pH-Dependent Solubility and Dissolution Behavior of Carvedilol--Case Example of a Weakly Basic BCS Class II Drug.

PubMed

Hamed, Rania; Awadallah, Areeg; Sunoqrot, Suhair; Tarawneh, Ola; Nazzal, Sami; AlBaraghthi, Tamadur; Al Sayyad, Jihan; Abbas, Aiman

2016-04-01

The objective of this study was to investigate the pH-dependent solubility and dissolution of weakly basic Biopharmaceutical Classification Systems (BCS) class II drugs, characterized by low solubility and high permeability, using carvedilol, a weak base with a pK a value of 7.8, as a model drug. A series of solubility and in vitro dissolution studies was carried out using media that simulate the gastric and intestinal fluids and cover the physiological pH range of the GI from 1.2 to 7.8. The effect of ionic strength, buffer capacity, and buffer species of the dissolution media on the solubility and dissolution behavior of carvedilol was also investigated. The study revealed that carvedilol exhibited a typical weak base pH-dependent solubility profile with a high solubility at low pH (545.1-2591.4 μg/mL within the pH range 1.2-5.0) and low solubility at high pH (5.8-51.9 μg/mL within the pH range 6.5-7.8). The dissolution behavior of carvedilol was consistent with the solubility results, where carvedilol release was complete (95.8-98.2% released within 60 min) in media simulating the gastric fluid (pH 1.2-5.0) and relatively low (15.9-86.2% released within 240 min) in media simulating the intestinal fluid (pH 6.5-7.8). It was found that the buffer species of the dissolution media may influence the solubility and consequently the percentage of carvedilol released by forming carvedilol salts of varying solubilities. Carvedilol solubility and dissolution decreased with increasing ionic strength, while lowering the buffer capacity resulted in a decrease in carvedilol solubility and dissolution rate.

High resolution electrolyte for thinning InP by anodic dissolution and its applications to EC-V profiling, defect revealing and surface passivation

NASA Technical Reports Server (NTRS)

Faur, Maria; Faur, Mircea; Weinberg, Irving; Goradia, Manju; Vargas, Carlos

1991-01-01

An extensive experimental study was conducted using various electrolytes in an effort to find an appropriate electrolyte for anodic dissolution of InP. From the analysis of electrochemical characteristics in the dark and under different illumination levels, x ray photoelectron spectroscopy and SEM/Nomarski inspection of the surfaces, it was determined that the anodic dissolution of InP front surface layers by FAP electrolyte is a very good choice for rendering smooth surfaces, free of oxides and contaminants and with good electrical characteristics. The FAP electrolyte, based on HF, CH3COOH, and H2O2 appears to be inherently superior to previously reported electrolytes for performing accurate EC-V profiling of InP at current densities of up to 0.3 mA/sq cm. It can also be used for accurate electrochemical revealing of either precipitates or dislocation density with application to EPD mapping as a function of depth, and for defect revealing of multilayer InP structures at any depth and/or at the interfaces.

Effect of Food Thickener on Dissolution and Laxative Activity of Magnesium Oxide Tablets in Mice.

PubMed

Tomita, Takashi; Goto, Hidekazu; Yoshimura, Yuya; Kato, Kazushige; Yoshida, Tadashi; Tanaka, Katsuya; Sumiya, Kenji; Kohda, Yukinao

2016-01-01

The present study examined the dissolution of magnesium oxide (MgO) from MgO tablets placed in a food thickening agent (food thickener) and its effects on laxative activity. We prepared mixtures of MgO tablets suspended in an aqueous suspension and food thickeners in order to evaluate the dissolution of MgO. The results of the dissolution tests revealed that agar-based food thickeners did not affect the MgO dissolution. In contrast, some xanthan gum-based food-thickener products show dissolution rates with certain mixtures containing disintegrated MgO tablets suspended in a food thickener that decrease over time. However, other xanthan gum-based food-thickener products show dissolution rates that decrease immediately after mixing, regardless of the time they were allowed to stand. In order to investigate the laxative activity of MgO, we orally administered a mixture of MgO suspension and food thickener to mice and observed their bowel movements. The animal experiments showed that when agar-based food thickeners were used, the laxative activity of MgO was not affected, but it decreased when xanthan gum-based food thickeners were used.

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

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.

Understanding and predicting the impact of critical dissolution variables for nifedipine immediate release capsules by multivariate data analysis.

PubMed

Mercuri, A; Pagliari, M; Baxevanis, F; Fares, R; Fotaki, N

2017-02-25

In this study the selection of in vivo predictive in vitro dissolution experimental set-ups using a multivariate analysis approach, in line with the Quality by Design (QbD) principles, is explored. The dissolution variables selected using a design of experiments (DoE) were the dissolution apparatus [USP1 apparatus (basket) and USP2 apparatus (paddle)], the rotational speed of the basket/or paddle, the operator conditions (dissolution apparatus brand and operator), the volume, the pH, and the ethanol content of the dissolution medium. The dissolution profiles of two nifedipine capsules (poorly soluble compound), under conditions mimicking the intake of the capsules with i. water, ii. orange juice and iii. an alcoholic drink (orange juice and ethanol) were analysed using multiple linear regression (MLR). Optimised dissolution set-ups, generated based on the mathematical model obtained via MLR, were used to build predicted in vitro-in vivo correlations (IVIVC). IVIVC could be achieved using physiologically relevant in vitro conditions mimicking the intake of the capsