drug with regard to the dissolution behavior from immediate release tablets. The influence of the API particle size on the percolation threshold was also studied. Formulations with increasing drug loads were manufactured via roll compaction using constant process parameters and subsequent tableting. Drug dissolution was investigated in biorelevant medium. The percolation threshold was estimated via a model dependent and a model independent method based on the dissolution data. The intragranular concentration of mefenamic acid had a significant effect on granules and tablet characteristics, such as particle size distribution, compactibility and tablet disintegration. Increasing the intragranular drug concentration of the tablets resulted in lower dissolution rates. A percolation threshold of approximately 20% v/v could be determined for both particle sizes of the API above which an abrupt decrease of the dissolution rate occurred. However, the increasing drug load had a more pronounced effect on dissolution rate of tablets containing the micronized API, which can be attributed to the high agglomeration tendency of micronized substances during manufacturing steps, such as roll compaction and tableting. Both methods that were applied for the estimation of percolation threshold provided comparable values.

Hydrogen Bonding: Between Strengthening the Crystal Packing and Improving Solubility of Three Haloperidol Derivatives.

PubMed

Saluja, Hardeep; Mehanna, Ahmed; Panicucci, Riccardo; Atef, Eman

2016-06-01

The purpose of this study is to confirm the impact of polar functional groups on inter and intra-molecular hydrogen bonding in haloperidol (HP) and droperidol (DP) and, hence, their effects on dissolution using a new approach. To confirm our theory, a new molecule: deshydroxy-haloperidol (DHP) was designed and its synthesis was requested from a contract laboratory. The molecule was then studied and compared to DP and HP. Unlike DHP, both the HP and DP molecules have hydrogen donor groups, therefore, DHP was used to confirm the relative effects of the hydrogen donor group on solubility and crystal packing. The solid dispersions of the three structurally related molecules: HP, DP, and DHP were prepared using PVPK30, and characterized using XRPD and IR. A comparative dissolution study was carried out in aqueous medium. The absence of a hydrogen bonding donor group in DHP resulted in an unexpected increase in its aqueous solubility and dissolution rate from solid dispersion, which is attributed to weaker crystal pack. The increased dissolution rate of HP and DP from solid dispersions is attributed to drug-polymer hydrogen bonding that interferes with the drug-drug intermolecular hydrogen bonding and provides thermodynamic stability of the dispersed drug molecules. The drug-drug intermolecular hydrogen bond is the driving force for precipitation and crystal packing.

Selection by current compliance of negative and positive bipolar resistive switching behaviour in ZrO2-x /ZrO2 bilayer memory

NASA Astrophysics Data System (ADS)

Huang, Ruomeng; Yan, Xingzhao; Morgan, Katrina A.; Charlton, Martin D. B.; (Kees de Groot, C. H.

2017-05-01

We report here a ZrO2-x /ZrO2-based bilayer resistive switching memory with unique properties that enables the selection of the switching mode by applying different electroforming current compliances. Two opposite polarity modes, positive bipolar and negative bipolar, correspond to the switching in the ZrO2 and ZrO2-x layer, respectively. The ZrO2 layer is proved to be responsible for the negative bipolar mode which is also observed in a ZrO2 single layer device. The oxygen deficient ZrO2-x layer plays the dominant role in the positive bipolar mode, which is exclusive to the bilayer memory. A systematic investigation of the ZrO2-x composition in the bilayer memory suggests that ZrO1.8 layer demonstrates optimum switching performance with low switching voltage, narrow switching voltage distribution and good cycling endurance. An excess of oxygen vacancies, beyond this composition, leads to a deterioration of switching properties. The formation and dissolution of the oxygen vacancy filament model has been proposed to explain both polarity switching behaviours and the improved properties in the bilayer positive bipolar mode are attributed to the confined oxygen vacancy filament size within the ZrO2-x layer.

Carbonate mineral dissolution kinetics in high pressure experiments

NASA Astrophysics Data System (ADS)

Dethlefsen, F.; Dörr, C.; Schäfer, D.; Ebert, M.

2012-04-01

The potential CO2 reservoirs in the North German Basin are overlain by a series of Mesozoic barrier rocks and aquifers and finally mostly by Tertiary and Quaternary close-to-surface aquifers. The unexpected rise of stored CO2 from its reservoir into close-to-surface aquifer systems, perhaps through a broken well casing, may pose a threat to groundwater quality because of the acidifying effect of CO2 dissolution in water. The consequences may be further worsening of the groundwater quality due to the mobilization of heavy metals. Buffer mechanisms counteracting the acidification are for instance the dissolution of carbonates. Carbonate dissolution kinetics is comparably fast and carbonates can be abundant in close-to-surface aquifers. The disadvantages of batch experiments compared to column experiments in order to determine rate constants are well known and have for instance been described by v. GRINSVEN and RIEMSDIJK (1992). Therefore, we have designed, developed, tested, and used a high-pressure laboratory column system to simulate aquifer conditions in a flow through setup within the CO2-MoPa project. The calcite dissolution kinetics was determined for CO2-pressures of 6, 10, and 50 bars. The results were evaluated by using the PHREEQC code with a 1-D reactive transport model, applying a LASAGA (1984) -type kinetic dissolution equation (PALANDRI and KHARAKA, 2004; eq. 7). While PALANDRI and KHARAKA (2004) gave calcite dissolution rate constants originating from batch experiments of log kacid = -0.3 and log kneutral = -5.81, the data of the column experiment were best fitted using log kacid = -2.3 and log kneutral = -7.81, so that the rate constants fitted using the lab experiment applying 50 bars pCO2 were approximately 100 times lower than according to the literature data. Rate constants of experiments performed at less CO2 pressure (pCO2 = 6 bars: log kacid = -1.78; log kneutral = -7.29) were only 30 times lower than literature data. These discrepancies in the reaction kinetics should be acknowledged when using reactive transport models, especially when modeling kinetically controlled pH-buffering processes between a CO2 leakage an a receptor like a ground water well. Currently, further experiments for the determination of the dolomite dissolution kinetics are being performed. Here, the knowledge of the dissolution rate constants can be even more important compared to the (still) fast calcite dissolution. This study is being funded by the German Federal Ministry of Education and Research (BMBF), EnBW Energie Baden-Württemberg AG, E.ON Energie AG, E.ON Gas Storage AG, RWE Dea AG, Vattenfall Europe Technology Research GmbH, Wintershall Holding AG and Stadtwerke Kiel AG as part of the CO2-MoPa joint project in the framework of the Special Program GEOTECHNOLOGIEN. Literature Lasaga, A. C., 1984. Chemical Kinetics of Water-Rock Interactions. Journal of Geophysical Research 89, 4009-4025. Palandri, J. L. and Kharaka, Y. K., 2004. A compilation of rate parameters of water-mineral interaction kinetics for application to geochemical modeling. USGS, Menlo Park, CA, USA. v. Grinsven, J. J. M. and Riemsdijk, W. H., 1992. Evaluation of batch and column techniques to measure weathering rates in soils. Geoderma 52, 41-57.

Disintegration/dissolution profiles of copies of Fosamax (alendronate).

PubMed

Epstein, S; Cryer, B; Ragi, S; Zanchetta, J R; Walliser, J; Chow, J; Johnson, M A; Leyes, A E

2003-01-01

Poor quality has been reported for some generics and other copies of original products. We performed a pilot study to compare the disintegration/dissolution profiles of FOSAMAX (alendronate) 70 mg tablets with those of copies of FOSAMAX that were manufactured outside the United States. We used the standard United States Pharmacopeia (USP) disintegration method to evaluate FOSAMAX 70 mg tablets and 13 copies. At least 12 (n = 12) dosage units were tested for each product (except Fosmin, n = 10). The dissolution profiles of FOSAMAX and one representative copy were also compared. Nine copies (Osteomax, Defixal, Fosmin, Endronax, Osteomix, Genalmen, Fixopan, Osteoplus, and Fosval) disintegrated two- to ten-fold faster than FOSAMAX. Three other copies (Neobon, Regenesis, and Ostenan) disintegrated at least five-fold slower than FOSAMAX. Neobon is a softgel capsule, so special consideration was given to this different dosage form. One copy (Arendal) did not fall into either category but exhibited potentially large inter- and intra-lot variability. Dissolution of alendronate from Regenesis lagged behind that from FOSAMAX. Slower disintegration may reduce efficacy because bisphosphonates must be taken in the fasting state and contact with food or even certain beverages severely reduces bioavailability. Faster disintegration (or the use of gel-caps or other alterations to the drug formulation) could increase the risk of esophagitis, an adverse event associated with prolonged contact of the esophagus with bisphosphonates. These disintegration and dissolution results suggest that important differences may exist between FOSAMAX and its copies with regard to bioavailability, pharmacokinetics, and clinical efficacy and safety profiles. Additional testing is warranted to evaluate the pharmacokinetics and clinical safety of these copies.

Dissolution enhancement of chlorzoxazone using cogrinding technique

PubMed Central

Raval, Mihir K.; Patel, Jaydeep M.; Parikh, Rajesh K.; Sheth, Navin R.

2015-01-01

Purpose: The aim of the present work was to improve rate of dissolution and processing parameters of BCS class II drug, chlorzoxazone using cogrinding technique in the presence of different excipients as a carrier. Materials and Methods: The drug was coground with various carriers like polyethylene glycol (PEG 4000), hydroxypropyl methylcellulose (HPMC) E50LV, polyvinylpyrrolidone (PVP)K30, Kaolin and Neusilin US2 using ball mill, where only PEG 4000 improved dissolution rate of drug by bringing amorphization in 1:3 ratio. The coground mixture after 3 and 6 h was evaluated for various analytical, physicochemical and mechanical parameters. Results: The analysis showed conversion of Chlorzoxazone from its crystalline to amorphization form upon grinding with PEG 4000. Coground mixture as well as its directly compressed tablet showed 2.5-fold increment in the dissolution rate compared with pure drug. Directly compressible tablets prepared from pure drug required a large quantity of microcrystalline cellulose (MCC) during compression. The coground mixture and formulation was found stable in nature even after storage (40°C/75% relative humidity). Conclusions: Cogrinding can be successfully utilized to improve the rate of dissolution of poorly water soluble drugs and hence bioavailability. PMID:26682195

Dissolution Rate Enhancement of Repaglinide Using Dietary Fiber as a Promising Carrier.

PubMed

Chatap, Vivekanand K; Patil, Savita D

2016-01-01

In present investigation, an innovative attempt has been made to enhance the solubility and dissolution rate of Repaglinide (RPGD) using hydrothermally treated water insoluble dietary bamboo fibers (HVBF) as potential nutraceutical used in the treatment of diabetes mellitus. RPGD was selected as a model drug due to its low aqueous solubility and dissolution rate. Characterization of HVBF demonstrated the outstanding features like high surface area, maximum drug loading and increase dissolution rate and making HVBF as an excellent drug carrier. RHVBF (Repaglinide loaded HVBF) tablets were prepared using direct compression method. Pre and post-compression parameters for blend and tablets were studied and found within acceptable limits. RHVBF and tablet showed significantly improved dissolution rate, when compared with pure crystalline RPGD, physical mixture, RVBF and commercial marketed tablet. This fact was further supported by FT-IR, DSC, XRPD and FESEM studies followed by in-vitro drug release profile. Stability studies showed no changes after exposing to accelerated conditions for a period of 3 months with respect to physical characteristics and in-vitro drug release studies. In a nut shell, it can be concluded that HVBF is a novel, smart and promising carrier for poorly water soluble drugs, when administered orally.

Ego-Dissolution and Psychedelics: Validation of the Ego-Dissolution Inventory (EDI)

PubMed Central

Nour, Matthew M.; Evans, Lisa; Nutt, David; Carhart-Harris, Robin L.

2016-01-01

Aims: The experience of a compromised sense of “self”, termed ego-dissolution, is a key feature of the psychedelic experience. This study aimed to validate the Ego-Dissolution Inventory (EDI), a new 8-item self-report scale designed to measure ego-dissolution. Additionally, we aimed to investigate the specificity of the relationship between psychedelics and ego-dissolution. Method: Sixteen items relating to altered ego-consciousness were included in an internet questionnaire; eight relating to the experience of ego-dissolution (comprising the EDI), and eight relating to the antithetical experience of increased self-assuredness, termed ego-inflation. Items were rated using a visual analog scale. Participants answered the questionnaire for experiences with classical psychedelic drugs, cocaine and/or alcohol. They also answered the seven questions from the Mystical Experiences Questionnaire (MEQ) relating to the experience of unity with one’s surroundings. Results: Six hundred and ninety-one participants completed the questionnaire, providing data for 1828 drug experiences (1043 psychedelics, 377 cocaine, 408 alcohol). Exploratory factor analysis demonstrated that the eight EDI items loaded exclusively onto a single common factor, which was orthogonal to a second factor comprised of the items relating to ego-inflation (rho = −0.110), demonstrating discriminant validity. The EDI correlated strongly with the MEQ-derived measure of unitive experience (rho = 0.735), demonstrating convergent validity. EDI internal consistency was excellent (Cronbach’s alpha 0.93). Three analyses confirmed the specificity of ego-dissolution for experiences occasioned by psychedelic drugs. Firstly, EDI score correlated with drug-dose for psychedelic drugs (rho = 0.371), but not for cocaine (rho = 0.115) or alcohol (rho = −0.055). Secondly, the linear regression line relating the subjective intensity of the experience to ego-dissolution was significantly steeper for psychedelics (unstandardized regression coefficient = 0.701) compared with cocaine (0.135) or alcohol (0.144). Ego-inflation, by contrast, was specifically associated with cocaine experiences. Finally, a binary Support Vector Machine classifier identified experiences occasioned by psychedelic drugs vs. cocaine or alcohol with over 85% accuracy using ratings of ego-dissolution and ego-inflation alone. Conclusion: Our results demonstrate the psychometric structure, internal consistency and construct validity of the EDI. Moreover, we demonstrate the close relationship between ego-dissolution and the psychedelic experience. The EDI will facilitate the study of the neuronal correlates of ego-dissolution, which is relevant for psychedelic-assisted psychotherapy and our understanding of psychosis. PMID:27378878

Effects of polyphosphates and fluoride on hydroxyapatite dissolution: A pH-stat investigation.

PubMed

do Amaral, Jackeline Gallo; Delbem, Alberto Carlos Botazzo; Pessan, Juliano Pelim; Manarelli, Michele Mauricio; Barbour, Michele E

2016-03-01

This study investigated the immediate and sustained effect of sodium trimetaphosphate (TMP) and sodium hexametaphosphate (HMP) associated or not with fluoride (F) on hydroxyapatite (HA) dissolution using an erosion-like model, considering as well as the influence of salivary coating. Baseline dissolution rates were determined for HA discs using a pH-stat system. In the first set of experiments, HA discs were treated with 1100μgF/mL, 1% or 8% of HMP, 1% or 8% of TMP and 1100μgF/mL associated with 1% or 8% of HMP or TMP, totaling 9 groups (n=8). In a second phase, HA discs were kept in pooled human saliva at 37°C for 2h before treatment with deionised water and 1100μgF/mL associated with 1% or 8% of HMP or TMP, totaling 5 groups (n=8). The post-treatment dissolution rate was determined from three consecutive 30-min assays. Data were analysed using 2 and 3-way ANOVA followed by Fisher and Holm-Sidak methods, respectively (α=0.05). All test solutions promoted reduction in HA dissolution rate when compared to baseline control in the first post-treatment run (p<0.001). However, a synergistic effect was only observed between fluoride and 1% HMP. Moreover, the duration of inhibitory effect was greater when 8% HMP and 1 or 8% HMP associated with F were assessed (p<0.001). The presence of salivary coating led to higher protection for all groups when compared to discs without coating (p<0.001). The reduction of HA dissolution rate, as well as the duration of this effect were influenced by fluoride, type and concentration of phosphate salt and the presence of a salivary coating. Copyright © 2015 Elsevier Ltd. All rights reserved.

Structural and silver/vanadium ratio effects on silver vanadium phosphorous oxide solution formation kinetics: impact on battery electrochemistry.

PubMed

Bock, David C; Takeuchi, Kenneth J; Marschilok, Amy C; Takeuchi, Esther S

2015-01-21

The detailed understanding of non-faradaic parasitic reactions which diminish battery calendar life is essential to the development of effective batteries for use in long life applications. The dissolution of cathode materials including manganese, cobalt and vanadium oxides in battery systems has been identified as a battery failure mechanism, yet detailed dissolution studies including kinetic analysis are absent from the literature. The results presented here provide a framework for the quantitative and kinetic analyses of the dissolution of cathode materials which will aid the broader community in more fully understanding this battery failure mechanism. In this study, the dissolution of silver vanadium oxide, representing the primary battery powering implantable cardioverter defibrillators (ICD), is compared with the dissolution of silver vanadium phosphorous oxide (Ag(w)VxPyOz) materials which were targeted as alternatives to minimize solubility. This study contains the first kinetic analyses of silver and vanadium solution formation from Ag0.48VOPO4·1.9H2O and Ag2VP2O8, in a non-aqueous battery electrolyte. The kinetic results are compared with those of Ag2VO2PO4 and Ag2V4O11 to probe the relationships among crystal structure, stoichiometry, and solubility. For vanadium, significant dissolution was observed for Ag2V4O11 as well as for the phosphate oxide Ag0.49VOPO4·1.9H2O, which may involve structural water or the existence of multiple vanadium oxidation states. Notably, the materials from the SVPO family with the lowest vanadium solubility are Ag2VO2PO4 and Ag2VP2O8. The low concentrations and solution rates coupled with their electrochemical performance make these materials interesting alternatives to Ag2V4O11 for the ICD application.

AFS-2 FLOWSHEET MODIFICATIONS TO ADDRESS THE INGROWTH OF PU(VI) DURING METAL DISSOLUTION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crapse, K.; Rudisill, T.; O'Rourke, P.

2014-07-02

In support of the Alternate Feed Stock Two (AFS-2) PuO{sub 2} production campaign, Savannah River National Laboratory (SRNL) conducted a series of experiments concluding that dissolving Pu metal at 95°C using a 6–10 M HNO{sub 3} solution containing 0.05–0.2 M KF and 0–2 g/L B could reduce the oxidation of Pu(IV) to Pu(VI) as compared to dissolving Pu metal under the same conditions but at or near the boiling temperature. This flowsheet was demonstrated by conducting Pu metal dissolutions at 95°C to ensure that PuO{sub 2} solids were not formed during the dissolution. These dissolution parameters can be used formore » dissolving both Aqueous Polishing (AP) and MOX Process (MP) specification materials. Preceding the studies reported herein, two batches of Pu metal were dissolved in the H-Canyon 6.1D dissolver to prepare feed solution for the AFS-2 PuO{sub 2} production campaign. While in storage, UV-visible spectra obtained from an at-line spectrophotometer indicated the presence of Pu(VI). Analysis of the solutions also showed the presence of Fe, Ni, and Cr. Oxidation of Pu(IV) produced during metal dissolution to Pu(VI) is a concern for anion exchange purification. Anion exchange requires Pu in the +4 oxidation state for formation of the anionic plutonium(IV) hexanitrato complex which absorbs onto the resin. The presence of Pu(VI) in the anion feed solution would require a valence adjustment step to prevent losses. In addition, the presence of Cr(VI) would result in absorption of chromate ion onto the resin and could limit the purification of Pu from Cr which may challenge the purity specification of the final PuO{sub 2} product. Initial experiments were performed to quantify the rate of oxidation of Pu(IV) to Pu(VI) (presumed to be facilitated by Cr(VI)) as functions of the HNO{sub 3} concentration and temperature in simulated dissolution solutions containing Cr, Fe, and Ni. In these simulated Pu dissolutions studies, lowering the temperature from near boiling to 95 °C reduced the oxidation rate of Pu(IV) to Pu(VI). For 8.1 M HNO{sub 3} simulated dissolution solutions, at near boiling conditions >35% Pu(VI) was present in 50 h while at 95 °C <10% Pu(VI) was present at 50 h. At near boiling temperatures, eliminating the presence of Cr and varying the HNO{sub 3} concentration in the range of 7–8.5 M had little effect on the rate of conversion of Pu(IV) to Pu(VI). HNO{sub 3} oxidation of Pu(IV) to Pu(VI) in a pure solution has been reported previously. Based on simulated dissolution experiments, this study concluded that dissolving Pu metal at 95°C using a 6 to 10 M HNO{sub 3} solution 0.05–0.2 M KF and 0–2 g/L B could reduce the rate of oxidation of Pu(IV) to Pu(VI) as compared to near boiling conditions. To demonstrate this flowsheet, two small-scale experiments were performed dissolving Pu metal up to 6.75 g/L. No Pu-containing residues were observed in the solutions after cooling. Using Pu metal dissolution rates measured during the experiments and a correlation developed by Holcomb, the time required to completely dissolve a batch of Pu metal in an H-Canyon dissolver using this flowsheet was estimated to require nearly 5 days (120 h). This value is reasonably consistent with an estimate based on the Batch 2 and 3 dissolution times in the 6.1D dissolver and Pu metal dissolution rates measured in this study and by Rudisill et al. Data from the present and previous studies show that the Pu metal dissolution rate decreases by a factor of approximately two when the temperature decreased from boiling (112 to 116°C) to 95°C. Therefore, the time required to dissolve a batch of Pu metal in an H-Canyon dissolver at 95°C would likely double (from 36 to 54 h) and require 72 to 108 h depending on the surface area of the Pu metal. Based on the experimental studies, a Pu metal dissolution flowsheet utilizing 6–10 M HNO{sub 3} containing 0.05–0.2 M KF (with 0–2 g/L B) at 95°C is recommended to reduce the oxidation of Pu(IV) to Pu(VI) as compared to near boiling conditions. The time required to completely dissolve a batch of Pu metal will increase, however, by approximately a factor of two as compared to initial dissolutions at near boiling (assuming the KF concentration is maintained at nominally 0.1 M). By lowering the temperature to 95°C under otherwise the same operating parameters as previous dissolutions, the Pu(VI) concentration should not exceed 15% after a 120 h heating cycle. Increasing the HNO{sub 3} concentration and lowering Pu concentration are expected to further limit the amount of Pu(VI) formed.« less

High-resolution InSAR constraints on flood-related subsidence and evaporite dissolution along the Dead Sea shores: Interplay between hydrology and rheology

NASA Astrophysics Data System (ADS)

Shviro, Maayan; Haviv, Itai; Baer, Gidon

2017-09-01

Sinkhole generation and land subsidence are commonly attributed to dissolution of subsurface layers by under-saturated groundwater and formation of cavities. Along the Dead Sea (DS) shorelines, this process also involves seasonal flash floods that are drained into the subsurface by existing and newly formed sinkholes. We quantify the contribution of flash-floods to salt dissolution and land subsidence using high-resolution interferometric synthetic aperture radar (InSAR). Subsidence rates during a 3-year period (2012-2015) were calculated from 57 COSMO SkyMed X-band interferograms bracketing major flood events and intra-flood periods in 21 sinkhole sites. The sites are located within channels and alluvial fans along the western shores of the Dead Sea, Israel. The observed subsidence reaches maximum rates of 2.5 mm/day, accumulating in specific sites to 500 mm/year. In most of the sinkhole sites a gradual increase in the annual subsidence rate is observed during the 3-year study period. Three different modes of response to floods were observed: (1) sites where floodwater is not directly channeled into sinkholes do not respond to floods; (2) sites adjacent to active channels with sinkholes are unaffected by specific floods but their subsidence rates increase gradually from early winter to mid-summer, and decay gradually until the following winter; and (3) sites in active channels with sinkholes are characterized by an abrupt increase in subsidence rates immediately after each flood (by a factor of up to 20) and by a subsequent quasi-exponential subsidence decay over periods of several months. In these latter sites, subsidence rates after each flood are temporally correlated with alternating groundwater levels in adjacent boreholes. The rapid rise in groundwater head following floods increases the hydraulic gradient of the under-saturated groundwater and hence also the groundwater discharge and the dissolution rate of the subsurface salt layer. A subsequent quasi-exponential water level drop results in similar deceleration in dissolution and subsidence rates, with a similar characteristic decay time of about 150 days. The observed subsidence decay pattern may also be explained by viscoelastic relaxation of the overburden in response to instantaneously-formed dissolution cavities. Utilizing a Kelvin viscoelastic model, we show that the contribution of this process is most probably < 30% of the total observed subsidence and is sensitive to the sediment mechanical properties. On a broader scale, this study demonstrates how high-resolution InSAR measurements can improve our understanding of subsurface dissolution and subsidence processes and provide independent constraints on the mechanical properties of heterogeneous alluvial sediments.

Effect of N-Methyl Substitution in the Glycine Molecule on the Enthalpy of Dissolution in Mixed Water-Alcohol Solvents at 298.15 K

NASA Astrophysics Data System (ADS)

Badelin, V. G.; Smirnov, V. I.

2018-07-01

The enthalpies of dissolution of N-methylglycine in water + ethanol, water + (1-propanol) and water + (2-propanol) are determined via calorimetry at an alcohol concentration of x 2 = 0-0.25 mole fraction. The standard values of enthalpies of dissolution (Δ_{sol}H°) and transfer (Δ_{tr}H°) of N-methylglycine from water to solution are calculated. The effect the structure and properties of N-methylglycine and the composition of a water-alcohol mixture have on N-methylglycine's enthalpy characteristics is examined. The enthalpy coefficients of pair interactions ( h xy ) between N-methylglycine and alcohol molecules are calculated. They have positive values and grow in the series ethanol (EtOH) < 1-propanol (1-PrOH), < 2-propanol (2-PrOH). A comparative analysis is performed of the enthalpy characteristics of dissolution and transfer of N-methylglycine and the analogous characteristics of glycine and DL-α-alanine in similar mixtures.

Hot-melt extrusion microencapsulation of quercetin for taste-masking.

PubMed

Khor, Chia Miang; Ng, Wai Kiong; Kanaujia, Parijat; Chan, Kok Ping; Dong, Yuancai

2017-02-01

Besides its poor dissolution rate, the bitterness of quercetin also poses a challenge for further development. Using carnauba wax, shellac or zein as the shell-forming excipient, this work aimed to microencapsulate quercetin by hot-melt extrusion for taste-masking. In comparison with non-encapsulated quercetin, the microencapsulated powders exhibited significantly reduced dissolution in the simulated salivary pH 6.8 medium indicative of their potentially good taste-masking efficiency in the order of zein > carnauba wax > shellac. In vitro bitterness analysis by electronic tongue confirmed the good taste-masking efficiency of the microencapsulated powders. In vitro digestion results showed that carnauba wax and shellac-microencapsulated powders presented comparable dissolution rate with the pure quercetin in pH 1.0 (gastric) and 6.8 (intestine) medium; while zein-microencapsulated powders exhibited a remarkably slower dissolution rate. Crystallinity of quercetin was slightly reduced after microencapsulation while its chemical structure remained unchanged. Hot-melt extrusion microencapsulation could thus be an attractive technique to produce taste-masked bioactive powders.

Behavior of bubbles in glassmelts. III - Dissolution and growth of a rising bubble containing a single gas

NASA Technical Reports Server (NTRS)

Onorato, P. I. K.; Weinberg, M. C.; Uhlmann, D. R.

1981-01-01

Finite difference solutions of the mass transport equations governing the dissolution (growth) of a rising gas bubble, containing a single gas, in a glassmelt were obtained. These solutions were compared with those obtained from an approximate procedure for a range of the controlling parameters. Applications were made to describe various aspects of O2 and CO2 gas-bubble behavior in a soda-lime-silicate melt.

Preventing Vision Loss from Blast Injuries with Regenerative Biomaterial

DTIC Science & Technology

2011-12-01

photorefractive keratectomy ( PRK ) procedure, which can be used to monitor epithelial healing rates. It was shown that the curved silk film bandage could...dissolution time on epithelial regeneration The PRK injury model was utilized to assess the rabbit cornea’s initial response to the application of the silk...dissolution time as compared to trial 1 within water. The PRK debridement procedure was performed and tracked over time with fluorescein staining. The films

21 CFR 314.53 - Submission of patent information.

Code of Federal Regulations, 2014 CFR

2014-04-01

... pharmaceutical equivalence and comparable product stability; and (v) Comparative in vitro dissolution testing on... copy, to the Central Document Room, Center for Drug Evaluation and Research, Food and Drug...

21 CFR 314.53 - Submission of patent information.

Code of Federal Regulations, 2012 CFR

2012-04-01

... pharmaceutical equivalence and comparable product stability; and (v) Comparative in vitro dissolution testing on... copy, to the Central Document Room, Center for Drug Evaluation and Research, Food and Drug...

21 CFR 314.53 - Submission of patent information.

Code of Federal Regulations, 2013 CFR

2013-04-01

... pharmaceutical equivalence and comparable product stability; and (v) Comparative in vitro dissolution testing on... copy, to the Central Document Room, Center for Drug Evaluation and Research, Food and Drug...

21 CFR 314.53 - Submission of patent information.

Code of Federal Regulations, 2010 CFR

2010-04-01

... pharmaceutical equivalence and comparable product stability; and (v) Comparative in vitro dissolution testing on... copy, to the Central Document Room, Center for Drug Evaluation and Research, Food and Drug...

21 CFR 314.53 - Submission of patent information.

Code of Federal Regulations, 2011 CFR

2011-04-01

... pharmaceutical equivalence and comparable product stability; and (v) Comparative in vitro dissolution testing on... copy, to the Central Document Room, Center for Drug Evaluation and Research, Food and Drug...

A probabilistic assessment of calcium carbonate export and dissolution in the modern ocean

NASA Astrophysics Data System (ADS)

Battaglia, Gianna; Steinacher, Marco; Joos, Fortunat

2016-05-01

The marine cycle of calcium carbonate (CaCO3) is an important element of the carbon cycle and co-governs the distribution of carbon and alkalinity within the ocean. However, CaCO3 export fluxes and mechanisms governing CaCO3 dissolution are highly uncertain. We present an observationally constrained, probabilistic assessment of the global and regional CaCO3 budgets. Parameters governing pelagic CaCO3 export fluxes and dissolution rates are sampled using a Monte Carlo scheme to construct a 1000-member ensemble with the Bern3D ocean model. Ensemble results are constrained by comparing simulated and observation-based fields of excess dissolved calcium carbonate (TA*). The minerals calcite and aragonite are modelled explicitly and ocean-sediment fluxes are considered. For local dissolution rates, either a strong or a weak dependency on CaCO3 saturation is assumed. In addition, there is the option to have saturation-independent dissolution above the saturation horizon. The median (and 68 % confidence interval) of the constrained model ensemble for global biogenic CaCO3 export is 0.90 (0.72-1.05) Gt C yr-1, that is within the lower half of previously published estimates (0.4-1.8 Gt C yr-1). The spatial pattern of CaCO3 export is broadly consistent with earlier assessments. Export is large in the Southern Ocean, the tropical Indo-Pacific, the northern Pacific and relatively small in the Atlantic. The constrained results are robust across a range of diapycnal mixing coefficients and, thus, ocean circulation strengths. Modelled ocean circulation and transport timescales for the different set-ups were further evaluated with CFC11 and radiocarbon observations. Parameters and mechanisms governing dissolution are hardly constrained by either the TA* data or the current compilation of CaCO3 flux measurements such that model realisations with and without saturation-dependent dissolution achieve skill. We suggest applying saturation-independent dissolution rates in Earth system models to minimise computational costs.

In Silico Modeling Approach for the Evaluation of Gastrointestinal Dissolution, Supersaturation, and Precipitation of Posaconazole.

PubMed

Hens, Bart; Pathak, Shriram M; Mitra, Amitava; Patel, Nikunjkumar; Liu, Bo; Patel, Sanjaykumar; Jamei, Masoud; Brouwers, Joachim; Augustijns, Patrick; Turner, David B

2017-12-04

The aim of this study was to evaluate gastrointestinal (GI) dissolution, supersaturation, and precipitation of posaconazole, formulated as an acidified (pH 1.6) and neutral (pH 7.1) suspension. A physiologically based pharmacokinetic (PBPK) modeling and simulation tool was applied to simulate GI and systemic concentration-time profiles of posaconazole, which were directly compared with intraluminal and systemic data measured in humans. The Advanced Dissolution Absorption and Metabolism (ADAM) model of the Simcyp Simulator correctly simulated incomplete gastric dissolution and saturated duodenal concentrations of posaconazole in the duodenal fluids following administration of the neutral suspension. In contrast, gastric dissolution was approximately 2-fold higher after administration of the acidified suspension, which resulted in supersaturated concentrations of posaconazole upon transfer to the upper small intestine. The precipitation kinetics of posaconazole were described by two precipitation rate constants, extracted by semimechanistic modeling of a two-stage medium change in vitro dissolution test. The 2-fold difference in exposure in the duodenal compartment for the two formulations corresponded with a 2-fold difference in systemic exposure. This study demonstrated for the first time predictive in silico simulations of GI dissolution, supersaturation, and precipitation for a weakly basic compound in part informed by modeling of in vitro dissolution experiments and validated via clinical measurements in both GI fluids and plasma. Sensitivity analysis with the PBPK model indicated that the critical supersaturation ratio (CSR) and second precipitation rate constant (sPRC) are important parameters of the model. Due to the limitations of the two-stage medium change experiment the CSR was extracted directly from the clinical data. However, in vitro experiments with the BioGIT transfer system performed after completion of the in silico modeling provided an almost identical CSR to the clinical study value; this had no significant impact on the PBPK model predictions.

Jarosite dissolution rates in perchlorate brine

NASA Astrophysics Data System (ADS)

Legett, Carey; Pritchett, Brittany N.; Elwood Madden, Andrew S.; Phillips-Lander, Charity M.; Elwood Madden, Megan E.

2018-02-01

Perchlorate salts and the ferric sulfate mineral jarosite have been detected at multiple locations on Mars by both landed instruments and orbiting spectrometers. Many perchlorate brines have eutectic temperatures <250 K, and may exist as metastable or stable liquids for extended time periods, even under current Mars surface conditions. Therefore, jarosite-bearing rocks and sediments may have been altered by perchlorate brines. Here we measured jarosite dissolution rates in 2 M sodium perchlorate brine as well as dilute water at 298 K to determine the effects of perchlorate anions on jarosite dissolution rates and potential reaction products. We developed a simple method for determining aqueous iron concentrations in high salinity perchlorate solutions using ultraviolet-visible spectrophotometry that eliminates the risk of rapid oxidation reactions during analyses. Jarosite dissolution rates in 2 M perchlorate brine determined by iron release rate (2.87 × 10-12 ±0.85 × 10-12 mol m-2 s-1) were slightly slower than the jarosite dissolution rate measured in ultrapure (18.2 MΩ cm-1) water (5.06 × 10-12 mol m-2 s-1) using identical methods. No additional secondary phases were observed in XRD analyses of the reaction products. The observed decrease in dissolution rate may be due to lower activity of water (ɑH2O = 0.9) in the 2 M NaClO4 brine compared with ultrapure water (ɑH2O = 1). This suggests that the perchlorate anion does not facilitate iron release, unlike chloride anions which accelerated Fe release rates in previously reported jarosite and hematite dissolution experiments. Since dissolution rates are slower in perchlorate-rich solutions, jarosite is expected to persist longer in perchlorate brines than in dilute waters or chloride-rich brines. Therefore, if perchlorate brines dominate aqueous fluids on the surface of Mars, jarosite may remain preserved over extended periods of time, despite active aqueous processes.

Monitoring carbonate dissolution using spatially resolved under-sampled NMR propagators and MRI

NASA Astrophysics Data System (ADS)

Sederman, A. J.; Colbourne, A.; Mantle, M. D.; Gladden, L. F.; Oliveira, R.; Bijeljic, B.; Blunt, M. J.

2017-12-01

The dissolution of a porous rock matrix by an acidic flow causes a change in the pore structure and consequently the pattern of fluid flow and rock permeability. This process is relevant to many areas of practical relevance such as enhanced oil recovery, water contaminant migration and sequestration of supercritical CO2. The most important governing factors for the type of change in the pore space are related by the Péclet (Pe) and Damköhler (Da) dimensionless numbers; these compare the transport properties of the fluid in the porous medium with the reactive properties of the solid matrix and the incident fluid respectively. Variation in Pe and Da can cause very different evolution regimes of the pore space and flow can occur, ranging from a uniform dissolution through different "wormholing" regimes (shown on the left hand side of figure 1) to face dissolution. NMR has a unique capability of measuring both the flow and structural changes during such dissolution whilst the characteristics of flow in the highly heterogeneous matrix that is formed can be predicted by the CTRW modelling approach. Here, NMR measurements of displacement probability distributions, or propagators, have been used to monitor the evolution of fluid flow during a reactive dissolution rock core floods. Developments in the NMR method by undersampling the acquisition data enable spatially resolved measurements of the propagators to be done at sufficient displacement resolution and in a timescale that is short enough to capture the changes in structure and flow. The highly under-sampled (4%) data, which typically reduces the acquisition time from 2 hours to 6 minutes, has been shown to produce equivalent propagator results to the fully sampled experiment. Combining these propagator measurements with quantitative and fast imaging techniques a full time-resolved picture of the dissolution reaction is built up. Experiments have been done for both Ketton and Estaillades carbonate rock cores, which exhibit very different dissolution behaviours, and for which experiments and model comparisons will be shown.

The Effect of Ultrafine Process on the Dissolution, Antibacterial Activity, and Cytotoxicity of Coptidis rhizoma

PubMed Central

Jiang, Zhen-Yu; Deng, Hai-Ying; Yu, Zhi-Jun; Ni, Jun-Yan; Kang, Si-He

2016-01-01

Background: The dosage of herb ultrafine particle (UFP) depended on the increased level of its dissolution, toxicity, and efficacy. Objective: The dissolution, antibacterial activity, and cytotoxicity of Coptidis rhizoma (CR) UFP were compared with those of traditional decoction (TD). Materials and Methods: The dissolution of berberine (BBR) of CR TD and UFP was determined by high-performance liquid chromatography. The antibacterial activity of CR extract was assayed by plate-hole diffusion and broth dilution method; the inhibitory effect of rat serums against bacteria growth was evaluated after orally given CR UFP or TD extract. The cytotoxicity of CR extract was evaluated by 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide assay. Results: The dissolution amount of BBR from CR UFP increased 6–8-folds in comparison to TD at 2 min, the accumulative amount of BBR in both UFP and TD group increased in a time-dependent manner. The minimal inhibitory concentrations and minimal bactericidal concentrations of CR UFP extract decreased to 1/2~1/4 of those of TD extract. The inhibitory effect of rat serums against bacteria growth decreased time-dependently, and no statistical difference was observed between two groups at each time point. The 50% cytotoxic concentrations of UFP extract increased 1.66~1.97 fold than those of TD. Conclusions: The antibacterial activity and cytotoxicity of CR UFP increased in a dissolution-effect manner in vitro, the increased level of cytotoxicity was lower than that of antibacterial activity, and the inhibitory effect of rat serums containing drugs of UFP group did not improve. SUMMARY Ultrafine grinding process caused a rapid increase of BBR dissolution from CR.The antibacterial activity and cytotoxicity of UFP extract in vitro increased in a dissolution-effect manner, but the cytotoxicity increased lower than the antibacterial activity.The antibacterial activity of rat serums of UFP group did not improve in comparison to that of TD group PMID:26941540

Physico-Chemical Properties, Aerosolization and Dissolution of Co-Spray Dried Azithromycin Particles with L-Leucine for Inhalation

PubMed Central

Mangal, Sharad; Nie, Haichen; Xu, Rongkun; Guo, Rui; Cavallaro, Alex; Zemlyanov, Dmitry; Zhou, Qi (Tony)

2018-01-01

Purpose Inhalation therapy is popular to treat lower respiratory tract infections. Azithromycin is effective against some bacteria that cause respiratory tract infections; but it has poor water solubility that may limit its efficacy when administrated as inhalation therapy. In this study, dry powder inhaler formulations were developed by co-spray drying azithromycin with L-leucine with a purpose to improve dissolution. Methods The produced powder formulations were characterized regarding particle size, morphology, surface composition and in-vitro aerosolization performance. Effects of L-leucine on the solubility and in-vitro dissolution of azithromycin were also evaluated. Results The spray dried azithromycin alone formulation exhibited a satisfactory aerosol performance with a fine particle fraction (FPF) of 62.5 ± 4.1%. Addition of L-leucine in the formulation resulted in no significant change in particle morphology and FPF, which can be attributed to enrichment of azithromycin on the surfaces of composite particles. Importantly, compared with the spray-dried amorphous azithromycin alone powder, the co-spray dried powder formulations of azithromycin and L-leucine demonstrated a substantially enhanced in-vitro dissolution rate. Such enhanced dissolution of azithromycin could be attributed to the formation of composite system and the acidic microenvironment around azithromycin molecules created by the dissolution of acidic L-leucine in the co-spray dried powder. Fourier transform infrared spectroscopic data showed intermolecular interactions between azithromycin and L-leucine in the co-spray dried formulations. Conclusions We developed the dry powder formulations with satisfactory aerosol performance and enhanced dissolution for a poorly water soluble weak base, azithromycin, by co-spray drying with an amino acid, L-leucine. PMID:29374368

Physico-Chemical Properties, Aerosolization and Dissolution of Co-Spray Dried Azithromycin Particles with L-Leucine for Inhalation.

PubMed

Mangal, Sharad; Nie, Haichen; Xu, Rongkun; Guo, Rui; Cavallaro, Alex; Zemlyanov, Dmitry; Zhou, Qi Tony

2018-01-08

Inhalation therapy is popular to treat lower respiratory tract infections. Azithromycin is effective against some bacteria that cause respiratory tract infections; but it has poor water solubility that may limit its efficacy when administrated as inhalation therapy. In this study, dry powder inhaler formulations were developed by co-spray drying azithromycin with L-leucine with a purpose to improve dissolution. The produced powder formulations were characterized regarding particle size, morphology, surface composition and in-vitro aerosolization performance. Effects of L-leucine on the solubility and in-vitro dissolution of azithromycin were also evaluated. The spray dried azithromycin alone formulation exhibited a satisfactory aerosol performance with a fine particle fraction (FPF) of 62.5 ± 4.1%. Addition of L-leucine in the formulation resulted in no significant change in particle morphology and FPF, which can be attributed to enrichment of azithromycin on the surfaces of composite particles. Importantly, compared with the spray-dried amorphous azithromycin alone powder, the co-spray dried powder formulations of azithromycin and L-leucine demonstrated a substantially enhanced in-vitro dissolution rate. Such enhanced dissolution of azithromycin could be attributed to the formation of composite system and the acidic microenvironment around azithromycin molecules created by the dissolution of acidic L-leucine in the co-spray dried powder. Fourier transform infrared spectroscopic data showed intermolecular interactions between azithromycin and L-leucine in the co-spray dried formulations. We developed the dry powder formulations with satisfactory aerosol performance and enhanced dissolution for a poorly water soluble weak base, azithromycin, by co-spray drying with an amino acid, L-leucine.

A kinetic rate model for crystalline basalt dissolution at temperature and pressure conditions relevant for geologic CO2 sequestration

NASA Astrophysics Data System (ADS)

Pollyea, R.; Rimstidt, J. D.

2016-12-01

Geologic carbon sequestration in terrestrial basalt reservoirs is predicated on permanent CO2 trapping through CO2-water-rock dissolution reactions followed by carbonate precipitation. Bench-scale experiments have shown these reaction paths to be rapid, occurring on a timescale 100 - 102 years. Moreover, recent results from the CarbFix basalt sequestration pilot project in Iceland demonstrate >95% CO2 isolation two years after a small-scale injection. In order to assess the viability of basalt sequestration worldwide (e.g., Deccan Traps, Columbia Plateau, etc.), flexible simulation tools are required that distill the dissolution reactions into a user-friendly format that is readily transmissible to existing reactive transport numerical simulators. In the present research, we combine experimental results extant in the literature for Icelandic basalt to develop kinetic rate models describing the pH-dependent dissolution of (1) basaltic glass and (2) an aggregate mineral assemblage for crystalline basalt comprising olivine, pyroxene, and plagioclase phases. In order to utilize these kinetic rate models with numerical simulation, a thermodynamic solubility model for each phase is developed for use with the reactive transport simulation code, TOUGHREACT. We use reactive transport simulation in a simple 1-D reactor to compare dissolution of the aggregate crystalline basalt phase with the traditional formulation comprising individual mineral phases for the crystalline basalt. Simulation results are in general agreement, illustrating the efficacy of this simplified approach for modeling basalt dissolution at temperature and pressure conditions typical of geologic CO2 reservoirs. Moreover, this approach may be of value to investigators seeking dissolution models for crystalline basalt in other mafic provinces.

The preparation and evaluation of salt forms of linogliride with reduced solubilities as candidates for extended release.

PubMed

Chrzanowski, Frank A; Ahmad, Kaleem

2017-03-01

Salts of linogliride with reduced solubilities were prepared and evaluated as potential candidates for extended-release oral dosage forms. A once-daily dose of 300-800 mg was intended. Seven acids were selected: p-acetamidobenzoic, benzoic, p-hydroxybenzoic, 3-hydroxy-2-naphthoic, 1-napsylic, pamoic, and p-toluenesulfonic acids but only four salts were able to be prepared in suitable quantities for evaluation: linogliride pamoate, p-hydroxybenzoate, 3-hydroxy-2-naphthoate, and 1-napsylate. The pH-solubility profiles of the four new salts, free base, and fumarate salt were compared over the pH 1.43-8.3 range and the intrinsic dissolution rates of the four new salts and the free base were determined at pH 1.43, 4.4, and 7.5. The range of the pH-solubility profile and intrinsic dissolution rates of the p-hydroxybenzoate salt were less than the free base and fumarate and higher than the other three new salts. The pH-solubilities and intrinsic dissolution rates of the 1-napsylate salt were pH-independent. The solubilities and intrinsic dissolution rates of the pamoate and 3-hydroxy-2-naphthoate were higher at pH 1.4-3.4 than at higher pH. At pH 4.4 and higher, the solubilities were essentially the same, in the 1-2 mg/mL range. The intrinsic dissolution rates were also very low and not very different. Dissolution studies with capsules containing 800 mg doses of the pamoate, 1-napsylate, free base, and fumarate performed in a dissolution medium of pH beginning at 2.2 and ending at 6.8 demonstrated that the pamoate and 1-napsylate salt forms dissolved slower and could be useful as extended-release forms.

Tissue dissolution by a novel multisonic ultracleaning system and sodium hypochlorite.

PubMed

Haapasalo, Markus; Wang, Zhejun; Shen, Ya; Curtis, Allison; Patel, Payal; Khakpour, Mehrzad

2014-08-01

This study aimed to evaluate the effectiveness of a novel Multisonic Ultracleaning System (Sonendo Inc, Laguna Hills, CA) in tissue dissolution in comparison with conventional irrigation devices. Pieces of bovine muscle tissue (68 ± 2 mg) were placed in 0.7-mL test tubes (height: 23.60 mm, inner diameter: 6.00 mm, outer diameter: 7.75 mm) and exposed to 5 minutes of irrigation by different devices. Endodontic devices included the Multisonic Ultracleaning System, the Piezon Master 700 (EMS, Dallas, TX) ultrasonic system with agitation, the EndoVac negative-pressure irrigation system (SybronEndo, Orange, CA), and a conventional positive-pressure 27-G irrigation needle at a flow rate of 10 mL/min. The systems were tested with 0.5%, 3%, and 6% sodium hypochlorite (NaOCl) at room temperature (21°C) as well as 40°C. Irrigation with sterile water was used as a control. The mass of tissue specimens was measured and recorded before and after the use of each device, and if the specimen was completely dissolved visually within 5 minutes, the dissolution time was recorded. The rate of tissue dissolution (%/s) was then calculated. The Multisonic Ultracleaning System had the fastest rate of tissue dissolution (P < .05), at 1.0% ± 0.1% per second using 0.5% NaOCl, 2.3% ± 0.9% per second using 3% NaOCl, and 2.9% ± 0.7% per second using 6% NaOCl. This tissue dissolution rate was more than 8 times greater than the second fastest device tested (P < .01), the Piezon Master 700 ultrasonic system, which resulted in a tissue dissolution rate of 0.328% ± 0.002% per second using 6% NaOCl at 40°C. For all irrigation devices tested, the rate of tissue dissolution increased with a higher concentration and temperature of the NaOCl solution. The novel Multisonic Ultracleaning System achieved a significantly faster tissue dissolution rate when compared with the other systems examined in vitro. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Size exclusion chromatography-gradients, an alternative approach to polymer gradient chromatography: 2. Separation of poly(meth)acrylates using a size exclusion chromatography-solvent/non-solvent gradient.

PubMed

Schollenberger, Martin; Radke, Wolfgang

2011-10-28

A gradient ranging from methanol to tetrahydrofuran (THF) was applied to a series of poly(methyl methacrylate) (PMMA) standards, using the recently developed concept of SEC-gradients. Contrasting to conventional gradients the samples eluted before the solvent, i.e. within the elution range typical for separations by SEC, however, the high molar mass PMMAs were retarded as compared to experiments on the same column using pure THF as the eluent. The molar mass dependence on retention volume showed a complex behaviour with a nearly molar mass independent elution for high molar masses. This molar mass dependence was explained in terms of solubility and size exclusion effects. The solubility based SEC-gradient was proven to be useful to separate PMMA and poly(n-butyl crylate) (PnBuA) from a poly(t-butyl crylate) (PtBuA) sample. These samples could be separated neither by SEC in THF, due to their very similar hydrodynamic volumes, nor by an SEC-gradient at adsorbing conditions, due to a too low selectivity. The example shows that SEC-gradients can be applied not only in adsorption/desorption mode, but also in precipitation/dissolution mode without risking blocking capillaries or breakthrough peaks. Thus, the new approach is a valuable alternative to conventional gradient chromatography. Copyright © 2011 Elsevier B.V. All rights reserved.

Effect of drug loading method against the dissolution mechanism of encapsulated amoxicillin trihidrate drug in matrix of semi-IPN chitosan-poly (N-vinyl pyrrolidone) hydrogel with pore forming agent CaCO3

NASA Astrophysics Data System (ADS)

Nurjannah, Yanah; Budianto, Emil

2018-04-01

Heliobacter pylori (H.pylori) is a type of bacteria that causes inflammation in the lining of the stomach. The treatment of the bacterial infection by using conventional medicine which is amoxicillin trihidrate has a very short retention time in the stomach which is about 1-1,5 hours. Floating drug delivery system is expected to have a long retention time in the stomach so the efficiency of drug can be achieved. In this study, has been synthesized matrix of semi-IPN chitosan-Poly(N-vinil pyrrolidone) hydrogel with a pore-forming agent of CaCO3 under optimum conditions. Amoxicillin is encapsulated in a matrix hydrogel to be applied as a floating drug delivery system by in situ loading and post loading methods. The encapsulation efficiency and dissolution of in situ loading and post loading hydrogels are performed in vitro on gastric pH. In situ loading hydrogel shows higer percentage of encapsulation efficiency and dissolution compared to post loading hydrogel. The encapsulation efficiency of in situ and post loading hydrogels were 92,1% and 89,4%, respectively. The aim of drug dissolution by mathematical equation model is to know kinetics and the mecanism of dissolution. The kinetics release of in situ hydrogel tends to follow first order kinetics, while the post loading hydrogel follow the Higuchi model. The dissolution mecanism of hydrogels is erosion.

Effects of growth and dissolution on the fractionation of silicon isotopes by estuarine diatoms

NASA Astrophysics Data System (ADS)

Sun, Xiaole; Olofsson, Martin; Andersson, Per S.; Fry, Brian; Legrand, Catherine; Humborg, Christoph; Mörth, Carl-Magnus

2014-04-01

Studies of silicon (Si) isotope fractionation during diatom growth in open ocean systems have documented lower Si isotopic values (δ30Si) in the biogenic silica of diatom frustules compared to dissolved silicon. Recent findings also indicate that Si isotope fractionation occurs during dissolution of diatom frustules, producing higher δ30Si values in the remaining biogenic silica. This study focuses on diatoms from high production areas in estuarine and coastal areas that represent approximately 30-50% of the global marine primary production. Two species of diatoms, Thalassiosira baltica and Skeletonema marinoi, were isolated from the brackish Baltic Sea, one of the largest estuarine systems in the world. These species were used for laboratory investigations of Si isotope fractionation during diatom growth and the subsequent dissolution of the diatom frustules. Both species of diatoms give an identical Si isotope fractionation factor during growth of -1.50 ± 0.36‰ (2σ) for 30Si, which falls in the range of -2.09‰ to -0.55‰ of published data. Our results also suggest a dissolution-induced Si isotope fractionation factor of -0.86‰ at early stage of dissolution, but this effect was observed only in DSi and no significant Si isotope change was observed for BSi. The growth and dissolution results are applied to a Baltic Sea sediment core to reconstruct DSi utilization by diatoms, and found to be in agreement with the observed DSi uptake rates in the overlying water column during diatom growth.

Influence of Concentration and Agitation of Sodium Hypochlorite and Peracetic Acid Solutions on Tissue Dissolution.

PubMed

Tanomaru-Filho, Mário; Silveira, Bruna Ramos Franco; Martelo, Roberta Bosso; Guerreiro-Tanomaru, Juliane Maria

2015-11-01

To evaluated the tissue dissolution of sodium hypochlorite (NaOCl) and peracetic acid (PA) solutions at different concentrations, with or without ultrasonic agitation. The following solutions were analyzed: 2.5% NaOCl, 0.5, 1 and 2% PA, 1% PA associated with 6.5% hydrogen peroxide (HP) and saline. Fragments of bovine pulp tissue with 25 ± 2g mg were immersed into test tubes containing 4 mL of the solutions for 10 minutes. In the groups with agitation, pulp tissues were submitted to 2 cycles of 1 minute of ultrasonic agitation. The specimens were weighed after the removal from the solutions. The percentage of mass loss was calculated according to the difference of mass before and after exposure to solutions. Data were submitted to ANOVA and Tukey tests (p < 0.05). A total of 2.5% NaOCl with or without agitation showed the higher tissue dissolution (between 64.5 and 67% of mass reduction) (p < 0.005). By comparing the PA solutions, the concentrations of 1 and 2% with or without agitation and the concentration of 0.5% with agitation showed similar dissolution activity (between 35.4 and 44% of mass reduction). The use of the ultrasonic agitation promoted an increase of the dissolution ability only for 0.5% PA. Peracetic acid solution has pulp tissue dissolution. However, this ability is lower than 2.5% NaOCl solution. The sodium hypochlorite solution shows higher ability to dissolve tissue than PA.

Effect of pulmonary surfactant on the dissolution, stability and uptake of zinc oxide nanowires by human respiratory epithelial cells

PubMed Central

Theodorou, Ioannis G.; Ruenraroengsak, Pakatip; Gow, Andrew; Schwander, Stephan; Zhang, Junfeng (Jim); Chung, Kian Fan; Tetley, Teresa D.; Ryan, Mary P.; Porter, Alexandra E.

2017-01-01

Inhaled nanoparticles have high deposition rates in the alveolar region of the lung but the effects of pulmonary surfactant (PS) on nanoparticle bioreactivity are unclear. Here, the impact of PS on the stability and dissolution of ZnO nanowires (ZnONWs) was investigated, and linked with their bioreactivity in vitro with human alveolar epithelial type 1-like cells (TT1). Pre-incubation of ZnONWs with Curosurf® (a natural porcine PS) decreased their dissolution at acidic pH, through the formation of a phospholipid corona. Confocal live cell microscopy confirmed that Curosurf® lowered intracellular dissolution, thus delaying the onset of cell death compared to bare ZnONWs. Despite reducing dissolution, Curosurf® significantly increased the uptake of ZnONWs within TT1 cells, ultimately increasing their toxicity after 24h. Although serum, improved ZnONW dispersion in suspension similar to Curosurf®, it had no effect on ZnONW internalization and toxicity, indicating a unique role of PS in promoting particle uptake. In the absence of PS, ZnONW length had no effect on dissolution kinetics or degree of cellular toxicity, indicating a less important role of length in determining ZnONW bioreactivity. This work provides unique findings on the effects of PS on the stability and toxicity of ZnONWs, which could be important in the study of pulmonary toxicity and epithelial-endothelial translocation of nanoparticles in general. PMID:27441789

Naproxen Microparticulate Systems Prepared Using In Situ Crystallisation and Freeze-Drying Techniques.

PubMed

Solaiman, Amanda; Tatari, Adam Keenan; Elkordy, Amal Ali

2017-07-01

Poor drug solubility and dissolution rate remain to be one of the major problems facing pharmaceutical scientists, with approximately 40% of drugs in the industry categorised as practically insoluble or poorly water soluble. This in turn can lead to serious delivery challenges and poor bioavailability. The aim of this research was to investigate the effects of the surfactants, poloxamer 407 (P407) and caprol® PGE 860 (CAP), at various concentrations (0.1, 0.5, 1 and 3% w/v) on the enhancement of the dissolution properties of poorly water-soluble drug, naproxen, using in situ micronisation by solvent change method and freeze-drying. The extent at which freeze-drying influences the dissolution rate of naproxen microcrystals is investigated in this study by comparison with desiccant-drying. All formulations were evaluated and characterised using particle size analysis and morphology, in vitro dissolution studies, differential scanning calorimetry (DSC), and Fourier transform infra-red (FT-IR) spectroscopy. An increase in poloxamer 407 concentration in freeze-dried formulations led to enhancement of drug dissolution compared to desiccator-dried formulations, naproxen/caprol® PGE 860 formulations and untreated drug. DSC and FT-IR results show no significant chemical interactions between drug and poloxamer 407, with only very small changes to drug crystallinity. On the other hand, caprol® PGE 860 showed some interactions with drug components, alterations to the crystal lattice of naproxen, and poor dissolution profiles using both drying methods, making it a poor choice of excipient.

How good is cola for dissolution of gastric phytobezoars?

PubMed Central

Lee, Beom Jae; Park, Jong-Jae; Chun, Hoon Jai; Kim, Ji Hoon; Yeon, Jong Eun; Jeen, Yoon Tae; Kim, Jae Seon; Byun, Kwan Soo; Lee, Sang Woo; Choi, Jae Hyun; Kim, Chang Duck; Ryu, Ho Sang; Bak, Young-Tae

2009-01-01

AIM: To evaluate the efficacy of cola treatment for gastric phytobezoars, including diospyrobezoars. METHODS: A total of 17 patients (range: 48 to 78 years) with symptomatic gastric phytobezoars treated with cola and adjuvant endoscopic therapy were reviewed. Three liters of cola lavage (10 cases) or drink (7 cases) were initially used, and then endoscopic fragmentation was done for the remnant bezoars by using a lithotripsy basket or a polypectomy snare. The overall success of dissolving a gastric phytobezoars with using three liters of cola and the clinical and endoscopic findings were compared retrospectively between four cases of complete dissolution by using only cola and 13 cases of partial dissolution with cola. RESULTS: After 3 L of cola lavage or drinking, a complete dissolution of bezoars was achieved in four patients (23.5%), while 13 cases (76.5%) were only partially dissolved. Phytobezoars (4 of 6 cases) were observed more frequently than diospyrobezoars (0 of 11) in the group that underwent complete dissolution (P = 0.006). Gender, symptom duration, size of bezoar and method of cola administration were not significantly different between the two groups. Twelve of 13 patients with residual bezoars were completely treated with a combination of cola and endoscopic fragmentation. CONCLUSION: The rate of complete dissolution with three liters of cola was 23.5%, but no case of diospyrobezoar was completely dissolved using this method. However, pretreatment with cola may be helpful and facilitate endoscopic fragmentation of gastric phytobezoars. PMID:19437568

Application of carrier and plasticizer to improve the dissolution and bioavailability of poorly water-soluble baicalein by hot melt extrusion.

PubMed

Zhang, Yilan; Luo, Rui; Chen, Yi; Ke, Xue; Hu, Danrong; Han, Miaomiao

2014-06-01

The objective of this study was to develop a suitable formulation for baicalein (a poorly water-soluble drug exhibiting high melting point) to prepare solid dispersions using hot melt extrusion (HME). Proper carriers and plasticizers were selected by calculating the Hansen solubility parameters, evaluating melting processing condition, and measuring the solubility of obtained melts. The characteristic of solid dispersions prepared by HME was evaluated. The dissolution performance of the extrudates was compared to the pure drug and the physical mixtures. Physicochemical properties of the extrudates were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). Relative bioavailability after oral administration in beagle dogs was assessed. As a result, Kollidon VA64 and Eudragit EPO were selected as two carriers; Cremophor RH was used as the plasticizer. The dissolution of all the extrudates was significantly improved. DSC and PXRD results suggested that baicalein in the extrudates was amorphous. FTIR spectroscopy revealed the interaction between drug and polymers. After oral administration, the relative bioavailability of solid dispersions with VA64 and EPO was comparative, about 2.4- and 2.9-fold greater compared to the pure drug, respectively.

Evaluating scale-up rules of a high-shear wet granulation process.

PubMed

Tao, Jing; Pandey, Preetanshu; Bindra, Dilbir S; Gao, Julia Z; Narang, Ajit S

2015-07-01

This work aimed to evaluate the commonly used scale-up rules for high-shear wet granulation process using a microcrystalline cellulose-lactose-based low drug loading formulation. Granule properties such as particle size, porosity, flow, and tabletability, and tablet dissolution were compared across scales using scale-up rules based on different impeller speed calculations or extended wet massing time. Constant tip speed rule was observed to produce slightly less granulated material at the larger scales. Longer wet massing time can be used to compensate for the lower shear experienced by the granules at the larger scales. Constant Froude number and constant empirical stress rules yielded granules that were more comparable across different scales in terms of compaction performance and tablet dissolution. Granule porosity was shown to correlate well with blend tabletability and tablet dissolution, indicating the importance of monitoring granule densification (porosity) during scale-up. It was shown that different routes can be chosen during scale-up to achieve comparable granule growth and densification by altering one of the three parameters: water amount, impeller speed, and wet massing time. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Let's stay together? Intrinsic and extrinsic factors involved in pair bond dissolution in a recolonizing wolf population.

PubMed

Milleret, Cyril; Wabakken, Petter; Liberg, Olof; Åkesson, Mikael; Flagstad, Øystein; Andreassen, Harry Peter; Sand, Håkan

2017-01-01

For socially monogamous species, breeder bond dissolution has important consequences for population dynamics, but the extent to which extrinsic or intrinsic population factors causes pair dissolution remain poorly understood, especially among carnivores. Using an extensive life-history data set, a survival analysis and competing risks framework, we examined the fate of 153 different wolf (Canis lupus) pairs in the recolonizing Scandinavian wolf population, during 14 winters of snow tracking and DNA monitoring. Wolf pair dissolution was generally linked to a mortality event and was strongly affected by extrinsic (i.e. anthropogenic) causes. No divorce was observed, and among the pair dissolution where causes have been identified, death of one or both wolves was always involved. Median time from pair formation to pair dissolution was three consecutive winters (i.e. approximately 2 years). Pair dissolution was mostly human-related, primarily caused by legal control actions (36·7%), verified poaching (9·2%) and traffic-related causes (2·1%). Intrinsic factors, such as disease and age, accounted for only 7·7% of pair dissolutions. The remaining 44·3% of dissolution events were from unknown causes, but we argue that a large portion could be explained by an additional source of human-caused mortality, cryptic poaching. Extrinsic population factors, such as variables describing the geographical location of the pair, had a stronger effect on risk of pair dissolution compared to anthropogenic landscape characteristics. Population intrinsic factors, such as the inbreeding coefficient of the male pair member, had a negative effect on pair bond duration. The mechanism behind this result remains unknown, but might be explained by lower survival of inbred males or more complex inbreeding effects mediated by behaviour. Our study provides quantitative estimates of breeder bond duration in a social carnivore and highlights the effect of extrinsic (i.e. anthropogenic) and intrinsic factors (i.e. inbreeding) involved in wolf pair bond duration. Unlike the effects of intrinsic and extrinsic factors that are commonly reported on individual survival or population growth, here we provide quantitative estimates of their potential effect on the social unit of the population, the wolf pair. © 2016 The Authors. Journal of Animal Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Society.

Reactive Transport at the Pore Scale with Applications to the Dissolution of Carbonate Rocks for CO2 Sequestration Operations

NASA Astrophysics Data System (ADS)

Boek, E.; Gray, F.; Welch, N.; Shah, S.; Crawshaw, J.

2014-12-01

In CO2 sequestration operations, CO2 injected into a brine aquifer dissolves in the liquid to create an acidic solution. This may result in dissolution of the mineral grains in the porous medium. Experimentally, it is hard to investigate this process at the pore scale. Therefore we develop a new hybrid particle simulation algorithm to study the dissolution of solid objects in a laminar flow field, as encountered in porous media flow situations. First, we calculate the flow field using a multi-relaxation-time lattice Boltzmann (LB) algorithm implemented on GPUs, which demonstrates a very efficient use of the GPU device and a considerable performance increase over CPU calculations. Second, using a stochastic particle approach, we solve the advection-diffusion equation for a single reactive species and dissolve solid voxels according to our reaction model. To validate our simulation, we first calculate the dissolution of a solid sphere as a function of time under quiescent conditions. We compare with the analytical solution for this problem [1] and find good agreement. Then we consider the dissolution of a solid sphere in a laminar flow field and observe a significant change in the sphericity with time due to the coupled dissolution - flow process. Second, we calculate the dissolution of a cylinder in channel flow in direct comparison with corresponding dissolution experiments. We discuss the evolution of the shape and dissolution rate. Finally, we calculate the dissolution of carbonate rock samples at the pore scale in direct comparison with micro-CT experiments. This work builds on our recent research on calculation of multi-phase flow [2], [3] and hydrodynamic dispersion and molecular propagator distributions for solute transport in homogeneous and heterogeneous porous media using LB simulations [4]. It turns out that the hybrid simulation model is a suitable tool to study reactive flow processes at the pore scale. This is of great importance for CO2 storage and Enhanced Oil Recovery applications. References[1] Rice, R. G. and Do, D.D., Chem. Eng. Sci., 61, 775-778 (2006)[2] Boek, E.S. and Venturoli, M., Comp. and Maths with Appl. 59, 2305-2314 (2010)[3] Yang, J. and Boek, E.S., Comp. and Maths with Appl. 65, 882-890 (2013)[4] Yang, J. Crawshaw, J. and Boek, E.S., Water Resources Research 49, 8531-8538 (2013)

A New Extrudable Form of Hypromellose: AFFINISOL™ HPMC HME.

PubMed

Huang, Siyuan; O'Donnell, Kevin P; Keen, Justin M; Rickard, Mark A; McGinity, James W; Williams, Robert O

2016-02-01

Hypromellose is a hydrophilic polymer widely used in immediate- and modified-release oral pharmaceutical dosage forms. However, currently available grades of hypromellose are difficult, if not impossible, to process by hot melt extrusion (HME) because of their high glass transition temperature, high melt viscosity, and low degradation temperature. To overcome these challenges, a modified grade of hypromellose, AFFINISOL™ HPMC HME, was recently introduced. It has a significantly lower glass transition temperature and melt viscosity as compared to other available grades of hypromellose. The objective of this paper is to assess the extrudability and performance of AFFINISOL™ HPMC HME (100LV and 4M) as compared to other widely used polymers in HME, including HPMC 2910 100cP (the currently available hypromellose), Soluplus®, Kollidon® VA 64, and EUDRAGIT® E PO. Formulations containing polymer and carbamazepine (CBZ) were extruded on a co-rotating 16-mm twin-screw extruder, and the effect of temperature, screw speed, and feed rate was investigated. The performance of the solid dispersions was evaluated based on Flory-Huggins modeling and characterized by differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), Raman spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, and dissolution. All formulations extruded well except for HPMC 2910 100cP, which resulted in over-torqueing the extruder (machine overloading because the motor cannot provide efficient energy to rotate the shaft). Among the HME extrudates, only the EUDRAGIT® E PO formulation was crystalline as confirmed by DSC, XRD, and Raman, which agreed with predictions from Flory-Huggins modeling. Dissolution testing was conducted under both sink and non-sink conditions. Sink dissolution testing in neutral media revealed that amorphous CBZ in the HME extrudates completely dissolved within 15 min, which was much more rapid than the time for complete dissolution of bulk CBZ (60 min) and EUDRAGIT® E PO solid dispersion (more than 6 h). Non-sink dissolution in acidic media testing revealed that only CBZ contained in the AFFINISOL™ HPMC HME, and EUDRAGIT® E PO solid dispersions rapidly supersaturated after 15 min, reaching a twofold drug concentration compared to the CBZ equilibrium solubility. In summary, AFFINISOL™ HPMC HME 100LV and AFFINISOL™ HPMC HME 4M are useful in the pharmaceutical HME process to increase wetting and dissolution properties of poorly water-soluble drugs like CBZ.

Tissue dissolution by sodium hypochlorite: effect of concentration, temperature, agitation, and surfactant.

PubMed

Stojicic, Sonja; Zivkovic, Slavoljub; Qian, Wei; Zhang, Hui; Haapasalo, Markus

2010-09-01

Sodium hypochlorite is the most commonly used endodontic irrigant because of its antimicrobial and tissue-dissolving activity. The aim of this study was to evaluate and compare the effects of concentration, temperature, and agitation on the tissue-dissolving ability of sodium hypochlorite. In addition, a hypochlorite product with added surface active agent was compared with conventional hypochlorite solutions. Three sodium hypochlorite solutions from two different manufacturers in concentrations of 1%, 2%, 4%, and 5.8% were tested at room temperature, 37 degrees C, and 45 degrees C with and without agitation by ultrasonic and sonic energy and pipetting. Distilled and sterilized tap water was used as controls. Pieces of bovine muscle tissue (68 +/- 3 mg) were placed in 10 mL of each solution for five minutes. In selected samples, agitation was performed for one, two, or four 15-second periods per each minute. The tissue specimens were weighed before and after treatment, and the percentage of weight loss was calculated. The contact angle on dentin of the three solutions at concentrations of 1% and 5.8% was measured. Weight loss (dissolution) of the tissue increased almost linearly with the concentration of sodium hypochlorite. Higher temperatures and agitation considerably enhanced the efficacy of sodium hypochlorite. The effect of agitation on tissue dissolution was greater than that of temperature; continuous agitation resulted in the fastest tissue dissolution. Hypochlorite with added surface active agent had the lowest contact angle on dentin and was most effective in tissue dissolution in all experimental situations. Optimizing the concentration, temperature, flow, and surface tension can improve the tissue-dissolving effectiveness of hypochlorite even 50-fold. Copyright 2010 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Comparative evaluation of human pulp tissue dissolution by different concentrations of chlorine dioxide, calcium hypochlorite and sodium hypochlorite: An in vitro study

PubMed Central

Taneja, Sonali; Mishra, Neha; Malik, Shubhra

2014-01-01

Introduction: Irrigation plays an indispensable role in removal of tissue remnants and debris from the complicated root canal system. This study compared the human pulp tissue dissolution by different concentrations of chlorine dioxide, calcium hypochlorite and sodium hypochlorite. Materials and Methods: Pulp tissue was standardized to a weight of 9 mg for each sample. In all,60 samples obtained were divided into 6 groups according to the irrigating solution used- 2.5% sodium hypochlorite (NaOCl), 5.25% NaOCl, 5% calcium hypochlorite (Ca(OCl)2), 10% Ca(OCl)2, 5%chlorine dioxide (ClO2) and 13% ClO2. Pulp tissue was placed in each test tube carrying irrigants of measured volume (5ml) according to their specified subgroup time interval: 30 minutes (Subgroup A) and 60 minutes (Subgroup B). The solution from each sample test tube was filtered and was left for drying overnight. The residual weight was calculated by filtration method. Results: Mean tissue dissolution increases with increase in time period. Results showed 5.25% NaOCl to be most effective at both time intervals followed by 2.5% NaOCl at 60 minutes, 10%Ca(OCl)2 and 13% ClO2 at 60 minutes. Least amount of tissue dissolving ability was demonstrated by 5% Ca(OCl)2 and 5% ClO2 at 30 minutes. Distilled water showed no pulp tissue dissolution. Conclusion: Withinthe limitations of the study, NaOCl most efficiently dissolved the pulp tissue at both concentrations and at both time intervals. Mean tissue dissolution by Ca(OCl)2 and ClO2 gradually increased with time and with their increase in concentration. PMID:25506141

Tissue dissolution ability of sodium hypochlorite activated by photon-initiated photoacoustic streaming technique.

PubMed

Guneser, Mehmet Burak; Arslan, Dilara; Usumez, Aslihan

2015-05-01

The aim of this study was to evaluate the effect of the photon-initiated photoacoustic streaming (PIPS) technique on the pulp tissue-dissolving capacity of sodium hypochlorite (NaOCl) and compare it with the EndoActivator System (Dentsply Tulsa Dental Specialties, Tulsa, OK) and the Er:YAG laser with an endodontic fiber tip. Bovine pulp tissue samples (45 ± 15 mg) and dentin powder (10 mg) were placed in 1.5-mL Eppendorf tubes with 1 mL 5.25% NaOCl (Wizard; Rehber Kimya, Istanbul, Turkey) or distilled water (control) for 5 minutes with activation by the EndoActivator System, the Er:YAG laser with an endodontic fiber tip, and the PIPS technique. Nonactivated NaOCl served as the positive control. All testing procedures were performed at room temperature. The tissue samples were weighed before and after treatment, and the percentage of weight loss was calculated. The differences were statistically analyzed. The highest rate of tissue dissolution was observed in the NaOCl + Er:YAG group (P < .05). The NaOCl + PIPS group dissolved more bovine pulp tissue than the nonactivated NaOCl group (P < .05). There was no statistically significant difference between the rates of tissue dissolution of the NaOCl + EA and the nonactivated NaOCl groups (P > .05). NaOCl activation with the Er:YAG laser with an endodontic fiber tip was the most effective in bovine pulp tissue dissolution. The PIPS technique also promoted superior tissue-dissolving effects when compared with no activation. However, the EndoActivator System had no direct effect on tissue dissolution. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

[Comparison of dissolution profile and plasma concentration-time profile of the thalidomide formulations made by Japanese, Mexican and British companies].

PubMed

Fujita, Yukiyoshi; Yamamoto, Koujirou; Aomori, Tohru; Murakami, Hirokazu; Horiuchi, Ryuya

2008-10-01

Thalidomide is an important advance in the treatment of multiple myeloma. In Japan thalidomide is now on the approval step for the treatment of multiple myeloma. The drug has some bothersome side effects such as defect of organogenesis, neuropathy, constipation and fatigue, but is likely more effective than standard chemotherapy and is changing multiple myeloma treatment. At this moment, Japanese patients must import the thalidomide preparations from Mexico, Britain and elsewhere, but after approval, they patients will be able to get the new Japanese thalidomide capsules. In order to determine appropriate amounts of Japanese thalidomide capsules in the treatment of multiple myeloma, we compared the dissolution profile and plasma thalidomide concentrations of Japanese and British capsules and Mexican tablets. The dissolution test was performed according to the Japanese and the United States Pharmacopoeia. The pharmacokinetic data for Japanese capsules were obtained from the clinical trial in Japanese subjects and compared with those data published for other formulations. The dissolution rate of the Japanese capsule was the fastest, followed by British and Mexican formulations. The pharmacokinetic profiles of Japanese and British capsules were similar, while the 100 mg Japanese thalidomide capsule demonstrated a 1.6-fold higher maximum plasma concentration than the 200 mg Mexican thalidomide tablet (1.7 vs. 1.1 microg/ml), greatly shortened t(max) (4.5 vs. 6.2 h), and the apparent half life was only one-third of the Mexican tablet (4.8 vs. 13.5 h). A comparison of the dissolution and the pharmacokinetic absorption profiles demonstrated a rank-order correlation. Physicians and pharmacists should be aware of the probable alteration in plasma thalidomide concentration when switching to the Japanese capsule, especially from the Mexican tablet, and should monitor clinical response carefully.

Formulation and Pharmacokinetic Evaluation of Polymeric Dispersions Containing Valsartan.

PubMed

Chella, Naveen; Daravath, Bhaskar; Kumar, Dinesh; Tadikonda, Rama Rao

2016-10-01

Valsartan exhibits poor aqueous solubility and dissolution rate limited absorption. The lower solubility in the upper part of gastrointestinal tract (pH-dependant solubility) where its absorption window exists further contributes to the low oral bioavailability of valsartan. The present work was aimed to improve the in vivo pharmacokinetics of valsartan by preparing amorphous polymeric dispersions using Eudragit E 100 as carrier. Eudragit E 100 is a cationic polymer soluble in gastric fluid up to pH 5.0 and exhibits pH-dependent release. Hence, the dispersions prepared using Eudragit E 100 rapidly dissolves at lower pH presenting drug in molecularly dispersed and soluble form at its absorption site. Polymeric solid dispersions were prepared in different drug-to-carrier ratios. The prepared dispersions were evaluated for drug-carrier interactions, solid-state transitions and drug-release properties with the help of Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and in vitro dissolution studies. The optimized formulation containing valsartan was tested in rats for bioavailability and pharmacokinetic parameters and compared with that of valsartan pure drug. The results from FTIR studies indicated no interactions between drug and excipients. DSC studies confirmed reduction in crystallinity of drug. The dissolution studies performed in 0.1 N HCl showed significant improvement (p < 0.05) in the dissolution of valsartan. In vivo pharmacokinetic studies showed 199 % relative bioavailability with significant improvement (p < 0.05) in area under the curve compared to valsartan pure drug. Eudragit E 100 can be used to improve the dissolution of drugs that show low solubility at lower pH and thereby enhancing the bioavailability.

Reactive Transport Models with Geomechanics to Mitigate Risks of CO2 Utilization and Storage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deo, Milind; Huang, Hai; Kweon, Hyukmin

2016-03-28

Reactivity of carbon dioxide (CO 2), rocks and brine is important in a number of practical situations in carbon dioxide sequestration. Injectivity of CO 2 will be affected by near wellbore dissolution or precipitation. Natural fractures or faults containing specific minerals may reactivate leading to induced seismicity. In this project, we first examined if the reactions between CO 2, brine and rocks affect the nature of the porous medium and properties including petrophysical properties in the timeframe of the injection operations. This was done by carrying out experiments at sequestration conditions (2000 psi for corefloods and 2400 psi for batchmore » experiments, and 600°C) with three different types of rocks – sandstone, limestone and dolomite. Experiments were performed in batch mode and corefloods were conducted over a two-week period. Batch experiments were performed with samples of differing surface area to understand the impact of surface area on overall reaction rates. Toughreact, a reactive transport model was used to interpret and understand the experimental results. The role of iron in dissolution and precipitation reactions was observed to be significant. Iron containing minerals – siderite and ankerite dissolved resulting in changes in porosity and permeability. Corefloods and batch experiments revealed similar patterns. With the right cationic balance, there is a possibility of precipitation of iron bearing carbonates. The results indicate that during injection operations mineralogical changes may lead to injectivity enhancements near the wellbore and petrophysical changes elsewhere in the system. Limestone and dolomite cores showed consistent dissolution at the entrance of the core. The dissolution led to formation of wormholes and interconnected dissolution zones. Results indicate that near wellbore dissolution in these rock-types may lead to rock failure. Micro-CT images of the cores before and after the experiments revealed that an initial high-permeability pathway facilitated the formation of wormholes. The peak cation concentrations and general trends were matched using Toughreact. Batch reactor modeling showed that the geometric factors obtained using powder data that related effective surface area to the BET surface area had to be reduced for fractured samples and cores. This indicates that the available surface area in consolidated samples is lower than that deduced from powder experiments. Field-scale modeling of reactive transport and geomechanics was developed in parallel at Idaho National Laboratory. The model is able to take into account complex chemistry, and consider interactions of natural fractures and faults. Poroelastic geomechanical considerations are also included in the model.« less

Water-rock interaction and geochemistry of groundwater from the Ain Azel aquifer, Algeria.

PubMed

Belkhiri, Lazhar; Mouni, Lotfi; Tiri, Ammar

2012-02-01

Hydrochemical, multivariate statistical, and inverse geochemical modeling techniques were used to investigate the hydrochemical evolution within the Ain Azel aquifer, Algeria. Cluster analysis based on major ion contents defined 3 main chemical water types, reflecting different hydrochemical processes. The first group water, group 1, has low salinity (mean EC = 735 μS/cm). The second group waters are classified as Cl-HCO(3)-alkaline earth type. The third group is made up of water samples, the cation composition of which is dominated by Ca and Mg with anion composition varying from dominantly Cl to dominantly HCO(3) plus SO(4). The varifactors obtained from R-mode FA indicate that the parameters responsible for groundwater quality variations are mainly related to the presence and dissolution of some carbonate, silicate, and evaporite minerals in the aquifer. Inverse geochemical modeling along groundwater flow paths indicates the dominant processes are the consumption of CO(2), the dissolution of dolomite, gypsum, and halite, along with the precipitation of calcite, Ca-montmorillonite, illite, kaolinite, and quartz. © Springer Science+Business Media B.V. 2011

Dissolution and bioavailability enhancement of alpha-asarone by solid dispersions via oral administration.

PubMed

Deng, Li; Wang, Yu; Gong, Tao; Sun, Xun; Zhang, Zhi-Rong

2017-11-01

Alpha (α)-asarone (1-propenyl-2,4,5-methoxybenzol) (ARE) has been extensively used to treat chronic obstructive pulmonary diseases (COPD), bronchial asthma, pneumonia, and epilepsy. Due to its poor solubility and bioavailability, ARE was clinically administered via intravenous injection. However, severe allergies were often reported due to the presence of solublizers in the injection formulation. In our study, we sought to explore the biopharmaceutical classification of ARE, elucidate the mechanisms behind ARE absorption, and to develop a viable formulation to improve the oral bioavailability of ARE. ARE was not a P-glycoprotein substrate, which was absorbed in the passive mode without site specificity in the gastrointestinal tract. Solid dispersions prepared using hydrophilic matrix materials such as Pluronic F68, and polyethylene glycol (PEG) of varying molecular weights (PEG4K, PEG10K, and PEG20K) were proven to significantly improve the dissolution of ARE in vitro and the oral bioavailability of ARE in rats, which represent a promising strategy for the oral administration of ARE and other BCS II compounds.

Calorimetric Investigation of Thermal Stability of 304H Cu (Fe-17.7Cr-9.3Ni-2.95Cu-0.91Mn-0.58Nb-0.24Si-0.1C-0.12N-Wt Pct) Austenitic Stainless Steel

NASA Astrophysics Data System (ADS)

Tripathy, Haraprasanna; Subramanian, Raju; Hajra, Raj Narayan; Rai, Arun Kumar; Rengachari, Mythili; Saibaba, Saroja; Jayakumar, Tammana

2016-12-01

The sequence of phase instabilities that take place in a Fe-17.7Cr-9.3Ni-0.58Nb-2.95Cu-0.12N (wt pct) austenitic stainless steel (304H Cu grade) as a function of temperature has been investigated using dynamic calorimetry. The results obtained from this investigation are supplemented by Thermocalc-based equilibrium and Scheil-Gulliver nonequilibrium solidification simulation. The following phase transformation sequence is found upon slow cooling from liquid: L → L + γ → L + γ + MX → γ + MX + δ → γ +MX + M23C6 → γ + MX + M23C6 + Cu. Under slow cooling, the solidification follows austenite + ferrite (AF) mode, which is in accordance with Thermocalc prediction and Scheil-Gulliver simulation. However, higher cooling rates result in skeletal δ-ferrite formation, due to increased segregation tendency of Nb and Cr to segregate to interdendritic liquid. The solidification mode is found to depend on combined Nb + Cu content. Experimental estimates of enthalpy change associated with melting and secondary phase precipitation are also obtained. In addition a semi-quantitative study on the dissolution kinetics of M23C6 type carbides has also been investigated. The standard solution treatment at 1413 K (1140 °C) is found to be adequate to dissolve both Cu and M23C6 into γ-austenite; but the complete dissolution of MX type carbonitrides occurs near the melting region.

The effect of electrolytes on dolomite dissolution: nanoscale observations using in situ Atomic Force Microscopy

NASA Astrophysics Data System (ADS)

Urosevic, Maja; Ruiz-Agudo, Encarnacion; Putnis, Christine V.; Cardell, Carolina; Rodriguez-Navarro, Carlos; Putnis, Andrew

2010-05-01

Dissolution of carbonate minerals is one of the main chemical reactions occurring at shallow levels in the crust of the Earth and has a paramount importance for a wide range of geological and biological processes. Calcite (CaCO3), and to a lesser extent dolomite (CaMg(CO3)2), are the major carbonate minerals in sedimentary rocks and building stone materials. The dissolution of calcite has been thoroughly investigated over a range of conditions and solution compositions. In contrast, dolomite dissolution studies have been traditionally hampered by its low reaction rates compared to calcite and its poorly constrained relationship between cation ordering and reactivity (Morse and Arvidson, 2002). Yet important questions like the so-called 'dolomite problem' (e.g. Higgins and Hu, 2005) remain unresolved and more experimental work is needed in order to understand the role of other dissolved species, such as soluble salts, on the kinetics and mechanism of dolomite dissolution and precipitation. We have explored the effect of different electrolytes on the dissolution rate of dolomite by using in situ Atomic Force Microcopy (AFM). Experiments were carried out by passing alkali halide, nitrate and sulfate salt solutions (NaCl, KCl, LiCl, NaI, NaNO3 and Na2SO4) with different ionic strengths (IS = 10-3, 10-2 and 10-1) over dolomite {1014} cleavage surfaces. We show that all electrolytes tested enhance dolomite dissolution. Moreover, the morphology and density of etch pits are controlled by the presence of different ions in solution. The etch pit spreading rate and dolomite dissolution rate depend on both (1) the nature of the electrolyte and (2) the ionic strength. This is in agreement with recent experimental studies on calcite dissolution (Ruiz-Agudo et al., 2010). This study highlights the role of electrolytes in dolomite dissolution and points to a common behavior for carbonate minerals. Our results suggest that soluble salts may play a critical role in the weathering of carbonate rocks, both in the natural environment, as well as in stone buildings and statuary, where the amount of solutes in pore waters is significant and can vary depending on evaporation and condensation phenomena. References Higgins, S.R.; Hu, X. Self-limiting growth on dolomite: Experimental observations with in situ atomic force microscopy. Geochimica et Cosmochimica Acta, 2005, 69 (8), 2085-2094. Morse, J.W.; Arvidson, R.S. The dissolution kinetics of major sedimentary carbonate minerals. Earth-Science Reviews, 2002, 58, 51-84. Ruiz-Agudo, E.; Kowacz, M.; Putnis, C.V.; Putnis, A. The role of background electrolytes on the kinetics and mechanism of calcite dissolution. Geochimica et Cosmochimica Acta, 2010, 74, 1256-1267.

Dissolution of Lipid-Based Matrices in Simulated Gastrointestinal Solutions to Evaluate Their Potential for the Encapsulation of Bioactive Ingredients for Foods.

PubMed

Raymond, Yves; Champagne, Claude P

2014-01-01

The goal of the study was to compare the dissolution of chocolate to other lipid-based matrices suitable for the microencapsulation of bioactive ingredients in simulated gastrointestinal solutions. Particles having approximately 750 μm or 2.5 mm were prepared from the following lipid-based matrices: cocoa butter, fractionated palm kernel oil (FPKO), chocolate, beeswax, carnauba wax, and paraffin. They were added to solutions designed to simulate gastric secretions (GS) or duodenum secretions (DS) at 37°C. Paraffin, carnauba wax, and bees wax did not dissolve in either the GS or DS media. Cocoa butter, FPKO, and chocolate dissolved in the DS medium. Cocoa butter, and to a lesser extent chocolate, also dissolved in the GS medium. With chocolate, dissolution was twice as fast as that with small particles (750 μm) as compared to the larger (2.5 mm) ones. With 750 μm particle sizes, 90% dissolution of chocolate beads was attained after only 60 minutes in the DS medium, while it took 120 minutes for 70% of FPKO beads to dissolve in the same conditions. The data are discussed from the perspective of controlled release in the gastrointestinal tract of encapsulated ingredients (minerals, oils, probiotic bacteria, enzymes, vitamins, and peptides) used in the development of functional foods.

Alternative Chemical Cleaning Methods for High Level Waste Tanks: Actual Waste Testing with SRS Tank 5F Sludge

DOE Office of Scientific and Technical Information (OSTI.GOV)

King, William D.; Hay, Michael S.

Solubility testing with actual High Level Waste tank sludge has been conducted in order to evaluate several alternative chemical cleaning technologies for the dissolution of sludge residuals remaining in the tanks after the exhaustion of mechanical cleaning and sludge sluicing efforts. Tests were conducted with archived Savannah River Site (SRS) radioactive sludge solids that had been retrieved from Tank 5F in order to determine the effectiveness of an optimized, dilute oxalic/nitric acid cleaning reagent toward dissolving the bulk non-radioactive waste components. Solubility tests were performed by direct sludge contact with the oxalic/nitric acid reagent and with sludge that had beenmore » pretreated and acidified with dilute nitric acid. For comparison purposes, separate samples were also contacted with pure, concentrated oxalic acid following current baseline tank chemical cleaning methods. One goal of testing with the optimized reagent was to compare the total amounts of oxalic acid and water required for sludge dissolution using the baseline and optimized cleaning methods. A second objective was to compare the two methods with regard to the dissolution of actinide species known to be drivers for SRS tank closure Performance Assessments (PA). Additionally, solubility tests were conducted with Tank 5 sludge using acidic and caustic permanganate-based methods focused on the “targeted” dissolution of actinide species.« less

Laboratory Experiments and Modeling of Pooled NAPL Dissolution in Porous Media

NASA Astrophysics Data System (ADS)

Copty, N. K.; Sarikurt, D. A.; Gokdemir, C.

2017-12-01

The dissolution of non-aqueous phase liquids (NAPLs) entrapped in porous media is commonly modeled at the continuum scale as the product of a chemical potential and an interphase mass transfer coefficient, the latter expressed in terms of Sherwood correlations that are related to flow and porous media properties. Because of the lack of precise estimates of the interface area separating the NAPL and aqueous phase, numerous studies have lumped the interfacial area into the interphase mass transfer coefficient. In this paper controlled dissolution experiments from a pooled NAPL were conducted. The immobile NAPL mass is placed at the bottom of a flow cell filled with porous media with water flowing on top. Effluent aqueous phase concentrations were measured for a wide range of aqueous phase velocities and for two types of porous media. To interpret the experimental results, a two-dimensional pore network model of the NAPL dissolution was developed. The well-defined geometry of the NAPL-water interface and the observed effluent concentrations were used to compute best-fit mass transfer coefficients and non-lumped Sherwood correlations. Comparing the concentrations predicted with the pore network model to simple previously used one-dimensional analytic solutions indicates that the analytic model which ignores the transverse dispersion can lead to over-estimation of the mass transfer coefficient. The predicted Sherwood correlations are also compared to previously published data and implications on NAPL remediation strategies are discussed.

Differential dissolution of Lake Baikal diatoms: correction factors and implications for palaeoclimatic reconstruction

NASA Astrophysics Data System (ADS)

Battarbee, Richard W.; Mackay, A. W.; Jewson, D. H.; Ryves, D. B.; Sturm, M.

2005-04-01

In order to assess how faithfully the composition of diatom assemblages in the recent sediments of Lake Baikal represents the composition of the planktonic diatom populations in the lake, we have compared the flux of diatoms from the water column (i.e., "expected" in the sediment) with the accumulation rates of the same diatom taxa (i.e., "observed" in the sediment) from BAIK 38, a sediment core collected in the south basin of the lake. Whilst there are many uncertainties, the results indicate that only approximately 1% of the phytoplankton crop is preserved in the sediment and some species are more affected by dissolution than others. These findings are comparable to similar studies undertaken in the marine environment. In terms of differential dissolution, our studies suggest that the endemic taxa (e.g., Cyclotella minuta and Aulacoseira baicalensis) are the most resilient, whereas cosmopolitan taxa such as Nitzschia acicularis and Synedra acus are the least resilient. N. acicularis dissolves in the water column, but for other taxa, most dissolution takes place at the surface sediment-water interface. We use the data to develop a series of species-specific correction factors that allow the composition of the source populations to be reconstituted, and we argue that failure to take these processes into account can undermine the use of the diatom and biogenic silica record in Lake Baikal for palaeo-productivity and palaeoclimate reconstruction.

Dissolution of Lipid-Based Matrices in Simulated Gastrointestinal Solutions to Evaluate Their Potential for the Encapsulation of Bioactive Ingredients for Foods

PubMed Central

Champagne, Claude P.

2014-01-01

The goal of the study was to compare the dissolution of chocolate to other lipid-based matrices suitable for the microencapsulation of bioactive ingredients in simulated gastrointestinal solutions. Particles having approximately 750 μm or 2.5 mm were prepared from the following lipid-based matrices: cocoa butter, fractionated palm kernel oil (FPKO), chocolate, beeswax, carnauba wax, and paraffin. They were added to solutions designed to simulate gastric secretions (GS) or duodenum secretions (DS) at 37°C. Paraffin, carnauba wax, and bees wax did not dissolve in either the GS or DS media. Cocoa butter, FPKO, and chocolate dissolved in the DS medium. Cocoa butter, and to a lesser extent chocolate, also dissolved in the GS medium. With chocolate, dissolution was twice as fast as that with small particles (750 μm) as compared to the larger (2.5 mm) ones. With 750 μm particle sizes, 90% dissolution of chocolate beads was attained after only 60 minutes in the DS medium, while it took 120 minutes for 70% of FPKO beads to dissolve in the same conditions. The data are discussed from the perspective of controlled release in the gastrointestinal tract of encapsulated ingredients (minerals, oils, probiotic bacteria, enzymes, vitamins, and peptides) used in the development of functional foods. PMID:26904647

Lurasidone-β-cyclodextrin complexes: Physicochemical characterization and comparison of their antidepressant, antipsychotic activities against that of self microemulsifying formulation

NASA Astrophysics Data System (ADS)

Londhe, Vaishali Y.; Deshmane, Aishwarya B.; Singh, Sarita R.; Kulkarni, Yogesh A.

2018-04-01

Lurasidone hydrochloride (LHD) is an atypical antipsychotic drug has poor aqueous solubility and low bioavailability (9-19%). This study describes effect of different methods of complex formation with β-cyclodextrin (BCD) on enhancement of dissolution and on antidepressant, antipsychotic effects of LHD. Other purpose of this study is to compare pharmacodynamic effects of complexes with that of self microemulsifying drug delivery system of LHD (SMEDDS). Inclusion complexes (IC) of LHD and BCD were prepared by physical mixing (PM), kneading (KN) and spray drying (SD) in a 1:1 M ratio. These complexes were characterized by different techniques. KN and SD showing enhancement in dissolution, were compared with SMEDDS using Forced swim test (FST) and Tail suspension test (TST) for antidepressant action and Paw test for antipsychotic activity. Characterization of complexes confirmed interaction between LHD and BCD. Enhancement in dissolution is seen in following order SD > KN > PM > LHD. In all three animal models, SD, KN and SMEDDS showed statistically significant effect (p < .05) than drug alone showing enhancement in bioavailability. Complexation of LHD with BCD enhances dissolution which reflected in improvement of antidepressant and antipsychotic activity of drug. Solubility enhancement methods like complexation and self microemulsion improves pharmacodynamic activities of drug. Improvement of pharmacodynamic effect is seen in order, SD ≥ SMEDDS ≥ KN > LHD.

Multiple-layer compression-coated tablets: formulation and humidity studies of novel chewable amoxicillin/clavulanate tablet formulations.

PubMed

Wardrop, J; Jaber, A B; Ayres, J W

1998-08-01

The purpose of this study was to produce novel multiple-layer, compression-coated, chewable tablet formulations containing amoxicillin trihydrate, and clavulanic acid as potassium clavulanate, and to test in vitro dissolution characteristics and the effect of humidity stability compared to Augmentin chewable tablets as a reference. Double- and triple-layer tablets were manufactured on a laboratory scale by multiple-layer dry compression, and dissolution profiles of both active ingredients were determined. Tablets were subjected to stability evaluation in laboratory-scale humidity tanks maintained at constant humidity. Assay of content was determined by HPLC or UV spectroscopy. Physical characteristics of the powder mixture, such as angle of repose, and of tablets for hardness and friability, were also determined. Chewable tablets showed similar dissolution profiles in vitro for both active ingredients, compared to the marketed reference, Augmentin. The stability of clavulanic acid, but not amoxicillin, was increased in the novel triple or bilayer formulation. The tablets showed suitable friability, hardness, and angle of repose for starting materials to suggest that industrial scale-up is feasible. This approach to formulation of drugs containing multiple or moisture-sensitive ingredients has been shown to increase the stability of the central core drug without changing the dissolution pattern of the active ingredients. This formulation is expected to be bioequivalent in vivo based on these in vitro results.

Enhancement of bioavailability of ketoprofen using dry elixir as a novel dosage form.

PubMed

Ahn, H J; Kim, K M; Kim, C K

1998-07-01

To enhance the dissolution rate and bioavailability of poorly water-soluble ketoprofen, a novel oral dosage form of ketoprofen, termed ketoprofen dry elixir, was developed by the spray-drying technique. Ketoprofen, dextrin, and sodium lauryl sulfate were dissolved in an ethanol-water mixture (20:25 w/w) and thereafter spray-dried to form the ketoprofen dry elixir. Comparative studies on the in vitro dissolution and in vivo adsorption of ketoprofen in the form of dry elixir and powder were carried out. Ketoprofen in the dry elixir completely dissolved within 5 min. On the other hand, only about 50.1% of ketoprofen powder alone dissolved during 60 min. The initial dissolution rate of ketoprofen in the dry elixir markedly increased in distilled water at 37 degrees C, becoming fourfold higher than that of ketoprofen powder alone. The maximal plasma concentration of ketoprofen (Cmax) and the area under the concentration-time curve from zero to 8 hr (AUC0-8 hr) after the oral administration of dry elixir increased about 3.2- (24.6 versus 7.6 micrograms/ml) and 2.2-(38.4 versus 17.3 micrograms hr/ml) fold compared with powder alone. It was obvious that ketoprofen dry elixir might be a useful solid dosage form to improve the dissolution rate and bioavailability of poorly water-soluble ketoprofen.

Amorphous stabilization and dissolution enhancement of amorphous ternary solid dispersions: combination of polymers showing drug-polymer interaction for synergistic effects.

PubMed

Prasad, Dev; Chauhan, Harsh; Atef, Eman

2014-11-01

The purpose of this study was to understand the combined effect of two polymers showing drug-polymer interactions on amorphous stabilization and dissolution enhancement of indomethacin (IND) in amorphous ternary solid dispersions. The mechanism responsible for the enhanced stability and dissolution of IND in amorphous ternary systems was studied by exploring the miscibility and intermolecular interactions between IND and polymers through thermal and spectroscopic analysis. Eudragit E100 and PVP K90 at low concentrations (2.5%-40%, w/w) were used to prepare amorphous binary and ternary solid dispersions by solvent evaporation. Stability results showed that amorphous ternary solid dispersions have better stability compared with amorphous binary solid dispersions. The dissolution of IND from the ternary dispersion was substantially higher than the binary dispersions as well as amorphous drug. Melting point depression of physical mixtures reveals that the drug was miscible in both the polymers; however, greater miscibility was observed in ternary physical mixtures. The IR analysis confirmed intermolecular interactions between IND and individual polymers. These interactions were found to be intact in ternary systems. These results suggest that the combination of two polymers showing drug-polymer interaction offers synergistic enhancement in amorphous stability and dissolution in ternary solid dispersions. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Gender and the Stability of Same-Sex and Different-Sex Relationships Among Young Adults.

PubMed

Joyner, Kara; Manning, Wendy; Bogle, Ryan

2017-12-01

Most research on the stability of adult relationships has focused on coresidential (cohabiting or married) unions and estimates rates of dissolution for the period of coresidence. Studies examining how the stability of coresidential unions differs by sex composition have typically found that same-sex female couples have higher rates of dissolution than same-sex male couples and different-sex couples. We argue that the more elevated rates of dissolution for same-sex female couples are a by-product of the focus on coresidential unions. We use data from the National Longitudinal Study of Adolescent to Adult Health to compare rates of dissolution based on the total duration of romantic and sexual relationships for same-sex male couples, same-sex female couples, and different-sex couples. Results from hazard models that track the stability of young adult relationships from the time they are formed demonstrate that male couples have substantially higher dissolution rates than female couples and different-sex couples. Results based on models restricted to the period of coresidence corroborate the counterintuitive finding from earlier studies that female couples have the highest rates of dissolving coresidential unions. This study underlines the importance of comparisons between these couple types for a better understanding of the role that institutions and gender play in the stability of contemporary relationships.

Testing signal enhancement mechanisms in the dissolution NMR of acetone

NASA Astrophysics Data System (ADS)

Alonso-Valdesueiro, Javier; Elliott, Stuart J.; Bengs, Christian; Meier, Benno; Levitt, Malcolm H.

2018-01-01

In cryogenic dissolution NMR experiments, a substance of interest is allowed to rest in a strong magnetic field at cryogenic temperature, before dissolving the substance in a warm solvent, transferring it to a high-resolution NMR spectrometer, and observing the solution-state NMR spectrum. In some cases, negative enhancements of the 13C NMR signals are observed, which have been attributed to quantum-rotor-induced polarization. We show that in the case of acetone (propan-2-one) the negative signal enhancements of the methyl 13C sites may be understood by invoking conventional cross-relaxation within the methyl groups. The 1H nuclei acquire a relative large net polarization through thermal equilibration in a magnetic field at low temperature, facilitated by the methyl rotation which acts as a relaxation sink; after dissolution, the 1H magnetization slowly returns to thermal equilibrium at high temperature, in part by cross-relaxation processes, which induce a transient negative polarization of nearby 13C nuclei. We provide evidence for this mechanism experimentally and theoretically by saturating the 1H magnetization using a radiofrequency field pulse sequence before dissolution and comparing the 13 C magnetization evolution after dissolution with the results obtained from a conventional 1 H-13 C cross relaxation model of the CH3 moieties in acetone.

Preparation and Characterization of Liquisolid Compacts for Improved Dissolution of Telmisartan

PubMed Central

Narra, Nataraj; Rama Rao, Tadikonda

2014-01-01

The objective of the present work was to obtain pH independent and improved dissolution profile for a poorly soluble drug, telmisartan using liquisolid compacts. Liquisolid compacts were prepared using Transcutol HP as vehicle, Avicel PH102 as carrier, and Aerosil 200 as a coating material. The formulations were evaluated for drug excipient interactions, change in crystallinity of drug, flow properties, and general quality control tests of tablets using Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD), angle of repose, and various pharmacopoeial tests. In vitro dissolution studies were performed at three pH conditions (1.2, 4.5 and 7.4). Stability studies were performed at 40°C and 75% RH for three months. The formulation was found to comply with Indian pharmacopoeial limits for tablets. FTIR studies confirmed no interaction between drug and excipients. XRD and DSC studies indicate change/reduction in crystallinity of drug. Dissolution media were selected based on the solubility studies. The optimized formulation showed pH independent release profile with significant improvement (P < 0.005) in dissolution compared to plain drug and conventional marketed formulation. No significant difference was seen in the tablet properties, and drug release profile after storage for 3 months. PMID:25371826

An interferometric study of the dissolution kinetics of anorthite: The role of reactive surface area

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luettge, A.; Bolton, E.W.; Lasaga, A.C.

1999-07-01

An optical interferometry system has been used to study the dynamics of the dissolution of anorthite (010) cleavage surfaces. With this technique, it is possible to measure directly the surface retreat of alumino-silicates as a function of time and thereby the dissolution rate using a new application of interferometry. The dissolution experiments are carried out in a flow-through cell system with a near endmember anorthite (An{sub 98}) from Miyake-Jima, Tokyo, Japan, Perchloric acid solutions (pH 3) were used at a constant temperature of 25 C. After having measured the topography of the original pristine anorthite surface, measurements of the surfacemore » normal retreat were taken after 48,84,120, and 168 hrs of run duration at 15 different regions on the surface. An internal-reference technique allows absolute measurements of the changes in surface height for the very first time. From these measurements, an average bulk rate for dissolution of the (010) anorthite surface is calculated to be 5.7 x 10{sup {minus}13} [moles/cm{sub 2}/sec]. Finally, their directly determined bulk rate for the (010) face is compared with the bulk rates calculated from the rate law obtained from powder experiments and using the BET or total surface area.« less

Comparative study on the in vitro performance of blister molded and conventional lornoxicam immediate release liquitablets: accelerated stability study and anti-inflammatory and ulcerogenic effects.

PubMed

El-Setouhy, Doaa Ahmed; Gamiel, Alaa Abdel-Rahman; Badawi, Alia Abd El-Latif; Osman, Afaf Sayed; Labib, Dina Ahmed

2017-03-01

Lornoxicam is a potent non-steroidal anti-inflammatory drug (NSAID). It shows limited solubility in the gastric pH, delayed bioavailability and pharmacodynamic effects with aggravated gastric side effects (due to longer residence in the stomach wall). To enhance dissolution of lornoxicam in the gastric fluid and expectedly absorption and pharmacological action, with less ulcerogenic effects. Formulation of immediate release (IR) lornoxicam liquitablets containing both liquid and solid release modulators (wetting agent, solubilizers and microenvironmental pH modifiers). Beside the traditional direct compression technique employed for the preparation of liquitablets a new technique, blister molding, was also used. The effect of the two different manufacturing methods on the fast release characteristics (rapid disintegration and dissolution) was studied. Stability and pharmacological activity of the optimum formula were also explored. Similarity factor pointed out the superiority of molding technique in enhancing dissolution of lornoxicam owing to significant crystallinity reduction (XRD). Optimum formula showed negligible change in drug content and dissolution profiles over 12 weeks, significantly improved anti-inflammatory activity and significantly reduced gastric ulcerative effect over pure lornoxicam and commercial formula. Blister molded lornoxicam liquitablet of improved dissolution and pharmacological activity and less gastric erosion was successfully prepared.

Improved stability and oral bioavailability of Ganneng dropping pills following transforming lignans of herpetospermum caudigerum into nanosuspensions.

PubMed

Li, Juan-Juan; Cheng, Ling; Shen, Gang; Qiu, Ling; Shen, Cheng-Ying; Zheng, Juan; Xu, Rong; Yuan, Hai-Long

2018-01-01

The present study was designed to improve storage stability and oral bioavailability of Ganneng dropping pills (GNDP) by transforming lignans of Herpetospermum caudigerum (HL) composed of herpetrione (HPE) and herpetin (HPN) into nanosuspension (HL-NS), the main active ingredient of GNDP, HL-NS was prepared by high pressure homogenization and lyophilized to transform into solid nanoparticles (HL nanoparticles), and then the formulated HL nanoparticles were perfused into matrix to obtain NS-GNDP by melting method. For a period of 3 months, the content uniformity, storage stability and pharmacokinetics test in vivo of NS-GNDP were evaluated and compared with regular GNDP at room temperature. The results demonstrated that uniformity of dosage units of NS-GNDP was acceptable according to the criteria of Chinese Pharmacopoeia 2015J. Physical stability of NS-GNDP was investigated systemically using photon correlation spectroscopy (PCS), zeta potential measurement, and scanning electron microscopy (SEM). There was a slight increase in particles and PI of HL-NS re-dispersed from NS-GNDP after storage for 3 months, compared with new formulated NS-GNDP, which indicated a good redispersibility of the NS-GNDP containing HL-NS after storage. Besides, chemical stability of NS-GNDP was studied and the results revealed that HPE and HPN degradation was less when compared with that of GNDP, providing more than 99% of drug residue after storage for 3 months. In the dissolution test in vitro, NS-GNDP remarkably exhibited an increased dissolution velocity compared with GNDP and no distinct dissolution difference existed within 3 months. The pharmacokinetic study showed that HPE and HPN in NS-GNDP exhibited a significant increase in AUC 0-t , C max and decrease in T max when compared with regular GNDP. These results indicated that NS-GNDP possessed superiority with improved storage stability and increased dissolution rate and oral bioavailability. Copyright © 2018 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Effect of compositional heterogeneity on dissolution of non-ideal LNAPL mixtures

NASA Astrophysics Data System (ADS)

Vasudevan, M.; Johnston, C. D.; Bastow, T. P.; Lekmine, G.; Rayner, J. L.; Nambi, I. M.; Suresh Kumar, G.; Ravi Krishna, R.; Davis, G. B.

2016-11-01

The extent of dissolution of petroleum hydrocarbon fuels into groundwater depends greatly on fuel composition. Petroleum fuels can consist of thousands of compounds creating different interactions within the non-aqueous phase liquid (NAPL), thereby affecting the relative dissolution of the components and hence a groundwater plume's composition over long periods. Laboratory experiments were conducted to study the variability in the effective solubilities and activity coefficients for common constituents of gasoline fuels (benzene, toluene, p-xylene and 1,2,4-trimethylbenzene) (BTX) in matrices with an extreme range of molar volumes and chemical affinities. Four synthetic mixtures were investigated comprising BTX with the bulk of the NAPL mixtures made up of either, ethylbenzene (an aromatic like BTX with similar molar volume); 1,3,5-trimethylbenzene (an aromatic with a greater molar volume); n-hexane (an aliphatic with a low molar volume); and n-decane (an aliphatic with a high molar volume). Equilibrium solubility values for the constituents were under-predicted by Raoult's law by up to 30% (higher experimental concentrations) for the mixture with n-hexane as a filler and over-predicted by up to 12% (lower experimental concentrations) for the aromatic mixtures with ethylbenzene and 1,3,5-trimethylbenzene as fillers. Application of PP-LFER (poly-parameter linear free energy relationship) model for non-ideal mixtures also resulted in poor correlation between experimentally measured and predicted concentrations, indicating that differences in chemical affinities can be the major cause of deviation from ideal behavior. Synthetic mixtures were compared with the dissolution behavior of fresh and naturally weathered unleaded gasoline. The presence of lighter aliphatic components in the gasoline had a profound effect on estimating effective solubility due to chemical affinity differences (estimated at 0.0055 per percentage increase in the molar proportion of aliphatic) as well as reduced molar volumes (estimated at - 0.0091 in the activity coefficient per unit increase in molar volume, mL/mol). Previously measured changes in activity coefficients due to natural weathering of 0.25 compares well to 0.27 calculated here based on changes in the chemical affinity and molar volumes. The study suggests that the initial estimation of the composition of a fuel is crucial in evaluating dissolution processes due to ideal and non-ideal dissolution, and in predicting long term dissolution trends and the longevity of NAPL petroleum plume risks.

Modes of fossil preservation

USGS Publications Warehouse

Schopf, J.M.

1975-01-01

The processes of geologic preservation are important for understanding the organisms represented by fossils. Some fossil differences are due to basic differences in organization of animals and plants, but the interpretation of fossils has also tended to be influenced by modes of preservation. Four modes of preservation generally can be distinguished: (1) Cellular permineralization ("petrifaction") preserves anatomical detail, and, occasionally, even cytologic structures. (2) Coalified compression, best illustrated by structures from coal but characteristic of many plant fossils in shale, preserves anatomical details in distorted form and produces surface replicas (impressions) on enclosing matrix. (3) Authigenic preservation replicates surface form or outline (molds and casts) prior to distortion by compression and, depending on cementation and timing, may intergrade with fossils that have been subject to compression. (4) Duripartic (hard part) preservation is characteristic of fossil skeletal remains, predominantly animal. Molds, pseudomorphs, or casts may form as bulk replacements following dissolution of the original fossil material, usually by leaching. Classification of the kinds of preservation in fossils will aid in identifying the processes responsible for modifying the fossil remains of both animals and plants. ?? 1975.

Green chiral HPLC study of the stability of Chiralcel OD under high temperature liquid chromatography and subcritical water conditions.

PubMed

Droux, S; Roy, M; Félix, G

2014-10-01

We report here the study of the stability under subcritical water conditions of one of the most popular polysaccharide chiral stationary phase (CSP): Chiralcel OD. This CSP was used under high temperature and reversed phase conditions with acetonitrile and 2-propanol as modifier, respectively. The evolution of selectivity and resolution was investigated both in normal and reversed mode conditions with five racemates after packing, heating at 150 °C and separations of some racemic compounds under different high temperatures and mobile phase conditions. The results show that after using at high temperature and subcritical water conditions the selectivity was only moderately affected while the resolution fell dramatically especially in reversed mode due to the creation of a void at the head of the columns which reflects the dissolution of the silica matrix. Copyright © 2014 Elsevier B.V. All rights reserved.

Water-soluble loratadine inclusion complex: analytical control of the preparation by microwave irradiation.

PubMed

Nacsa, A; Ambrus, R; Berkesi, O; Szabó-Révész, P; Aigner, Z

2008-11-04

The majority of active pharmaceutical ingredients are poorly soluble in water. The rate-determining step of absorption is the dissolution of these drugs. Inclusion complexation with cyclodextrin derivatives can lead to improved aqueous solubility and bioavailability of pharmacons due to the formation of co-crystals through hydrogen-bonding between the components. Inclusion complexes of loratadine were prepared by a convenient new method involving microwave irradiation and the products were compared with those of a conventional preparation method. Dissolution studies demonstrated that the solubility and rate of dissolution of loratadine increased in both of the methods used. The interactions between the components were investigated by thermal analysis and Fourier Transform Infrared studies. The microwave treatment did not cause any chemical changes in the loratadine molecule.

Zirconium-nickel crystals—hydrogen accumulators: Dissolution and penetration of hydrogen atoms in alloys

NASA Astrophysics Data System (ADS)

Matysina, Z. A.; Zaginaichenko, S. Yu.; Shchur, D. V.; Gabdullin, M. T.; Kamenetskaya, E. A.

2016-07-01

The calculation of the free energy, thermodynamic equilibrium equations, and kinetic equations of the intermetallic compound Zr2NiH x has been carried out based on molecular-kinetic concepts. The equilibrium hydrogen concentration depending on the temperature, pressure, and energy parameters has been calculated. The absorption-desorption of hydrogen has been studied, and the possibility of the realization of the hysteresis effect has been revealed. The kinetics of the dissolution and permeability of hydrogen is considered, the time dependence of these values has been found, and conditions for the extremum character of their time dependence have been determined. Relaxation times of the dissolution and permeability of hydrogen into the alloy have been calculated. The calculation results are compared with the experimental data available in the literature.

Automated Dissolution for Enteric-Coated Aspirin Tablets: A Case Study for Method Transfer to a RoboDis II.

PubMed

Ibrahim, Sarah A; Martini, Luigi

2014-08-01

Dissolution method transfer is a complicated yet common process in the pharmaceutical industry. With increased pharmaceutical product manufacturing and dissolution acceptance requirements, dissolution testing has become one of the most labor-intensive quality control testing methods. There is an increased trend for automation in dissolution testing, particularly for large pharmaceutical companies to reduce variability and increase personnel efficiency. There is no official guideline for dissolution testing method transfer from a manual, semi-automated, to automated dissolution tester. In this study, a manual multipoint dissolution testing procedure for an enteric-coated aspirin tablet was transferred effectively and reproducibly to a fully automated dissolution testing device, RoboDis II. Enteric-coated aspirin samples were used as a model formulation to assess the feasibility and accuracy of media pH change during continuous automated dissolution testing. Several RoboDis II parameters were evaluated to ensure the integrity and equivalency of dissolution method transfer from a manual dissolution tester. This current study provides a systematic outline for the transfer of the manual dissolution testing protocol to an automated dissolution tester. This study further supports that automated dissolution testers compliant with regulatory requirements and similar to manual dissolution testers facilitate method transfer. © 2014 Society for Laboratory Automation and Screening.

Replication in plastic of three-dimensional fossils preserved in indurated clastic sedimentary rocks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zapasink, H.T.; Johnston, P.A.

A new technique for replicating in plastic the fossils preserved in clastic rocks should now make available reliable morphologic and frequency data, comparable in quality to those derived from acid-prepared silicified faunas, for a major segment of the fossil record. The technique involves 3 steps: the dissolution of carbonate in fossiliferous rocks with hydrochloric acid, impregnation of resulting voids with liquid plastic, and dissolution of the rock matrix with hydrofluoric acid, leaving a concentrate of plastic-replaced fossils.

Carbonate dissolution rates in high salinity brines: Implications for post-Noachian chemical weathering on Mars

NASA Astrophysics Data System (ADS)

Phillips-Lander, Charity M.; Parnell, S. R.; McGraw, L. E.; Elwood Madden, M. E.

2018-06-01

A diverse suite of carbonate minerals including calcite (CaCO3) and magnesite (MgCO3) have been observed on the martian surface and in meteorites. Terrestrial carbonates usually form via aqueous processes and often record information about the environment in which they formed, including chemical and textural biosignatures. In addition, terrestrial carbonates are often found in association with evaporite deposits on Earth. Similar high salinity environments and processes were likely active on Mars and some areas may contain active high salinity brines today. In this study, we directly compare calcite and magnesite dissolution in ultrapure water, dilute sulfate and chloride solutions, as well as near-saturated sulfate and chloride brines with known activity of water (aH2O) to determine how dissolution rates vary with mineralogy and aH2O, as well as aqueous cation and anion chemistry to better understand how high salinity fluids may have altered carbonate deposits on Mars. We measured both calcite and magnesite initial dissolution rates at 298 K and near neutral pH (6-8) in unbuffered solutions containing ultrapure water (18 MΩ cm-1 UPW; aH2O = 1), dilute (0.1 mol kg-1; aH2O = 1) and near-saturated Na2SO4 (2.5 mol kg-1, aH2O = 0.92), dilute (0.1 mol kg-1, aH2O = 1) and near-saturated NaCl (5.7 mol kg-1, aH2O = 0.75). Calcite dissolution rates were also measured in dilute and near-saturated MgSO4 (0.1 mol kg-1, aH2O = 1 and 2.7 mol kg-1, aH2O = 0.92, respectively) and MgCl2 (0.1 mol kg-1, aH2O = 1 and 3 mol kg-1, aH2O = 0.73, respectively), while magnesite dissolution rates were measured in dilute and near-saturated CaCl2 (0.1 mol kg-1, aH2O = 1 and 9 mol kg-1, aH2O = 0.35). Initial calcite dissolution rates were fastest in near-saturated MgCl2 brine, while magnesite dissolution rates were fastest in dilute (0.1 mol kg-1) NaCl and CaCl2 solutions. Calcite dissolution rates in near-saturated Na2SO4 were similar to those observed in the dilute solutions (-8.00 ± 0.12 log mol m-2 s-1), while dissolution slowed in both NaCl solutions (0.1 mol kg-1; -8.23 ± 0.10 log mol m-2 s-1 and (5.7 mol kg-1; -8.44 ± 0.11 log mol m-2 s-1), as well as near-saturated MgSO4 brine (2.7 mol kg-1; -8.35 ± 0.05 log mol m-2 s-1). The slowest calcite dissolution rates observed in the near-saturated NaCl brine. Magnesite dissolution rates were ∼5 times faster in the dilute salt solutions relative to UPW, but similar to UPW (-8.47 ± 0.06 log mol m-2 s-1) in near-saturated Na2SO4 brines (-8.41 ± 0.18 log mol m-2 s-1). Magnesite dissolution slowed significantly in near-saturated CaCl2 brine (-9.78 ± 0.10 log mol m-2 s-1), likely due to the significantly lower water activity in these experiments. Overall, magnesite dissolution rates are slower than calcite dissolution rates and follow the trend: All dilute salt solutions >2.5 mol kg-1 Na2SO4 ≈ UPW > 5.7 mol kg-1 NaCl >> 9 mol kg-1 CaCl2. Calcite rates follow the trend 3 mol kg-1 MgCl2 > 2.5 mol kg-1 Na2SO4 ≈ UPW ≈ all dilute salt solutions >2.7 mol kg-1 MgSO4 ≈ 5.7 mol kg-1 NaCl. Magnesite dissolution rates in salt solutions generally decrease with decreasing aH2O in both chloride and sulfate brines, which indicates water molecules act as ligands and participate in the rate-limiting magnesite dissolution step. However, there is no general trend associated with water activity observed in the calcite dissolution rates. Calcite dissolution accelerates in near-saturated MgCl2, but slows in near-saturated NaCl brine despite both brines having similar water activities (aH2O = 0.73 and 0.75, respectively). High Mg calcite was observed as a reaction product in the near-saturated MgCl2, indicating Mg2+ from solution likely substituted for Ca2+ in the initial calcite, releasing additional Ca2+ into solution and increasing the observed calcite dissolution rate. Calcite dissolution rates also increase slightly as Na2SO4 concentration increases, while calcite dissolution rates slow slightly with increasing concentration of MgSO4 and NaCl. However, all of the carbonate rates vary by less than 0.5 log units and are within or near the standard deviation observed for each set of replicate experiments. Carbonate mineral lifetimes in high salinity brines indicate magnesite may be preferentially preserved compared to calcite on Mars. Therefore, Mg-carbonates that have experienced post-depositional aqueous alteration are more likely to preserve paleoenvironmental indicators and potential biosignatures. Rapid weathering of carbonates in circum-neutral pH sulfate brines may provide a potential source of cations for abundant sulfate minerals observed on Mars, Ceres, and other planetary bodies.

Platinum supported on titanium–ruthenium oxide is a remarkably stable electrocatayst for hydrogen fuel cell vehicles

PubMed Central

Parrondo, Javier; Han, Taehee; Niangar, Ellazar; Wang, Chunmei; Dale, Nilesh; Adjemian, Kev; Ramani, Vijay

2014-01-01

We report a unique and highly stable electrocatalyst—platinum (Pt) supported on titanium–ruthenium oxide (TRO)—for hydrogen fuel cell vehicles. The Pt/TRO electrocatalyst was exposed to stringent accelerated test protocols designed to induce degradation and failure mechanisms identical to those seen during extended normal operation of a fuel cell automobile—namely, support corrosion during vehicle startup and shutdown, and platinum dissolution during vehicle acceleration and deceleration. These experiments were performed both ex situ (on supports and catalysts deposited onto a glassy carbon rotating disk electrode) and in situ (in a membrane electrode assembly). The Pt/TRO was compared against a state-of-the-art benchmark catalyst—Pt supported on high surface-area carbon (Pt/HSAC). In ex situ tests, Pt/TRO lost only 18% of its initial oxygen reduction reaction mass activity and 3% of its oxygen reduction reaction-specific activity, whereas the corresponding losses for Pt/HSAC were 52% and 22%. In in situ-accelerated degradation tests performed on membrane electrode assemblies, the loss in cell voltage at 1 A · cm−2 at 100% RH was a negligible 15 mV for Pt/TRO, whereas the loss was too high to permit operation at 1 A · cm−2 for Pt/HSAC. We clearly show that electrocatalyst support corrosion induced during fuel cell startup and shutdown is a far more potent failure mode than platinum dissolution during fuel cell operation. Hence, we posit that the need for a highly stable support (such as TRO) is paramount. Finally, we demonstrate that the corrosion of carbon present in the gas diffusion layer of the fuel cell is only of minor concern. PMID:24367118

Platinum supported on titanium-ruthenium oxide is a remarkably stable electrocatayst for hydrogen fuel cell vehicles.

PubMed

Parrondo, Javier; Han, Taehee; Niangar, Ellazar; Wang, Chunmei; Dale, Nilesh; Adjemian, Kev; Ramani, Vijay

2014-01-07

We report a unique and highly stable electrocatalyst-platinum (Pt) supported on titanium-ruthenium oxide (TRO)-for hydrogen fuel cell vehicles. The Pt/TRO electrocatalyst was exposed to stringent accelerated test protocols designed to induce degradation and failure mechanisms identical to those seen during extended normal operation of a fuel cell automobile-namely, support corrosion during vehicle startup and shutdown, and platinum dissolution during vehicle acceleration and deceleration. These experiments were performed both ex situ (on supports and catalysts deposited onto a glassy carbon rotating disk electrode) and in situ (in a membrane electrode assembly). The Pt/TRO was compared against a state-of-the-art benchmark catalyst-Pt supported on high surface-area carbon (Pt/HSAC). In ex situ tests, Pt/TRO lost only 18% of its initial oxygen reduction reaction mass activity and 3% of its oxygen reduction reaction-specific activity, whereas the corresponding losses for Pt/HSAC were 52% and 22%. In in situ-accelerated degradation tests performed on membrane electrode assemblies, the loss in cell voltage at 1 A · cm(-2) at 100% RH was a negligible 15 mV for Pt/TRO, whereas the loss was too high to permit operation at 1 A · cm(-2) for Pt/HSAC. We clearly show that electrocatalyst support corrosion induced during fuel cell startup and shutdown is a far more potent failure mode than platinum dissolution during fuel cell operation. Hence, we posit that the need for a highly stable support (such as TRO) is paramount. Finally, we demonstrate that the corrosion of carbon present in the gas diffusion layer of the fuel cell is only of minor concern.

Characteristics of streams and aquifers and processes affecting the salinity of water in the upper Colorado River basin, Texas

USGS Publications Warehouse

Slade, R.M.; Buszka, P.M.

1994-01-01

The chemical characteristics of the saline water in streams and shallow aquifers in the study area were compared to characteristics of water that would result from the probable processes affecting the salinity of water, such as evapotranspiration, mineral dissolution, and mixing of water from streams and shallow-aquifer water with brines from deep aquifers. Dissolution of halite or mixing with deep-aquifer water was the most common cause of increased salinity in 48.0 percent of 77 water samples from shallow aquifers, as classified using salt-norm analysis; the second most common cause was the weathering and dissolution of sulfur-bearing minerals. Mixing with water from soil-mineral dissolution was classified as the principal source of chloride in 28.4 percent of 67 water samples from shallow aquifers with nitrate determinations. Trace-species/chloride ratios indicated that mixing with water from deep aquifers in rocks of the Pennsylvanian System was the principal source of chloride in 24.4 percent of 45 shallow-aquifer samples lacking nitrate determinations.

Effect of modeling factors on the dissolution-diffusion-convection process during CO2 geological storage in deep saline formations

NASA Astrophysics Data System (ADS)

Zhang, Wei

2013-06-01

It is well known that during CO2 geological storage, density-driven convective activity can significantly accelerate the dissolution of injected CO2 into water. This action could limit the escape of supercritical CO2 from the storage formation through vertical pathways such as fractures, faults and abandoned wells, consequently increasing permanence and security of storage. First, we investigated the effect of numerical perturbation caused by time and grid resolution and the convergence criteria on the dissolution-diffusion-convection (DDC) process. Then, using the model with appropriate spatial and temporal resolution, some uncertainty parameters investigated in our previous paper such as initial gas saturation and model boundaries, and other factors such as relative liquid permeability and porosity modification were used to examine their effects on the DDC process. Finally, we compared the effect of 2D and 3D models on the simulation of the DDC process. The above modeling results should contribute to clear understanding and accurate simulation of the DDC process, especially the onset of convective activity, and the CO2 dissolution rate during the convection-dominated stage.

Solid dispersion tablets of breviscapine with polyvinylpyrrolidone K30 for improved dissolution and bioavailability to commercial breviscapine tablets in beagle dogs.

PubMed

Cong, Wenjuan; Shen, Lan; Xu, Desheng; Zhao, Lijie; Ruan, Kefeng; Feng, Yi

2014-09-01

Breviscapine, one of cardiovascular drugs extracted from a Chinese herb Erigeron breviscapinus, has been frequently used to treat cardiovascular diseases such as hypertension, angina pectoris, coronary heart disease and stroke. However, its poor water solubility and low bioavailability in vivo severely restrict the clinical application. To overcome these drawbacks, breviscapine solid dispersion tablets consisting of breviscapine, polyvinylpyrrolidone K30 (PVP K30), microcrystalline cellulose and crospovidone were appropriately prepared. In vitro dissolution profiles showed that breviscapine released percentage of solid dispersion tablets reached 90 %, whereas it was only 40 % for commercial breviscapine tablets. Comparative pharmacokinetic study between solid dispersion tablets and commercial products was investigated on the normal beagle dogs after oral administration. Results showed that the bioavailability of breviscapine was greatly increased by 3.45-fold for solid dispersion tablets. The greatly improved dissolution rate and bioavailability might be attributed to intermolecular hydrogen bonding reactions between PVP K30 and scutellarin. These findings suggest that our solid dispersion tablets can greatly improve the bioavailability as well as the dissolution rate of breviscapine.

Increasing dissolution of trospium chloride by co-crystallization with urea

NASA Astrophysics Data System (ADS)

Skořepová, Eliška; Hušák, Michal; Čejka, Jan; Zámostný, Petr; Kratochvíl, Bohumil

2014-08-01

The search for various solid forms of an active pharmaceutical ingredient (API) is an important step in drug development. Our aim was to prepare co-crystals of trospium chloride, an anticholinergic drug used for the treatment of incontinence, and to investigate if they have advantageous properties for drug formulation. Phase identification was done by powder X-ray diffraction and single-crystal X-ray diffraction. The chemical composition was verified by solution NMR and the dissolution rate of the prepared phases was studied by IDR (intrinsic dissolution rate). For further analysis of phase stability and transitions, combined thermal analysis and temperature-resolved X-ray powder diffraction were used. Urea was selected as a co-crystallization partner. Trospium chloride urea (1:1) co-crystal was prepared by a solvent evaporation. From single-crystal data, the co-crystal structure was solved in a space group P21/c and compared to previously published structures of trospium chloride. Intrinsic dissolution rate revealed that the co-crystal dissolves 32% faster than pure API. However, its low thermal and pressure stability makes it a challenging choice for the final drug formulation.

Characterization and evaluation of miconazole salts and cocrystals for improved physicochemical properties.

PubMed

Tsutsumi, Shunichirou; Iida, Motoo; Tada, Norio; Kojima, Takashi; Ikeda, Yukihiro; Moriwaki, Toshiya; Higashi, Kenjirou; Moribe, Kunikazu; Yamamoto, Keiji

2011-12-15

Miconazole salts and cocrystals were studied to improve the physicochemical properties of miconazole. Maleate, hemifumarate, and hemisuccinate were prepared and characterized by powder X-ray diffractometry, differential scanning calorimetry, and single crystal X-ray diffractometry. The intrinsic dissolution rate and stability of each miconazole crystal form were compared to those of freebase and nitrate to evaluate the optimal crystal form. Crystal structure analysis indicated that maleate was a salt formed by proton transfer from the acid to the imidazole group of miconazole. Hemifumarate and hemisuccinate were determined to be cocrystals formed by hydrogen bonding between the acids and the base in their crystal lattices. Intrinsic dissolution tests showed that the formation of salts and cocrystals improved the dissolution rate of miconazole. Stability tests of preliminary formulations prepared with each crystal form indicated that maleate and hemifumarate were unstable at 80°C and generated a specific degraded product, i.e., a Michael adduct, between miconazole and the acids. Hemisuccinate had a superior intrinsic dissolution rate and stability, and is thus considered a promising crystal form of miconazole. Copyright © 2011 Elsevier B.V. All rights reserved.

Preparation and Physical Characterization of a Diclofenac-Ranitidine Co-precipitate for Improving the Dissolution of Diclofenac.

PubMed

Gaitano, Robertino O; Calvo, Natalia L; Narda, Griselda E; Kaufman, Teodoro S; Maggio, Rubén M; Brusau, Elena V

2016-03-01

Mixing aqueous solutions of sodium diclofenac (DIC-Na) and ranitidine hydrochloride (RAN·HCl) afforded an off-white solid (DIC-RAN) that was investigated from the microscopic, thermal, diffractometric, spectroscopic, and functional (chemometrics-assisted dissolution) points of view. The solid has a 2:1 (DIC:RAN) molar ratio according to (1)H nuclear magnetic resonance spectroscopy. It is thermally stable, displaying a broad endothermic signal centered at 105°C in the thermogram, and its characteristic reflections in the powder X-ray diffractogram remained unchanged after a 3-month aging period. Scanning electron microscopy micrographs uncovered its morphology, whereas the spectral data suggested an interaction between the carboxylic acid of DIC and the alkyldimethylamino moiety of RAN. The dissolution of DIC-RAN was monitored at different pH values by an ultraviolet/chemometrics procedure, being complete within 5 min at pH 6.8. This compares favorably with the dissolution of a DIC-Na sample of the same particle size. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Do you need to shop around? Age at marriage, spousal alternatives, and marital dissolution.

PubMed

South, S J

1995-07-01

"This article attempts to shed light on the oft-observed relationship between age at marriage and marital dissolution by first deriving a hypothesis from marital search theory that relates both variables to the supply of spousal alternatives in the local marriage market. This hypothesis states that, relative to people who marry later in life, persons who marry at comparatively young ages will be especially susceptible to divorce when confronted with abundant alternatives to their current spouse. Marital history data from the National Longitudinal Survey of Youth were then merged with aggregated data from the Public Use Microdata Samples of the 1980 U.S. census to test this hypothesis." The author finds that "discrete-time event history analyses offer no support for this hypothesis. Although the risk of marital dissolution is highest where either husbands or wives chance numerous spousal alternatives, the impact of age at marriage on divorce is significantly weaker in marriage markets containing abundant remarriage opportunities. Some of the effect of age at marriage on marital dissolution is attributable to the detrimental impact of early marriage on educational attainment." excerpt

The structure of biocoats based on TiO2 doped with nitrogen study

NASA Astrophysics Data System (ADS)

Boytsova, E. L.; Leonova, L. A.; Pichugin, V. F.

2018-04-01

Nitrogen-doped titanium dioxide (N-TiO2) nanofilms were deposited by reactive magnetron sputtering under different bias voltage. The mode of sputtering influences to formation and properties of titanium films. X-ray diffraction (XRD) was used to study the phase transition and crystallinity of the nanofilms. A technique of layer-by-layer measurement of Raman scattering from nanostructured titanium dioxide films based on a preliminary sputtering of the films by argon beam under an angle of 45° and less has been developed. Experimentally confirmed low dissolution rate of the coating in NaCl saline (0.9%).

Molten salt bath circulation design for an electrolytic cell

DOEpatents

Dawless, Robert K.; LaCamera, Alfred F.; Troup, R. Lee; Ray, Siba P.; Hosler, Robert B.

1999-01-01

An electrolytic cell for reduction of a metal oxide to a metal and oxygen has an inert anode and an upwardly angled roof covering the inert mode. The angled roof diverts oxygen bubbles into an upcomer channel, thereby agitating a molten salt bath in the upcomer channel and improving dissolution of a metal oxide in the molten salt bath. The molten salt bath has a lower velocity adjacent the inert anode in order to minimize corrosion by substances in the bath. A particularly preferred cell produces aluminum by electrolysis of alumina in a molten salt bath containing aluminum fluoride and sodium fluoride.

Nanocomposite formation between alpha-glucosyl stevia and surfactant improves the dissolution profile of poorly water-soluble drug.

PubMed

Uchiyama, Hiromasa; Tozuka, Yuichi; Nishikawa, Masahiro; Takeuchi, Hirofumi

2012-05-30

The formation of a hybrid-nanocomposite using α-glucosyl stevia (Stevia-G) and surfactant was explored to improve the dissolution of flurbiprofen (FP). As reported previously, the dissolution amount of FP was enhanced in the presence of Stevia-G, induced by the formation of an FP and Stevia-G-associated nanostructure. When a small amount of sodium dodecyl sulfate (SDS) was present with Stevia-G, the amount of dissolved FP was extremely enhanced. This dissolution-enhancement effect was also observed with the cationic surfactant of dodecyl trimethyl ammonium bromide, but not with the non-ionic surfactant of n-octyl-β-D-maltopyranoside. To investigate the dissolution-enhancement effect of Stevia-G/SDS mixture, the pyrene I(1)/I(3) ratio was plotted versus the Stevia-G concentration. The pyrene I(1)/I(3) ratio of Stevia-G/SDS mixture had a sigmoidal curve at lower Stevia-G concentrations compared to the Stevia-G solution alone. These results indicate that the Stevia-G/SDS mixture provides a hydrophobic core around pyrene molecules at lower Stevia-G concentrations, leading to nanocomposite formation between Stevia-G and SDS. The nanocomposite of Stevia-G/SDS showed no cytotoxicity to Caco-2 cells at a mixture of 0.1% SDS and 1% Stevia-G solution, whereas 0.1% SDS solution showed high toxicity. These results suggest that the nanocomposite formation of Stevia-G/SDS may be useful way to enhance the dissolution of poorly water-soluble drugs without special treatment. Copyright © 2012 Elsevier B.V. All rights reserved.

Effect of iron on the dissolution of bovine enamel powder in vitro by carbonated beverages.

PubMed

Kato, Melissa Thiemi; Maria, Andrea Gutierrez; Sales-Peres, Sílvia Helena de Carvalho; Buzalaf, Marília Afonso Rabelo

2007-07-01

The aim of this study was to evaluate, in vitro, the effect of iron on the dissolution of bovine enamel powder, when added to two carbonated beverages. Powdered enamel was produced by griding enamel fragments of bovine incisor in a steel pestle and mortar. Particles between 75 and 106 microm were selected using appropriated meshes. At time zero, the carbonated beverage (Coke or Sprite Zero) was added to powdered enamel (1 mg enamel powder/10 microL of beverage) and vortexed for 30 s. The sample was immediately centrifuged (11,000 rpm) for 30 s and the supernatant was removed at 1 min 40 s. This procedure was repeated five times with the beverage containing increasing ferrous sulphate concentrations (1.25, 2.5, 5, 10, 15, 30 and 60 mmol/L). The phosphate released in the medium was analysed spectrophotometrically. Data were analysed using ANOVA and Tukey's test (p<0.05). When iron at 30 and 60 mmol/L was added to Coke, a significant reduction in the dissolution of powdered enamel was observed when compared to control (11 and 17%, respectively), while lower iron concentrations did not have any effect on enamel powder dissolution. Regarding Sprite Zero, iron concentrations up to 10 mmol/L had no significant effect, while higher concentrations significantly increased enamel powder dissolution. The results suggest that iron can interfere with the dissolution of dental enamel powder in the presence of acidic beverages and the type of acid in these beverages seems to modulate this effect.

Influence of formulation parameters on dissolution rate enhancement of glyburide using liquisolid technique.

PubMed

Singh, Sachin Kumar; Srinivasan, K K; Gowthamarajan, K; Prakash, Dev; Gaikwad, Narayan B; Singare, Dhananjay S

2012-08-01

The aim of this study was to investigate the use of liquisolid technique in improving the dissolution of glyburide in a solid dosage form. This study was designed to evaluate the effects of different formulation variables, i.e. type of non-volatile liquid vehicles and drug concentrations, on drug dissolution rates. The liquisolid tablets were formulated with Propylene glycol, as liquid vehicle. Microcrystalline cellulose was used as a carrier material, silica as a coating material and croscaremellose as a disintegrant. In vitro drug dissolution profiles of the liquisolid formulations were studied and compared with direct compressed non-micronized and micronized tablets of glyburide using USP II, paddle apparatus at 50 rpm for 60 min using 900 ml of 0.05 M Phosphate Buffer, pH 7.5. The stability studies showed that the dissolution profiles of liquisolid tablets prepared with propylene glycol were not affected by ageing significantly, as f2 value found between aged and fresh samples was 51.92. Differential scanning calorimetry revealed that the drug has got solubilized in the liquid vehicle. This was further supported by the powder X-ray diffraction studies of pure drug and the liquisolid powder system. It can be concluded that it is possible to load poorly soluble drug into liquisolid tablets by addition of PVP to the liquid vehicle. This is valuable for the preparation of liquisolid tablets of poorly soluble drugs. The liquisolid tablets prepared with PVP showed a remarkably improved dissolution rate in comparison with DC tablet and other formulations.

Consumer vinegar test for determining calcium disintegration.

PubMed

Mason, N A; Patel, J D; Dressman, J B; Shimp, L A

1992-09-01

A consumer test and standardized methods were compared for measuring the disintegration of calcium tablets, and the disintegration results were compared with results of dissolution testing to determine the ability of the consumer test of disintegration to predict bioavailability of calcium. Disintegration of 17 calcium supplement products, in tablet form, was studied in Simulated Gastric Fluid Test Solution, USP, without pepsin (GF), in distilled water, and in white distilled vinegar. For disintegration testing with GF and with distilled water, six tablets of each product were placed in an apparatus and immersed in the solution at 37 degrees C for 60 minutes. Six tablets of each product were tested in 200 mL of vinegar at room temperature for 30 minutes. Disintegration was determined by visual observation. Seven products were tested for dissolution in GF or water. Three samples of each product were tested at intervals over 120 minutes for calcium content. Results of testing with an ion-selective electrode were converted to milligrams and compared with the calcium content of the tablets (as claimed on the package label). The mean disintegration times of various calcium products in vinegar ranged from 1.8 to greater than 30 minutes. The mean time in distilled water and GF ranged from 1.6 to greater than 60 minutes and from 1.0 to greater than 60 minutes, respectively. Results were in agreement in 87% to 93% of cases between the consumer vinegar test and the standardized disintegration test methods, a significant correlation. No correlation was found between disintegration time and the extent of dissolution. The disintegration and dissolution of commercially available calcium tablets was highly variable.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial dissolution of fluorapatite as a possible source of elevated dissolved phosphate in the environment

NASA Astrophysics Data System (ADS)

Feng, Mu-hua; Ngwenya, Bryne T.; Wang, Lin; Li, Wenchao; Olive, Valerie; Ellam, Robert M.

2011-10-01

In order to understand the contribution of geogenic phosphorus to lake eutrophication, we have investigated the rate and extent of fluorapatite dissolution in the presence of two common soil bacteria ( Pantoea agglomerans and Bacillus megaterium) at T = 25 °C for 26 days. The release of calcium (Ca), phosphorus (P), and rare earth elements (REE) under biotic and abiotic conditions was compared to investigate the effect of microorganism on apatite dissolution. The release of Ca and P was enhanced under the influence of bacteria. Apatite dissolution rates obtained from solution Ca concentration in the biotic reactors increased above error compared with abiotic controls. Chemical analysis of biomass showed that bacteria scavenged Ca, P, and REE during their growth, which lowered their fluid concentrations, leading to apparent lower release rates. The temporal evolution of pH in the reactors reflected the balance of apatite weathering, solution reactions, bacterial metabolism, and potentially secondary precipitation, which was implied in the variety of REE patterns in the biotic and abiotic reactors. Light rare earth elements (LREE) were preferentially adsorbed to cell surfaces, whereas heavy rare earth elements (HREE) were retained in the fluid phase. Decoupling of LREE and HREE could possibly be due to preferential release of HREE from apatite or selective secondary precipitation of LREE enriched phosphates, especially in the presence of bacteria. When corrected for intracellular concentrations, both biotic reactors showed high P and REE release compared with the abiotic control. We speculate that lack of this correction explains the conflicting findings about the role of bacteria in mineral weathering rates. The observation that bacteria enhance the release rates of P and REE from apatite could account for some of the phosphorus burden and metal pollution in aquatic environments.

Mineral dissolution and precipitation in carbonate dominated terranes assessed using Mg isotopes

NASA Astrophysics Data System (ADS)

Tipper, E.; Calmels, D.; Gaillardet, J.; Galy, A.

2013-12-01

Carbonate weathering by carbonic acid consumes atmospheric CO2 during mineral dissolution, fixing it as aqueous bicarbonate over millennial time-scales. Ocean acidification has increased the solubility of CO2 in seawater by changing the balance of pH to alkalinity (the oceanic reservoir of carbon). This has lengthened the time-scale for CO2 sequestration by carbonate weathering to tens of thousands of years. At a global scale, the net consumption of CO2 is at least equal to that from silicate weathering, but there is far less work on carbonate weathering compared to silicate weathering because it has generally been assumed to be CO2 neutral on geological time-scales. Carbonate rocks are more readily dissolved than silicate rocks, meaning that their dissolution will likely respond much more rapidly to global environmental change when compared with the dissolution of silicate minerals. Although far less concentrated than Ca in many carbonates, Mg substitutes for Ca and is more concentrated than any other metal ion. Tracing the behavior of Mg in river waters, using Mg stable isotopes (26Mg/24Mg ratio expressed as delta26Mg in per mil units) is therefore a novel way to understand the complex series of dissolution/precipitation reactions that govern solute concentrations of Ca and Mg, and hence CO2 transfer by carbonate weathering. We present new Mg isotope data on a series of river and spring waters from the Jura mountains in North-East France. The stratigraphic column is relatively uniform throughout the Jura mountains and is dominated by limestones. As the limestone of the Jura Mountains were deposited in high-energy shallow water environments (shore line, lagoon and coral reefs), they are usually clay and organic poor. The delta26Mg of the local rocks is very constant at circa -4permil. The delta26Mg of the river waters is also fairly constant, but offset from the rock at -2.5permil. This is an intriguing observation because the dissolution of limestones is expected to be congruent, meaning that the Mg released to solutes during mineral dissolution should have the same composition as the host rock. Some of this difference is likely accounted for by atmospheric deposition or cyclic inputs, but this cannot account for all of the 1.5permil shift between rock and water. It is plausible that some of the difference is explained by trace levels of Mg-silicate dissolution (with a delta26Mg of circa 0permil), but equally carbonate precipitation and attendant Mg isotope fractionation could theoretically account for the difference between rock and water. The various plausible explications will be discussed, as well as the implications of the data for better understanding carbonate weathering.

Does the dose-solubility ratio affect the mean dissolution time of drugs?

PubMed

Lánský, P; Weiss, M

1999-09-01

To present a new model for describing drug dissolution. On the basis of the new model to characterize the dissolution profile by the distribution function of the random dissolution time of a drug molecule, which generalizes the classical first order model. Instead of assuming a constant fractional dissolution rate, as in the classical model, it is considered that the fractional dissolution rate is a decreasing function of the dissolved amount controlled by the dose-solubility ratio. The differential equation derived from this assumption is solved and the distribution measures (half-dissolution time, mean dissolution time, relative dispersion of the dissolution time, dissolution time density, and fractional dissolution rate) are calculated. Finally, instead of monotonically decreasing the fractional dissolution rate, a generalization resulting in zero dissolution rate at time origin is introduced. The behavior of the model is divided into two regions defined by q, the ratio of the dose to the solubility level: q < 1 (complete dissolution of the dose, dissolution time) and q > 1 (saturation of the solution, saturation time). The singular case q = 1 is also treated and in this situation the mean as well as the relative dispersion of the dissolution time increase to infinity. The model was successfully fitted to data (1). This empirical model is descriptive without detailed physical reasoning behind its derivation. According to the model, the mean dissolution time is affected by the dose-solubility ratio. Although this prediction appears to be in accordance with preliminary application, further validation based on more suitable experimental data is required.

Dissolution of Simulated and Radioactive Savannah River Site High-Level Waste Sludges with Oxalic Acid & Citric Acid Solutions

DOE Office of Scientific and Technical Information (OSTI.GOV)

STALLINGS, MARY

This report presents findings from tests investigating the dissolution of simulated and radioactive Savannah River Site sludges with 4 per cent oxalic acid and mixtures of oxalic and citric acid previously recommended by a Russian team from the Khlopin Radium Institute and the Mining and Chemical Combine (MCC). Testing also included characterization of the simulated and radioactive waste sludges. Testing results showed the following: Dissolution of simulated HM and PUREX sludges with oxalic and citric acid mixtures at SRTC confirmed general trends reported previously by Russian testing. Unlike the previous Russian testing six sequential contacts of a mixture of oxalicmore » acid citric acids at a 2:1 ratio (v/w) of acid to sludge did not produce complete dissolution of simulated HM and PUREX sludges. We observed that increased sludge dissolution occurred at a higher acid to sludge ratio, 50:1 (v/w), compared to the recommended ratio of 2:1 (v/w). We observed much lower dissolution of aluminum in a simulated HM sludge by sodium hydroxide leaching. We attribute the low aluminum dissolution in caustic to the high fraction of boehmite present in the simulated sludge. Dissolution of HLW sludges with 4 per cent oxalic acid and oxalic/citric acid followed general trends observed with simulated sludges. The limited testing suggests that a mixture of oxalic and citric acids is more efficient for dissolving HM and PUREX sludges and provides a more homogeneous dissolution of HM sludge than oxalic acid alone. Dissolution of HLW sludges in oxalic and oxalic/citric acid mixtures produced residual sludge solids that measured at higher neutron poison to equivalent 235U weight ratios than that in the untreated sludge solids. This finding suggests that residual solids do not present an increased nuclear criticality safety risk. Generally the neutron poison to equivalent 235U weight ratios of the acid solutions containing dissolved sludge components are lower than those in the untreated sludge solids. We recommend that these results be evaluated further to determine if these solutions contain sufficient neutron poisons. We observed low general corrosion rates in tests in which carbon steel coupons were contacted with solutions of oxalic acid, citric acid and mixtures of oxalic and citric acids. Wall thinning can be minimized by maintaining short contact times with these acid solutions. We recommend additional testing with oxalic and oxalic/citric acid mixtures to measure dissolution performance of sludges that have not been previously dried. This testing should include tests to clearly ascertain the effects of total acid strength and metal complexation on dissolution performance. Further work should also evaluate the downstream impacts of citric acid on the SRS High-Level Waste System (e.g., radiochemical separations in the Salt Waste Processing Facility and addition of organic carbon in the Saltstone and Defense Waste Processing facilities).« less

In vitro solubility, dissolution and permeability studies combined with semi-mechanistic modeling to investigate the intestinal absorption of desvenlafaxine from an immediate- and extended release formulation.

PubMed

Franek, F; Jarlfors, A; Larsen, F; Holm, P; Steffansen, B

2015-09-18

Desvenlafaxine is a biopharmaceutics classification system (BCS) class 1 (high solubility, high permeability) and biopharmaceutical drug disposition classification system (BDDCS) class 3, (high solubility, poor metabolism; implying low permeability) compound. Thus the rate-limiting step for desvenlafaxine absorption (i.e. intestinal dissolution or permeation) is not fully clarified. The aim of this study was to investigate whether dissolution and/or intestinal permeability rate-limit desvenlafaxine absorption from an immediate-release formulation (IRF) and Pristiq(®), an extended release formulation (ERF). Semi-mechanistic models of desvenlafaxine were built (using SimCyp(®)) by combining in vitro data on dissolution and permeation (mechanistic part of model) with clinical data (obtained from literature) on distribution and clearance (non-mechanistic part of model). The model predictions of desvenlafaxine pharmacokinetics after IRF and ERF administration were compared with published clinical data from 14 trials. Desvenlafaxine in vivo dissolution from the IRF and ERF was predicted from in vitro solubility studies and biorelevant dissolution studies (using the USP3 dissolution apparatus), respectively. Desvenlafaxine apparent permeability (Papp) at varying apical pH was investigated using the Caco-2 cell line and extrapolated to effective intestinal permeability (Peff) in human duodenum, jejunum, ileum and colon. Desvenlafaxine pKa-values and octanol-water partition coefficients (Do:w) were determined experimentally. Due to predicted rapid dissolution after IRF administration, desvenlafaxine was predicted to be available for permeation in the duodenum. Desvenlafaxine Do:w and Papp increased approximately 13-fold when increasing apical pH from 5.5 to 7.4. Desvenlafaxine Peff thus increased with pH down the small intestine. Consequently, desvenlafaxine absorption from an IRF appears rate-limited by low Peff in the upper small intestine, which "delays" the predicted time to the maximal plasma concentration (tmax), consistent with clinical data. Conversely, desvenlafaxine absorption from the ERF appears rate-limited by dissolution due to the formulation, which tends to negate the influence of pH-dependent permeability on absorption. We suggest that desvenlafaxine Peff is mainly driven by transcellular diffusion of the unionized form. In the case of desvenlafaxine, poor metabolism does not imply low intestinal permeability, as indicated by the BDDCS, merely low duodenal/jejunal permeability. Copyright © 2015 Elsevier B.V. All rights reserved.

Can accurate kinetic laws be created to describe chemical weathering?

NASA Astrophysics Data System (ADS)

Schott, Jacques; Oelkers, Eric H.; Bénézeth, Pascale; Goddéris, Yves; François, Louis

2012-11-01

Knowledge of the mechanisms and rates of mineral dissolution and growth, especially close to equilibrium, is essential for describing the temporal and spatial evolution of natural processes like weathering and its impact on CO2 budget and climate. The Surface Complexation approach (SC) combined with Transition State Theory (TST) provides an efficient framework for describing mineral dissolution over wide ranges of solution composition, chemical affinity, and temperature. There has been a large debate for several years, however, about the comparative merits of SC/TS versus classical growth theories for describing mineral dissolution and growth at near-to-equilibrium conditions. This study considers recent results obtained in our laboratory on oxides, hydroxides, silicates, and carbonates on near-equilibrium dissolution and growth via the combination of complementary microscopic and macroscopic techniques including hydrothermal atomic force microscopy, hydrogen-electrode concentration cell, mixed flow and batch reactors. Results show that the dissolution and precipitation of hydroxides, kaolinite, and hydromagnesite powders of relatively high BET surface area closely follow SC/TST rate laws with a linear dependence of both dissolution and growth rates on fluid saturation state (Ω) even at very close to equilibrium conditions (|ΔG| < 500 J/mol). This occurs because sufficient reactive sites (e.g. at kink, steps, and edges) are available at the exposed faces for dissolution and/or growth, allowing reactions to proceed via the direct and reversible detachment/attachment of reactants at the surface. In contrast, for magnesite and quartz, which have low surface areas, fewer active sites are available for growth and dissolution. Such minerals exhibit rates dependencies on Ω at near equilibrium conditions ranging from linear to highly non-linear functions of Ω, depending on the treatment of the crystals before the reaction. It follows that the form of the f(ΔG) function describing the growth and dissolution of minerals with low surface areas depends on the availability of reactive sites at the exposed faces and thus on the history of the mineral-fluid interaction and the hydrodynamic conditions under which the crystals are reacted. It is advocated that the crystal surface roughness could serve as a proxy of the density of reactive sites. The consequences of the different rate laws on the quantification of loess weathering along the Mississippi valley for the next one hundred years are examined.

Experimental study of terrestrial plant litter interaction with aqueous solutions

NASA Astrophysics Data System (ADS)

Fraysse, F.; Pokrovsky, O. S.; Meunier, J.-D.

2010-01-01

Quantification of silicon and calcium recycling by plants is hampered by the lack of physico-chemical data on reactivity of plant litter in soil environments. We applied a laboratory experimental approach for determining the silica and calcium release rates from litter of typical temperate and boreal plants: pine ( Pinus laricio), birch ( Betula pubescens), larch ( Larix gmelinii), elm ( Ulmus laevis Pall.), tree fern ( Dicksonia squarrosa), and horsetail (Equisetum arvense) in 0.01 M NaCl solutions, pH of 2-10 and temperature equals to 5, 25 and 40 °C. Open system, mixed-flow reactors equipped with dialysis compartment and batch reactors were used. Comparative measurements were performed on intact larch needles and samples grounded during different time, sterilized or not and with addition or not of sodium azide in order to account for the effect of surface to mass ratio and possible microbiological activity on the litter dissolution rates. Litter degradation results suggest that the silica release rate is independent on dissolved organic carbon release (cell breakdown) which implies the presence of phytoliths in a pure "inorganic" pool not complexed with organic matter. Calcium and DOC are released at the very first stage of litter dissolution while Si concentration increases gradually suggesting the presence of Ca and Si in two different pools. The dry-weight normalized dissolution rate at circum-neutral pH range (approx. 1-10 μmol/g DW/day) is 2 orders of magnitude higher than the rates of Si release from common soil minerals (kaolinite, smectite, illite). Minimal Ca release rates evaluated from batch and mixed-flow reactors are comparable with those of most reactive soil minerals such as calcite and apatite, and several orders of magnitude higher than the dissolution rates of major rock-forming silicates (feldspars, pyroxenes). The activation energy for Si liberation from plant litter is approx. 50 kJ/mol which is comparable with that of surface-controlled mineral dissolutions. It is shown that the Si release rate from the above-ground forest biomass is capable of producing the Si concentrations observed in soil solutions of surficial horizons and contribute significantly to the Si flux from the soil to the river.

A probabilistic assessment of calcium carbonate export and dissolution in the modern ocean

NASA Astrophysics Data System (ADS)

Battaglia, G.; Steinacher, M.; Joos, F.

2015-12-01

The marine cycle of calcium carbonate (CaCO3) is an important element of the carbon cycle and co-governs the distribution of carbon and alkalinity within the ocean. However, CaCO3 fluxes and mechanisms governing CaCO3 dissolution are highly uncertain. We present an observationally-constrained, probabilistic assessment of the global and regional CaCO3 budgets. Parameters governing pelagic CaCO3 export fluxes and dissolution rates are sampled using a Latin-Hypercube scheme to construct a 1000 member ensemble with the Bern3D ocean model. Ensemble results are constrained by comparing simulated and observation-based fields of excess dissolved calcium carbonate (TA*). The minerals calcite and aragonite are modelled explicitly and ocean-sediment fluxes are considered. For local dissolution rates either a strong, a weak or no dependency on CaCO3 saturation is assumed. Median (68 % confidence interval) global CaCO3 export is 0.82 (0.67-0.98) Gt PIC yr-1, within the lower half of previously published estimates (0.4-1.8 Gt PIC yr-1). The spatial pattern of CaCO3 export is broadly consistent with earlier assessments. Export is large in the Southern Ocean, the tropical Indo-Pacific, the northern Pacific and relatively small in the Atlantic. Dissolution within the 200 to 1500 m depth range (0.33; 0.26-0.40 Gt PIC yr-1) is substantially lower than inferred from the TA*-CFC age method (1 ± 0.5 Gt PIC yr-1). The latter estimate is likely biased high as the TA*-CFC method neglects transport. The constrained results are robust across a range of diapycnal mixing coefficients and, thus, ocean circulation strengths. Modelled ocean circulation and transport time scales for the different setups were further evaluated with CFC11 and radiocarbon observations. Parameters and mechanisms governing dissolution are hardly constrained by either the TA* data or the current compilation of CaCO3 flux measurements such that model realisations with and without saturation-dependent dissolution achieve skill. We suggest to apply saturation-independent dissolution rates in Earth System Models to minimise computational costs.

A Model for Dissolution of Lime in Steelmaking Slags

NASA Astrophysics Data System (ADS)

Sarkar, Rahul; Roy, Ushasi; Ghosh, Dinabandhu

2016-08-01

In a previous study by Sarkar et al. (Metall. Mater. Trans. B 46B:961 2015), a dynamic model of the LD steelmaking was developed. The prediction of the previous model (Sarkar et al. in Metall. Mater. Trans. B 46B:961 2015) for the bath (metal) composition matched well with the plant data (Cicutti et al. in Proceedings of 6th International Conference on Molten Slags, Fluxes and Salts, Stockholm City, 2000). However, with respect to the slag composition, the prediction was not satisfactory. The current study aims to improve upon the previous model Sarkar et al. (Metall. Mater. Trans. B 46B:961 2015) by incorporating a lime dissolution submodel into the earlier one. From the industrial point of view, the understanding of the lime dissolution kinetics is important to meet the ever-increasing demand of producing low-P steel at a low basicity. In the current study, three-step kinetics for the lime dissolution is hypothesized on the assumption that a solid layer of 2CaO·SiO2 should form around the unreacted core of the lime. From the available experimental data, it seems improbable that the observed kinetics should be controlled singly by any one kinetic step. Accordingly, a general, mixed control model has been proposed to calculate the dissolution rate of the lime under varying slag compositions and temperatures. First, the rate equation for each of the three rate-controlling steps has been derived, for three different lime geometries. Next, the rate equation for the mixed control kinetics has been derived and solved to find the dissolution rate. The model predictions have been validated by means of the experimental data available in the literature. In addition, the effects of the process conditions on the dissolution rate have been studied, and compared with the experimental results wherever possible. Incorporation of this submodel into the earlier global model (Sarkar et al. in Metall. Mater. Trans. B 46B:961 2015) enables the prediction of the lime dissolution rate in the dynamic system of LD steelmaking. In addition, with the inclusion of this submodel, significant improvement in the prediction of the slag composition during the main blow period has been observed.

Effects of Bacillus subtilis endospore surface reactivity on the rate of forsterite dissolution

NASA Astrophysics Data System (ADS)

Harrold, Z.; Gorman-Lewis, D.

2013-12-01

Primary mineral dissolution products, such as silica (Si), calcium (Ca) and magnesium (Mg), play an important role in numerous biologic and geochemical cycles including microbial metabolism, plant growth and secondary mineral precipitation. The flux of these and other dissolution products into the environment is largely controlled by the rate of primary silicate mineral dissolution. Bacteria, a ubiquitous component in water-rock systems, are known to facilitate mineral dissolution and may play a substantial role in determining the overall flux of dissolution products into the environment. Bacterial cell walls are complex and highly reactive organic surfaces that can affect mineral dissolution rates directly through microbe-mineral adsorption or indirectly by complexing dissolution products. The effect of bacterial surface adsorption on chemical weathering rates may even outweigh the influence of active processes in environments where a high proportion of cells are metabolically dormant or cell metabolism is slow. Complications associated with eliminating or accounting for ongoing metabolic processes in long-term dissolution studies have made it challenging to isolate the influence of cell wall interactions on mineral dissolution rates. We utilized Bacillus subtilis endospores, a robust and metabolically dormant cell type, to isolate and quantify the effects of bacterial surface reactivity on forsterite (Mg2SiO4) dissolution rates. We measured the influence of both direct and indirect microbe-mineral interactions on forsterite dissolution. Indirect pathways were isolated using dialysis tubing to prevent mineral-microbe contact while allowing free exchange of dissolved mineral products and endospore-ion adsorption. Homogenous experimental assays allowed both direct microbe-mineral and indirect microbe-ion interactions to affect forsterite dissolution rates. Dissolution rates were calculated based on silica concentrations and zero-order dissolution kinetics. Additional analyses including Mg concentrations, microprobe and BET analyses support mineral dissolution rate calculations and stoichiometry considerations. All experimental assays containing endospores show increased forsterite dissolution rates relative to abiotic controls. Forsterite dissolution rates increased by approximately one order of magnitude in dialysis bound, biotic experiments relative to abiotic assays. Homogenous biotic assays exhibited a more complex dissolution rate profile that changes over time. All microbially mediated forsterite dissolution rates returned to abiotic control rates after 10 to 15 days of incubation. This shift in dissolution rate likely corresponds to maximum endospore surface adsorption capacity. The Bacillus subtilis endospore surface serves as a first-order proxy for studying the effect of metabolizing microbe surfaces on silicate dissolution rates. Comparisons with published abiotic, microbial, and organic acid mediated forsterite dissolution rates will provide insight on the importance of bacterial surfaces in primary mineral dissolution processes.

Bulk Dissolution Rates of Cadmium and Bismuth Tellurides As a Function of pH, Temperature and Dissolved Oxygen.

PubMed

Biver, Marc; Filella, Montserrat

2016-05-03

The toxicity of Cd being well established and that of Te suspected, the bulk, surface-normalized steady-state dissolution rates of two industrially important binary tellurides-polycrystalline cadmium and bismuth tellurides- were studied over the pH range 3-11, at various temperatures (25-70 °C) and dissolved oxygen concentrations (0-100% O2 in the gas phase). The behavior of both tellurides is strikingly different. The dissolution rates of CdTe monotonically decreased with increasing pH, the trend becoming more pronounced with increasing temperature. Activation energies were of the order of magnitude associated with surface controlled processes; they decreased with decreasing acidity. At pH 7, the CdTe dissolution rate increased linearly with dissolved oxygen. In anoxic solution, CdTe dissolved at a finite rate. In contrast, the dissolution rate of Bi2Te3 passed through a minimum at pH 5.3. The activation energy had a maximum in the rate minimum at pH 5.3 and fell below the threshold for diffusion control at pH 11. No oxygen dependence was detected. Bi2Te3 dissolves much more slowly than CdTe; from one to more than 3.5 orders of magnitude in the Bi2Te3 rate minimum. Both will readily dissolve under long-term landfill deposition conditions but comparatively slowly.

Hot Melt Extrudates Formulated Using Design Space: One Simple Process for Both Palatability and Dissolution Rate Improvement.

PubMed

Malaquias, Lorena F B; Schulte, Heidi L; Chaker, Juliano A; Karan, Kapish; Durig, Thomas; Marreto, Ricardo N; Gratieri, Tais; Gelfuso, Guilherme M; Cunha-Filho, Marcilio

2018-01-01

This work aimed at obtaining an optimized itraconazole (ITZ) solid oral formulation in terms of palatability and dissolution rate by combining different polymers using hot melt extrusion (HME), according to a simplex centroid mixture design. For this, the polymers Plasdone ® (poly(1-vinylpyrrolidone-co-vinyl acetate) [PVP/VA]), Klucel ® ELF (2-hydroxypropyl ether cellulose [HPC]), and Soluplus ® (SOL, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol) were processed using a laboratory HME equipment operating without recirculation at constant temperature. Samples were characterized by physicochemical assays, as well as dissolution rate and palatability using an e-tongue. All materials became homogeneous and dense after HME processing. Thermal and structural analyses demonstrated drug amorphization, whereas IR spectroscopy evidenced drug stability and drug-excipient interactions in HME systems. Extrudates presented a significant increase in dissolution rate compared to ITZ raw material, mainly with formulations containing PVP/VA and HPC. A pronounced improvement in taste masking was also identified for HME systems, especially in those containing higher amounts of SOL and HPC. Data showed polymers act synergistically favoring formulation functional properties. Predicted best formulation should contain ITZ 25.0%, SOL 33.2%, HPC 28.9%, and PVP/VA 12.9% (w/w). Optimized response considering dissolution rate and palatability reinforces the benefit of polymer combinations. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Preparation and characterization of poly(lactic acid) nanoparticles for sustained release of pyridostigmine bromide.

PubMed

Tan, Q Y; Xu, M L; Wu, J Y; Yin, H F; Zhang, J Q

2012-04-01

A novel pyridostigmine bromide poly (lactic acid) nanoparticles (PBPNPs) was prepared to obtain sustained release characteristics of PB. A central composite design approach was employed for process optimization. The in vitro release studies were carried out by dialysis method and conducted using four different dissolution media. Similar factor method was investigated for dissolution profile comparison. Multiple linear regression analysis for process optimization revealed that the optimal PBPNPs were obtained where the values of the amount of PB (X1, mg), PLA concentration (X2, % w:v), and PVA concentration (X3, % w:v) were 49.20 mg, 3.31% and 3.41%, respectively. The average particle size and zeta potential of PBPNPs with the optimized formulation were 722.9 +/- 4.3 nm, and -25.12 +/- 1.2 mV, respectively. PBPNPs provided an initial burst of drug release followed by a very slow release over an extended period of time (72 h). Compared with free PB, PBPNPs had a significantly lower release rate of PB in vitro. The in vitro release profile of the PBPNPs could be described by Weibull models, regardless of type of dissolution medium. Statistical significance of similarity between every two dissolution profiles of PBPNPs in different dissolution media was found, and the difference between the curves of PBPNPs and pure PB was statistically significant.

An understanding of modified release matrix tablets behavior during drug dissolution as the key for prediction of pharmaceutical product performance - case study of multimodal characterization of quetiapine fumarate tablets.

PubMed

Kulinowski, Piotr; Woyna-Orlewicz, Krzysztof; Rappen, Gerd-Martin; Haznar-Garbacz, Dorota; Węglarz, Władysław P; Dorożyński, Przemysław P

2015-04-30

Motivation for the study was the lack of dedicated and effective research and development (R&D) in vitro methods for oral, generic, modified release formulations. The purpose of the research was to assess multimodal in vitro methodology for further bioequivalence study risk minimization. Principal results of the study are as follows: (i) Pharmaceutically equivalent quetiapine fumarate extended release dosage form of Seroquel XR was developed using a quality by design/design of experiment (QbD/DoE) paradigm. (ii) The developed formulation was then compared with originator using X-ray microtomography, magnetic resonance imaging and texture analysis. Despite similarity in terms of compendial dissolution test, developed and original dosage forms differed in micro/meso structure and consequently in mechanical properties. (iii) These differences were found to be the key factors of failure of biorelevant dissolution test using the stress dissolution apparatus. Major conclusions are as follows: (i) Imaging methods allow to assess internal features of the hydrating extended release matrix and together with the stress dissolution test allow to rationalize the design of generic formulations at the in vitro level. (ii) Technological impact on formulation properties e.g., on pore formation in hydrating matrices cannot be overlooked when designing modified release dosage forms. Copyright © 2015 Elsevier B.V. All rights reserved.

Preformulation studies and optimization of sodium alginate based floating drug delivery system for eradication of Helicobacter pylori.

PubMed

Diós, Péter; Nagy, Sándor; Pál, Szilárd; Pernecker, Tivadar; Kocsis, Béla; Budán, Ferenc; Horváth, Ildikó; Szigeti, Krisztián; Bölcskei, Kata; Máthé, Domokos; Dévay, Attila

2015-10-01

The aim of this study was to design a local, floating, mucoadhesive drug delivery system containing metronidazole for Helicobacter pylori eradication. Face-centered central composite design (with three factors, in three levels) was used for evaluation and optimization of in vitro floating and dissolution studies. Sodium alginate (X1), low substituted hydroxypropyl cellulose (L-HPC B1, X2) and sodium bicarbonate (X3) concentrations were the independent variables in the development of effervescent floating tablets. All tablets showed acceptable physicochemical properties. Statistical analysis revealed that tablets with 5.00% sodium alginate, 38.63% L-HPC B1 and 8.45% sodium bicarbonate content showed promising in vitro floating and dissolution properties for further examinations. Optimized floating tablets expressed remarkable floating force. Their in vitro dissolution studies were compared with two commercially available non-floating metronidazole products and then microbiologically detected dissolution, ex vivo detachment force, rheological mucoadhesion studies and compatibility studies were carried out. Remarkable similarity (f1, f2) between in vitro spectrophotometrically and microbiologically detected dissolutions was found. Studies revealed significant ex vivo mucoadhesion of optimized tablets, which was considerably increased by L-HPC. In vivo X-ray CT studies of optimized tablets showed 8h gastroretention in rats represented by an animation prepared by special CT technique. Copyright © 2015 Elsevier B.V. All rights reserved.

Evolution of a detailed physiological model to simulate the gastrointestinal transit and absorption process in humans, part II: extension to describe performance of solid dosage forms.

PubMed

Thelen, Kirstin; Coboeken, Katrin; Willmann, Stefan; Dressman, Jennifer B; Lippert, Jörg

2012-03-01

The physiological absorption model presented in part I of this work is now extended to account for dosage-form-dependent gastrointestinal (GI) transit as well as disintegration and dissolution processes of various immediate-release and modified-release dosage forms. Empirical functions of the Weibull type were fitted to experimental in vitro dissolution profiles of solid dosage forms for eight test compounds (aciclovir, caffeine, cimetidine, diclofenac, furosemide, paracetamol, phenobarbital, and theophylline). The Weibull functions were then implemented into the model to predict mean plasma concentration-time profiles of the various dosage forms. On the basis of these dissolution functions, pharmacokinetics (PK) of six model drugs was predicted well. In the case of diclofenac, deviations between predicted and observed plasma concentrations were attributable to the large variability in gastric emptying time of the enteric-coated tablets. Likewise, oral PK of furosemide was found to be predominantly governed by the gastric emptying patterns. It is concluded that the revised model for GI transit and absorption was successfully integrated with dissolution functions of the Weibull type, enabling prediction of in vivo PK profiles from in vitro dissolution data. It facilitates a comparative analysis of the parameters contributing to oral drug absorption and is thus a powerful tool for formulation design. Copyright © 2011 Wiley Periodicals, Inc.

Enhanced dissolution and oral bioavailability of valsartan solid dispersions prepared by a freeze-drying technique using hydrophilic polymers.

PubMed

Xu, Wei-Juan; Xie, Hong-Juan; Cao, Qing-Ri; Shi, Li-Li; Cao, Yue; Zhu, Xiao-Yin; Cui, Jing-Hao

2016-01-01

This study aimed to improve the dissolution rate and oral bioavailability of valsartan (VAL), a poorly soluble drug using solid dispersions (SDs). The SDs were prepared by a freeze-drying technique with polyethylene glycol 6000 (PEG6000) and hydroxypropylmethylcellulose (HPMC 100KV) as hydrophilic polymers, sodium hydroxide (NaOH) as an alkalizer, and poloxamer 188 as a surfactant without using any organic solvents. In vitro dissolution rate and physicochemical properties of the SDs were characterized using the USP paddle method, differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and Fourier transform-infrared (FT-IR) spectroscopy, respectively. In addition, the oral bioavailability of SDs in rats was evaluated by using VAL (pure drug) as a reference. The dissolution rates of the SDs were significantly improved at pH 1.2 and pH 6.8 compared to those of the pure drug. The results from DSC, XRD showed that VAL was molecularly dispersed in the SDs as an amorphous form. The FT-IR results suggested that intermolecular hydrogen bonding had formed between VAL and its carriers. The SDs exhibited significantly higher values of AUC 0-24 h and Cmax in comparison with the pure drug. In conclusion, hydrophilic polymer-based SDs prepared by a freeze-drying technique can be a promising method to enhance dissolution rate and oral bioavailability of VAL.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neeway, James J.; Rieke, Peter C.; Parruzot, Benjamin P.

In far-from-equilibrium conditions, the dissolution of borosilicate glasses used to immobilize nuclear waste is known to be a function of both temperature and pH. The aim of this paper is to study effects of these variables on three model waste glasses (SON68, ISG, AFCI). To do this, experiments were conducted at temperatures of 23, 40, 70, and 90 °C and pH(RT) values of 9, 10, 11, and 12 with the single-pass flow-through (SPFT) test method. The results from these tests were then used to parameterize a kinetic rate model based on transition state theory. Both the absolute dissolution rates andmore » the rate model parameters are compared with previous results. Discrepancies in the absolute dissolution rates as compared to those obtained using other test methods are discussed. Rate model parameters for the three glasses studied here are nearly equivalent within error and in relative agreement with previous studies. The results were analyzed with a linear multivariate regression (LMR) and a nonlinear multivariate regression performed with the use of the Glass Corrosion Modeling Tool (GCMT), which is capable of providing a robust uncertainty analysis. This robust analysis highlights the high degree of correlation of various parameters in the kinetic rate model. As more data are obtained on borosilicate glasses with varying compositions, the effect of glass composition on the rate parameter values could possibly be obtained. This would allow for the possibility of predicting the forward dissolution rate of glass based solely on composition« less

Preparation and characterization of fast dissolving flurbiprofen and esomeprazole solid dispersion using spray drying technique.

PubMed

Pradhan, Roshan; Tran, Tuan Hiep; Kim, Sung Yub; Woo, Kyu Bong; Choi, Yong Joo; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

2016-04-11

We aimed to develop an immediate-release flurbiprofen (FLU) and esomeprazole (ESO) combination formulation with enhanced gastric aqueous solubility and dissolution rate. Aqueous solubility can be enhanced by formulating solid dispersions (SDs) with a polyvinylpyrrolidone (PVP)-K30 hydrophilic carrier, using spray-drying technique. Aqueous and gastric pH dissolution can be achieved by macro-environmental pH modulation using sodium bicarbonate (NaHCO3) and magnesium hydroxide (Mg(OH)2) as the alkaline buffer. FLU/ESO-loaded SDs (FLU/ESO-SDs) significantly improved aqueous solubility of both drugs, compared to each drug powder. Dissolution studies in gastric pH and water were compared with the microenvironmental pH modulated formulations. The optimized FLU/ESO-SD powder formulation consisted of FLU/ESO/PVP-K30/sodium carbonate (Na2CO3) in a weight ratio 1:0.22:1.5:0.3, filled in the inner capsule. The outer capsule consisted of NaHCO3 and Mg(OH)2, which created the macro-environmental pH modulation. Increased aqueous and gastric pH dissolution of FLU and ESO from the SD was attributed to the alkaline buffer effects and most importantly, to drug transformation from crystalline to amorphous SD powder, clearly revealed by scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffraction studies. Thus, the combined FLU and ESO SD powder can be effectively delivered as an immediate-release formulation using the macro-environmental pH modulation concept. Copyright © 2016. Published by Elsevier B.V.

Biotic and abiotic interactions in aquatic microcosms determine fate and toxicity of Ag nanoparticles. Part 1. Aggregation and dissolution.

PubMed

Unrine, Jason M; Colman, Benjamin P; Bone, Audrey J; Gondikas, Andreas P; Matson, Cole W

2012-07-03

To better understand their fate and toxicity in aquatic environments, we compared the aggregation and dissolution behavior of gum arabic (GA) and polyvinylpyrrolidone (PVP) coated Ag nanoparticles (NPs) in aquatic microcosms. There were four microcosm types: surface water; water and sediment; water and aquatic plants; or water, sediment, and aquatic plants. Dissolution and aggregation behavior of AgNPs were examined using ultracentrifugation, ultrafiltration, and asymmetrical flow field flow fractionation coupled to ultraviolet-visible spectroscopy, dynamic and static laser light scattering, and inductively coupled plasma mass spectrometry. Plants released dissolved organic matter (DOM) into the water column either through active or passive processes in response to Ag exposure. This organic matter fraction readily bound Ag ions. The plant-derived DOM had the effect of stabilizing PVP-AgNPs as primary particles, but caused GA-AgNPs to be removed from the water column, likely by dissolution and binding of released Ag ions on sediment and plant surfaces. The destabilization of the GA-AgNPs also corresponded with X-ray absorption near edge spectroscopy results which suggest that 22-28% of the particulate Ag was associated with thiols and 5-14% was present as oxides. The results highlight the potential complexities of nanomaterial behavior in response to biotic and abiotic modifications in ecosystems, and may help to explain differences in toxicity of Ag observed in realistic exposure media compared to simplified laboratory exposures.

Development of a New Aprepitant Liquisolid Formulation with the Aid of Artificial Neural Networks and Genetic Programming.

PubMed

Barmpalexis, Panagiotis; Grypioti, Agni; Eleftheriadis, Georgios K; Fatouros, Dimitris G

2018-02-01

In the present study, liquisolid formulations were developed for improving dissolution profile of aprepitant (APT) in a solid dosage form. Experimental studies were complemented with artificial neural networks and genetic programming. Specifically, the type and concentration of liquid vehicle was evaluated through saturation-solubility studies, while the effect of the amount of viscosity increasing agent (HPMC), the type of wetting (Soluplus® vs. PVP) and solubilizing (Poloxamer®407 vs. Kolliphor®ELP) agents, and the ratio of solid coating (microcrystalline cellulose) to carrier (colloidal silicon dioxide) were evaluated based on in vitro drug release studies. The optimum liquisolid formulation exhibited improved dissolution characteristics compared to the marketed product Emend®. X-ray diffraction (XRD), scanning electron microscopy (SEM) and a novel method combining particle size analysis by dynamic light scattering (DLS) and HPLC, revealed that the increase in dissolution rate of APT in the optimum liquisolid formulation was due to the formation of stable APT nanocrystals. Differential scanning calorimetry (DSC) and attenuated total reflection FTIR spectroscopy (ATR-FTIR) revealed the presence of intermolecular interactions between APT and liquisolid formulation excipients. Multilinear regression analysis (MLR), artificial neural networks (ANNs), and genetic programming (GP) were used to correlate several formulation variables with dissolution profile parameters (Y 15min and Y 30min ) using a full factorial experimental design. Results showed increased correlation efficacy for ANNs and GP (RMSE of 0.151 and 0.273, respectively) compared to MLR (RMSE = 0.413).

Increased dissolution rates of tranilast solid dispersions extruded with inorganic excipients.

PubMed

Maniruzzaman, Mohammed; Ross, Steven A; Islam, Muhammad Tariqul; Scoutaris, Nikolaos; Nair, Arun; Douroumis, Dennis

2017-06-01

The purpose of this study was to evaluate the performance of Neusilin® (NEU) a synthetic magnesium aluminometasilicate as an inorganic drug carrier co-processed with the hydrophilic surfactants Labrasol and Labrafil to develop Tranilast (TLT)-based solid dispersions using continuous melt extrusion (HME) processing. Twin-screw extrusion was optimized to develop various TLT/excipient/surfactant formulations followed by continuous capsule filling in the absence of any downstream equipment. Physicochemical characterization showed the existence of TLT in partially crystalline state in the porous network of inorganic NEU for all extruded formulations. Furthermore, in-line NIR studies revealed a possible intermolecular H-bonding formation between the drug and the carrier resulting in the increase of TLT dissolution rates. The capsules containing TLT-extruded solid dispersions showed enhanced dissolution rates and compared with the marketed Rizaben ® product.

A novel determination of calcite dissolution kinetics in seawater

NASA Astrophysics Data System (ADS)

Subhas, Adam V.; Rollins, Nick E.; Berelson, William M.; Dong, Sijia; Erez, Jonathan; Adkins, Jess F.

2015-12-01

We present a novel determination of the dissolution kinetics of inorganic calcite in seawater. We dissolved 13 C -labeled calcite in unlabeled seawater, and traced the evolving δ13 C composition of the fluid over time to establish dissolution rates. This method provides sensitive determinations of dissolution rate, which we couple with tight constraints on both seawater saturation state and surface area of the dissolving minerals. We have determined dissolution rates for two different abiotic calcite materials and three different grain sizes. Near-equilibrium dissolution rates are highly nonlinear, and are well normalized by geometric surface area, giving an empirical dissolution rate dependence on saturation state (Ω) of: This result substantiates the non-linear response of calcite dissolution to undersaturation. The bulk dissolution rate constant calculated here is in excellent agreement with those determined in far from equilibrium and dilute solution experiments. Plots of dissolution versus undersaturation indicates the presence of at least two dissolution mechanisms, implying a criticality in the calcite-seawater system. Finally, our new rate determination has implications for modeling of pelagic and seafloor dissolution. Nonlinear dissolution kinetics in a simple 1-D lysocline model indicate a possible transition from kinetic to diffusive control with increasing water depth, and also confirm the importance of respiration-driven dissolution in setting the shape of the calcite lysocline.

Modification of crystal habit of ibuprofen using the phase partition technique: effect of aerosil and tween 80 in binding solvent.

PubMed

Umprayn, K; Luengtummuen, A; Kitiyadisai, C; Pornpiputsakul, T

2001-11-01

A ternary diagram, representing the solubility of binding solvent (chloroform) in a mixture of ethanol and water, was constructed. For this study, the solvent mixture that gave the best ibuprofen pellets (IPs) was composed of chloroform.ethanol:water at a ratio of 1.5%:8%:90.5%. The suitable agitator speed, temperature, and mixing time were found to be 1,500 rpm, 25 degrees C +/- 2 degrees C, and 20 min, respectively. In addition, suitable stirring time when the phase partition process of IPs began was 15 min. IPs obtained from these conditions were small and round, approximately 1 mm; surface determination by scanning electron microscopy (SEM) indicated that the IPs were composed of drug microcrystals rearranged on the surface. For the dissolution, IPs showed lower drug release when compared with pure ibuprofen crystal (IC) (f2 analysis). An attempt to modify the dissolution property of IP by incorporating various concentrations of Aerosil and Tween 80 in the binding solvent was made. Microscopic appearance showed that both Aerosil and Tween 80 gave less spherical pellets when compared with the use of binding solvent alone. For both the Aerosil and Tween 80 employed, the results indicated a change in rearrangement of drug microcrystals and a change in crystal habit. However, Tween 80 gave more change of the crystallographic direction of drug microcrystals than Aerosil. In term of dissolution, the results showed that employing Tween 80 at 1.2% gave the highest drug release compared to the use of Aerosil and IC alone (f2 analysis). These pellets had a good flow property, as indicated by Carr's compressibility, flow rate, and angle of repose, and they can be compressed into a tablet, encapsulated by suitable polymer, or pulverized to obtain micronized crystals. In the case of compression into tablets, the dissolution profiles of these tablets compared with those of commercial product meet the USP 24 requirement (Q > or = 80% at 60 min).

Reaction kinetics of cellulose hydrolysis in subcritical and supercritical water

NASA Astrophysics Data System (ADS)

Olanrewaju, Kazeem Bode

The uncertainties in the continuous supply of fossil fuels from the crisis-ridden oil-rich region of the world is fast shifting focus on the need to utilize cellulosic biomass and develop more efficient technologies for its conversion to fuels and chemicals. One such technology is the rapid degradation of cellulose in supercritical water without the need for an enzyme or inorganic catalyst such as acid. This project focused on the study of reaction kinetics of cellulose hydrolysis in subcritical and supercritical water. Cellulose reactions at hydrothermal conditions can proceed via the homogeneous route involving dissolution and hydrolysis or the heterogeneous path of surface hydrolysis. The work is divided into three main parts. First, the detailed kinetic analysis of cellulose reactions in micro- and tubular reactors was conducted. Reaction kinetics models were applied, and kinetics parameters at both subcritical and supercritical conditions were evaluated. The second major task was the evaluation of yields of water soluble hydrolysates obtained from the hydrolysis of cellulose and starch in hydrothermal reactors. Lastly, changes in molecular weight distribution due to hydrothermolytic degradation of cellulose were investigated. These changes were also simulated based on different modes of scission, and the pattern generated from simulation was compared with the distribution pattern from experiments. For a better understanding of the reaction kinetics of cellulose in subcritical and supercritical water, a series of reactions was conducted in the microreactor. Hydrolysis of cellulose was performed at subcritical temperatures ranging from 270 to 340 °C (tau = 0.40--0.88 s). For the dissolution of cellulose, the reaction was conducted at supercritical temperatures ranging from 375 to 395 °C (tau = 0.27--0.44 s). The operating pressure for the reactions at both subcritical and supercritical conditions was 5000 psig. The results show that the rate-limiting step in converting cellulose to fermentable sugars in subcritical and supercritical water differs because of the difference in their activation energies. Cellulose and starch were both hydrolyzed in micro- and tubular reactors and at subcritical and supercritical conditions. Due to the difficulty involved in generating an aqueous based dissolved cellulose and having it reacted in subcritical water, dissolved starch was used instead. Better yield of water soluble hydrolysates, especially fermentable sugars, were observed from the hydrolysis of cellulose and dissolved starch in subcritical water than at supercritical conditions. The concluding phase of this project focuses on establishing the mode of scission of cellulose chains in the hydrothermal reactor. This was achieved by using the simulated degradation pattern generated based on different scission modes to fingerprint the degradation pattern obtained from experiment.

Antisolvent precipitation technique: A very promising approach to crystallize curcumin in presence of polyvinyl pyrrolidon for solubility and dissolution enhancement.

PubMed

Sadeghi, Fatemeh; Ashofteh, Mohammad; Homayouni, Alireza; Abbaspour, Mohammadreza; Nokhodchi, Ali; Garekani, Hadi Afrasiabi

2016-11-01

Curcumin with a vast number of pharmacological activities is a poorly water soluble drug which its oral bioavailability is profoundly limited by its dissolution or solubility in GI tract. Curcumin could be a good anticancer drug if its solubility could be increased. Therefore, the aim of the present study was to increase the dissolution rate of curcumin by employing antisolvent crystallization technique and to investigate the effect of polyvinyl pyrrolidone K30 (PVP) as colloidal particles in crystallization medium on resultant particles. Curcumin was crystalized in the presence of different amounts of PVP by antisolvent crystallization method and their physical mixtures were prepared for comparison purposes. The samples were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and Fourier transform infrared spectroscopy (FT-IR). The solubility and dissolution of the treated and untreated curcumin were also determined. Antisolvent crystallization of curcumin led to the formation of particles with no definite geometric shape. It was interesting to note that the DSC and XRPD studies indicated the formation of a new polymorph and less crystallinity for particles crystallized in the absence of PVP. However, the crystallized curcumin in the presence of PVP was completely amorphous. All crystalized curcumin samples showed much higher dissolution rate compared to untreated curcumin. The amount of curcumin dissolved within 10 for treated curcumin in the presence of PVP (1:1 curcumin:PVP) was 7 times higher than untreated curcumin and this enhancement in the dissolution for curcumin samples crystallized in the absence of PVP was around 5 times. Overall' the results of this study showed that antisolvent crystallization method in the absence or presence of small amounts of PVP is very efficient in increasing the dissolution rate of curcumin to achieve better efficiency for curcumin. Copyright © 2016 Elsevier B.V. All rights reserved.

Moisture-Induced Amorphous Phase Separation of Amorphous Solid Dispersions: Molecular Mechanism, Microstructure, and Its Impact on Dissolution Performance.

PubMed

Chen, Huijun; Pui, Yipshu; Liu, Chengyu; Chen, Zhen; Su, Ching-Chiang; Hageman, Michael; Hussain, Munir; Haskell, Roy; Stefanski, Kevin; Foster, Kimberly; Gudmundsson, Olafur; Qian, Feng

2018-01-01

Amorphous phase separation (APS) is commonly observed in amorphous solid dispersions (ASD) when exposed to moisture. The objective of this study was to investigate: (1) the phase behavior of amorphous solid dispersions composed of a poorly water-soluble drug with extremely low crystallization propensity, BMS-817399, and PVP, following exposure to different relative humidity (RH), and (2) the impact of phase separation on the intrinsic dissolution rate of amorphous solid dispersion. Drug-polymer interaction was confirmed in ASDs at different drug loading using infrared (IR) spectroscopy and water vapor sorption analysis. It was found that the drug-polymer interaction could persist at low RH (≤75% RH) but was disrupted after exposure to high RH, with the advent of phase separation. Surface morphology and composition of 40/60 ASD at micro-/nano-scale before and after exposure to 95% RH were also compared. It was found that hydrophobic drug enriched on the surface of ASD after APS. However, for the 40/60 ASD system, the intrinsic dissolution rate of amorphous drug was hardly affected by the phase behavior of ASD, which may be partially attributed to the low crystallization tendency of amorphous BMS-817399 and enriched drug amount on the surface of ASD. Intrinsic dissolution rate of PVP decreased resulting from APS, leading to a lower concentration in the dissolution medium, but supersaturation maintenance was not anticipated to be altered after phase separation due to the limited ability of PVP to inhibit drug precipitation and prolong the supersaturation of drug in solution. This study indicated that for compounds with low crystallization propensity and high hydrophobicity, the risk of moisture-induced APS is high but such phase separation may not have profound impact on the drug dissolution performance of ASDs. Therefore, application of ASD technology on slow crystallizers could incur low risks not only in physical stability but also in dissolution performance. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

In Vitro Dissolution as a Tool for Formulation Selection: Telmisartan Two-Step IVIVC.

PubMed

Ruiz Picazo, Alejandro; Martinez-Martinez, Ma Teresa; Colón-Useche, Sarin; Iriarte, Ramon; Sánchez-Dengra, Bárbara; González-Álvarez, Marta; García-Arieta, Alfredo; González-Álvarez, Isabel; Bermejo, Marival

2018-05-17

The purpose of this investigation was to develop an exploratory two-step level A IVIVC for three telmisartan oral immediate release formulations, the reference product Micardis, and two generic formulations (X1 and X2). Correlation was validated with a third test formulation, Y1. Experimental solubility and permeability data were obtained to confirm that telmisartan is a class II compound under the Biopharmaceutic Classification System. Bioequivalence (BE) studies plasma profiles were combined using a previously published reference scaling procedure. X2 demonstrated in vivo BE, while X1 and Y1 failed to show BE due to the lower boundary of the 90% confidence interval for C max being outside the acceptance limits. Average plasma profiles were deconvoluted by the Loo-Riegelman method to obtain the oral fractions absorbed ( f a ). Fractions dissolved ( f diss ) were obtained in several conditions in USP II and USP IV apparatus, and later, the results were compared in order to find the most biopredictive model, calculating the f 2 similarity factor. The apparatus and conditions showing the same rank order than in vivo data were selected for further refinement of conditions. A Levy plot was constructed to estimate the time scaling factor and to make both processes, dissolution and absorption, superimposable. The in vitro dissolution experiment that reflected more accurately the in vivo behavior of the different formulations of telmisartan employed the USP IV dissolution apparatus and a dissolution environment with a flow rate of 8 mL/min and a three-step pH change, from 1.2 to 4.5 and 6.8, with a 0.05% of Tween 80. Thus, these conditions gave rise to a biopredictive dissolution test. This new model is able to predict the formulation differences in dissolution that were previously observed in vivo, which could be used as a risk-analysis tool for formulation selection in future bioequivalence trials.

Oral hesperidin-Amorphization and improved dissolution properties by controlled loading onto porous silica.

PubMed

Wei, Qionghua; Keck, Cornelia M; Müller, Rainer H

2017-02-25

The oral bioavailability of poorly soluble drugs can be improved by amorphization generated by loading into the pores of mesoporous particles (pore size 2-50nm). The main mechanisms are increased kinetic saturation solubility and dissolution velocity due to the amorphous drug state and the nano-size of the drug (=increased dissolution pressure). In this study, the maximum achievable drug loading compared to the theoretical drug loading, and the effect of drug loading degree on the dissolution properties (solubility, dissolution velocity) were investigated. Hesperidin was used as the model active (having also practical relevance for e.g. nutraceutical products), loading was performed onto AEROPERL ® 300 Pharma. Degree of successful drug loading could be easily followed by simple light microscopy (=useful tool for formulation optimization), and was in agreement with scanning electron microscopy. Amorphous versus crystalline state was followed by X-ray diffraction and differential scanning calorimetry. Loadings prepared were 28.6wt.%, 54.5wt.% and 60.0wt.%, the maximum theoretical loading was 72.5wt.%. Obviously the maximum drug loading is not achievable, the 54.5wt.% drug loading was the practical maximum with already some minor crystalline hesperidin on the surface. Interestingly, the maximum kinetic saturation solubility was obtained for the 54.5wt.% drug loading (941.74μg/ml in pH 6.8 PBS), versus 408.80μg/ml for the 60.0wt.% drug loading (=overloaded system). The raw drug powder had a thermodynamic solubility of only 18.40μg/ml. The fastest in vitro release was obtained with the 28.6wt.% loaded system, followed by the 54.5wt.% and 60.0wt.% loadings. The dissolution properties (solubility, dissolution velocity) can obviously be influenced by a "controlled loading". This is a simple, cost-effective technological alternative to modulating this property by chemical modification of silica, requiring a new costly regulatory approval of these chemically modified materials. Copyright © 2016. Published by Elsevier B.V.

Influence of acidic and alkaline waste solution properties on uranium migration in subsurface sediments.

PubMed

Szecsody, Jim E; Truex, Mike J; Qafoku, Nikolla P; Wellman, Dawn M; Resch, Tom; Zhong, Lirong

2013-08-01

This study shows that acidic and alkaline wastes co-disposed with uranium into subsurface sediments have significant impact on changes in uranium retardation, concentration, and mass during downward migration. For uranium co-disposal with acidic wastes, significant rapid (i.e., hours) carbonate and slow (i.e., 100 s of hours) clay dissolution resulted, releasing significant sediment-associated uranium, but the extent of uranium release and mobility change was controlled by the acid mass added relative to the sediment proton adsorption capacity. Mineral dissolution in acidic solutions (pH2) resulted in a rapid (<10 h) increase in aqueous carbonate (with Ca(2+), Mg(2+)) and phosphate and a slow (100 s of hours) increase in silica, Al(3+), and K(+), likely from 2:1 clay dissolution. Infiltration of uranium with a strong acid resulted in significant shallow uranium mineral dissolution and deeper uranium precipitation (likely as phosphates and carbonates) with downward uranium migration of three times greater mass at a faster velocity relative to uranium infiltration in pH neutral groundwater. In contrast, mineral dissolution in an alkaline environment (pH13) resulted in a rapid (<10h) increase in carbonate, followed by a slow (10 s to 100 s of hours) increase in silica concentration, likely from montmorillonite, muscovite, and kaolinite dissolution. Infiltration of uranium with a strong base resulted in not only uranium-silicate precipitation (presumed Na-boltwoodite) but also desorption of natural uranium on the sediment due to the high ionic strength solution, or 60% greater mass with greater retardation compared with groundwater. Overall, these results show that acidic or alkaline co-contaminant disposal with uranium can result in complex depth- and time-dependent changes in uranium dissolution/precipitation reactions and uranium sorption, which alter the uranium migration mass, concentration, and velocity. Copyright © 2013 Elsevier B.V. All rights reserved.

The temporal evolution of magnesium isotope fractionation during hydromagnesite dissolution, precipitation, and at equilibrium

NASA Astrophysics Data System (ADS)

Oelkers, Eric H.; Berninger, Ulf-Niklas; Pérez-Fernàndez, Andrea; Chmeleff, Jérôme; Mavromatis, Vasileios

2018-04-01

This study provides experimental evidence of the resetting of the magnesium (Mg) isotope signatures of hydromagnesite in the presence of an aqueous fluid during its congruent dissolution, precipitation, and at equilibrium at ambient temperatures over month-long timescales. All experiments were performed in batch reactors in aqueous sodium carbonate buffer solutions having a pH from 7.8 to 9.2. The fluid phase in all experiments attained bulk chemical equilibrium within analytical uncertainty with hydromagnesite within several days, but the experiments were allowed to continue for up to 575 days. During congruent hydromagnesite dissolution, the fluid first became enriched in isotopically light Mg compared to the dissolving hydromagnesite, but this Mg isotope composition became heavier after the fluid attained chemical equilibrium with the mineral. The δ26Mg composition of the fluid was up to ∼0.35‰ heavier than the initial dissolving hydromagnesite at the end of the dissolution experiments. Hydromagnesite precipitation was provoked during one experiment by increasing the reaction temperature from 4 to 50 °C. The δ26Mg composition of the fluid increased as hydromagnesite precipitated and continued to increase after the fluid attained bulk equilibrium with this phase. These observations are consistent with the hypothesis that mineral-fluid equilibrium is dynamic (i.e. dissolution and precipitation occur at equal, non-zero rates at equilibrium). Moreover the results presented in this study confirm (1) that the transfer of material from the solid to the fluid phase may not be conservative during stoichiometric dissolution, and (2) that the isotopic compositions of carbonate minerals can evolve even when the mineral is in bulk chemical equilibrium with its coexisting fluid. This latter observation suggests that the preservation of isotopic signatures of carbonate minerals in the geological record may require a combination of the isolation of fluid-mineral system from external chemical input and/or the existence of a yet to be defined dissolution/precipitation inhibition mechanism.

Human impact on regional groundwater composition through intervention in natural flow patterns and changes in land use

NASA Astrophysics Data System (ADS)

Schot, P. P.; van der Wal, J.

1992-06-01

The relations between groundwater composition, land use, soil conditions and flow patterns on a regional scale are studied for the Gooi and Vechtstreek area in the Netherlands. This densely populated area consists of a glacier-created ridge with dry sand soils bordered by the Vecht and Eem River plains with wet peat and clay soils. R-mode factor analysis and Q-mode cluster analysis were applied to a set of 1349 groundwater analyses to determine the factors controlling groundwater composition and the main resulting water types. The results indicate that groundwater composition in the study area is affected on a regional scale by human activities through changes in land use and intervention in natural flow patterns. On the ridge, ground water is recharged by precipitation, which dissolves carbonates from the matrix of the sandy aquifer. Increased solute concentrations in shallow ground water, especially of nitrate, sulphate and potassium, indicate increased pollution resulting from urbanization and increasingly intensive agricultural activity over the past decades. In the Vecht River plain infiltration occurs as a result of drainage of polders and groundwater extraction on the ridge. Recharge occurs by precipitation and from polluted surface water to which ammonium, organic complexes and carbonic acid are added through decomposition of organic matter in the peat and clay soils. The carbonic acid results in enhanced dissolution of carbonates present in the soil and the underlying sandy aquifer. Oxygen depletion and subsequent low redox potentials result in denitrification, dissolution of manganese and iron oxides, and sulphate reduction. The flow of ground water from high-level to low-level polders causes displacement of a former stagnant brakish groundwater body under the Vecht River plain accompanied by increased mixing of fresh and brackish ground water.

Development of megestrol acetate solid dispersion nanoparticles for enhanced oral delivery by using a supercritical antisolvent process.

PubMed

Ha, Eun-Sol; Kim, Jeong-Soo; Baek, In-Hwan; Yoo, Jin-Wook; Jung, Yunjin; Moon, Hyung Ryong; Kim, Min-Soo

2015-01-01

In the present study, solid dispersion nanoparticles with a hydrophilic polymer and surfactant were developed using the supercritical antisolvent (SAS) process to improve the dissolution and oral absorption of megestrol acetate. The physicochemical properties of the megestrol acetate solid dispersion nanoparticles were characterized using scanning electron microscopy, differential scanning calorimetry, powder X-ray diffraction, and a particle-size analyzer. The dissolution and oral bioavailability of the nanoparticles were also evaluated in rats. The mean particle size of all solid dispersion nanoparticles that were prepared was <500 nm. Powder X-ray diffraction and differential scanning calorimetry measurements showed that megestrol acetate was present in an amorphous or molecular dispersion state within the solid dispersion nanoparticles. Hydroxypropylmethyl cellulose (HPMC) solid dispersion nanoparticles significantly increased the maximum dissolution when compared with polyvinylpyrrolidone K30 solid dispersion nanoparticles. The extent and rate of dissolution of megestrol acetate increased after the addition of a surfactant into the HPMC solid dispersion nanoparticles. The most effective surfactant was Ryoto sugar ester L1695, followed by D-α-tocopheryl polyethylene glycol 1000 succinate. In this study, the solid dispersion nanoparticles with a drug:HPMC:Ryoto sugar ester L1695 ratio of 1:2:1 showed >95% rapid dissolution within 30 minutes, in addition to good oral bioavailability, with approximately 4.0- and 5.5-fold higher area under the curve (0-24 hours) and maximum concentration, respectively, than raw megestrol acetate powder. These results suggest that the preparation of megestrol acetate solid dispersion nanoparticles using the supercritical antisolvent process is a promising approach to improve the dissolution and absorption properties of megestrol acetate.

In vitro dissolution of proton-pump inhibitor products intended for paediatric and geriatric use in physiological bicarbonate buffer.

PubMed

Liu, Fang; Shokrollahi, Honaz

2015-05-15

Proton-pump inhibitor (PPI) products based on enteric coated multiparticulates are design to meet the needs of patients who cannot swallow tablets such as children and older adults. Enteric coated PPI preparations exhibit delays in in vivo absorption and onset of antisecretory effects, which is not reflected by the rapid in vitro dissolution in compendial pH 6.8 phosphate buffer commonly used for assessment of these products. A more representative and physiological medium, pH 6.8 mHanks bicarbonate buffer, was used in this study to evaluate the in vitro dissolution of enteric coated multiparticulate-based PPI products. Commercially available omeprazole, lansoprazole and esomeprazole products were subject to dissolution tests using USP-II apparatus in pH 4.5 phosphate buffer saline for 45 min (acid stage) followed by pH 6.8 phosphate buffer or pH 6.8 mHanks bicarbonate buffer. In pH 6.8 phosphate buffer, all nine tested products displayed rapid and comparable dissolution profiles meeting the pharmacopeia requirements for delayed release preparations. In pH 6.8 mHanks buffer, drug release was delayed and failed the pharmacopeia requirements from most enteric coated preparations. Despite that the same enteric polymer, methacrylic acid-ethyl acrylate copolymer (1:1), was applied to all commercial multiparticulate-based products, marked differences were observed between dissolution profiles of these preparations. The use of pH 6.8 physiological bicarbonate (mHanks) buffer can serve as a useful tool to provide realistic and discriminative in vitro release assessment of enteric coated PPI preparations and to assist rational formulation development of these products. Copyright © 2015 Elsevier B.V. All rights reserved.

Formulation studies for mirtazapine orally disintegrating tablets.

PubMed

Yıldız, Simay; Aytekin, Eren; Yavuz, Burçin; Bozdağ Pehlivan, Sibel; Ünlü, Nurşen

2016-01-01

Orally disintegrating tablets (ODTs) recently have gained much attention to fulfill the needs for pediatric, geriatric, and psychiatric patients with dysphagia. Aim of this study was to develop new ODT formulations containing mirtazapine, an antidepressant drug molecule having bitter taste, by using simple and inexpensive preparation methods such as coacervation, direct compression and to compare their characteristics with those of reference product (Remereon SolTab). Coacervation method was chosen for taste masking of mirtazapine. In vitro characterization studies such as diameter and thickness, weight variation, tablet hardness, tablet friability and disintegration time were performed on tablet formulations. Wetting time and in vitro dissolution tests of developed ODTs also studied using 900 mL 0.1 N HCl medium, 900 mL pH 6.8 phosphate buffer or 900 mL pH 4.5 acetate buffer at 37 ± 0.2 °C as dissolution medium. Ratio of Eudragit® E-100 was chosen as 6% (w/w) since the dissolution profile of A1 (6% Eudragit® E-100) was found closer to the reference product than A2 (4% Eudragit® E-100) and A3 (8% Eudragit® E-100). Group D, E and F formulations were presented better results in terms of disintegration time. Dissolution results indicated that Group E and F formulations showed optimum properties in all three dissolution media. Formulations D1, D4, D5, E3, E4, F1 and F5 found suitable as ODT formulations due to their favorable disintegration times and dissolution profiles. Developed mirtazapine ODTs were found promising in terms of showing the similar characteristics to the original formulation.

Anodic Behavior of the Aluminum Current Collector in Imide-Based Electrolytes: Influence of Solvent, Operating Temperature, and Native Oxide-Layer Thickness.

PubMed

Meister, Paul; Qi, Xin; Kloepsch, Richard; Krämer, Elisabeth; Streipert, Benjamin; Winter, Martin; Placke, Tobias

2017-02-22

The inability of imide salts to form a sufficiently effective passivation layer on aluminum current collectors is one of the main obstacles that limit their broad application in electrochemical energy-storage systems. However, under certain circumstances, the use of electrolytes with imide electrolyte salts in combination with the aluminum current collector is possible. In this contribution, the stability of the aluminum current collector in electrolytes containing either lithium bis(trifluoromethanesulfonyl) imide (LiTFSI) or lithium fluorosulfonyl-(trifluoromethanesulfonyl) imide (LiFTFSI) as conductive salt was investigated by electrochemical techniques, that is, cyclic voltammetry (CV) and chronocoulometry (CC) in either room-temperature ionic liquids or in ethyl methyl sulfone. In particular, the influence of the solvent, operating temperature, and thickness of the native oxide layer of aluminum on the pit formation at the aluminum current collector surface was studied by means of scanning electron microscopy. In general, a more pronounced aluminum dissolution and pit formation was found at elevated temperatures as well as in solvents with a high dielectric constant. An enhanced thickness of the native aluminum oxide layer increases the oxidative stability versus dissolution. Furthermore, we found a different reaction rate depending on dwell time at the upper cut-off potential for aluminum dissolution in TFSI- and FTFSI-based electrolytes during the CC measurements; the use of LiFTFSI facilitated the dissolution of aluminum compared to LiTFSI. Overall, the mechanism of anodic aluminum dissolution is based on: i) the attack of the Al 2 O 3 surface by acidic species and ii) the dissolution of bare aluminum into the electrolyte, which, in turn, is influenced by the electrolyte's dielectric constant. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Influence of spray drying and dispersing agent on surface and dissolution properties of griseofulvin micro and nanocrystals.

PubMed

Shah, Dhaval A; Patel, Manan; Murdande, Sharad B; Dave, Rutesh H

2016-11-01

The purpose for the current research is to compare and evaluate physiochemical properties of spray-dried (SD) microcrystals (MCs), nanocrystals (NCs), and nanocrystals with a dispersion agent (NCm) from a poorly soluble compound. The characterization was carried out by performing size and surface analysis, interfacial tension (at particle moisture interface), and in-vitro drug dissolution rate experiments. Nanosuspensions were prepared by media milling and were spray-dried. The SD powders that were obtained were characterized morphologically using scanning electron microscopy (SEM), polarized light microscopy (PLM), and Flowchem. Solid-state characterization was performed using X-ray powder diffraction (XRPD), Fourier transfer infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC) for the identification of the crystalline nature of all the SD powders. The powders were characterized for their redispersion tendency in the water and in pH 1.2. Significant differences in redispersion were noted for both the NCs in both dissolution media. The interfacial tension for particle moisture interface was determined by applying the BET (Braunauer-Emmett-Teller) equation to the vapor sorption data. No significant reduction in the interfacial tension was observed between MCs and NCs; however, a significant reduction in the interfacial tension was observed for NCm at both 25 °C and 35 °C temperatures. The difference in interfacial tension and redispersion behavior can be attributed to a difference in the wetting tendency for all the SD powders. The dissolution studies were carried out under sink and under non-sink conditions. The non-sink dissolution approach was found suitable for quantification of the dissolution rate enhancement, and also for providing the rank order to the SD formulations.

Dissolution enhancement of glibenclamide by solid dispersion: solvent evaporation versus a supercritical fluid-based solvent -antisolvent technique

PubMed Central

Tabbakhian, M.; Hasanzadeh, F.; Tavakoli, N.; Jamshidian, Z.

2014-01-01

Glibenclamide (GLIB) is a poorly soluble drug with formulation-dependent bioavailability. Therefore, we attempted in this study to improve GLIB dissolution rate by preparing drug solid dispersions by solvent evaporation (SE) and supercritical fluid solvent-antisolvent techniques (SCF-SAS). A D-optimal mixture design was used to investigate the effects of different ratios of HPMCE5 (50-100%), PEG6000 (0-40%), and Poloxamer407 (0-20%) on drug dissolution from different solid dispersion (SD) formulations prepared by SE. The ratios of carriers used in SCF-SAS method were HPMCE5 (fixed at 60%), PEG6000 (20-40%), and Poloxamer407 (0-20%). A constant drug: carrier weight ratio of 1:10 was used in all experiments. The SDs obtained were physically characterized and subjected to the dissolution study. The major GLIB bands in FTIR spectra were indicative of drug integrity. The reduced intensity and the fewer number of peaks observed in X-ray diffractograms (XRD) of GLIB formulations was the indicative of at least partial transformation of crystalline to amorphous GLIB. This change and/or dilution of drug in much higher amounts of carriers present caused disappearance of distinctive endothermic peaks in differential scanning calorimetry thermograms of GLIB formulations. The model generated according to the results of the D-optimal mixture design indicated that GLIB formulations comprising HPMC (50%-60%), PEG (34-40%), and poloxamer (6-10%) had enhanced dissolution performances. As compared to SE method, the SCF-SAS technique produced formulations of higher dissolution performances, likely due to the effects of solution and the supercritical CO2 (SC-CO2) on enhanced plasticization of polymers and thus increased diffusion of the drug into the polymer matrix. PMID:25657806

Improving Crotalidae polyvalent immune Fab reconstitution times.

PubMed

Quan, Asia N; Quan, Dan; Curry, Steven C

2010-06-01

Crotalidae polyvalent immune Fab (CroFab) is used to treat rattlesnake envenomations in the United States. Time to infusion may be a critical factor in the treatment of these bites. Per manufacturer's instructions, 10 mL of sterile water for injection (SWI) and hand swirling are recommended for reconstitution. We wondered whether completely filling vials with 25 mL of SWI would result in shorter reconstitution times than using 10-mL volumes and how hand mixing compared to mechanical agitation of vials or leaving vials undisturbed. Six sets of 5 vials were filled with either 10 mL or 25 mL. Three mixing techniques were used as follows: undisturbed; agitation with a mechanical agitator; and continuous hand rolling and inverting of vials. Dissolution was determined by observation and time to complete dissolution for each vial. Nonparametric 2-tailed P values were calculated. Filling vials completely with 25 mL resulted in quicker dissolution than using 10-mL volumes, regardless of mixing method (2-tailed P = .024). Mixing by hand was shorter than other methods (P < .001). Reconstitution with 25 mL and hand mixing resulted in the shortest dissolution times (median, 1.1 minutes; range, 0.9-1.3 minutes). This appeared clinically important because dissolution times using 10 mL and mechanical rocking of vials (median, 26.4 minutes) or leaving vials undisturbed (median, 33.6 minutes) was several-fold longer. Hand mixing after filling vials completely with 25 mL results in shorter dissolution times than using 10 mL or other methods of mixing and is recommended, especially when preparing initial doses of CroFab. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Polymer brush hexadecyltrimethylammonium bromide (CTAB) modified poly (propylene-g-styrene sulphonic acid) fiber (ZB-1): CTAB/ZB-1 as a promising strategy for improving the dissolution and physical stability of poorly water-soluble drugs.

PubMed

Cao, Jinxu; Yang, Baixue; Wang, Yumei; Wei, Chen; Wang, Hongyu; Li, Sanming

2017-11-01

The feasibility of polymer brush as drug delivery vehicle was demonstrated with the goal of improving the dissolution and physical stability of poorly water-soluble drugs. Polymer brush CTAB/ZB-1 was synthesized by electrostatic interaction using a physical modification method with anionic poly (propylene-g-styrene sulphonic acid) fiber (ZB-1) as the substrate and cationic hexadecyltrimethylammonium bromide (CTAB) as the modifier. The polymer brush structure of CTAB/ZB-1 was validated by atomic force microscopy (AFM) and the channels of brush provided the drug loading sites. Flurbiprofen (FP), a BCS class II representative drug, was selected as the model poorly water-soluble drug to be loaded into this polymer brush. Then the drug loading and release were systematically investigated. Besides, the transformation from crystalline FP to amorphous state was observed by differential scanning calorimeter (DSC). In vitro dissolution in pure water and pH1.2 HCl media with/without 0.1% sodium dodecyl sulfate (SDS) was tested. Moreover, the optimal formulations (namely carrier/drug ratios) were determined. The results demonstrated prominent improvement of dissolution when FP was released from CTAB/ZB-1. After a long time storage, FP remained amorphous in CTAB/ZB-1 according to DSC determinations and performed an approximately equivalent dissolution compared with fresh samples, suggesting the advantage of CTAB/ZB-1 as carrier in enhancing the physical stability of drugs. The study introduced the versatile easily formulated polymer brush CTAB/ZB-1 and demonstrated the potential of polymer brush as an alternative approach for improving the dissolution and physical stability of poorly water-soluble drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

The Effect of Micrite on Velocity, Its Sensitivity to Pressure, and Dissolution of Carbonates

NASA Astrophysics Data System (ADS)

El Husseiny, A.; Vanorio, T.

2014-12-01

This study investigates the effect of micrite on the acoustic properties of well-controlled microstructures created in the laboratory to closely mimic carbonate rocks. In particular, we examine the effect of micrite content on the elastic stiffness rock, its sensitivity to pressure, and induced dissolution upon saturation with a reactive fluid. We followed Dunham's classification and fabricated the samples by mixing coarse (sand size) and very fine (micrite size) calcite grains in different ratios, with the addition of cement and then cold-compressing the mixture. The acoustic velocities were measured under bench-top conditions and as functions of confining pressure before and after the injection of a CO2aqueous solution. Our bench-top measurements indicated that micrite makes the frame of the carbonate samples stiffer. Since the sensitivity of the elastic stiffness to pressure decreases as the content of micrite increases (see figure 1), we hypothesize a stiffer pore structure (i.e., rounder pores) in micrite-richer fabrics. Furthermore, the presence of micrite makes the carbonate sample more reactive upon dissolution. The concentration of Ca+2 cations in the fluid measured at the outlet after the injection of the CO2 aqueous solution shows larger dissolution in the micrite-rich samples likely due to the higher surface area of the micrite aggregates. The content of micrite also seems to affect the evolution of stiffness as dissolution proceeds. As the content of micrite increases, the enhanced dissolution translates into a marked softening of the rock frame. We conclude that the content of micrite can play an important role in the complex rock-fluid interaction of carbonates as well as when comparing Gassmann's predictions to velocity measurements of saturated carbonates.

Alternate Fuel Cycle Technologies/Thorium Fuel Cycle Technology Programs. Quarterly report for period 1 April--30 June 1978

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vondra, B.L.

1978-08-01

Voloxidation and dissolution studies: rotary-kiln heat-transfer tests are under way using a small rotary kiln along with the development of a mathematical model to determine kiln-heat-flux profiles necessary to maintain a desired temperature gradient. The erosion/corrosion test for evaluating materials of construction is operational. Fuel from a BWR (Big Rock Point) yielded more fine solid residue on dissolution than in previous tests with PWR fuel. Two additional parametric voloxidation tests with H.B. Robinson fuel compared air vs pure oxygen atmospheres at 550{sup 0}C; overall tritium release and subsequent fuel dissolution were equivalent. Thorium dissolution studies: the dissolution rate of thoriamore » in fluoride-catalyzed 8 to 14 M HNO{sub 3} (100{sup 0}C) was max between 0.04 to 0.06 M HF; at higher fluoride concentrations, ThF{sub 4}.5H{sub 2}O precipitated. The rate of zircaloy dissolution continued to increase with increasing fluoride concentration. Stainless-steel-clad (Th,U)0{sub 2} fuel rods irradiated in the NRX reactor were sheared, voloxidized, and dissolved. {le}10% of the tritium was released during voloxidation in air at 600{sup 0}C. Carbon-14 removal from off-gas and fixation: carbon dioxide removal with Linde 13X molecular sieves to less than 100 ppB was experimentally verified using 300 ppM CO in air. Decontamination factors from 3000 to 7500 were obtained for CO{sub 2} removal in the gas-slurry stirred-tank reactor with CA(OH){sub 2}.or Ba(0H){sub 2}/sup .8H2O./. With Ba(OH){sub 2}.H{sub 2}0{sup 2} in a fixed-bed column, decontamination factors of about 30,000 were obtained.« less

DSM-IV Alcohol Dependence and Marital Dissolution: Evidence From the National Epidemiologic Survey on Alcohol and Related Conditions

PubMed Central

Cranford, James A

2014-01-01

Objective: The purpose of this study was to examine the cross-sectional and longitudinal associations among alcohol use disorder (AUD), stressful life events, and marital dissolution in a probability sample of adults. Method: The National Epidemiologic Survey on Alcohol and Related Conditions is a prospective, longitudinal study of a probability sample of 43,083 adults 18 years of age and older living in the United States. The interval between Wave 1 (W1) and Wave 2 (W2) was approximately 3 years. Cross-sectional analyses included 32,359 adults ages 18 and older who were ever married at W1, and longitudinal analyses included 17,192 adults who were currently married at W1 and who completed relevant W2 measures. Participants completed inhome surveys conducted with computer-assisted personal interviewing. Results: Rates of lifetime marital dissolution were significantly higher among those with lifetime AUD (48.3%) than in those with no lifetime AUD (30.1%). The incidence of marital dissolution from W1 to W2 was 15.5% for those with a past-12-month AUD at W1, compared to 4.8% among those with no AUD. Proportional hazards regression analyses showed that past-12-month AUD, tobacco use disorder, other substance use disorder, stressful life events, older age at marriage, being married more than once, and being married to an alcoholic at W1 predicted greater hazards of marital dissolution at W2. These associations were not moderated by gender. Conclusions: AUD and stressful life events predict subsequent marital dissolution independently of other substance use disorders, mood and anxiety disorders, and personality disorders. Results were discussed within the framework of the Vulnerability–Stress–Adaptation model of marriage. PMID:24766764

Engineering Silver Nanoparticles: Towards a Tunable Antimicrobial

NASA Astrophysics Data System (ADS)

Puppala, Hema Lakshmi

Overwhelming production of commercially available products containing silver nanoparticles (AgNPs) underscores the studies determining their fate in the environment. In order to regulate the use, assess the environmental impact and develop eco-responsible silver products, models that can predict AgNP toxicity based on physicochemical properties are vital. With that vision, this thesis developed well-characterized model libraries of uniform AgNPs stabilized with oleate in the range of 2-45 nm diameter with variable surface coating and investigated the dissolution properties that link AgNP structure to antimicrobial activity. High temperature organic synthesis allowed controlled growth of AgNPs (sigma<15%) by an Ostwald ripening mechanism in the first few hours, and followed by size dependent growth rates yielding uniform nanocrystals. Characterization of these materials revealed a crystalline nature, bidentate binding mode of oleate and non-oxidized pristine silver surface. Phase transfer of these AgNPs from organics to water was facilitated by encapsulation and ligand exchange methods using amphiphilic polymers and methoxy poly (ethylene glycol) (mPEGSH) respectively. Among these surface coatings, steric stabilization by mPEGSH not only helped retain their optical properties but also reduced the dissolution (<1(w/w)%) of AgNPs. This enhanced the stability in various environmentally relevant high ionic strength media (such as Hoaglands, EPA hard water and OECD medium), thereby increasing the shelf life. In addition, size, surface coating, pH of the medium and grafting density of the polymer mediated the dissolution of AgNPs. For instance, the rate of dissolution was decreased by 40% when the polymer coating possessed a mushroom conformation and increased with reducing core size. Analogous to dissolution, physicochemical properties also influenced the antimicrobial activity which were studied by minimum inhibitory concentration (MIC) and bactericidal efficacy assays. For example, surface passivation with mPEGSH prevented the oxidation of active silver atoms on the surface, and resulted in reduced toxicity against E. coli. Moreover citrate stabilized AgNPs when surface modified with mPEGSH had reduced toxicity, which was correlated with residual Ag+ in AgNP solution. Therefore this study demonstrates that processes in the environment that increase stability of AgNPs could make them more persistent due to low dissolution. Furthermore, the size and surface chemistry effects of AgNPs studied here make the intrinsic antimicrobial property of silver tunable and hence more versatile. This work also served as a material support for research on investigating toxicity of AgNPs to C. elegans, Daphnia Magna, Populus and Arabidopsis. In the future, this data will be used to develop nanomaterial bioavailability & environmental exposure (nanoBEE) models that predict the environmental impact of AgNPs.

[Dissolution behavior of Fuzi Lizhong pill based on simultaneous determination of two components in Glycyrrhizae Radix et Rhizoma].

PubMed

Jiang, Mao-Yuan; Zhang, Zhen; Shi, Jin-Feng; Zhang, Jin-Ming; Fu, Chao-Mei; Lin, Xia; Liu, Yu-Mei

2018-03-01

To preliminarily investigate the dissolution behavior of Fuzi Lizhong pill, provide the basis for its quality control and lay foundation for in vivo dissolution behavior by determining the dissolution rate of liquiritin and glycyrrhizic acid. High-performance liquid chromatography (HPLC) method for simultaneous content determination of the two active ingredients of liquiritin and glycyrrhizic acid in Fuzi Lizhong pill was established; The dissolution amount of these two active ingredients in fifteen batches of Fuzi Lizhong pill from five manufacturers was obtained at different time points, and then the cumulative dissolution rate was calculated and cumulative dissolution curve was drawn. The similarity of cumulative dissolution curve of different batches was evaluated based on the same factory, and the similarity of cumulative dissolution curve of different factories was evaluated based on the same active ingredients. The dissolution model of Fuzi Lizhong pill based on two kinds of active ingredients was established by fitting with the dissolution data. The best dissolution medium was 0.25% sodium lauryl sulfate. The dissolution behavior of liquiritin and glycyrrhizic acid in Fuzi Lizhong pill was basically the same and sustained release in 48 h. Three batches of the factories (factory 2, factory 3, factory 4 and factory 5) appeared to be similar in dissolution behavior, indicating similarity in dissolution behavior in most factories. Two of the three batches from factory 1 appeared to be not similar in dissolution behavior of liquiritin and glycyrrhizic acid. The dissolution data of the effective ingredients from different factories were same in fitting, and Weibull model was the best model in these batches. Fuzi Lizhong pill in 15 batches from 5 factories showed sustained release in 48 h, proving obviously slow releasing characteristics "pill is lenitive and keeps a long-time efficacy". The generally good dissolution behavior also suggested that quality of different batches from most factories was stable. The dissolution behavior of liquiritin and glycyrrhizic acid in different factories was different, suggesting that the source of medicinal materials and preparation technology parameters in five factories were different. Copyright© by the Chinese Pharmaceutical Association.

Comparative study of the influence of natural convection on directional solidification of Al 3.5 wt% Ni and Al 7 wt% Si alloys

NASA Astrophysics Data System (ADS)

Zhou, B. H.; Jung, H.; Mangelinck-Noël, N.; Nguyen-Thi, H.; Billia, B.; Liu, Q. S.; Lan, C. W.

We present numerical simulations of thermosolutal convection for directional solidification of Al 3.5 wt% Ni and Al 7 wt% Si. Numerical results predict that fragmentation of dendrite arms resulting from dissolution could be favored in Al 7 wt% Si, but not in Al 3.5 wt% Ni. Corresponding experiments are in qualitative agreement with the numerical predictions. Distinguishing the two fragmentation mechanisms, namely dissolution and remelting, is critical during experiments on earth, when fluid flow is dominant.

Corrosion protection of copper by polypyrrole film studied by electrochemical impedance spectroscopy and the electrochemical quartz microbalance

NASA Astrophysics Data System (ADS)

Lei, Yanhua; Ohtsuka, Toshiaki; Sheng, Nan

2015-12-01

Polypyrrole (PPy) films were synthesized on copper in solution of sodium di-hydrogen phosphate and phytate for corrosion protection. The protection properties of PPy films were comparatively investigated in NaCl solution. During two months immersion, the PPy film doped with phytate anions, working as a cationic perm-selective membrane, inhibited the dissolution of copper to 1% of bare copper. Differently, the PPy film doped with di-hydrogen phosphate anions, possessing anionic perm-selectivity, was gradually reduced, and inhibited the dissolution to 7.8% of bare copper. Degradation of the PPy films was studied by comparing the electrochemical impedance spectroscopy change at different immersion time and Raman spectra change after immersion.

Optimization of Dissolution Compartments in a Biorelevant Dissolution Apparatus Golem v2, Supported by Multivariate Analysis.

PubMed

Stupák, Ivan; Pavloková, Sylvie; Vysloužil, Jakub; Dohnal, Jiří; Čulen, Martin

2017-11-23

Biorelevant dissolution instruments represent an important tool for pharmaceutical research and development. These instruments are designed to simulate the dissolution of drug formulations in conditions most closely mimicking the gastrointestinal tract. In this work, we focused on the optimization of dissolution compartments/vessels for an updated version of the biorelevant dissolution apparatus-Golem v2. We designed eight compartments of uniform size but different inner geometry. The dissolution performance of the compartments was tested using immediate release caffeine tablets and evaluated by standard statistical methods and principal component analysis. Based on two phases of dissolution testing (using 250 and 100 mL of dissolution medium), we selected two compartment types yielding the highest measurement reproducibility. We also confirmed a statistically ssignificant effect of agitation rate and dissolution volume on the extent of drug dissolved and measurement reproducibility.

Comparing the mechanism of water condensation and evaporation in glassy aerosol.

PubMed

Bones, David L; Reid, Jonathan P; Lienhard, Daniel M; Krieger, Ulrich K

2012-07-17

Atmospheric models generally assume that aerosol particles are in equilibrium with the surrounding gas phase. However, recent observations that secondary organic aerosols can exist in a glassy state have highlighted the need to more fully understand the kinetic limitations that may control water partitioning in ambient particles. Here, we explore the influence of slow water diffusion in the condensed aerosol phase on the rates of both condensation and evaporation, demonstrating that significant inhibition in mass transfer occurs for ultraviscous aerosol, not just for glassy aerosol. Using coarse mode (3-4 um radius) ternary sucrose/sodium chloride/aqueous droplets as a proxy for multicomponent ambient aerosol, we demonstrate that the timescale for particle equilibration correlates with bulk viscosity and can be ≫10(3) s. Extrapolation of these timescales to particle sizes in the accumulation mode (e.g., approximately 100 nm) by applying the Stokes-Einstein equation suggests that the kinetic limitations imposed on mass transfer of water by slow bulk phase diffusion must be more fully investigated for atmospheric aerosol. Measurements have been made on particles covering a range in dynamic viscosity from < 0.1 to > 10(13) Pa s. We also retrieve the radial inhomogeneities apparent in particle composition during condensation and evaporation and contrast the dynamics of slow dissolution of a viscous core into a labile shell during condensation with the slow percolation of water during evaporation through a more homogeneous viscous particle bulk.

Landform elevation suggests ecohydrologic footprints in subsurface geomorphology

NASA Astrophysics Data System (ADS)

Watts, A. C.; Watts, D.; Kaplan, D. A.; Mclaughlin, D. L.; Heffernan, J. B.; Martin, J. B.; Murray, A.; Osborne, T.; Cohen, M. J.; Kobziar, L. N.

2012-12-01

Many landscapes exhibit patterns in their arrangement of biota, or in their surface geomorphology as a result of biotic activity. Examples occur around the globe and include northern peatlands, Sahelian savannas, and shallow marine reefs. Such self-organized patterning is strongly suggestive of coupled, reciprocal feedbacks (i.e. locally positive, and distally negative) among biota and their environment. Much research on patterned landscapes has concerned emergent biogeomorphologic surfaces such as those found in peatlands, or the influence of biota on soil formation or transport. Our research concerns ecohydrologic feedbacks hypothesized to produce patterned occurrence of depressions in a subtropical limestone karst landscape. Our findings show strong evidence of self-organized patterning, in the form of overdispersed dissolution basins. Distributions of randomized bedrock elevation measurements on the landscape are bimodal, with means clustered about either higher- or lower-elevation modes. Measurements on the thin mantle of soil overlying this landscape, however, display reduced bimodality and mode separation. These observations indicate abiotic processes in diametric opposition to the biogenic forces which may be responsible for generating landscape pattern. Correlograms show higher spatial autocorrelation among soil measurements compared to bedrock measurements, and measurements of soil-layer thickness show high negative correlation with bedrock elevation. Our results are consistent with predictions of direct ecohydrologic feedbacks that would produce patterned "footprints" directly on bedrock, and of abiotic processes operating to obfuscate this pattern. The study suggests new steps to identify biogeochemical mechanisms for landscape patterning: an "ecological drill" by which plant communities modify geology.

Prediction of glass durability as a function of environmental conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jantzen, C M

1988-01-01

A thermodynamic model of glass durability is applied to natural, ancient, and nuclear waste glasses. The durabilities of over 150 different natural and man-made glasses, including actual ancient Roman and Islamic glasses (Jalame ca. 350 AD, Nishapur 10-11th century AD and Gorgon 9-11th century AD), are compared. Glass durability is a function of the thermodynamic hydration free energy, ..delta..G/sub hyd/, which can be calculated from glass composition and solution pH. The durability of the most durable nuclear waste glasses examined was /approximately/10/sup 6/ years. The least durable waste glass formulations were comparable in durability to the most durable simulated medievalmore » window glasses of /approximately/10/sup 3/ years. In this manner, the durability of nuclear waste glasses has been interpolated to be /approximately/10/sup 6/ years and no less than 10/sup 3/ years. Hydration thermodynamics have been shown to be applicable to the dissolution of glass in various natural environments. Groundwater-glass interactions relative to geologic disposal of nuclear waste, hydration rind dating of obsidians, andor other archeological studies can be modeled, e.g., the relative durabilities of six simulated medieval window glasses have been correctly predicted for both laboratory (one month) and burial (5 years) experiments. Effects of solution pH on glass dissolution has been determined experimentally for the 150 different glasses and can be predicted theoretically by hydration thermodynamics. The effects of solution redox on dissolution of glass matrix elements such as SI and B have shown to be minimal. The combined effects of solution pH and Eh have been described and unified by construction of thermodynamically calculated Pourbaix (pH-Eh) diagrams for glass dissolution. The Pourbaix diagrams have been quantified to describe glass dissolution as a function of environmental conditions by use of the data derived from hydration thermodynamics. 56 refs., 7 figs.« less

Use of acidifier and solubilizer in tadalafil solid dispersion to enhance the in vitro dissolution and oral bioavailability in rats.

PubMed

Choi, Jin-Seok; Kwon, Soon-Hyung; Lee, Sang-Eun; Jang, Woo Suk; Byeon, Jong Chan; Jeong, Hyeong Mo; Park, Jeong-Sook

2017-06-30

The purpose of this study is to improve the solubility, in vitro dissolution, and oral bioavailability in rats of tadalafil (TDF) by using SD technique with a weak acid and a copolymer. TDF-SD was prepared via solvent evaporation, coupled with the incorporation of an acidifier and solubilizer. Tartaric acid enhanced the solubility of TDF over 5-fold in DW, and Soluplus ® enhanced the solubility of TDF over 8.7-fold and 19.2-fold compared to that of TDF (pure) in DW and pH 1.2 for 1h, respectively. The optimal formulation of TDF-SD3 was composed of TDF vs Tartaric acid vs Soluplus ® vs Aerosil=1:1:3:3. The in vitro dissolution rate of TDF-SD3 in DW, pH 1.2 and pH 6.8 buffer (51.5%, 53.3%, and 33.2%, respectively) was significantly higher than that of the commercial product (Cialis ® ) powder (16.5%, 15.2%, and 14.8%, respectively). TDF was completely transformed to an amorphous form as shown in SEM, DSC and PXRD data. The stability of TDF-SD3 included drug contents and in vitro dissolution for 1 month were similar to those of Cialis ® , and the amorphous form of TDF-SD3 was well maintained for 6 months. The TDF-SD3 formulation improved the relative bioavailability (BA) and peak plasma concentration (C max ) compared to that of Cialis ® powder after oral administration in rats as 117.3% and 135.7%, respectively. From the results, we found that the acidifier increased the wettability of TDF, and the solubilizer improved solubility through hydrogen bonding with TDF, thereby increasing the solubility, dissolution and oral bioavailability of TDF in TDF-SD3. Copyright © 2017 Elsevier B.V. All rights reserved.

Cyclodextrin-water soluble polymer ternary complexes enhance the solubility and dissolution behaviour of poorly soluble drugs. Case example: itraconazole.

PubMed

Taupitz, Thomas; Dressman, Jennifer B; Buchanan, Charles M; Klein, Sandra

2013-04-01

The aim of the present series of experiments was to improve the solubility and dissolution/precipitation behaviour of a poorly soluble, weakly basic drug, using itraconazole as a case example. Binary inclusion complexes of itraconazole with two commonly used cyclodextrin derivatives and a recently introduced cyclodextrin derivative were prepared. Their solubility and dissolution behaviour was compared with that of the pure drug and the marketed formulation Sporanox®. Ternary complexes were prepared by addition of Soluplus®, a new highly water soluble polymer, during the formation of the itraconazole/cyclodextrin complex. A solid dispersion made of itraconazole and Soluplus® was also studied as a control. Solid state analysis was performed for all formulations and for pure itraconazole using powder X-ray diffraction (pX-RD) and differential scanning calorimetry (DSC). Solubility tests indicated that with all formulation approaches, the aqueous solubility of itraconazole formed with hydroxypropyl-β-cyclodextrin (HP-β-CD) or hydroxybutenyl-β-cyclodextrin (HBen-β-CD) and Soluplus® proved to be the most favourable formulation approaches. Whereas the marketed formulation and the pure drug showed very poor dissolution, both of these ternary inclusion complexes resulted in fast and extensive release of itraconazole in all test media. Using the results of the dissolution experiments, a newly developed physiologically based pharmacokinetic (PBPK) in silico model was applied to compare the in vivo behaviour of Sporanox® with the predicted performance of the most promising ternary complexes from the in vitro studies. The PBPK modelling predicted that the bioavailability of itraconazole is likely to be increased after oral administration of ternary complex formulations, especially when itraconazole is formulated as a ternary complex comprising HP-β-CD or HBen-β-CD and Soluplus®. Copyright © 2012 Elsevier B.V. All rights reserved.

Low-energy collision induced dissociation (low-energy CID), collision induced dissociation (CID) and higher-energy collision dissociation (HCD) mass spectrometry for structural elucidation of saccharides and clarification of their dissolution mechanism in DMAc/LiCl.

PubMed

Bayat, Parisa; Lesage, Denis; Cole, Richard B

2018-05-29

The dissolution mechanism of oligosaccharides in N,N-dimethylacetamide/lithium chloride (DMAc/LiCl), a solvent used for cellulose dissolution, and the capabilities of low-energy collision induced dissociation (low-energy CID), collision induced dissociation (CID) and higher-energy collision dissociation (HCD) for structural analysis of carbohydrates were investigated. Comparing the spectra obtained using three techniques shows that, generally, when working with mono-lithiated sugars, CID spectra provide more structurally informative fragments, and glycosidic bond cleavage is the main pathway. However, when working with di-lithiated sugars, HCD spectra can be more informative providing predominately cross-ring cleavage fragments. This is because HCD is a non-resonant activation technique and it allows a higher amount of energy to be deposited in a short time, giving access to more endothermic decomposition pathways as well as consecutive fragmentations. The difference in preferred dissociation pathways of mono-lithiated and di-lithiated sugars indicates that the presence of the second lithium strongly influences the relative rate constants for cross-ring cleavages (rearrangement) vs. direct glycosidic bond cleavages, and disfavors the latter. Regarding the dissolution mechanism of sugars in DMAc/LiCl, CID and HCD experiments on di-lithiated and tri-lithiated sugars reveal that intensities of product ions containing two Li + or three Li + , respectively, are higher than those bearing only one Li + . In addition, comparing the fragmentation spectra (both HCD and CID) of LiCl adducted lithiated sugar and NaCl adducted sodiated sugar shows that while, in the latter case, loss of NaCl is dominant, in the former case, loss of HCl occurs preferentially. The compiled evidence implies that there is a strong and direct interaction between lithium and the saccharide during the dissolution process in the DMAc/LiCl solvent system. This article is protected by copyright. All rights reserved.

Etching of semiconductor cubic crystals: Determination of the dissolution slowness surfaces

NASA Astrophysics Data System (ADS)

Tellier, C. R.

1990-03-01

Equations of the representative surface of dissolution slowness for cubic crystals are determined in the framework of a tensorial approach of the orientation-dependent etching process. The independent dissolution constants are deduced from symmetry considerations. Using previous data on the chemical etching of germanium and gallium arsenide crystals, some possible polar diagrams of the dissolution slowness are proposed. A numerical and graphical simulation method is used to obtain the derived dissolution shapes. The influence of extrema in the dissolution slowness on the successive dissolution shapes is also examined. A graphical construction of limiting shapes of etched crystals appears possible using the tensorial representation of the dissolution slowness.

Coherent anti-Stokes Raman Scattering (CARS) Microscopy Visualizes Pharmaceutical Tablets During Dissolution

PubMed Central

Fussell, Andrew L.; Kleinebudde, Peter; Herek, Jennifer; Strachan, Clare J.; Offerhaus, Herman L.

2014-01-01

Traditional pharmaceutical dissolution tests determine the amount of drug dissolved over time by measuring drug content in the dissolution medium. This method provides little direct information about what is happening on the surface of the dissolving tablet. As the tablet surface composition and structure can change during dissolution, it is essential to monitor it during dissolution testing. In this work coherent anti-Stokes Raman scattering microscopy is used to image the surface of tablets during dissolution while UV absorption spectroscopy is simultaneously providing inline analysis of dissolved drug concentration for tablets containing a 50% mixture of theophylline anhydrate and ethyl cellulose. The measurements showed that in situ CARS microscopy is capable of imaging selectively theophylline in the presence of ethyl cellulose. Additionally, the theophylline anhydrate converted to theophylline monohydrate during dissolution, with needle-shaped crystals growing on the tablet surface during dissolution. The conversion of theophylline anhydrate to monohydrate, combined with reduced exposure of the drug to the flowing dissolution medium resulted in decreased dissolution rates. Our results show that in situ CARS microscopy combined with inline UV absorption spectroscopy is capable of monitoring pharmaceutical tablet dissolution and correlating surface changes with changes in dissolution rate. PMID:25045833

Effect of Low-Temperature Environment on Stress Corrosion Cracking Behavior of X80 Pipeline Steel in Simulated Alkaline Soil Solution

NASA Astrophysics Data System (ADS)

Xie, Fei; Wang, Dan; Wu, Ming; Yu, Chengxiang; Sun, Dongxu; Yang, Xu; Xu, Changhao

2018-04-01

The stress corrosion cracking (SCC) of X80 pipeline steel in simulated alkaline soil solution under different temperatures was investigated by slow-strain-rate testing, scanning electron microscopy and energy-dispersive spectroscopy. Results showed that the fracture was transgranular and brittle at 273 K to 278 K (0 °C to 5 °C), and the metal surface was dissolved by a large number of chloride ions. Furthermore, hydrogen embrittlement was caused by the hydrogen atom extended to the high-stress region. The fracture process was controlled by hydrogen-induced cracking, and SCC was highly sensitive at this stage. At 288 K to 298 K (15 °C to 25 °C), the fracture morphology was attributed to the mixed mode of ductile and brittle fractures, the fracture process was controlled by the mechanism of hydrogen-induced cracking and anodic dissolution, and the susceptibility to SCC decreased. When the temperature reached 308 K to 318 K (35 °C to 45 °C), the fracture was mainly intergranular and ductile, the fracture process was controlled by anodic dissolution, and SCC sensitivity was the smallest in this temperature range.

Effect of the Addition of a Labile Gelatin Component on the Degradation and Solute Release Kinetics of a Stable PEG Hydrogel

PubMed Central

Waldeck, H.; Kao, W. J.

2013-01-01

Characterization of the degradation mechanisms and resulting products of biodegradable materials is critical in understanding the behavior of the material including solute transport and biological response. Previous mathematical analyses of a semi-interpenetrating network (sIPN) containing both labile gelatin and a stable cross-linked poly(ethylene glycol) (PEG) network found that diffusion-based models alone were unable to explain the release kinetics of solutes from the system. In this study, degradation of the sIPN and its effect on solute release and swelling kinetics were investigated. The kinetics of the primary mode of degradation, gelatin dissolution, was dependent on temperature, preparation methods, PEGdA and gelatin concentration, and the weight ratio between the gelatin and PEG. The gelatin dissolution rate positively correlated with both matrix swelling and the release kinetics of high-molecular-weight model compound, FITC-dextran. Coupled with previous in vitro studies, the kinetics of sIPN degradation provided insights into the time-dependent changes in cellular response including adhesion and protein expression. These results provide a facile guide in material formulation to control the delivery of high-molecular-weight compounds with concomitant modulation of cellular behavior. PMID:21801489

Influence of mass transfer on bubble plume hydrodynamics.

PubMed

Lima Neto, Iran E; Parente, Priscila A B

2016-03-01

This paper presents an integral model to evaluate the impact of gas transfer on the hydrodynamics of bubble plumes. The model is based on the Gaussian type self-similarity and functional relationships for the entrainment coefficient and factor of momentum amplification due to turbulence. The impact of mass transfer on bubble plume hydrodynamics is investigated considering different bubble sizes, gas flow rates and water depths. The results revealed a relevant impact when fine bubbles are considered, even for moderate water depths. Additionally, model simulations indicate that for weak bubble plumes (i.e., with relatively low flow rates and large depths and slip velocities), both dissolution and turbulence can affect plume hydrodynamics, which demonstrates the importance of taking the momentum amplification factor relationship into account. For deeper water conditions, simulations of bubble dissolution/decompression using the present model and classical models available in the literature resulted in a very good agreement for both aeration and oxygenation processes. Sensitivity analysis showed that the water depth, followed by the bubble size and the flow rate are the most important parameters that affect plume hydrodynamics. Lastly, dimensionless correlations are proposed to assess the impact of mass transfer on plume hydrodynamics, including both the aeration and oxygenation modes.

DISSOLUTION OF PLUTONIUM METAL IN 8-10 M NITRIC ACID

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rudisill, T. S.; Pierce, R. A.

2012-07-02

The H-Canyon facility will be used to dissolve Pu metal for subsequent purification and conversion to plutonium dioxide (PuO{sub 2}) using Phase II of HB-Line. To support the new mission, the development of a Pu metal dissolution flowsheet which utilizes concentrated (8-10 M) nitric acid (HNO{sub 3}) solutions containing potassium fluoride (KF) is required. Dissolution of Pu metal in concentrated HNO{sub 3} is desired to eliminate the need to adjust the solution acidity prior to purification by anion exchange. The preferred flowsheet would use 8-10 M HNO{sub 3}, 0.015-0.07 M KF, and 0.5-1.0 g/L Gd to dissolve the Pu upmore » to 6.75 g/L. An alternate flowsheet would use 8-10 M HNO{sub 3}, 0.05-0.2 M KF, and 1-2 g/L B to dissolve the Pu. The targeted average Pu metal dissolution rate is 20 mg/min-cm{sup 2}, which is sufficient to dissolve a “standard” 2250-g Pu metal button in 24 h. Plutonium metal dissolution rate measurements showed that if Gd is used as the nuclear poison, the optimum dissolution conditions occur in 10 M HNO{sub 3}, 0.04-0.05 M KF, and 0.5-1.0 g/L Gd at 112 to 116 °C (boiling). These conditions will result in an estimated Pu metal dissolution rate of ~11-15 mg/min-cm{sup 2} and will result in dissolution times of 36-48 h for standard buttons. The recommended minimum and maximum KF concentrations are 0.03 M and 0.07 M, respectively. The data also indicate that lower KF concentrations would yield dissolution rates for B comparable to those observed with Gd at the same HNO{sub 3} concentration and dissolution temperature. To confirm that the optimal conditions identified by the dissolution rate measurements can be used to dissolve Pu metal up to 6.75 g/L in the presence of representative concentrations of Fe and Gd or B, a series of experiments was performed to demonstrate the flowsheets. In three of the five experiments, the offgas generation rate during the dissolution was measured and samples were analyzed for hydrogen gas (H{sub 2}). The use of 10 M HNO{sub 3} containing 0.03-0.05 M KF, 0.5-1.0 g/L Gd, and 1.9 g/L Fe resulted in complete dissolution of the metal in 2.0-3.5 h. When B was used as the neutron poison, 10 M HNO{sub 3} solutions containing 0.05-0.1 M KF, 1.9 g/L Fe, and 1 g/L B resulted in complete dissolution of the metal in 0.75-2.0 h. Dissolution rates estimated using data from the flowsheet demonstrations agreed reasonably well with the measured rates; although, a discrepancy was observed in the Gd system. The presence of 1 g/L Gd or B in the dissolving solution had about the same effect on the dissolution rate. The predominant Pu valence in the dissolving solution was Pu(IV). The concentration of Pu(VI) was evaluated by UV-visible spectroscopy and was estimated to be significantly less than 1 wt %. The offgas generation rates and H{sub 2} concentrations measured in the offgas from experiments performed using 10 M HNO{sub 3} containing 0.05 M KF, 1.9 g/L Fe and either 1 g/L Gd or B were approximately the same. These data support the conclusion that the presence of either 1 g/L Gd or B had the same general effect on the dissolution rate. The calculated offgas generation during the dissolutions was 0.6 mol offgas/mol of Pu. The H{sub 2} concentration measured in the offgas from the dissolution using Gd as the neutron poison was approximately 0.5 vol %. In the B system, the H{sub 2} ranged from nominally 0.8 to 1 vol % which is about the same as measured in the Gd system within the uncertainty of the analysis. The offgas generation rate for the dissolution performed using 10 M HNO{sub 3} containing 0.03 M KF, 0.5 g/L Gd, and 1.9 g/L Fe was approximately a factor of two less than produced in the other dissolutions; however, the concentration of H{sub 2} measured in the offgas was higher. The adjusted concentration ranged from 2.7 to 8.8 vol % as the dissolution proceeded. Higher concentrations of H{sub 2} occur when the Pu dissolution proceeds by a metal/acid reaction rather than nitrate oxidation. The higher H{sub 2} concentration could be attributed to the reduced activity of the fluoride due to complexation with Pu as the dissolution progressed. Dissolution of Pu metal at 20 °C in 10 M HNO{sub 3} containing 0.05 M KF showed that the Pu metal dissolves slowly without any visible gas generation. As the Pu metal dissolves, it forms a more-dense Pu-bearing solution which sank to the bottom of the dissolution vessel. The dissolved Pu did not form a boundary layer around the sample and failed to distribute homogeneously due to minimal (thermally-induced) mixing. This indicates that in the H-Canyon dissolver insert, the Pu will diffuse out of the insert into the bulk dissolver solution where it will disperse. At 35 °C, the Pu metal dissolved without visible gas generation. However, due to thermal currents caused by maintaining the solution at 35 °C, the dissolved Pu distributed evenly throughout the dissolver solution. It did not form a boundary layer around the sample.« less

Assessment of hupu gum for its carrier property in the design and evaluation of solid mixtures of poorly water soluble drug - rofecoxib.

PubMed

Vadlamudi, Harini Chowdary; Raju, Y Prasanna; Asuntha, G; Nair, Rahul; Murthy, K V Ramana; Vulava, Jayasri

2014-01-01

There are no reports about the pharmaceutical applications of hupu gum (HG). Hence the present study was undertaken to test its suitability in the dissolution enhancement of poorly water soluble drug. Rofecoxib (RFB) was taken as model drug. For comparison solid mixtures were prepared with carriers such as poly vinyl pyrrolidone (PVP), sodium starch glycollate (SSG) and guar gum (GG). Physical mixing (PM), co-grinding (CG), kneading (KT) and solvent evaporation (SE) techniques were used to prepare the solid mixtures, using all the carriers in different carrier and drug ratios. The solid mixtures were characterized by powder X-ray diffraction (XRD) and Fourier-transformed infrared spectroscopy (FTIR). There was a significant improvement in the dissolution rate of solid mixtures of HG, when compared with the solid mixtures of other carriers. There was an increase in dissolution rate with increase in concentration of HG upto 1:1 ratio of carrier and drug. No drug-carrier interaction was found by FTIR studies. XRD studies indicated reduction in crystallinity of the drug with increase in HG concentration. Hence HG could be a useful carrier for the dissolution enhancement of poorly water soluble drugs.

Effects of ocean acidification on the dissolution rates of reef-coral skeletons.

PubMed

van Woesik, Robert; van Woesik, Kelly; van Woesik, Liana; van Woesik, Sandra

2013-01-01

Ocean acidification threatens the foundation of tropical coral reefs. This study investigated three aspects of ocean acidification: (i) the rates at which perforate and imperforate coral-colony skeletons passively dissolve when pH is 7.8, which is predicted to occur globally by 2100, (ii) the rates of passive dissolution of corals with respect to coral-colony surface areas, and (iii) the comparative rates of a vertical reef-growth model, incorporating passive dissolution rates, and predicted sea-level rise. By 2100, when the ocean pH is expected to be 7.8, perforate Montipora coral skeletons will lose on average 15 kg CaCO3 m(-2) y(-1), which is approximately -10.5 mm of vertical reduction of reef framework per year. This rate of passive dissolution is higher than the average rate of reef growth over the last several millennia and suggests that reefs composed of perforate Montipora coral skeletons will have trouble keeping up with sea-level rise under ocean acidification. Reefs composed of primarily imperforate coral skeletons will not likely dissolve as rapidly, but our model shows they will also have trouble keeping up with sea-level rise by 2050.

Investigation of corrosion behavior of biodegradable magnesium alloys using an online-micro-flow capillary flow injection inductively coupled plasma mass spectrometry setup with electrochemical control

NASA Astrophysics Data System (ADS)

Ulrich, A.; Ott, N.; Tournier-Fillon, A.; Homazava, N.; Schmutz, P.

2011-07-01

The development of biodegradable metallic materials designed for implants or medical stents is new and is one of the most interesting new fields in material science. Besides biocompatibility, a detailed understanding of corrosion mechanisms and dissolution processes is required to develop materials with tailored degradation behavior. The materials need to be sufficiently stable as long as they have to fulfill their medical task. However, subsequently they should dissolve completely in a controlled manner in terms of maximum body burden. This study focuses on the elemental and time resolved dissolution processes of a magnesium rare earth elements alloy which has been compared to pure magnesium with different impurity level. The here described investigations were performed using a novel analytical setup based on a micro-flow capillary online-coupled via a flow injection system to a plasma mass spectrometer. Differences in element-specific and time-dependent dissolution were monitored for various magnesium alloys in contact with sodium chloride or mixtures of sodium and calcium chloride as corrosive media. The dissolution behavior strongly depends on bulk matrix elements, secondary alloying elements and impurities, which are usually present even in pure magnesium.

Preparation, characterization, and scale-up of ketoconazole with enhanced dissolution and bioavailability.

PubMed

Elder, Edmund J; Evans, Jonathan C; Scherzer, Brian D; Hitt, James E; Kupperblatt, Gary B; Saghir, Shakil A; Markham, Dan A

2007-07-01

Many new molecular entities targeted for pharmaceutical applications face serious development challenges because of poor water solubility. Although particle engineering technologies such as controlled precipitation have been shown to enhance aqueous dissolution and bioavailability of poorly water soluble active pharmaceutical ingredients, the data available are the results of laboratory-scale experiments. These technologies must be evaluated at larger scale to ensure that the property enhancement is scalable and that the modified drugs can be processed on conventional equipment. In experiments using ketoconazole as the model drug, the controlled precipitation process was shown to produce kg-scale modified drug powder with enhanced dissolution comparable to that of lab-scale powder. Ketoconazole was demonstrated to be stable throughout the controlled precipitation process, with a residual methanol level below the ICH limit. The modified crystalline powder can be formulated, and then compressed using conventional high-speed tableting equipment, and the resulting tablets showed bioavailability more than double that of commercial tablets. When appropriately protected from moisture, both the modified powder and tablets prepared from the modified powder showed no change in dissolution performance for at least 6 months following storage at accelerated conditions and for at least 18 months following storage at room temperature.

In-vitro dissolution rate and molecular docking studies of cabergoline drug with β-cyclodextrin

NASA Astrophysics Data System (ADS)

Shanmuga priya, Arumugam; Balakrishnan, Suganya bharathi; Veerakanellore, Giri Babu; Stalin, Thambusamy

2018-05-01

The physicochemical properties and dissolution profile of cabergoline drug (CAB) with β-cyclodextrin (β-CD) inclusion complex were investigated by the UV spectroscopy. The inclusion complex has used to calculate the stability constant and gives the stoichiometry molar ratio is 1:1 between CAB and β-CD. The phase solubility diagram and the aqueous solubility of CAB (60%) was found to be enhanced by β-CD. In addition, the phase solubility profile of CAB with β-CD was classified as AL-type. Binary systems of CAB with β-CD were prepared by Physical mixture, Kneading and solvent evaporation methods. The solid-state properties of the inclusion complex were characterized by Fourier transformation-infrared spectroscopy, Differential scanning calorimetry, Powder X-ray diffractometric patterns and Scanning electron microscopic techniques. Theoretically, β-CD and CAB inclusion complex obtained by molecular docking studies, it is in good correlation with the results obtained through experimental methods using the Schrödinger software program. In-vitro dissolution profiles of the inclusion complexes were carried out and obvious increase in dissolution rate was observed when compared with pure CAB drug and the complexes.

Later Life Marital Dissolution and Repartnership Status: A National Portrait.

PubMed

Brown, Susan L; Lin, I-Fen; Hammersmith, Anna M; Wright, Matthew R

2016-04-30

Our study compares two types of later life marital dissolution that occur after age 50-divorce and widowhood-and their associations with repartnership status (i.e., remarried, cohabiting, or unpartnered). We used data from the Health and Retirement Study to provide a portrait of later life divorce and widowhood for women and men. Next, we tested whether marital dissolution type is related to women's and men's repartnered status, distinguishing among remarrieds, cohabitors, and unpartnereds, net of key sociodemographic indicators. Divorcees are more often repartnered through either remarriage or cohabitation than are widoweds. This gap persists among women net of an array of sociodemographic factors. For men, the differential is reduced to nonsignificance with the inclusion of these factors. Later life marital dissolution increasingly occurs through divorce rather than widowhood, and divorce is more often followed by repartnership. The results from this study suggest that gerontological research should not solely focus on widowhood but also should pay attention to divorce and repartnering during later life. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effect of Phosphate, Fluoride, and Nitrate on Gibbsite Dissolution Rate and Solubility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herting, Daniel L.

2014-01-29

Laboratory tests have been completed with simulated tank waste samples to investigate the effects of phosphate, fluoride, and nitrate on the dissolution rate and equilibrium solubility of gibbsite in sodium hydroxide solution at 22 and 40{degrees}C. Results are compared to relevant literature data and to computer model predictions. The presence of sodium nitrate (3 M) caused a reduction in the rate of gibbsite dissolution in NaOH, but a modest increase in the equilibrium solubility of aluminum. The increase in solubility was not as large, though, as the increase predicted by the computer model. The presence of phosphate, either as sodiummore » phosphate or sodium fluoride phosphate, had a negligible effect on the rate of gibbsite dissolution, but caused a slight increase in aluminum solubility. The magnitude of the increased solubility, relative to the increase caused by sodium nitrate, suggests that the increase is due to ionic strength (or water activity) effects, rather than being associated with the specific ion involved. The computer model predicted that phosphate would cause a slight decrease in aluminum solubility, suggesting some Al-PO4 interaction. No evidence was found of such an interaction.« less

Preliminary study of the effects of a reversible chemical reaction on gas bubble dissolution. [for space glass refining

NASA Technical Reports Server (NTRS)

Weinberg, M. C.

1982-01-01

A preliminary investigation is carried out of the effects of a reversible chemical reaction on the dissolution of an isolated, stationary gas bubble in a glass melt. The exact governing equations for the model system are formulated and analyzed. The approximate quasi-steady-state version of these equations is solved analytically, and a calculation is made of bubble dissolution rates. The results are then compared with numerical solutions obtained from the finite difference form of the exact governing equations. It is pointed out that in the microgravity condition of space, the buoyant rise of a gas bubble in a glass melt will be negligible on the time scale of most experiments. For this reason, a determination of the behavior of a stationary gas bubble in a melt is relevant for an understanding of glass refining in space.

Electrical neurostimulation with imbalanced waveform mitigates dissolution of platinum electrodes

PubMed Central

Kumsa, Doe; Hudak, Eric M; Montague, Fred W; Kelley, Shawn C; Untereker, Darrel F; Hahn, Benjamin P; Condit, Chris; Cholette, Martin; Lee, Hyowon; Bardot, Dawn; Takmakov, Pavel

2017-01-01

Objective Electrical neurostimulation has traditionally been limited to the use of charge-balanced waveforms. Charge-imbalanced and monophasic waveforms are not used to deliver clinical therapy, because it is believed that these stimulation paradigms may generate noxious electrochemical species that cause tissue damage. Approach In this study, we investigated the dissolution of platinum as one of such irreversible reactions over a range of charge densities up to 160 µC cm−2 with current-controlled first phase, capacitive discharge second phase waveforms of both cathodic-first and anodic-first polarity. We monitored the concentration of platinum in solution under different stimulation delivery conditions including charge-balanced, charge-imbalanced, and monophasic pulses. Main results We observed that platinum dissolution decreased during charge-imbalanced and monophasic stimulation when compared to charge-balanced waveforms. Significance This observation provides an opportunity to re-evaluate the charge-balanced waveform as the primary option for sustainable neural stimulation. PMID:27650936

Particular Film Formation of Phenytoin at Silica Surfaces

PubMed Central

2014-01-01

Given the increasing number of poorly soluble and thus poorly bioavailable active pharmaceutical materials, there is a demand for innovative formulation platforms for such molecules. Thus a focus on enhancing dissolution properties of poorly soluble drugs exists. Within this study, the spin coating of acetone solutions containing 5,5-diphenyl-2,4-imidazolidinedione (phenytoin) in various concentrations is evaluated. The results reveal strong variations of the morphology of deposited phenytoin crystals at silica surfaces. Individual separated particles are obtained on low phenytoin concentrations, and closely packed particular films form when the concentration is increased. As the material is isomorphic, these various morphologies have the same crystalline structure. Dissolution experiments reveal that both the apparent maximum solubility and as the dissolution rate are strongly enhanced compared to bulk powder, suggesting that formulation based on this preparative technique will allow overcoming the low solubility problematic for a variety of drugs. PMID:24417472

Controlled Dissolution of Phenytoin by Hybridizing with Silica Nanoparticles

NASA Astrophysics Data System (ADS)

Goto, H.; Isobe, T.; Senna, M.

1999-06-01

A sparingly soluble model drug, phenytoin (5,5-diphenyl-hydantoin, denoted as PT), was incorporated during or after hydrolysis and polycondensation of tetra orthoethyl silicate (TEOS) to obtain silica-drug hybrids. We also compare the hybrids obtained by sol-gel process with those obtained by simple adsorption on nonporous silica particles. The initial rate of dissolution in water increases by a factor of 40 with respect to the intact PT by aging silica before drug addition. The IR results show that νC=O in the position 2 of PT and νN-H shift toward the higher wavenumber, showing that intermolecular hydrogen bonds between C=O and N-H are loosened or broken to form new hydrogen bonds between C=O in PT and Si-OH in silica. The dissolution rate of PT is determined by the degree of the breakage of hydrogen bonds between PT molecules and the intensity of the interaction between silica and PT.

First-Principles and Thermodynamic Simulation of Elastic Stress Effect on Energy of Hydrogen Dissolution in Alpha Iron

NASA Astrophysics Data System (ADS)

Rakitin, M. S.; Mirzoev, A. A.; Mirzaev, D. A.

2018-04-01

Mobile hydrogen, when dissolving in metals, redistributes due to the density gradients and elastic stresses, and enables destruction processes or phase transformations in local volumes of a solvent metal. It is rather important in solid state physics to investigate these interactions. The first-principle calculations performed in terms of the density functional theory, are used for thermodynamic simulation of the elastic stress effect on the energy of hydrogen dissolution in α-Fe crystal lattice. The paper presents investigations of the total energy of Fe-H system depending on the lattice parameter. As a result, the relation is obtained between the hydrogen dissolution energy and stress. A good agreement is shown between the existing data and simulation results. The extended equation is suggested for the chemical potential of hydrogen atom in iron within the local stress field. Two parameters affecting the hydrogen distribution are compared, namely local stress and phase transformations.

Crystal forms of the hydrogen oxalate salt of o-desmethylvenlafaxine.

PubMed

Dichiarante, Elena; Curzi, Marco; Giaffreda, Stefano L; Grepioni, Fabrizia; Maini, Lucia; Braga, Dario

2015-06-01

To prepare new crystalline forms of the antidepressant o-desmethylvenlafaxine salt as potential new commercial forms and evaluate their physicochemical properties, in particular the dissolution rate. A new hydrogen oxalate salt of o-desmethylvenlafaxine hydrogen oxalate (ODV-OX) was synthesized, and a polymorph screening was performed using different solvents and crystallization conditions. Crystalline forms were characterized by a combination of solid-state techniques: X-ray powder diffraction, differential scanning calorimetry, thermogravimetric analysis, FT-IR spectroscopy and single crystal X-ray diffraction. The stability of all crystalline phases was tested under International Conference on Harmonisation (ICH) conditions (40°C and 75% Relative Humidity (RH)) for 1 week. Dissolution tests were performed on the hydrogen oxalate salt ODV-OX Form 1 and compared with dissolution test on the commercial form of the succinate salt of o-desmethylvenlafaxine. Five crystalline forms of ODV-OX were isolated, namely three hydrated forms (Form 1, Form 2, Form 3) and two anhydrous forms (Form 4 and Form 5). Comparative solubility tests on ODV-OX Form 1 and o-desmethylvenlafaxine succinate evidenced a significant increase in solubility for the hydrogen oxalate salt (142 g/l) with respect to the succinate salt (70 g/l). © 2015 Royal Pharmaceutical Society.

Autogenous teeth used for bone grafting: a comparison with traditional grafting materials.

PubMed

Kim, Young-Kyun; Kim, Su-Gwan; Yun, Pil-Young; Yeo, In-Sung; Jin, Seung-Chan; Oh, Ji-Su; Kim, Heung-Joong; Yu, Sun-Kyoung; Lee, Sook-Young; Kim, Jae-Sung; Um, In-Woong; Jeong, Mi-Ae; Kim, Gyung-Wook

2014-01-01

This study evaluated the surface structures and physicochemical characteristics of a novel autogenous tooth bone graft material currently in clinical use. The material's surface structure was compared with a variety of other bone graft materials via scanning electron microscope (SEM). The crystalline structure of the autogenous tooth bone graft material from the crown (AutoBT crown) and root (AutoBT root), xenograft (BioOss), alloplastic material (MBCP), allograft (ICB), and autogenous mandibular cortical bone were compared using x-ray diffraction (XRD) analysis. The solubility of each material was measured with the Ca/P dissolution test. The results of the SEM analysis showed that the pattern associated with AutoBT was similar to that from autogenous cortical bones. In the XRD analysis, AutoBT root and allograft showed a low crystalline structure similar to that of autogenous cortical bones. In the CaP dissolution test, the amount of calcium and phosphorus dissolution in AutoBT was significant from the beginning, while displaying a pattern similar to that of autogenous cortical bones. In conclusion, autogenous tooth bone graft materials can be considered to have physicochemical characteristics similar to those of autogenous bones. Copyright © 2014 Elsevier Inc. All rights reserved.

Measuring the Influence of Pearlite Dissolution on the Transient Dynamic Strength of Rapidly Heated Plain Carbon Steels

NASA Astrophysics Data System (ADS)

Mates, Steven; Stoudt, Mark; Gangireddy, Sindhura

2016-07-01

Carbon steels containing ferrite-pearlite microstructures weaken dramatically when pearlite dissolves into austenite on heating. The kinetics of this phase transformation, while fast, can play a role during dynamic, high-temperature manufacturing processes, including high-speed machining, when the time scale of this transformation is on the order of the manufacturing process itself. In such a regime, the mechanical strength of carbon steel can become time dependent. The present work uses a rapidly heated, high-strain-rate mechanical test to study the effect of temperature and time on the amount of pearlite dissolved and on the resulting transient effect on dynamic strength of a low and a high carbon (eutectoid) steel. Measurements indicate that the transient effect occurs for heating times less than about 3 s. The 1075 steel loses about twice the strength compared to the 1018 steel (85 MPa to 45 MPa) owing to its higher initial pearlite volume fraction. Pearlite dissolution is confirmed by metallographic examination of tested samples. Despite the different starting pearlite fractions, the kinetics of dissolution are comparable for the two steels, owing to the similarity in their initial pearlite morphology.

Cefuroxime axetil solid dispersion with polyglycolized glycerides for improved stability and bioavailability.

PubMed

Dhumal, Ravindra S; Biradar, Shailesh V; Aher, Suyog; Paradkar, Anant R

2009-06-01

Cefuroxime axetil (CA), a poorly soluble, broad spectrum cephalosporin ester prodrug, is hydrolysed by intestinal esterase prior to absorption, leading to poor and variable bioavailability. The objective was therefore to formulate a stable amorphous solid dispersion of the drug with enhanced solubility and stability against enzymatic degradation. Spray drying was used to obtain a solid dispersion of CA with Gelucire 50/13 and Aerosil 200 (SDCAGA), and a solid dispersion of CA with polyvinyl pyrrolidone (SDCAP); amorphous CA (ACA) was obtained by spray drying CA alone. The formulations were characterized by differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy and Fourier transform infrared spectroscopy studies, and compared for solubility, dissolution and bioavailability in rats. SDCAP and SDCAGA showed improved solubility and dissolution profiles owing to amorphization and formation of solid dispersions with hydrophilic carriers. The improved stability of amorphous CA in solid dispersions compared to ACA alone was attributed to hydrogen bonding interactions involving the amide of CA with the carbonyl of polyvinyl pyrrolidone in SDCAP, whereas in SDCAGA the interactions were at multiple sites involving the amide and carbonyl of CA with the carbonyl and hydroxyl of Gelucire 50/13. However, SDCAGA showed superior bioavailability compared to SDCAP, ACA and CA. Improvement in physical stability of solid dispersions was attributed to hydrogen bonding, while improvement in bioavailability of SDCAGA compared to SDCAP, in spite of comparable solubility and dissolution profile, may be attributed to Gelucire, which utilizes intestinal esterase for lipolysis, protecting the prodrug from enzymatic degradation to its non-absorbable base form.

Highly efficient and durable TiN nanofiber electrocatalyst supports.

PubMed

Kim, Hyun; Cho, Min Kyung; Kwon, Jeong An; Jeong, Yeon Hun; Lee, Kyung Jin; Kim, Na Young; Kim, Min Jung; Yoo, Sung Jong; Jang, Jong Hyun; Kim, Hyoung-Juhn; Nam, Suk Woo; Lim, Dong-Hee; Cho, EunAe; Lee, Kwan-Young; Kim, Jin Young

2015-11-28

To date, carbon-based materials including various carbon nanostructured materials have been extensively used as an electrocatalyst support for proton exchange membrane fuel cell (PEMFC) applications due to their practical nature. However, carbon dissolution or corrosion caused by high electrode potential in the presence of O2 and/or water has been identified as one of the main failure modes for the device operation. Here, we report the first TiN nanofiber (TNF)-based nonwoven structured materials to be constructed via electrospinning and subsequent two-step thermal treatment processes as a support for the PEMFC catalyst. Pt catalyst nanoparticles (NPs) deposited on the TNFs (Pt/TNFs) were electrochemically characterized with respect to oxygen reduction reaction (ORR) activity and durability in an acidic medium. From the electrochemical tests, the TNF-supported Pt catalyst was better and more stable in terms of its catalytic performance compared to a commercially available carbon-supported Pt catalyst. For example, the initial oxygen reduction performance was comparable for both cases, while the Pt/TNF showed much higher durability from an accelerated degradation test (ADT) configuration. It is understood that the improved catalytic roles of TNFs on the supported Pt NPs for ORR are due to the high electrical conductivity arising from the extended connectivity, high inertness to the electrochemical environment and strong catalyst-support interactions.

Dissolution Studies of Papaverine Hydrochloride from Tablets in Three Pharmacopoeia Apparatuses.

PubMed

Polski, Andrzej; Kasperek, Regina; Rogowska, Magdalena; Iwaniak, Karol; Sobòtka-Polska, Karolina; Poleszak, Ewa

2015-01-01

In tablet production, the most important aspects are the physical properties of the tablets and their dissolution studies, which can be performed in four pharmacopoeial apparatuses. There are differences between them in construction and action, so differences in the results obtained are possible. The aim of the study was to compare the release of a model drug substance (papaverine hydrochloride) from tablets in three pharmacopoeial dissolution apparatus: a basket, a paddle (closed system) and flow-through cell (open system). The one series of tablets were produced by direct compression in a tablet press. The physical properties of the tablets (weight and size uniformity test, friability and hardness tests, disintegration time test), drug content and the release study of papaverine hydrochloride from tablets were studied in three dissolution apparatuses. The content of the active substance was studied spectrophotometrically. All tablets met the pharmacopoeic requirements. Over 80% of the model substance released from the tablets after 14 min in flow through the cell apparatus, while in the basket and paddle apparatuses after about 7 min 30 sec. After 20 min, the amount of the substance released in all apparatuses was over 90%. The release profiles of the drug substance in paddle and basket apparatuses were similar, while in the flow-through cell apparatus it was slightly slower. When the study conditions and composition of the tablets are the same, the release profile of the drug can be affected by the type of dissolution apparatus.

Real-Time X-ray Imaging Reveals Interfacial Growth, Suppression, and Dissolution of Zinc Dendrites Dependent on Anions of Ionic Liquid Additives for Rechargeable Battery Applications.

PubMed

Song, Yuexian; Hu, Jiugang; Tang, Jia; Gu, Wanmiao; He, Lili; Ji, Xiaobo

2016-11-23

The dynamic interfacial growth, suppression, and dissolution of zinc dendrites have been studied with the imidazolium ionic liquids (ILs) as additives on the basis of in situ synchrotron radiation X-ray imaging. The phase contrast difference of real-time images indicates that zinc dendrites are preferentially developed on the substrate surface in the ammoniacal electrolytes. After adding imidazolium ILs, both nucleation overpotential and polarization extent increase in the order of additive-free < EMI-Cl < EMI-PF 6 < EMI-TFSA < EMI-DCA. The real-time X-ray images show that the EMI-Cl can suppress zinc dendrites, but result in the formation of the loose deposits. The EMI-PF 6 and EMI-TFSA additives can smooth the deposit morphology through suppressing the initiation and growth of dendritic zinc. The addition of EMI-DCA increases the number of dendrite initiation sites, whereas it decreases the growth rate of dendrites. Furthermore, the dissolution behaviors of zinc deposits are compared. The zinc dendrites show a slow dissolution process in the additive-free electrolyte, whereas zinc deposits are easily detached from the substrate in the presence of EMI-Cl, EMI-PF 6 , or EMI-TFSA due to the formation of the loose structure. Hence, the dependence of zinc dendrites on anions of imidazolium IL additives during both electrodeposition and dissolution processes has been elucidated. These results could provide the valuable information in perfecting the performance of zinc-based rechargeable batteries.

Molten salt bath circulation design for an electrolytic cell

DOEpatents

Dawless, R.K.; LaCamera, A.F.; Troup, R.L.; Ray, S.P.; Hosler, R.B.

1999-08-17

An electrolytic cell for reduction of a metal oxide to a metal and oxygen has an inert anode and an upwardly angled roof covering the inert mode. The angled roof diverts oxygen bubbles into an upcomer channel, thereby agitating a molten salt bath in the upcomer channel and improving dissolution of a metal oxide in the molten salt bath. The molten salt bath has a lower velocity adjacent the inert anode in order to minimize corrosion by substances in the bath. A particularly preferred cell produces aluminum by electrolysis of alumina in a molten salt bath containing aluminum fluoride and sodium fluoride. 4 figs.

5 CFR 2634.410 - Dissolution.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 3 2014-01-01 2014-01-01 false Dissolution. 2634.410 Section 2634.410..., QUALIFIED TRUSTS, AND CERTIFICATES OF DIVESTITURE Qualified Trusts § 2634.410 Dissolution. Within thirty days of dissolution of a qualified trust, the interested party shall file a report of the dissolution...

5 CFR 2634.410 - Dissolution.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Dissolution. 2634.410 Section 2634.410..., QUALIFIED TRUSTS, AND CERTIFICATES OF DIVESTITURE Qualified Trusts § 2634.410 Dissolution. Within thirty days of dissolution of a qualified trust, the interested party shall file a report of the dissolution...

Absorption Study of Genistein Using Solid Lipid Microparticles and Nanoparticles: Control of Oral Bioavailability by Particle Sizes.

PubMed

Kim, Jeong Tae; Barua, Sonia; Kim, Hyeongmin; Hong, Seong-Chul; Yoo, Seung-Yup; Jeon, Hyojin; Cho, Yeongjin; Gil, Sangwon; Oh, Kyungsoo; Lee, Jaehwi

2017-07-01

In this study, the effect of particle size of genistein-loaded solid lipid particulate systems on drug dissolution behavior and oral bioavailability was investigated. Genistein-loaded solid lipid microparticles and nanoparticles were prepared with glyceryl palmitostearate. Except for the particle size, other properties of genistein-loaded solid lipid microparticles and nanoparticles such as particle composition and drug loading efficiency and amount were similarly controlled to mainly evaluate the effect of different particle sizes of the solid lipid particulate systems on drug dissolution behavior and oral bioavailability. The results showed that genistein-loaded solid lipid microparticles and nanoparticles exhibited a considerably increased drug dissolution rate compared to that of genistein bulk powder and suspension. The microparticles gradually released genistein as a function of time while the nanoparticles exhibited a biphasic drug release pattern, showing an initial burst drug release, followed by a sustained release. The oral bioavailability of genistein loaded in solid lipid microparticles and nanoparticles in rats was also significantly enhanced compared to that in bulk powders and the suspension. However, the bioavailability from the microparticles increased more than that from the nanoparticles mainly because the rapid drug dissolution rate and rapid absorption of genistein because of the large surface area of the genistein-solid lipid nanoparticles cleared the drug to a greater extent than the genistein-solid lipid microparticles did. Therefore, the findings of this study suggest that controlling the particle size of solid-lipid particulate systems at a micro-scale would be a promising strategy to increase the oral bioavailability of genistein.

Poly (amidoamine) dendrimer-mediated hybrid formulation for combination therapy of ramipril and hydrochlorothiazide.

PubMed

Singh, Mayank Kumar; Pooja, Deep; Kulhari, Hitesh; Jain, Sanjay Kumar; Sistla, Ramakrishna; Chauhan, Abhay Singh

2017-01-01

We present a dendrimer-based hybrid formulation strategy to explore the potential of poly (amidoamine) PAMAM dendrimers to be used as drug carriers for combination therapy of an anti-hypertensive drug ramipril (RAPL) and a diuretic hydrochlorothiazide (HCTZ). The drug-dendrimer complexes were prepared by phase-equilibration method. The results showed that the solubility of RAPL and HCTZ was dependent on dendrimer concentration and pH of dendrimer solution. The solubility profile of both RAPL and HCTZ dendrimer complexes illustrated a non-linear relationship with dendrimer concentration. At 0.8% (w/v) dendrimer concentration, solubility of RAPL was increased 4.91 folds with amine-terminated while for HCTZ, solubility enhancement was highest (3.72 folds) with carboxy-terminated. The complexes were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance analysis and high performance liquid chromatography. In-vitro drug dissolution performance of pure drugs, individual drug loaded dendrimer formulations and hybrid formulations was studied in USP dissolution medium (pH7.0) and in simulated gastric fluid (pH1.2). Dendrimer mediated formulations showed faster and complete dissolution compared to pure RAPL or HCTZ. Surprisingly, similar pattern of dissolution profile was established with hybrid formulations as compared to individual drug loaded dendrimers. The dendrimer-based hybrid formulations were found to be stable at dark and refrigerated conditions up to 5weeks. Conclusively, the proposed formulation strategy establishes a novel multitasking platform using dendrimer for simultaneous loading and delivery of multiple drugs for pharmaceutical applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Experimental Study on the Behavior of TiN and Ti2O3 Inclusions in Contact with CaO‐Al2O3‐SiO2‐MgO Slags

PubMed Central

Bernhard, C.

2017-01-01

TiN and Ti2O3 are the predominant inclusion types in Ti-alloyed ferritic chromium stainless steels. In order to ensure the required steel cleanness level, an effective removal of such inclusions in the slag during secondary metallurgy is essential. This inclusion removal predominantly takes place via dissolution of the inclusion in the slag. The dissolution behavior of TiN and Ti2O3 in CaO-SiO2-Al2O3-MgO slags as well as their agglomeration behavior in the liquid steel is investigated using High Temperature Laser Scanning Confocal Microscopy and Tammann Furnace experiments. Thermodynamic calculations are performed using FactSage 7.0. The behavior of TiN is observed to be completely different to that of oxides. Ti2O3 dissolves quickly in slags, and its dissolution behavior is comparable to that of other already well examined oxides. In contrast, TiN shows a very intense gas reaction which is attributed to the release of nitrogen during contact with slag. Slags with higher SiO2 content show a significantly higher ability for the dissolution of TiN as compared to Al2O3-rich slags. The gas reaction is found to also significantly influence the final steel cleanness. Despite the easy absorption of TiN in the slag, the formed nitrogen supports the formation of pinholes in the steel. PMID:29109805

[Studies on six heavy metal elements dissolution characteristics of Andrographis herb by ICP-OES].

PubMed

Tang, Rui; Li, Tian-Peng; Gu, Xue-Shi; Li, Yong-Jian; Yang, Yi

2010-02-01

A simple and accurate method for the simultaneous determination of As, Ba, Cd, Cr, Cu and Pb in andrographis herb by inductively coupled plasma optical emission spectrometry (ICP-OES) was developed. The samples were digested by HNO3-HClO4. The digestion-determination method was evaluated with the relative standard deviations for all these elements between 2.1% and 4.6%, and the recoveries were between 92.0% and 103.2%. The measuring method was proved to be simple, reliable and highly sensitive. The dissolution characteristics of the 6 heavy metal elements in different solvents and with different extraction methods such as refluxing, soaking, and ultrasonic assisted extraction were studied. The experimental results showed that Ba was in the highest concentration followed by Cu and Cr, and the concentration of As, Pb and Cd was relatively lower in the herb. With the increase in ethanol concentration, the dissolution amount of Ba decreased but that of Cu and Cr increased, and the highest concentration of Cd was dissolved in acidic solution. Overall, Cd and Pb were difficult to dissolve out with 85% ethanol refluxing, but As dissolved comparatively more under the same condition. Comparing the extraction methods, the higher concentration of these 6 metals was obtained by refluxing water or alkaline water than that by 85% ethanol maceration. These differences might be related to the existent forms of these six elements in the herb. The determination and study on dissolution characteristics of these elements by using ICP-OES was important for rational using medicinal resources and ensuring the safety of drugs.

Dissolution of solid dosage form. II. Equations for the dissolution of nondisintegrating tablet under the sink condition.

PubMed

Yonezawa, Y; Shirakura, K; Otsuka, A; Sunada, H

1991-03-01

An equation for dissolution from the whole surface of a nondisintegrating single component tablet under the sink condition was derived. Also, equations for several dissolution manners of the tablet under the sink condition were derived in the postulation of the dominant dissolution rate constant which determines the dissolution manner. The applicability or validity of these equations were examined by the dissolution measurements with nondisintegrating single component tablets. About one-tenth the amount of the amount needed to saturate the solution was used to prepare a tablet, and dissolution measurements were carried out with the tablet whose flat or side surface was masked with an adhesive tape in accordance with the conditions for derivation of equations. Among the derived equations, dissolution from the whole surface of a tablet was expressed by a form similar to the cube root law equation for particles. Hence, a single component tablet compressed by the use of a suitable amount was thought to behave like a single crystal. Also, equations derived for several dissolution manners were thought to be applicable for the dissolution of a nonspherical particle and crystal concerning the crystal's habit and its dissolution property, and the extended applicability was examined by converting the crystal into a simplified or idealized form, i.e., rectangle or plate.

Interlaboratory studies on in vitro test methods for estimating in vivo resorption of calcium phosphate ceramics.

PubMed

Ito, Atsuo; Sogo, Yu; Yamazaki, Atsushi; Aizawa, Mamoru; Osaka, Akiyoshi; Hayakawa, Satoshi; Kikuchi, Masanori; Yamashita, Kimihiro; Tanaka, Yumi; Tadokoro, Mika; de Sena, Lídia Ágata; Buchanan, Fraser; Ohgushi, Hajime; Bohner, Marc

2015-10-01

A potential standard method for measuring the relative dissolution rate to estimate the resorbability of calcium-phosphate-based ceramics is proposed. Tricalcium phosphate (TCP), magnesium-substituted TCP (MgTCP) and zinc-substituted TCP (ZnTCP) were dissolved in a buffer solution free of calcium and phosphate ions at pH 4.0, 5.5 or 7.3 at nine research centers. Relative values of the initial dissolution rate (relative dissolution rates) were in good agreement among the centers. The relative dissolution rate coincided with the relative volume of resorption pits of ZnTCP in vitro. The relative dissolution rate coincided with the relative resorbed volume in vivo in the case of comparison between microporous MgTCPs with different Mg contents and similar porosity. However, the relative dissolution rate was in poor agreement with the relative resorbed volume in vivo in the case of comparison between microporous TCP and MgTCP due to the superimposition of the Mg-mediated decrease in TCP solubility on the Mg-mediated increase in the amount of resorption. An unambiguous conclusion could not be made as to whether the relative dissolution rate is predictive of the relative resorbed volume in vivo in the case of comparison between TCPs with different porosity. The relative dissolution rate may be useful for predicting the relative amount of resorption for calcium-phosphate-based ceramics having different solubility under the condition that the differences in the materials compared have little impact on the resorption process such as the number and activity of resorbing cells. The evaluation and subsequent optimization of the resorbability of calcium phosphate are crucial in the use of resorbable calcium phosphates. Although the resorbability of calcium phosphates has usually been evaluated in vivo, establishment of a standard in vitro method that can predict in vivo resorption is beneficial for accelerating development and commercialization of new resorbable calcium phosphate materials as well as reducing use of animals. However, there are only a few studies to propose such an in vitro method within which direct comparison was carried out between in vitro and in vivo resorption. We propose here an in vitro method based on measuring dissolution rate. The efficacy and limitations of the method were evaluated by international round-robin tests as well as comparison with in vivo resorption studies for future standardization. This study was carried out as one of Versailles Projects on Advanced Materials and Standards (VAMAS). Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Justification of disintegration testing beyond current FDA criteria using in vitro and in silico models.

PubMed

Uebbing, Lukas; Klumpp, Lukas; Webster, Gregory K; Löbenberg, Raimar

2017-01-01

Drug product performance testing is an important part of quality-by-design approaches, but this process often lacks the underlying mechanistic understanding of the complex interactions between the disintegration and dissolution processes involved. Whereas a recent draft guideline by the US Food and Drug Administration (FDA) has allowed the replacement of dissolution testing with disintegration testing, the mentioned criteria are not globally accepted. This study provides scientific justification for using disintegration testing rather than dissolution testing as a quality control method for certain immediate release (IR) formulations. A mechanistic approach, which is beyond the current FDA criteria, is presented. Dissolution testing via United States Pharmacopeial Convention Apparatus II at various paddle speeds was performed for immediate and extended release formulations of metronidazole. Dissolution profile fitting via DDSolver and dissolution profile predictions via DDDPlus™ were performed. The results showed that Fickian diffusion and drug particle properties (DPP) were responsible for the dissolution of the IR tablets, and that formulation factors (eg, coning) impacted dissolution only at lower rotation speeds. Dissolution was completely formulation controlled if extended release tablets were tested and DPP were not important. To demonstrate that disintegration is the most important dosage form attribute when dissolution is DPP controlled, disintegration, intrinsic dissolution and dissolution testing were performed in conventional and disintegration impacting media (DIM). Tablet disintegration was affected by DIM and model fitting to the Korsmeyer-Peppas equation showed a growing effect of the formulation in DIM. DDDPlus was able to predict tablet dissolution and the intrinsic dissolution profiles in conventional media and DIM. The study showed that disintegration has to occur before DPP-dependent dissolution can happen. The study suggests that disintegration can be used as performance test of rapidly disintegrating tablets beyond the FDA criteria. The scientific criteria and justification is that dissolution has to be DPP dependent, originated from active pharmaceutical ingredient characteristics and formulations factors have to be negligible.

Justification of disintegration testing beyond current FDA criteria using in vitro and in silico models

PubMed Central

Uebbing, Lukas; Klumpp, Lukas; Webster, Gregory K; Löbenberg, Raimar

2017-01-01

Drug product performance testing is an important part of quality-by-design approaches, but this process often lacks the underlying mechanistic understanding of the complex interactions between the disintegration and dissolution processes involved. Whereas a recent draft guideline by the US Food and Drug Administration (FDA) has allowed the replacement of dissolution testing with disintegration testing, the mentioned criteria are not globally accepted. This study provides scientific justification for using disintegration testing rather than dissolution testing as a quality control method for certain immediate release (IR) formulations. A mechanistic approach, which is beyond the current FDA criteria, is presented. Dissolution testing via United States Pharmacopeial Convention Apparatus II at various paddle speeds was performed for immediate and extended release formulations of metronidazole. Dissolution profile fitting via DDSolver and dissolution profile predictions via DDDPlus™ were performed. The results showed that Fickian diffusion and drug particle properties (DPP) were responsible for the dissolution of the IR tablets, and that formulation factors (eg, coning) impacted dissolution only at lower rotation speeds. Dissolution was completely formulation controlled if extended release tablets were tested and DPP were not important. To demonstrate that disintegration is the most important dosage form attribute when dissolution is DPP controlled, disintegration, intrinsic dissolution and dissolution testing were performed in conventional and disintegration impacting media (DIM). Tablet disintegration was affected by DIM and model fitting to the Korsmeyer–Peppas equation showed a growing effect of the formulation in DIM. DDDPlus was able to predict tablet dissolution and the intrinsic dissolution profiles in conventional media and DIM. The study showed that disintegration has to occur before DPP-dependent dissolution can happen. The study suggests that disintegration can be used as performance test of rapidly disintegrating tablets beyond the FDA criteria. The scientific criteria and justification is that dissolution has to be DPP dependent, originated from active pharmaceutical ingredient characteristics and formulations factors have to be negligible. PMID:28442890

12 CFR 546.4 - Voluntary dissolution.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 Banks and Banking 6 2014-01-01 2012-01-01 true Voluntary dissolution. 546.4 Section 546.4 Banks... ASSOCIATIONS-MERGER, DISSOLUTION, REORGANIZATION, AND CONVERSION § 546.4 Voluntary dissolution. A Federal savings association's board of directors may propose a plan for dissolution of the association. The plan...

12 CFR 546.4 - Voluntary dissolution.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 6 2013-01-01 2012-01-01 true Voluntary dissolution. 546.4 Section 546.4 Banks... ASSOCIATIONS-MERGER, DISSOLUTION, REORGANIZATION, AND CONVERSION § 546.4 Voluntary dissolution. A Federal savings association's board of directors may propose a plan for dissolution of the association. The plan...

12 CFR 546.4 - Voluntary dissolution.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Voluntary dissolution. 546.4 Section 546.4... ASSOCIATIONS-MERGER, DISSOLUTION, REORGANIZATION, AND CONVERSION § 546.4 Voluntary dissolution. A Federal savings association's board of directors may propose a plan for dissolution of the association. The plan...

12 CFR 146.4 - Voluntary dissolution.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 Banks and Banking 1 2014-01-01 2014-01-01 false Voluntary dissolution. 146.4 Section 146.4... ASSOCIATIONS-MERGER, DISSOLUTION, REORGANIZATION, AND CONVERSION § 146.4 Voluntary dissolution. (a) A Federal savings association's board of directors may propose a plan for dissolution of the association. The plan...

12 CFR 146.4 - Voluntary dissolution.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 1 2013-01-01 2013-01-01 false Voluntary dissolution. 146.4 Section 146.4... ASSOCIATIONS-MERGER, DISSOLUTION, REORGANIZATION, AND CONVERSION § 146.4 Voluntary dissolution. (a) A Federal savings association's board of directors may propose a plan for dissolution of the association. The plan...

12 CFR 546.4 - Voluntary dissolution.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 5 2011-01-01 2011-01-01 false Voluntary dissolution. 546.4 Section 546.4... ASSOCIATIONS-MERGER, DISSOLUTION, REORGANIZATION, AND CONVERSION § 546.4 Voluntary dissolution. A Federal savings association's board of directors may propose a plan for dissolution of the association. The plan...

12 CFR 546.4 - Voluntary dissolution.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 6 2012-01-01 2012-01-01 false Voluntary dissolution. 546.4 Section 546.4... ASSOCIATIONS-MERGER, DISSOLUTION, REORGANIZATION, AND CONVERSION § 546.4 Voluntary dissolution. A Federal savings association's board of directors may propose a plan for dissolution of the association. The plan...

12 CFR 146.4 - Voluntary dissolution.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 1 2012-01-01 2012-01-01 false Voluntary dissolution. 146.4 Section 146.4... ASSOCIATIONS-MERGER, DISSOLUTION, REORGANIZATION, AND CONVERSION § 146.4 Voluntary dissolution. (a) A Federal savings association's board of directors may propose a plan for dissolution of the association. The plan...

A novel bile salts-lipase polymeric film-infused minitablet system for enhanced oral delivery of cholecalciferol.

PubMed

Braithwaite, Miles C; Choonara, Yahya E; Kumar, Pradeep; Tomar, Lomas K; Du Toit, Lisa C; Pillay, Viness

2016-11-01

Few researchers have investigated the use of multiple physiological enhancers combined with synthetic carriers to augment delivery of nutraceuticals. The current work describes the development of an oral delivery system termed a bioactive association platform (BAP) capable of delivering nutraceutical actives from a formulation framework specifically for enhancing the in vitro and in vivo performance of model vitamin, cholecalciferol (Vitamin D 3 ). Synthesis of a novel triple vitamin minitablet and an optimized bile salt/lipase alginate-glycerin film provided unique oral components for inclusion in a BAP capsule. Component validation and physicochemical characterizations included comparative ex vivo permeability, chemical structure mapping, thermodynamic analysis and magnetic resonance imaging. In vitro dissolution studies of the BAP produced an area under the dissolution curve (AUC) for cholecalciferol release that was 28% greater than a conventional comparator product. A total of 84.01% of cholecalciferol was released from the BAP within 3 h versus only 59% from a comparator. Ex vivo permeation studies revealed superior cholecalciferol membrane diffusion from the triple vitamin minitablet BAP component. In vivo performance showed a greater mean change from baseline cholecalciferol to peak plasma levels (C max ) from the BAP compared to the comparator (55.66 versus 46.05 ng/mL). Cholecalciferol bioavailability was improved in vivo with an AUC 0-inf from the BAP that was 3.2× greater than the conventional product. The BAP was also superior at improving and maintaining serum levels of the main metabolite, 25-hydroxyvitamin D 3 , compared to the conventional system. In vitro and in vivo results thus confirmed improvements in cholecalciferol dissolution, membrane permeability and plasma drug levels. The study results position the BAP as an ideal oral vehicle for enhanced delivery of cholecalciferol.

The role of mineral heterogeneity on the hydrogeochemical response of two fractured reservoir rocks in contact with dissolved CO2

NASA Astrophysics Data System (ADS)

Garcia Rios, Maria; Luquot, Linda; Soler, Josep M.; Cama, Jordi

2017-04-01

In this study we compare the hydrogeochemical response of two fractured reservoir rocks (limestone composed of 100 wt.% calcite and sandstone composed of 66 wt.% calcite, 28 wt.% quartz and 6 wt.% microcline) in contact with CO2-rich sulfate solutions. Flow-through percolation experiments were performed using artificially fractured limestone and sandstone cores and injecting a CO2-rich sulfate solution under a constant volumetric flow rate (from 0.2 to 60 mL/h) at P = 150 bar and T = 60 °C. Measurements of the pressure difference between the inlet and the outlet of the samples and of the aqueous chemistry enabled the determination of fracture permeability changes and net reaction rates. Additionally, X-ray computed microtomography (XCMT) was used to characterize and localized changes in fracture volume induced by dissolution and precipitation reactions. In all reacted cores an increase in fracture permeability and in fracture volume was always produced even when gypsum precipitation happened. The presence of inert silicate grains in sandstone samples favored the occurrence of largely distributed dissolution structures in contrast to localized dissolution in limestone samples. This phenomenon promoted greater dissolution and smaller precipitation in sandstone than in limestone experiments. As a result, in sandstone reservoirs, the larger increase in fracture volume as well as the more extended distribution of the created volume would favor the CO2 storage capacity. The different distribution of created volume between limestone and sandstone experiments led to a different variation in fracture permeability. The progressive stepped permeability increase for sandstone would be preferred to the sharp permeability increase for limestone to minimize risks related to CO2 injection, favor capillary trapping and reduce energetic storage costs. 2D reactive transport simulations that reproduce the variation in aqueous chemistry and the fracture geometry (dissolution pattern) were performed using CrunchFlow. The calcite reactive surface area had to be diminished with respect to the geometric surface area in order to account for the transport control of the calcite dissolution reaction at pH < 5. The fitted reactive surface area was higher under faster flow conditions, reflecting a decrease in transport control and a more distributed reaction in sandstone compared to limestone.

Interface dissolution control of the 14C profile in marine sediment

USGS Publications Warehouse

Keir, R.S.; Michel, R.L.

1993-01-01

The process of carbonate dissolution at the sediment-water interface has two possible endmember boundary conditions. Either the carbonate particles dissolve mostly before they are incorporated into the sediment by bioturbation (interface dissolution), or the vertical mixing is rapid relative to their extermination rate (homogeneous dissolution). In this study, a detailed radiocarbon profile was determined in deep equatorial Pacific sediment that receives a high rate of carbonate supply. In addition, a box model of sediment mixing was used to simulate radiocarbon, carbonate content and excess thorium profiles that result from either boundary process following a dissolution increase. Results from homogeneous dissolution imply a strong, very recent erosional event, while interface dissolution suggests that moderately increased dissolution began about 10,000 years ago. In order to achieve the observed mixed layer radiocarbon age, increased homogeneous dissolution would concentrate a greater amount of clay and 230Th than is observed, while for interface dissolution the predicted concentrations are too small. These results together with small discontinuities beneath the mixed layer in 230Th profiles suggest a two-stage increase in interface dissolution in the deep Pacific, the first occurring near the beginning of the Holocene and the second more recently, roughly 5000 years ago. ?? 1993.

Deep water dissolution in Marine Isotope Stage 3 from the northern South China Sea

NASA Astrophysics Data System (ADS)

Huang, B.

2015-12-01

The production, transport, deposition, and dissolution of carbonate profoundly implicate the global carbon cycle affect the inventory and distribution of dissolved organic carbon (DIC) and alkalinity (ALK), which drive atmospheric CO2 change on glacial-interglacial timescale. the process may provide significant clues for improved understanding of the mechanisms that control the global climate system. In this study, we calculate and analyze the foraminiferal dissolution index (FDX) and the fragmentation ratios of planktonic foraminifera over 60-25 ka based on samples from 17924 and ODP 1144 in the northeastern South China Sea (SCS) to reconstruct the deep water carbonate dissolution during Marine Isotope Stage 3 (MIS 3). Result shows that the dissolution of carbonate increases gradually at 17924 but keeps stable at ODP 1144. The changes of FDX coincidence with that of fragmentation ratios at 17924 and ODP 1144 suggest both indexes can be used as reliable dissolving proxies of planktonic foraminifera. Comparing FDX and fragmentation ratios at both sites, we find the FDX and fragmentation ratios at 17924 are higher than those at 1144, indicating that carbonate dissolution is intenser in 17924 core during MIS 3. The increasing total percentage of both N. dutertrei and G. bulloides during MIS 3 reveals the rising primary productivity that may lead to deep water [CO32-] decrease. The slow down of thermohaline circulation may increase deep water residence time and accelerate carbonate dissolution. In addition, the covering of ice caps, iron supply and increased surface-water stratification also contribute to atmosphere CO2 depletion and [CO32-] decrease in deep water. In the meanwhile, regression result from colder temperature increases the input of ALK and DIC to the deep ocean and deepens the carbonate saturation depth, which makes the deep water [CO32-] rise. In ODP Site 1144, the decrease in [CO32-] caused by more CO2 restored in deep water is equal to the increase in [CO32-] because of regression, so dissolution keeps steady. However, [CO32-] is probably more strongly controlled by regression, the decrease in [CO32-] result from more CO2 restored in deep water overwhelms the increase in [CO32-] due to regression at 17924, so more carbonate dissolved from MIS 3 to the Last Glacial Maximum (LGM).

Microbially mediated barite dissolution in anoxic brines

USGS Publications Warehouse

Ouyang, Bingjie; Akob, Denise M.; Dunlap, Darren S.; Renock, Devon

2017-01-01

Fluids injected into shale formations during hydraulic fracturing of black shale return with extraordinarily high total-dissolved-solids (TDS) and high concentrations of barium (Ba) and radium (Ra). Barite, BaSO4, has been implicated as a possible source of Ba as well as a problematic mineral scale that forms on internal well surfaces, often in close association with radiobarite, (Ba,Ra)SO4. The dissolution of barite by abiotic processes is well quantified. However, the identification of microbial communities in flowback and produced water necessitates the need to understand barite dissolution in the presence of bacteria. Therefore, we evaluated the rates and mechanisms of abiotic and microbially-mediated barite dissolution under anoxic and hypersaline conditions in the laboratory. Barite dissolution experiments were conducted with bacterial enrichment cultures established from produced water from Marcellus Shale wells located in northcentral Pennsylvania. These cultures were dominated by anaerobic halophilic bacteria from the genus Halanaerobium. Dissolved Ba was determined by ICP-OES and barite surfaces were investigated by SEM and AFM. Our results reveal that: 1) higher amounts of barium (up to ∼5 × ) are released from barite in the presence of Halanaerobium cultures compared to brine controls after 30 days of reaction, 2) etch pits that develop on the barite (001) surface in the presence of Halanaerobium exhibit a morphology that is distinct from those that form during control experiments without bacteria, 3) etch pits that develop in the presence of Halanaerobium exhibit a morphology that is similar to the morphology of etch pits formed in the presence of strong organic chelators, EDTA and DTPA, and 4) experiments using dialysis membranes to separate barite from bacteria suggest that direct contact between the two is not required in order to promote dissolution. These results suggest that Halanaerobium increase the rate of barite dissolution in anoxic and high ionic strength solutions. Additionally, the increase in rate occurs without direct microbe-mineral contact suggesting that metabolites secreted by the bacteria may be responsible for promotion of dissolution. The findings of this study have implications for understanding barium cycling in marine/hypersaline environments, release of barium (and associated radium) from waste solids generated from energy and mining industries, as well as potential for developing new anti-scaling chemicals.

Oxidation and the Effects of High Temperature Exposures on Notched Fatigue Life of an Advanced Powder Metallurgy Disk Superalloy

NASA Technical Reports Server (NTRS)

Sudbrack, Chantal K.; Draper, Susan L.; Gorman, Timothy T.; Telesman, Jack; Gab, Timothy P.; Hull, David R.

2012-01-01

Oxidation and the effects of high temperature exposures on notched fatigue life were considered for a powder metallurgy processed supersolvus heat-treated ME3 disk superalloy. The isothermal static oxidation response at 704 C, 760 C, and 815 C was consistent with other chromia forming nickel-based superalloys: a TiO2-Cr2O3 external oxide formed with a branched Al2O3 internal subscale that extended into a recrystallized - dissolution layer. These surface changes can potentially impact disk durability, making layer growth rates important. Growth of the external scales and dissolution layers followed a cubic rate law, while Al2O3 subscales followed a parabolic rate law. Cr- rich M23C6 carbides at the grain boundaries dissolved to help sustain Cr2O3 growth to depths about 12 times thicker than the scale. The effect of prior exposures was examined through notched low cycle fatigue tests performed to failure in air at 704 C. Prior exposures led to pronounced debits of up to 99 % in fatigue life, where fatigue life decreased inversely with exposure time. Exposures that produced roughly equivalent 1 m thick external scales at the various isotherms showed statistically equivalent fatigue lives, establishing that surface damage drives fatigue debit, not exposure temperature. Fractographic evaluation indicated the failure mode for the pre-exposed specimens involved surface crack initiations that shifted with exposure from predominately single intergranular initiations with transgranular propagation to multi-initiations from the cracked external oxide with intergranular propagation. Weakened grain boundaries at the surface resulting from the M23C6 carbide dissolution are partially responsible for the intergranular cracking. Removing the scale and subscale while leaving a layer where M23C6 carbides were dissolved did not lead to a significant fatigue life improvement, however, also removing the M23C6 carbide dissolution layer led to nearly full recovery of life, with a transgranular initiation typical to that observed in unexposed specimens.

Versatile ligands for high-performance liquid chromatography: An overview of ionic liquid-functionalized stationary phases.

PubMed

Zhang, Mingliang; Mallik, Abul K; Takafuji, Makoto; Ihara, Hirotaka; Qiu, Hongdeng

2015-08-05

Ionic liquids (ILs), a class of unique substances composed purely by cation and anions, are renowned for their fascinating physical and chemical properties, such as negligible volatility, high dissolution power, high thermal stability, tunable structure and miscibility. They are enjoying ever-growing applications in a great diversity of disciplines. IL-modified silica, transforming the merits of ILs into chromatographic advantages, has endowed the development of high-performance liquid chromatography (HPLC) stationary phase with considerable vitality. In the last decade, IL-functionalized silica stationary phases have evolved into a series of branches to accommodate to different HPLC modes. An up-to-date overview of IL-immobilized stationary phases is presented in this review, and divided into five parts according to application mode, i.e., ion-exchange, normal-phase, reversed-phase, hydrophilic interaction and chiral recognition. Specific attention is channeled to synthetic strategies, chromatographic behavior and separation performance of IL-functionalized silica stationary phases. Copyright © 2015 Elsevier B.V. All rights reserved.

Early to middle Miocene climate evolution: New insights from IODP Sites U1335, U1337 and U1338 (eastern equatorial Pacific Ocean)

NASA Astrophysics Data System (ADS)

Kochhann, Karlos G. D.; Holbourn, Ann; Kuhnt, Wolfgang; Lyle, Mitch; Raffi, Isabella; Channell, James E.; Andersen, Nils

2015-04-01

The lower to middle Miocene (~20 to 13 Ma) carbonate-rich sedimentary successions recovered at Integrated Ocean Drilling Program (IODP) Sites U1335, U1337 and U1338 allow unsurpassed resolution over the Climatic Optimum (16.9-14.7 Ma) and the transition into a colder climate mode after 13.9 Ma with re-establishment of permanent Antarctic ice sheets. High-resolution (1-10 kyr) stable carbon (δ13C) and oxygen (δ18O) isotopes of well-preserved epibenthic foraminifera (Cibicidoides mundulus and Planulina wuellerstorfi) from these three sites show that the Climatic Optimum was characterized by high-amplitude climate variations and intense perturbations of the carbon cycle. Episodes of peak warmth coincided with transient shoaling of the carbonate compensation depth and enhanced carbonate dissolution in the deep ocean. The U1335 and U1337 records additionally reveal that the rapid global warming and/or polar ice melting event, marking the onset of the Climatic Optimum at ~16.9 Ma, was coupled to a massive increase in carbonate dissolution, indicated by sharp drops in carbonate percentages and accumulation rates and by the fragmentation or complete dissolution of planktonic foraminifers. After ~14.7 Ma, stepwise global cooling, culminating with extensive ice growth over Antarctica at ~13.8 Ma, coincide with enhanced opal and benthic foraminiferal accumulation rates, suggesting that increased siliceous productivity and organic carbon burial may have contributed to CO2 drawdown. Integration of age models derived from orbitally-tuned, high-resolution isotopes, biostratigraphic data and magnetic reversals allows further constraints on the temporal sequence of events and helps unravel the drivers of early to middle Miocene climate variations.

The Controversial Role of Inter-diffusion in Glass Alteration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gin, Stephane; Neill, Lindsay; Fournier, M.

2016-11-15

Current kinetic models for nuclear waste glasses (e.g. GM2001, GRAAL) are based on a set of mechanisms that have been generally agreed upon within the international waste glass community. These mechanisms are: hydration of the glass, ion exchange reactions (the two processes are referred as inter-diffusion), hydrolysis of the silicate network, and condensation/precipitation of partly or completely hydrolyzed species that produces a porous and amorphous layer and crystalline phases on surface of the altered glass. Recently, a new idea with origins in the mineral dissolution community has been proposed that excludes inter-diffusion process as a potential rate-limiting mechanism. To understandmore » how the so-called interfacial dissolution/precipitation model can change the current understanding of glass behavior, a key experiment used to account for this model was replicated to further revisit the interpretation. This experiment was performed at 50°C, with SON68 glass, in static mode, deionized water and S/V ratio of 10 m-1 for 6 months. It turn out that glass alters in an intermediate kinetic regime between the forward and the residual rate. According to previous and new solid characterizations, it is concluded that neither a simple inter-diffusion model nor the interfacial dissolution precipitation model can account for the observed elemental profiles within the alteration layer. More generally, far and close-to-saturation conditions must be distinguished and literature provides evidences that inter-diffusion takes place in slightly acidic conditions and far from saturation. However, closer to saturation, when a sufficiently dense layer is formed, a new approach is proposed requiring a full description of chemical reactions taking place within the alteration layer and involving water molecules as it is thought that water accessibility to the pristine glass is the rate-limiting process.« less

Simulation of Corrosion Process for Structure with the Cellular Automata Method

NASA Astrophysics Data System (ADS)

Chen, M. C.; Wen, Q. Q.

2017-06-01

In this paper, from the mesoscopic point of view, under the assumption of metal corrosion damage evolution being a diffusive process, the cellular automata (CA) method was proposed to simulate numerically the uniform corrosion damage evolution of outer steel tube of concrete filled steel tubular columns subjected to corrosive environment, and the effects of corrosive agent concentration, dissolution probability and elapsed etching time on the corrosion damage evolution were also investigated. It was shown that corrosion damage increases nonlinearly with increasing elapsed etching time, and the longer the etching time, the more serious the corrosion damage; different concentration of corrosive agents had different impacts on the corrosion damage degree of the outer steel tube, but the difference between the impacts was very small; the heavier the concentration, the more serious the influence. The greater the dissolution probability, the more serious the corrosion damage of the outer steel tube, but with the increase of dissolution probability, the difference between its impacts on the corrosion damage became smaller and smaller. To validate present method, corrosion damage measurements for concrete filled square steel tubular columns (CFSSTCs) sealed at both their ends and immersed fully in a simulating acid rain solution were conducted, and Faraday’s law was used to predict their theoretical values. Meanwhile, the proposed CA mode was applied for the simulation of corrosion damage evolution of the CFSSTCs. It was shown by the comparisons of results from the three methods aforementioned that they were in good agreement, implying that the proposed method used for the simulation of corrosion damage evolution of concrete filled steel tubular columns is feasible and effective. It will open a new approach to study and evaluate further the corrosion damage, loading capacity and lifetime prediction of concrete filled steel tubular structures.

Dissolution Flowsheet for High Flux Isotope Reactor Fuel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Daniel, W. E.; Rudisill, T. S.; O'Rourke, P. E.

2016-09-27

As part of the Spent Nuclear Fuel (SNF) processing campaign, H-Canyon is planning to begin dissolving High Flux Isotope Reactor (HFIR) fuel in late FY17 or early FY18. Each HFIR fuel core contains inner and outer fuel elements which were fabricated from uranium oxide (U 3O 8) dispersed in a continuous Al phase using traditional powder metallurgy techniques. Fuels fabricated in this manner, like other SNF’s processed in H-Canyon, dissolve by the same general mechanisms with similar gas generation rates and the production of H 2. The HFIR fuel cores will be dissolved and the recovered U will be down-blendedmore » into low-enriched U. HFIR fuel was previously processed in H-Canyon using a unique insert in both the 6.1D and 6.4D dissolvers. Multiple cores will be charged to the same dissolver solution maximizing the concentration of dissolved Al. The objective of this study was to identify flowsheet conditions through literature review and laboratory experimentation to safely and efficiently dissolve the HFIR fuel in H-Canyon. Laboratory-scale experiments were performed to evaluate the dissolution of HFIR fuel using both Al 1100 and Al 6061 T6 alloy coupons. The Al 1100 alloy was considered a representative surrogate which provided an upper bound on the generation of flammable (i.e., H 2) gas during the dissolution process. The dissolution of the Al 6061 T6 alloy proceeded at a slower rate than the Al 1100 alloy, and was used to verify that the target Al concentration in solution could be achieved for the selected Hg concentration. Mass spectrometry and Raman spectroscopy were used to provide continuous monitoring of the concentration of H 2 and other permanent gases in the dissolution offgas, allowing the development of H 2 generation rate profiles. The H 2 generation rates were subsequently used to evaluate if a full HFIR core could be dissolved in an H-Canyon dissolver without exceeding 60% of the calculated lower flammability limit (LFL) for H 2 at a given Hg concentration. Complete dissolution of the Al 1100 and Al 6061 T6 alloys up to a final Al concentration of 2 M was obtained using a 7 M HNO 3 solution containing a 0.002 M Hg catalyst. However, following the dissolutions, solids were observed in the solution. The solids were amorphous, but likely originated from the Si present in the alloys. No crystalline materials, such as Al(NO 3) 3 were observed. During the course of the dissolution experiments, it was determined that delaying the addition of Hg once the HNO 3 solution reached the boiling point can reduce the total offgas and H 2 generation rates. The delay in starting the Hg addition is not necessary for HFIR fuel dissolution, but could be useful in other research reactor dissolution campaigns. The potential to generate flammable concentrations of H 2 in the offgas during a HFIR fuel dissolution was evaluated using the experimental data. The predicted H 2 concentration in the dissolver offgas stream was compared with 60% of the calculated H 2 LFL at 200 °C using several prototypical experiments. The calculations showed that a full HFIR core can be dissolved using nominally 0.002 M Hg to catalyze the dissolution. The margin between the predicted H 2 concentration and the calculated LFL was greater when the solution was allowed to boil for 45 min prior to initiating the Hg addition. When the Hg was increased to 0.004 M, the predicted H 2 concentration exceeded the calculated LFL early in the dissolution. The dissolution experiments also demonstrated that additional Hg (beyond the initial 0.002 M) could be added as the Al concentration increases. The ability to add more Hg during a HFIR fuel dissolution could be beneficial if slow dissolution rates are observed at high Al concentrations. Experimental data were used to demonstrate that the predicted H 2 concentration in a dissolver was below 60% of the calculated LFL at 200 °C when 0.004 M Hg was used to catalyze the dissolution if the Al concentration is conservatively greater than 0.5 M. Data also show that the Hg concentration during a HFIR fuel dissolution can be increased from 0.002 to 0.008 M at an Al concentration of 1.3 M.« less

26 CFR 301.6501(d)-1 - Request for prompt assessment.

Code of Federal Regulations, 2014 CFR

2014-04-01

... which is contemplating dissolution, is in the process of dissolution, or has been dissolved, may be... that the corporation contemplates dissolution at or before the expiration of such 18-month period; the dissolution is in good faith begun before the expiration of such 18-month period; and the dissolution so begun...

27 CFR 70.74 - Request for prompt assessment.

Code of Federal Regulations, 2014 CFR

2014-04-01

... contemplating dissolution, is in the process of dissolution, or has been dissolved, may be liable, shall be... dissolution at or before the expirationof such 18-month period; the dissolution is in good faith begun before the expiration of such 18-month period; and the dissolution so begun is completed either before or...

27 CFR 70.74 - Request for prompt assessment.

Code of Federal Regulations, 2012 CFR

2012-04-01

... contemplating dissolution, is in the process of dissolution, or has been dissolved, may be liable, shall be... dissolution at or before the expirationof such 18-month period; the dissolution is in good faith begun before the expiration of such 18-month period; and the dissolution so begun is completed either before or...

27 CFR 70.74 - Request for prompt assessment.

Code of Federal Regulations, 2010 CFR

2010-04-01

... contemplating dissolution, is in the process of dissolution, or has been dissolved, may be liable, shall be... dissolution at or before the expirationof such 18-month period; the dissolution is in good faith begun before the expiration of such 18-month period; and the dissolution so begun is completed either before or...

27 CFR 70.74 - Request for prompt assessment.

Code of Federal Regulations, 2013 CFR

2013-04-01

... contemplating dissolution, is in the process of dissolution, or has been dissolved, may be liable, shall be... dissolution at or before the expirationof such 18-month period; the dissolution is in good faith begun before the expiration of such 18-month period; and the dissolution so begun is completed either before or...

26 CFR 301.6501(d)-1 - Request for prompt assessment.

Code of Federal Regulations, 2012 CFR

2012-04-01

... which is contemplating dissolution, is in the process of dissolution, or has been dissolved, may be... that the corporation contemplates dissolution at or before the expiration of such 18-month period; the dissolution is in good faith begun before the expiration of such 18-month period; and the dissolution so begun...

26 CFR 301.6501(d)-1 - Request for prompt assessment.

Code of Federal Regulations, 2011 CFR

2011-04-01

... which is contemplating dissolution, is in the process of dissolution, or has been dissolved, may be... that the corporation contemplates dissolution at or before the expiration of such 18-month period; the dissolution is in good faith begun before the expiration of such 18-month period; and the dissolution so begun...

27 CFR 70.74 - Request for prompt assessment.

Code of Federal Regulations, 2011 CFR

2011-04-01

... contemplating dissolution, is in the process of dissolution, or has been dissolved, may be liable, shall be... dissolution at or before the expirationof such 18-month period; the dissolution is in good faith begun before the expiration of such 18-month period; and the dissolution so begun is completed either before or...

26 CFR 301.6501(d)-1 - Request for prompt assessment.

Code of Federal Regulations, 2013 CFR

2013-04-01

... which is contemplating dissolution, is in the process of dissolution, or has been dissolved, may be... that the corporation contemplates dissolution at or before the expiration of such 18-month period; the dissolution is in good faith begun before the expiration of such 18-month period; and the dissolution so begun...

26 CFR 301.6501(d)-1 - Request for prompt assessment.

Code of Federal Regulations, 2010 CFR

2010-04-01

... which is contemplating dissolution, is in the process of dissolution, or has been dissolved, may be... that the corporation contemplates dissolution at or before the expiration of such 18-month period; the dissolution is in good faith begun before the expiration of such 18-month period; and the dissolution so begun...

Dry powder inhalers: An overview of the in vitro dissolution methodologies and their correlation with the biopharmaceutical aspects of the drug products.

PubMed

Velaga, Sitaram P; Djuris, Jelena; Cvijic, Sandra; Rozou, Stavroula; Russo, Paola; Colombo, Gaia; Rossi, Alessandra

2018-02-15

In vitro dissolution testing is routinely used in the development of pharmaceutical products. Whilst the dissolution testing methods are well established and standardized for oral dosage forms, i.e. tablets and capsules, there are no pharmacopoeia methods or regulatory requirements for testing the dissolution of orally inhaled powders. Despite this, a wide variety of dissolution testing methods for orally inhaled powders has been developed and their bio-relevance has been evaluated. This review provides an overview of the in vitro dissolution methodologies for dry inhalation products, with particular emphasis on dry powder inhalers, where the dissolution behavior of the respirable particles can have a role on duration and absorption of the drug. Dissolution mechanisms of respirable particles as well as kinetic models have been presented. A more recent biorelevant dissolution set-ups and media for studying inhalation biopharmaceutics were also reviewed. In addition, factors affecting interplay between dissolution and absorption of deposited particles in the context of biopharmaceutical considerations of inhalation products were examined. Copyright © 2017 Elsevier B.V. All rights reserved.

Developing a quality by design approach to model tablet dissolution testing: an industrial case study.

PubMed

Yekpe, Ketsia; Abatzoglou, Nicolas; Bataille, Bernard; Gosselin, Ryan; Sharkawi, Tahmer; Simard, Jean-Sébastien; Cournoyer, Antoine

2018-07-01

This study applied the concept of Quality by Design (QbD) to tablet dissolution. Its goal was to propose a quality control strategy to model dissolution testing of solid oral dose products according to International Conference on Harmonization guidelines. The methodology involved the following three steps: (1) a risk analysis to identify the material- and process-related parameters impacting the critical quality attributes of dissolution testing, (2) an experimental design to evaluate the influence of design factors (attributes and parameters selected by risk analysis) on dissolution testing, and (3) an investigation of the relationship between design factors and dissolution profiles. Results show that (a) in the case studied, the two parameters impacting dissolution kinetics are active pharmaceutical ingredient particle size distributions and tablet hardness and (b) these two parameters could be monitored with PAT tools to predict dissolution profiles. Moreover, based on the results obtained, modeling dissolution is possible. The practicality and effectiveness of the QbD approach were demonstrated through this industrial case study. Implementing such an approach systematically in industrial pharmaceutical production would reduce the need for tablet dissolution testing.

Results of Characterization and Retrieval Testing on Tank 241-C-109 Heel Solids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Callaway, William S.

Eight samples of heel solids from tank 241-C-109 were delivered to the 222-S Laboratory for characterization and dissolution testing. After being drained thoroughly, one-half to two-thirds of the solids were off-white to tan solids that, visually, were fairly evenly graded in size from coarse silt (30-60 μm) to medium pebbles (8-16 mm). The remaining solids were mostly strongly cemented aggregates ranging from coarse pebbles (16-32 mm) to fine cobbles (6-15 cm) in size. Solid phase characterization and chemical analysis indicated that the air-dry heel solids contained ≈58 wt% gibbsite [Al(OH){sub 3}] and ≈37 wt% natrophosphate [Na{sub 7}F(PO{sub 4}){sub 2}·19H{sub 2}O].more » The strongly cemented aggregates were mostly fine-grained gibbsite cemented with additional gibbsite. Dissolution testing was performed on two test samples. One set of tests was performed on large pieces of aggregate solids removed from the heel solids samples. The other set of dissolution tests was performed on a composite sample prepared from well-drained, air-dry heel solids that were crushed to pass a 1/4-in. sieve. The bulk density of the composite sample was 2.04 g/mL. The dissolution tests included water dissolution followed by caustic dissolution testing. In each step of the three-step water dissolution tests, a volume of water approximately equal to 3 times the initial volume of the test solids was added. In each step, the test samples were gently but thoroughly mixed for approximately 2 days at an average ambient temperature of 25 °C. The caustic dissolution tests began with the addition of sufficient 49.6 wt% NaOH to the water dissolution residues to provide ≈3.1 moles of OH for each mole of Al estimated to have been present in the starting composite sample and ≈2.6 moles of OH for each mole of Al potentially present in the starting aggregate sample. Metathesis of gibbsite to sodium aluminate was then allowed to proceed over 10 days of gentle mixing of the test samples at temperatures ranging from 26-30 °C. The metathesized sodium aluminate was then dissolved by addition of volumes of water approximately equal to 1.3 times the volumes of caustic added to the test slurries. Aluminate dissolution was allowed to proceed for 2 days at ambient temperatures of ≈29 °C. Overall, the sequential water and caustic dissolution tests dissolved and removed 80.0 wt% of the tank 241-C-109 crushed heel solids composite test sample. The 20 wt% of solids remaining after the dissolution tests were 85-88 wt% gibbsite. If the density of the residual solids was approximately equal to that of gibbsite, they represented ≈17 vol% of the initial crushed solids composite test sample. In the water dissolution tests, addition of a volume of water ≈6.9 times the initial volume of the crushed solids composite was sufficient to dissolve and recover essentially all of the natrophosphate present. The ratio of the weight of water required to dissolve the natrophosphate solids to the estimated weight of natrophosphate present was 8.51. The Environmental Simulation Program (OLI Systems, Inc., Morris Plains, New Jersey) predicts that an 8.36 w/w ratio would be required to dissolve the estimated weight of natrophosphate present in the absence of other components of the heel solids. Only minor amounts of Al-bearing solids were removed from the composite solids in the water dissolution tests. The caustic metathesis/aluminate dissolution test sequence, executed at temperatures ranging from 27-30 °C, dissolved and recovered ≈69 wt% of the gibbsite estimated to have been present in the initial crushed heel solids composite. This level of gibbsite recovery is consistent with that measured in previous scoping tests on the dissolution of gibbsite in strong caustic solutions. Overall, the sequential water and caustic dissolution tests dissolved and removed 80.3 wt% of the tank 241-C-109 aggregate solids test sample. The residual solids were 92-95 wt% gibbsite. Only a minor portion (≈4.5 wt%) of the aggregate solids was dissolved and recovered in the water dissolution test. Other than some smoothing caused by continuous mixing, the aggregates were essentially unaffected by the water dissolution tests. During the caustic metathesis/aluminate dissolution test sequence, ≈81 wt% of the gibbsite estimated to have been present in the aggregate solids was dissolved and recovered. The pieces of aggregate were significantly reduced in size but persisted as distinct pieces of solids. The increased level of gibbsite recovery, as compared to that for the crushed heel solids composite, suggests that the way the gibbsite solids and caustic solution are mixed is a key determinant of the overall efficiency of gibbsite dissolution and recovery. The liquids recovered after the caustic dissolution tests on the crushed solids composite and the aggregate solids were observed for 170 days. No precipitation of gibbsite was observed. The distribution of particle sizes in the residual solids recovered following the dissolution tests on the crushed heel solids composite was characterized. Wet sieving indicated that 21.4 wt% of the residual solids were >710 μm in size, and laser light scattering indicated that the median equivalent spherical diameter in the <710-μm solids was 35 μm. The settling behavior of the residual solids following the large-scale dissolution tests was also studied. When dispersed at a concentration of ≈1 vol% in water, ≈24 wt% of the residual solids settled at a rate >0.43 in./s; ≈68 wt% settled at rates between 0.02 and 0.43 in./s; and ≈7 wt% settled slower than 0.02 in./s.« less

Chalcopyrite dissolution: Scanning photoelectron microscopy examination of the evolution of sulfur species with and without added iron or pyrite

NASA Astrophysics Data System (ADS)

Li, Yubiao; Qian, Gujie; Brown, Paul L.; Gerson, Andrea R.

2017-09-01

Dissolution and oxidation of sulfide minerals play key roles in both acid and metalliferous rock drainage and supergene enrichment. Surface speciation heterogeneity, critical to understanding mechanisms of mineral sulfide dissolution, has to date largely not been considered. To this end synchrotron scanning photoelectron microscopy (SPEM) was employed to examine freshly fractured and partially dissolved chalcopyrite (CuFeS2) surfaces (pH 1.0 HClO4 solution, redox potential 650 mV relative to a standard hydrogen electrode, 75 °C). S2- (bulk), S22- and Sn2- were found to be present on all samples at varying concentrations. Oxidation was observed to take place heterogeneously at the sub-micron scale. As compared to chalcopyrite partially dissolved for 5 days, extended dissolution to 10 days did not show appreciably enhanced oxidation of surface species; however surface roughness increased markedly due to the growth/overlap of oxidised sulfur species. On addition of 4 mM iron both S0 and SO42- were observed but not SO32-, indicating that the greater Fe3+ activity/concentration promotes heterogeneous sulfur oxidation. On contact of pyrite (FeS2) with chalcopyrite, significantly greater chalcopyrite surface oxidation was observed than for the other systems examined, with S0, SO32- and SO42- being identified heterogeneously across the surface. It is proposed that chalcopyrite oxidative dissolution is enhanced by increasing its cathodic area, e.g. contacting with pyrite, while increased Fe3+ activity/concentration also contributes to increased dissolution rates. The high degree of surface heterogeneity of these surface products indicates that these surfaces are not passivated by their formation. These results suggest that chalcopyrite dissolution will be accelerated when in contact with pyrite at solution redox potential intermediate between the rest potentials of chalcopyrite and pyrite (560 mV and 660 mV, respectively) and/or iron rich acidic waters with resulting enhanced formation of secondary sulfur containing species and release of copper and iron. This in turn suggests accelerated supergene formation and enhanced metalliferous drainage under these conditions.

Interdisciplinary Research to Elucidate Mechanisms Governing Silver Nanoparticle Fate and Transport in Porous Media

NASA Astrophysics Data System (ADS)

Pennell, K. D.; Mittleman, A.; Taghavy, A.; Fortner, J.; Lantagne, D.; Abriola, L. M.

2014-12-01

Interdisciplinary Research to Elucidate Mechanisms Governing Silver Nanoparticle Fate and Transport in Porous Media Anjuliee M. Mittelman, Amir Taghavy, Yonggang Wang, John D. Fortner, Daniele S. Lantagne, Linda M. Abriola and Kurt D. Pennell* Detailed knowledge of the processes governing nanoparticle transport and reactivity in porous media is essential for accurate predictions of environmental fate, water and wastewater treatment system performance, and assessment of potential risks to ecosystems and water supplies. To address these issues, an interdisciplinary research team combined experimental and mathematical modeling studies to investigate the mobility, dissolution, and aging of silver nanoparticles (nAg) in representative aquifer materials and ceramic filters. Results of one-dimensional column studies, conducted with water-saturated sands maintained at pH 4 or 7 and three levels of dissolved oxygen (DO), revealed that fraction of silver mass eluted as Ag+ increased with increasing DO level, and that the dissolution of attached nAg decreased over time as a result of surface oxidation. A hybrid Eulerain-Lagragian nanoparticle transport model, which incorporates DO-dependent dissolution kinetics and particle aging, was able to accurately simulate nAg mobility and Ag+ release measured in the column experiments. Model sensitivity analysis indicated that as the flow velocity and particle size decrease, nAg dissolution and Ag+ transport processes increasingly govern silver mobility. Consistent results were obtained in studies of ceramic water filters treated with nAg, where silver elution was shown to be governed by nAg dissolution to form Ag+ and subsequent cation exchange reactions. Recent studies explored the effects of surface coating aging on nAg aggregation, mobility and dissolution. Following ultraviolet light, nAg retention in water saturated sand increased by 25-50%, while up to 50% of the applied mass eluted as Ag+ compared to less than 1% for un-aged nAg. In batch experiments, the addition of tert-butyl alcohol, a reactive oxygen species scavenger, reduced nAg aggregation and dissolution by up to 50%, indicating that free radical activity played an important role in the surface coating aging. Taken in concert, these findings demonstrate the value of undertaking

Interdisciplinary Research to Elucidate Mechanisms Governing Silver Nanoparticle Fate and Transport in Porous Media

NASA Astrophysics Data System (ADS)

Pennell, K. D.; Mittleman, A.; Taghavy, A.; Fortner, J.; Lantagne, D.; Abriola, L. M.

2015-12-01

Interdisciplinary Research to Elucidate Mechanisms Governing Silver Nanoparticle Fate and Transport in Porous Media Anjuliee M. Mittelman, Amir Taghavy, Yonggang Wang, John D. Fortner, Daniele S. Lantagne, Linda M. Abriola and Kurt D. Pennell* Detailed knowledge of the processes governing nanoparticle transport and reactivity in porous media is essential for accurate predictions of environmental fate, water and wastewater treatment system performance, and assessment of potential risks to ecosystems and water supplies. To address these issues, an interdisciplinary research team combined experimental and mathematical modeling studies to investigate the mobility, dissolution, and aging of silver nanoparticles (nAg) in representative aquifer materials and ceramic filters. Results of one-dimensional column studies, conducted with water-saturated sands maintained at pH 4 or 7 and three levels of dissolved oxygen (DO), revealed that fraction of silver mass eluted as Ag+ increased with increasing DO level, and that the dissolution of attached nAg decreased over time as a result of surface oxidation. A hybrid Eulerain-Lagragian nanoparticle transport model, which incorporates DO-dependent dissolution kinetics and particle aging, was able to accurately simulate nAg mobility and Ag+ release measured in the column experiments. Model sensitivity analysis indicated that as the flow velocity and particle size decrease, nAg dissolution and Ag+ transport processes increasingly govern silver mobility. Consistent results were obtained in studies of ceramic water filters treated with nAg, where silver elution was shown to be governed by nAg dissolution to form Ag+ and subsequent cation exchange reactions. Recent studies explored the effects of surface coating aging on nAg aggregation, mobility and dissolution. Following ultraviolet light, nAg retention in water saturated sand increased by 25-50%, while up to 50% of the applied mass eluted as Ag+ compared to less than 1% for un-aged nAg. In batch experiments, the addition of tert-butyl alcohol, a reactive oxygen species scavenger, reduced nAg aggregation and dissolution by up to 50%, indicating that free radical activity played an important role in the surface coating aging. Taken in concert, these findings demonstrate the value of undertaking

Montmorillonite Dissolution in Simulated Lung Fluids

NASA Astrophysics Data System (ADS)

Schmidt, M.; Wendlandt, R. F.

2008-12-01

Because lung fluids" first interaction is with the surface of inhaled grains, the surface properties of inhaled mineral dusts may have a generally mitigating effect on cytotoxicity and carcinogenicity. Wendlandt et al. (Appl. Geochem. 22, 2007) investigated the surface properties of respirable-sized quartz grains in bentonites and recognized pervasive montmorillonite surface coatings on silica grains. The purpose of this study was to determine the dissolution rate and biodurability of montmorillonite in simulated lung fluids and to assess its potential to mitigate silica cytotoxicity. Modified batch reaction experiments were conducted on purified and size fractionated calcic (SAz-2; 0.4-5 μm) and sodic (DC-2; 0.4-2 μm) montmorillonites for 120 to 160 days of reaction time at 37°C in both simulated extracellular lung fluid (Lu) and simulated lysosomal fluid (Ly). Modified batch experiments simulated a flow-through setup and minimized sample handling difficulties. Reacted Lu and Ly fluid was analyzed for Mg, Al, and Si on an ICP-OE spectrometer. Steady state dissolution was reached 90-100 days after the start of the experiment and maintained for 40-60 days. Measured montmorillonite dissolution rates based on BET surface areas and Si steady state release range from 4.1x10-15 mol/m2/s at the slowest to 1.0x10-14 mol/m2/s at the fastest with relative uncertainties of less than 10%. Samples reacting in Ly (pH = 4.55) dissolved faster than those in Lu (pH = 7.40), and DC-2 dissolved faster than SAz-2. The measured range of biodurabilities was 1,300 to 3,400 years for a 1 μm grain assuming a spherical volume and a molar volume equal to that of illite. The difference in salinities of the two fluids was too slight to draw conclusions about the relationship of ionic strength to dissolution rate. Results indicate that montmorillonite dissolution is incongruent and edge controlled. Dissolution rates for DC- 2 and SAz-2 clays were comparable to those reported in the literature. Biodurability results fall well beyond the lifespan of humans confirming montmorillonite's potential to mitigate silica cytotoxicity.

Investigation of nanosized crystalline form to improve the oral bioavailability of poorly water soluble cilostazol.

PubMed

Miao, Xiaoqing; Sun, Changshan; Jiang, Tongying; Zheng, Li; Wang, Tianyi; Wang, Siling

2011-01-01

The aim of this study was to develop cilostazol (CLT) nanocrystals intended to improve its dissolution rate and enhance its bioavailability. In this study, CLT nanosuspension was prepared by the anti-solvent and high-pressure homogenization method. The effects of the production parameters, such as the stabilizer concentration, pressure and number of cycles, were investigated. Characterization of the product was performed by scanning electron microscopy (SEM), Nitrogen adsorption, differential scanning calorimetry (DSC), X-ray powder diffraction analysis (XRPD), X-ray Photoelectron Spectroscopy (XPS), particle size analysis and dissolution testing. Additionally, the comparison studies of oral bioavailability in beagle dogs of three type tables were performed. The images of SEM showed a spherical smooth CLT powder, and Nitrogen adsorption test revealed spray dried powder were porous with high BET surface area compared with that of raw CLT. DSC and XRPD results demonstrated that the combination of preferred polymorph B and C of CLT were prepared successfully, the saturation solubility of the nanosized crystalline powder is about 5 fold greater than that of raw CLT, and the dissolution rate was enhanced 4 fold than that of raw CLT. The Cmax and AUC0-48h of CLT nanosized crystalline tablets were 2.1 fold and 1.9 fold, and 3.0 fold and 2.3 fold compared with those of the nanosized tablets and commercial tablets, respectively. The anti-solvent-high-pressure homogenization technique was employed successfully to produce cilostazol nanosuspensions. The bioavailability of CLT tablets prepared using spray dried nanosized crystalline powder after oral administration to dogs was markedly increased compared with that produced by nanosized tablets and commercial tablets, because of its greater dissolution rate owing to its transition of the crystalline state to form C and form B, reduced particle size and porous structure with increased surface area.

A novel matrix dispersion based on phospholipid complex for improving oral bioavailability of baicalein: preparation, in vitro and in vivo evaluations.

PubMed

Zhou, Yang; Dong, Wujun; Ye, Jun; Hao, Huazhen; Zhou, Junzhuo; Wang, Renyun; Liu, Yuling

2017-11-01

Phospholipid complex is one of the most successful approaches for enhancing oral bioavailability of poorly absorbed plant constituents. But the sticky property of phospholipids results in an unsatisfactory dissolution of drugs. In this study, a matrix dispersion of baicalein based on phospholipid complex (BaPC-MD) was first prepared by a discontinuous solvent evaporation method, in which polyvinylpyrrolidone-K30 (PVP-K30) was employed for improving the dispersibility of baicalein phospholipid complex (BaPC) and increasing dissolution of baicalein. The combination ratio of baicalein and phospholipids in BaPC-MD was 99.39% and baicalein was still in a complete complex state with phospholipid in BaPC-MD. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM) and Fourier Transform Infrared (FTIR) analyzes demonstrated that baicalein was fully transformed to an amorphous state in BaPC-MD and phospholipid complex formed. The water-solubility and n-octanol solubility of baicalein in BaPC-MD significantly increased compared with those of pure baicalein. Compared with baicalein and BaPC, the cumulative dissolution of BaPC-MD at 120 min increased 2.77- and 1.23-fold, respectively. In vitro permeability study in Caco-2 cells indicated that the permeability of BaPC-MD was remarkably higher than those of baicalein and BaPC. Pharmacokinetic study showed that the average C max of BaPC-MD was significantly increased compared to baicalein and BaPC. AUC 0-14 h of BaPC-MD was 5.01- and 1.91-fold of baicalein and BaPC, respectively. The novel BaPC-MD significantly enhanced the oral bioavailability of baicalein by improving the dissolution and permeability of baicalein without destroying the complexation state of baicalein and phospholipids. The current drug delivery system provided an optimal strategy to significantly enhance oral bioavailability for poorly water-soluble drugs.

Dolomite dissolution rates and possible Holocene dedolomitization of water-bearing units in the Edwards aquifer, south-central Texas

USGS Publications Warehouse

Deike, R.G.

1990-01-01

Rates of dolomite dissolution can be used to test the concept, based on geomorphologic evidence, that a major part of the Edwards aquifer could have formed within the Holocene, a timeframe of approximately 10,000 years. During formation of the aquifer in the Edwards limestone (Cretaceous, Albian) of the Balcones fault zone, dolomite dissolution and porosity development were synchronous and the result of mixing-zone dedolomitization. Initiation of the mixing zone in the early Holocene (???11,000 years before present) is suggested by the maximum age of formation of major discharge sites that allowed the influx of meteoric water into brine-filled, dolomitic preaquifer units. Dedolomitization, the dissolution of dolomite and net precipitation of calcite, has left aquifer units that are calcitic, and 40 vol.% interconnected pore space. The mass of dolomite missing is obtained by comparison of stratigraphically equivalent altered and unaltered units. One dissolution rate (1.76 ?? 10-4 mmol dolomite kgH2O-1yr-1) is determined from this mass, 104yr reaction time, and a log-linear function describing the increase in mass discharge (three orders of magnitude) during aquifer formation. The second estimated dissolution rate is obtained from the mass transfer of dolomite to solution calculated from the increase in magnesium in pore fluids selected from the modern aquifer to represent a typical flowpath during aquifer formation. A reaction time of 104yr for this mass transfer yields a rate of 0.56 ?? 10-4 mmol dolomite kgH2O-1yr-1. Both of these rates are comparable to modern rates of dolomite dissolution (0.3 to 4.5 ?? 10-4 mmol dolomite kgH2O-1yr-1) calculated from measured reaction times in the Tertiary Floridan aquifer system in Florida and the Madison aquifer in the Mississippian Madison Limestone of the Northern Great Plains. Similarity of these rates to the estimated paleo-rates of dolomite dissolution supports a 104 yr reaction timeframe. The Holocene reaction time also can be compared to a series of reaction times calculated by assuming that the mass of dolomite missing from the Edwards was removed at rates observed in the Floridan and Madison aquifers. These reaction times (for complete removal of dolomite) range from 2700 to 58,500 yr and span the Pleistocene-Holocene boundary. Finally, an estimated dolomite reaction rate during dedolomitization of the Edwards aquifer based on surface area of exposed dolomite [mmol cm-2s-1 (millimoles per square centimeter per second)] may be approximated from reaction times. This rate is directly a function of the mass of dolomite removed and the surface area exposed per pore volume passing through the rock. The surface area is available from the observed dolomite rhomb size in unaltered rock. The rate of pore fluid movement is obtained from the averaged annual discharge. Rates during formation of the Edwards aquifer calculated from all reaction times range from 10-13 to 10-14 mmol dolomite cm-2s-1. These rates are faster than rates (10-18 mmol cm-2s-1), measured in the pure laboratory system, CaMg(CO3)2CO2H2O, but slower than rates determined in an alpine stream study (10-10 to 10-11 mmol cm-2s-1) where cold glacial melt water flows over dolostone. Dolomite dissolution rates from both the Edwards and other aquifers support the concept that a major part of the Edwards aquifer could have formed within the Holocene. ?? 1990.

General solution for diffusion-controlled dissolution of spherical particles. 1. Theory.

PubMed

Wang, J; Flanagan, D R

1999-07-01

Three classical particle dissolution rate expressions are commonly used to interpret particle dissolution rate phenomena. Our analysis shows that an assumption used in the derivation of the traditional cube-root law may not be accurate under all conditions for diffusion-controlled particle dissolution. Mathematical analysis shows that the three classical particle dissolution rate expressions are approximate solutions to a general diffusion layer model. The cube-root law is most appropriate when particle size is much larger than the diffusion layer thickness, the two-thirds-root expression applies when the particle size is much smaller than the diffusion layer thickness. The square-root expression is intermediate between these two models. A general solution to the diffusion layer model for monodispersed spherical particles dissolution was derived for sink and nonsink conditions. Constant diffusion layer thickness was assumed in the derivation. Simulated dissolution data showed that the ratio between particle size and diffusion layer thickness (a0/h) is an important factor in controlling the shape of particle dissolution profiles. A new semiempirical general particle dissolution equation is also discussed which encompasses the three classical particle dissolution expressions. The success of the general equation in explaining limitations of traditional particle dissolution expressions demonstrates the usefulness of the general diffusion layer model.

Development and Validation of Discriminating and Biorelevant Dissolution Test for Lornoxicam Tablets

PubMed Central

Anumolu, P. D.; Sunitha, G.; Bindu, S. Hima; Satheshbabu, P. R.; Subrahmanyam, C. V. S.

2015-01-01

The establishment of biorelevant and discriminating dissolution procedure for drug products with limited water solubility is a useful technique for qualitative forecasting of the in vivo behavior of formulations. It also characterizes the drug product performance in pharmaceutical development. Lornoxicam, a BCS class-II drug is a nonsteroidal antiinflammatory drug of the oxicam class, has no official dissolution media available in the literature. The objective of present work was to develop and validate a discriminating and biorelevant dissolution test for lornoxicam tablet dosage forms. To quantify the lornoxicam in dissolution samples, UV spectrophotometric method was developed using 0.01M sodium hydroxide solution as solvent at λma×376 nm. After evaluation of saturation solubility, dissolution, sink conditions and stability of lornoxicam bulk drug in different pH solutions and biorelevant media, the dissolution method was optimized using USP paddle type apparatus at 50 rpm rotation speed and 500 ml simulated intestinal fluid as discriminating and biorelevant dissolution medium. The similarity factor (f2) were investigated for formulations with changes in composition and manufacturing variations, values revealed that dissolution method having discriminating power and method was validated as per standard guidelines. The proposed dissolution method can be effectively applied for routine quality control in vitro dissolution studies of lornoxicam in tablets and helpful to pharmacopoeias. PMID:26180277

Development and Validation of Discriminating and Biorelevant Dissolution Test for Lornoxicam Tablets.

PubMed

Anumolu, P D; Sunitha, G; Bindu, S Hima; Satheshbabu, P R; Subrahmanyam, C V S

2015-01-01

The establishment of biorelevant and discriminating dissolution procedure for drug products with limited water solubility is a useful technique for qualitative forecasting of the in vivo behavior of formulations. It also characterizes the drug product performance in pharmaceutical development. Lornoxicam, a BCS class-II drug is a nonsteroidal antiinflammatory drug of the oxicam class, has no official dissolution media available in the literature. The objective of present work was to develop and validate a discriminating and biorelevant dissolution test for lornoxicam tablet dosage forms. To quantify the lornoxicam in dissolution samples, UV spectrophotometric method was developed using 0.01M sodium hydroxide solution as solvent at λma×376 nm. After evaluation of saturation solubility, dissolution, sink conditions and stability of lornoxicam bulk drug in different pH solutions and biorelevant media, the dissolution method was optimized using USP paddle type apparatus at 50 rpm rotation speed and 500 ml simulated intestinal fluid as discriminating and biorelevant dissolution medium. The similarity factor (f2) were investigated for formulations with changes in composition and manufacturing variations, values revealed that dissolution method having discriminating power and method was validated as per standard guidelines. The proposed dissolution method can be effectively applied for routine quality control in vitro dissolution studies of lornoxicam in tablets and helpful to pharmacopoeias.

Influence of pH and temperature on alunite dissolution rates and products

NASA Astrophysics Data System (ADS)

Acero, Patricia; Hudson-Edwards, Karen

2015-04-01

Aluminium is one of the main elements in most mining-affected environments, where it may influence the mobility of other elements and play a key role on pH buffering. Moreover, high concentrations of Al can have severe effects on ecosystems and humans; Al intake, for example, has been implicated in neurological pathologies (e.g., Alzheimer's disease; Flaten, 2001). The behaviour of Al in mining-affected environments is commonly determined, at least partially, by the dissolution of Al sulphate minerals and particularly by the dissolution of alunite (KAl3(SO4)2(OH)6), which is one of the most important and ubiquitous Al sulphates in mining-affected environments (Nordstrom, 2011). The presence of alunite has been described in other acid sulphate environments, including some soils (Prietzel & Hirsch, 1998) and on the surface of Mars (Swayze et al., 2008). Despite the important role of alunite, its dissolution rates and products, and their controlling factors under conditions similar to those found in these environments, remain largely unknown. In this work, batch dissolution experiments have been carried out in order to shed light on the rates, products and controlling factors of alunite dissolution under different pH conditions (between 3 and 8) and temperatures (between 279 and 313K) similar to those encountered in natural systems. The obtained initial dissolution rates using synthetic alunite, based on the evolution of K concentrations, are between 10-9.7 and 10-10.9 mol-m-2-s-1, with the lowest rates obtained at around pH 4.8, and increases in the rates recorded with both increases and decreases in pH. Increases of temperature in the studied range also cause increases in the dissolution rates. The dissolution of alunite dissolution is incongruent, as has been reported for jarosite (isostructural with alunite) by Welch et al. (2008). Compared with the stoichiometric ratio in the bulk alunite (Al/K=3), K tends to be released to the solution preferentially over Al, leading to dissolved Al/K ratios between 0.5 and 2.5. This depletion of Al in the solution is especially clear for the experiments at pH 4.5-4.8 and 8 and it is consistent with the results of elemental quantifications of the same proportions in the reacted alunite surfaces using X-ray Photoelectron Spectroscopy (XPS). REFERENCES Flaten, T.P. (2001): Aluminium as a risk factor in Alzheimzer's disease, with emphasis on drinking water. Brain Research Bulletin 55: 187-196. Nordstrom, D.K. (2011): Hydrogeochemical processes governing the origin, transport and fate of major and trace elements from mine wastes and mineralized rock to surface waters. Applied Geochemistry 26: 1777-1791. Prietzel, J., & Hirsch, C. (1998). Extractability and dissolution kinetics of pure and soil-added synthesized aluminium hydroxy sulphate minerals. European journal of soil science, 49(4), 669-681. Swayze, G.A., Ehlmann, B.L., Milliken, R.E., Poulet, F., Wray, J.J., Rye, R.O., Clark, R.N., Desborough, G.A., Crowley, J.K., Gondet, B., Mustard, J.F., Seelos, K.D. and Murchie, S.L., 2008. Discovery of the Acid-Sulfate Mineral Alunite in Terra Sirenum, Mars, Using MRO CRISM: Possible Evidence for Acid-Saline Lacustrine Deposits?, American Geophysical Union, Fall Meeting 2008, abstract #P44A-04. Welch, S. A., Kirste, D., Christy, A. G., Beavis, F. R., & Beavis, S. G. (2008): Jarosite dissolution II'Reaction kinetics, stoichiometry and acid flux. Chemical Geology, 254(1), 73-86.

Estimation of dissolution rate from in vivo studies of synthetic vitreous fibers.

PubMed

Eastes, W; Potter, R M; Hadley, J G

2000-11-01

Although the dissolution rate of a fiber was originally defined by a measurement of dissolution in simulated lung fluid in vitro, it is feasible to determine it from animal studies as well. The dissolution rate constant for a fiber may be extracted from the decrease in long fiber diameter observed in certain intratracheal instillation experiments or from the observed long fiber retention in short-term biopersistence studies. These in vivo dissolution rates agree well with those measured in vitro for the same fibers. For those special types of fibers, the high-alumina rock wool fibers that could not be measured in vitro, the method provides a way of obtaining a chemical dissolution rate constant from an animal study. The inverse of the in vivo dissolution rate, the fiber dissolution time, correlates well with the weighted half life of long fibers in a biopersistence study, and the in vivo dissolution rate may be estimated accurately from this weighted half-life.

Clustered Single Cellulosic Fiber Dissolution Kinetics and Mechanisms through Optical Microscopy under Limited Dissolving Conditions.

PubMed

Mäkelä, Valtteri; Wahlström, Ronny; Holopainen-Mantila, Ulla; Kilpeläinen, Ilkka; King, Alistair W T

2018-05-14

Herein, we describe a new method of assessing the kinetics of dissolution of single fibers by dissolution under limited dissolving conditions. The dissolution is followed by optical microscopy under limited dissolving conditions. Videos of the dissolution were processed in ImageJ to yield kinetics for dissolution, based on the disappearance of pixels associated with intact fibers. Data processing was performed using the Python language, utilizing available scientific libraries. The methods of processing the data include clustering of the single fiber data, identifying clusters associated with different fiber types, producing average dissolution traces and also extraction of practical parameters, such as, time taken to dissolve 25, 50, 75, 95, and 99.5% of the clustered fibers. In addition to these simple parameters, exponential fitting was also performed yielding rate constants for fiber dissolution. Fits for sample and cluster averages were variable, although demonstrating first-order kinetics for dissolution overall. To illustrate this process, two reference pulps (a bleached softwood kraft pulp and a bleached hardwood pre-hydrolysis kraft pulp) and their cellulase-treated versions were analyzed. As expected, differences in the kinetics and dissolution mechanisms between these samples were observed. Our initial interpretations are presented, based on the combined mechanistic observations and single fiber dissolution kinetics for these different samples. While the dissolution mechanisms observed were similar to those published previously, the more direct link of mechanistic information with the kinetics improve our understanding of cell wall structure and pre-treatments, toward improved processability.

Dissolution of Uranium Oxides Under Alkaline Oxidizing Conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Steven C.; Peper, Shane M.; Douglas, Matthew

2009-11-01

Bench scale experiments were conducted to determine the dissolution characteristics of uranium oxide powders (UO2, U3O8, and UO3) in aqueous peroxide-carbonate solutions. Experimental parameters included H2O2 concentration, carbonate counter cation (NH4+, Na+, K+, and Rb+), and pH. Results indicate the dissolution rate of UO2 in 1 M (NH4)2CO3 increases linearly with peroxide concentration ranging from 0.05 – 2 M. The three uranium oxide powders exhibited different dissolution patterns however, UO3 exhibited prompt complete dissolution. Carbonate counter cation affected the dissolution kinetics. There is minimal impact of solution pH, over the range 8.8 to 10.6, on initial dissolution rate.

20(S)-Protopanaxadiol Phospholipid Complex: Process Optimization, Characterization, In Vitro Dissolution and Molecular Docking Studies.

PubMed

Pu, Yiqiong; Zhang, Xitong; Zhang, Qi; Wang, Bing; Chen, Yuxi; Zang, Chuanqi; Wang, Yuqin; Dong, Tina Ting-Xia; Zhang, Tong

2016-10-19

20( S )-Protopanaxadiol (PPD), a bioactive compound extracted from ginseng, possesses cardioprotective, neuroprotective, anti-inflammatory, antiestrogenic, anticancer and anxiolytic effects. However, the clinical application of PPD is limited by its weak aqueous solubility. In this study, we optimized an efficient method of preparing its phospholipid complex (PPD-PLC) using a central composite design and response surface analysis. The prepared PPD-PLC was characterized by differential scanning calorimetric, powder X-ray diffraction, Fourier-transformed infrared spectroscopy and nuclear magnetic resonance analyses associated with molecular docking calculation. The equilibrium solubility of PPD-PLC in water and n -octanol increased 6.53- and 1.53-times, respectively. Afterwards, using PPD-PLC as the intermediate, the PPD-PLC-loaded dry suspension (PPD-PLC-SU) was prepared with our previous method. In vitro evaluations were conducted on PPD-PLC and PPD-PLC-SU, including dissolution behaviors and stability properties under different conditions. Results of in vitro dissolution behavior revealed the improved dissolution extents and rates of PPD-PLC and PPD-PLC-SU ( p < 0.05). Results of the formulation stability investigation also exposed the better stability of PPD-PLC-SU compared with free PPD. Therefore, phospholipid complex technology is a useful formulation strategy for BCS II drugs, as it could effectively improve their hydrophilicity and lipophilicity.

Orally Disintegrating Tablets Containing Melt Extruded Amorphous Solid Dispersion of Tacrolimus for Dissolution Enhancement.

PubMed

Ponnammal, Poovizhi; Kanaujia, Parijat; Yani, Yin; Ng, Wai Kiong; Tan, Reginald B H

2018-03-16

In order to improve the aqueous solubility and dissolution of Tacrolimus (TAC), amorphous solid dispersions of TAC were prepared by hot melt extrusion with three hydrophilic polymers, Polyvinylpyrrolidone vinyl acetate (PVP VA64), Soluplus ® and Hydroxypropyl Cellulose (HPC), at a drug loading of 10% w / w . Molecular modeling was used to determine the miscibility of the drug with the carrier polymers by calculating the Hansen Solubility Parameters. Powder X-ray diffraction and differential scanning calorimetry (DSC) studies of powdered solid dispersions revealed the conversion of crystalline TAC to amorphous form. Fourier transform Infrared (FTIR) spectroscopy results indicated formation of hydrogen bond between TAC and polymers leading to stabilization of TAC in amorphous form. The extrudates were found to be stable under accelerated storage conditions for 3 months with no re-crystallization, indicating that hot melt extrusion is suitable for producing stable amorphous solid dispersions of TAC in PVP VA64, Soluplus ® and HPC. Stable solid dispersions of amorphous TAC exhibited higher dissolution rate, with the solid dispersions releasing more than 80% drug in 15 min compared to the crystalline drug giving 5% drug release in two hours. These stable solid dispersions were incorporated into orally-disintegrating tablets in which the solid dispersion retained its solubility, dissolution and stability advantage.

Orally Disintegrating Tablets Containing Melt Extruded Amorphous Solid Dispersion of Tacrolimus for Dissolution Enhancement

PubMed Central

Ponnammal, Poovizhi; Kanaujia, Parijat; Ng, Wai Kiong; Tan, Reginald B. H.

2018-01-01

In order to improve the aqueous solubility and dissolution of Tacrolimus (TAC), amorphous solid dispersions of TAC were prepared by hot melt extrusion with three hydrophilic polymers, Polyvinylpyrrolidone vinyl acetate (PVP VA64), Soluplus® and Hydroxypropyl Cellulose (HPC), at a drug loading of 10% w/w. Molecular modeling was used to determine the miscibility of the drug with the carrier polymers by calculating the Hansen Solubility Parameters. Powder X-ray diffraction and differential scanning calorimetry (DSC) studies of powdered solid dispersions revealed the conversion of crystalline TAC to amorphous form. Fourier transform Infrared (FTIR) spectroscopy results indicated formation of hydrogen bond between TAC and polymers leading to stabilization of TAC in amorphous form. The extrudates were found to be stable under accelerated storage conditions for 3 months with no re-crystallization, indicating that hot melt extrusion is suitable for producing stable amorphous solid dispersions of TAC in PVP VA64, Soluplus® and HPC. Stable solid dispersions of amorphous TAC exhibited higher dissolution rate, with the solid dispersions releasing more than 80% drug in 15 min compared to the crystalline drug giving 5% drug release in two hours. These stable solid dispersions were incorporated into orally-disintegrating tablets in which the solid dispersion retained its solubility, dissolution and stability advantage. PMID:29547585

Berberine nanoparticles with enhanced in vitro bioavailability: characterization and antimicrobial activity

PubMed Central

Faidah, Hani S; Khurram, Muhammad; Amin, Muhammad Usman; Haseeb, Abdul; Kakar, Maria

2018-01-01

Background Berberine is an isoquinoline alkaloid widely used in Ayurveda and traditional Chinese medicine to treat illnesses such as hypertension and inflammatory conditions, and as an anticancer and hepato-protective agent. Berberine has low oral bioavailability due to poor aqueous solubility and insufficient dissolution rate, which can reduce the efficacy of drugs taken orally. In this study, evaporative precipitation of nanosuspension (EPN) and anti-solvent precipitation with a syringe pump (APSP) were used to address the problems of solubility, dissolution rate and bioavailability of berberine. Methods Semi-crystalline nanoparticles (NPs) of 90–110 nm diameter for APSP and 65–75 nm diameter for EPN were prepared and then characterized using differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRD). Thereafter, drug content solubility and dissolution studies were undertaken. Berberine and its NPs were evaluated for their antibacterial activity. Results The results indicate that the NPs have significantly increased solubility and dissolution rate due to conversion of the crystalline structure to a semi-crystalline form. Conclusion Berberine NPs produced by both APSP and EPN methods have shown promising activities against Gram-positive and Gram-negative bacteria, and yeasts, with NPs prepared through the EPN method showing superior results compared to those made with the APSP method and the unprocessed drug. PMID:29491706

In vitro and in vivo studies on the complexes of glipizide with water-soluble β-cyclodextrin-epichlorohydrin polymers.

PubMed

Nie, Shufang; Zhang, Shu; Pan, Weisan; Liu, Yanli

2011-05-01

The purpose of this study was to evaluate the potential of a newly modified cyclodextrin derivative, water-soluble β-cyclodextrin-epichlorohydrin polymer (β-CDP), as an effective drug carrier to enhance the dissolution rate and oral bioavailability of glipizide as a poorly water-soluble model drug. Inclusion complexes of glipizide with β-CDP were prepared by the co-evaporation method and characterized by phase solubility, dissolution, and differential scanning calorimetry. The solubility curve was classified as type A(L), which indicated the formation of 1:1 complex between glipizide and β-CDP. β-CDP had better properties of increasing the aqueous solubility of glipizide compared with HP-β-CD. The dissolution rate of drug from the β-CDP complexes was significantly greater than that of the corresponding physical mixtures indicating that the formation of amorphous complex increased the solubility of glipizide. Moreover, the increment in drug dissolution rate from the glipizide/β-CDP systems was higher than that from the corresponding ones with HP-β-CD, which indicated that β-CDP could provide greater capability of solubilization for poorly soluble drugs. Furthermore, in vivo study revealed that the bioavailability of glipizide was significantly improved by glipizide /β-CDP inclusion complex after oral administration to beagle dogs.

Corrosion of dental aluminium bronze in neutral saline and saline lactic acid.

PubMed

Tibballs, J E; Erimescu, Raluca

2006-09-01

To compare the corrosion behaviours of two aluminium bronze, dental casting alloys during a standard immersion test and for immersion in neutral saline. Cast specimens of aluminium bronzes with 1.4 wt% Fe (G) and 4 wt% Fe (N) were subject to progressively longer periods (up to in total 7 days) immersed in 0.1 M saline, 0.1 M lactic acid solutions and examined by scanning electron microscopy with EDX analysis. Immersion in 0.1M neutral saline was for 7 days. In the acidic solution, exposed interdendritic volumes in alloy N corroded completely away in 7 days with dissolution of Ni-enriched precipitate species as well as the copper-rich matrix. Alloy G begins to corrode more slowly but by a similar mechanism. The number density of an Fe-enriched species is insufficient to maintain a continuous galvanic potential to the copper matrix, and dissolution becomes imperceptible. In neutral saline solution, galvanic action alone caused pit-etching, without the dissolution of either precipitate species. The upper limit for the total dissolution of metallic ions in the standard immersion test can be set at 200 microg cm(-2). Aluminium bronze dental alloys can be expected to release both copper and nickel ions into an acidic oral environment.

Importance of interlayer H bonding structure to the stability of layered minerals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Conroy, Michele; Soltis, Jennifer A.; Wittman, Rick S.

Layered (oxy) hydroxide minerals often possess out-of-plane hydrogen atoms that form hydrogen bonding networks which stabilize the layered structure. However, less is known about how the ordering of these bonds affects the structural stability and solubility of these minerals. Here, we report a new strategy that uses the focused electron beam to probe the effect of differences in hydrogen bonding networks on mineral solubility. In this regard, the dissolution behavior of boehmite (γ-AlOOH) and gibbsite (γ-Al(OH)3) were compared and contrasted in real time via liquid cell electron microscopy. Under identical such conditions, 2D-nanosheets of boehmite (γ-AlOOH) exfoliated from the bulkmore » and then rapidly dissolved, whereas gibbsite was stable. Further, substitution of only 1% Fe(III) for Al(III) in the structure of boehmite inhibited delamination and dissolution. Factors such as pH, radiolytic species, and knock on damage were systematically studied and eliminated as proximal causes for boehmite dissolution. Instead, the creation of electron/hole pairs was considered to be the mechanism that drove dissolution. The widely disparate behaviors of boehmite, gibbsite, and Fe-doped boehmite are discussed in the context of differences in the OH bond strengths, hydrogen bonding networks, and the presence or absence of electron/hole recombination centers.« less

Spray drying of poorly soluble drugs from aqueous arginine solution.

PubMed

Ojarinta, Rami; Lerminiaux, Louise; Laitinen, Riikka

2017-10-30

Co-amorphous drug-amino acid mixtures have shown potential for improving the solid-state stability and dissolution behavior of amorphous drugs. In previous studies, however these mixtures have been produced mainly with small-scale preparation methods, or with methods that have required the use of organic solvents or other dissolution enhancers. In the present study, co-amorphous ibuprofen-arginine and indomethacin-arginine mixtures were spray dried from water. The mixtures were prepared at two drug-arginine molar ratios (1:1 and 1:2). The properties of the prepared mixtures were investigated with differential scanning calorimetry, X-ray powder diffractometry, Fourier-transform infrared spectroscopy and a 24h, non-sink, dissolution study. All mixtures exhibited a single glass transition temperature (T g ), evidence of the formation of homogenous single-phase systems. Fourier transform infrared spectroscopy revealed strong interactions (mainly salt formation) that account for the positive deviation between measured and estimated T g values. No crystallization was observed during a 1-year stability study in either 1:1 or 1:2 mixtures, but in the presence of moisture, handling difficulties were encountered. The formation of co-amorphous salts led to improved dissolution characteristics when compared to the corresponding physical mixtures or to pure crystalline drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Importance of interlayer H bonding structure to the stability of layered minerals

DOE PAGES

Conroy, Michele; Soltis, Jennifer A.; Wittman, Rick S.; ...

2017-10-16

Layered (oxy) hydroxide minerals often possess out-of-plane hydrogen atoms that form hydrogen bonding networks which stabilize the layered structure. However, less is known about how the ordering of these bonds affects the structural stability and solubility of these minerals. Here, we report a new strategy that uses the focused electron beam to probe the effect of differences in hydrogen bonding networks on mineral solubility. In this regard, the dissolution behavior of boehmite (γ-AlOOH) and gibbsite (γ-Al(OH)3) were compared and contrasted in real time via liquid cell electron microscopy. Under identical such conditions, 2D-nanosheets of boehmite (γ-AlOOH) exfoliated from the bulkmore » and then rapidly dissolved, whereas gibbsite was stable. Further, substitution of only 1% Fe(III) for Al(III) in the structure of boehmite inhibited delamination and dissolution. Factors such as pH, radiolytic species, and knock on damage were systematically studied and eliminated as proximal causes for boehmite dissolution. Instead, the creation of electron/hole pairs was considered to be the mechanism that drove dissolution. The widely disparate behaviors of boehmite, gibbsite, and Fe-doped boehmite are discussed in the context of differences in the OH bond strengths, hydrogen bonding networks, and the presence or absence of electron/hole recombination centers.« less

A novel hot-melt extrusion formulation of albendazole for increasing dissolution properties.

PubMed

Martinez-Marcos, Laura; Lamprou, Dimitrios A; McBurney, Roy T; Halbert, Gavin W

2016-02-29

The main aim of the research focused on the production of hot-melt extrusion (HME) formulations with increased dissolution properties of albendazole (ABZ). Therefore, HME was applied as a continuous manufacturing technique to produce amorphous solid dispersions of the poorly water soluble drug ABZ combined with the polymer matrix polyvinylpyrrolidone PVP K12. HME formulations of ABZ-PVP K12 comprised a drug content of 1%, 5% and 10% w/w. The main analytical characterisation techniques used were scanning electron microscopy (SEM), micro-computed tomography (μ-CT), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and dissolution profile studies. The application of SEM, XRPD and DSC evidenced drug physical transformation from crystalline to amorphous state and therefore, the achievement of an amorphous solid dispersion. The introduction of a novel technique, μ-CT, to characterise the internal structure of these materials revealed key information regarding materials distribution and void content. Dissolution profile studies evidenced a high increase in drug release profile compared to pure ABZ. These promising results can lead to a great enhancement of the oral bioavailability of ABZ dosage forms. Therefore, HME is a potential continuous manufacturing technique to overcome ABZ poor solubility properties and lead to a significant increase in the therapeutic effect. Copyright © 2016 Elsevier B.V. All rights reserved.

Berberine nanoparticles with enhanced in vitro bioavailability: characterization and antimicrobial activity.

PubMed

Sahibzada, Muhammad Umar Khayam; Sadiq, Abdul; Faidah, Hani S; Khurram, Muhammad; Amin, Muhammad Usman; Haseeb, Abdul; Kakar, Maria

2018-01-01

Berberine is an isoquinoline alkaloid widely used in Ayurveda and traditional Chinese medicine to treat illnesses such as hypertension and inflammatory conditions, and as an anticancer and hepato-protective agent. Berberine has low oral bioavailability due to poor aqueous solubility and insufficient dissolution rate, which can reduce the efficacy of drugs taken orally. In this study, evaporative precipitation of nanosuspension (EPN) and anti-solvent precipitation with a syringe pump (APSP) were used to address the problems of solubility, dissolution rate and bioavailability of berberine. Semi-crystalline nanoparticles (NPs) of 90-110 nm diameter for APSP and 65-75 nm diameter for EPN were prepared and then characterized using differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRD). Thereafter, drug content solubility and dissolution studies were undertaken. Berberine and its NPs were evaluated for their antibacterial activity. The results indicate that the NPs have significantly increased solubility and dissolution rate due to conversion of the crystalline structure to a semi-crystalline form. Berberine NPs produced by both APSP and EPN methods have shown promising activities against Gram-positive and Gram-negative bacteria, and yeasts, with NPs prepared through the EPN method showing superior results compared to those made with the APSP method and the unprocessed drug.

Enhanced in vivo absorption of CB-1 antagonist in rats via solid solutions prepared by hot-melt extrusion.

PubMed

Ranzani, L S; Font, J; Galimany, F; Santanach, A; Gomez-Gomar, A M; Casadevall, G; Gryczke, A

2011-06-01

The aim of the present work was to investigate in vitro dissolution properties of three binary solid solutions prepared by a hot-melt extrusion (HME) process with vinyl pirrolidone--vinyl acetate copolymer (Kollidon VA 64), ethyl acrylate, methyl methacrylate polymer (Eudragit E) polyetilenglicol 8000 (PEG 8000) with a cannabinoid type 1 (CB-1) antagonist. Hansen solubility parameters were calculated from the chemical structures of the drug and the individual polymers in order to predict miscibility. Solid state characterizations of drug substance, physical blends and HME formulations were performed with differential scanning calorimetry. The dissolution testing conducted under sink conditions revealed that the dissolution rate of HME formulations improved around 1.8-fold vs drug substance. Supersaturation dissolution study demonstrated that HME formulations composed by Eudragit E and Kollidon VA64 increased drug solubility between 30- and 35-fold, respectively comparing to the drug substance. Physical and chemical stability of formulations were studied at 40°C/75%HR with open dish during 15 days. The formulation composed by the drug and Eudragit E at 10:90 was evaluated for in vivo drug absorption in male Wistar-Hannover rats and it was found to increase CB-1 absorption threefold greater than pure drug oral suspension.

A Kinetics and Equilibrium Study of Vanadium Dissolution from Vanadium Oxides and Phosphates in Battery Electrolytes: Possible Impacts on ICD Battery Performance.

PubMed

Bock, David C; Marschilok, Amy C; Takeuchi, Kenneth J; Takeuchi, Esther S

2013-06-01

Silver vanadium oxide (Ag 2 V 4 O 11 , SVO) has enjoyed widespread commercial success over the past 30 years as a cathode material for implantable cardiac defibrillator (ICD) batteries. Recently, silver vanadium phosphorous oxide (Ag 2 VO 2 PO 4 , SVPO) has been studied as possibly combining the desirable thermal stability aspects of LiFePO 4 with the electrical conductivity of SVO. Further, due to the noted insoluble nature of most phosphate salts, a lower material solubility of SVPO relative to SVO is anticipated. Thus, the first vanadium dissolution studies of SVPO in battery electrolyte solutions are described herein. The equilibrium solubility of SVPO was ~5 times less than SVO, with a rate constant of dissolution ~3.5 times less than that of SVO. The vanadium dissolution in SVO and SVPO can be adequately described with a diffusion layer model, as supported by the Noyes-Whitney equation. Cells prepared with vanadium-treated anodes displayed higher AC impedance and DC resistance relative to control anodes. These data support the premise that SVPO cells are likely to exhibit reduced cathode solubility and thus less affected by increased cell resistance due to cathode solubility compared to SVO based cells.

Influence of coating material on the flowability and dissolution of dry-coated fine ibuprofen powders.

PubMed

Qu, Li; Zhou, Qi Tony; Denman, John A; Stewart, Peter J; Hapgood, Karen P; Morton, David A V

2015-10-12

This study investigates the effects of a variety of coating materials on the flowability and dissolution of dry-coated cohesive ibuprofen powders, with the ultimate aim to use these in oral dosage forms. A mechanofusion approach was employed to apply a 1% (w/w) dry coating onto ibuprofen powder with coating materials including magnesium stearate (MgSt), L-leucine, sodium stearyl fumarate (SSF) and silica-R972. No significant difference in particle size or shape was measured following mechanofusion with any material. Powder flow behaviours characterised by the Freeman FT4 system indicated coatings of MgSt, L-leucine and silica-R972 produced a notable surface modification and substantially improved flow compared to the unprocessed and SSF-mechanofused powders. ToF-SIMS provided a qualitative measure of coating extent, and indicated a near-complete layer on the drug particle surface after dry coating with MgSt or silica-R972. Of particular note, the dissolution rates of all mechanofused powders were enhanced even with a coating of a highly hydrophobic material such as magnesium stearate. This surprising increase in dissolution rate of the mechanofused powders was attributed to the lower cohesion and the reduced agglomeration after mechanical coating. Copyright © 2015 Elsevier B.V. All rights reserved.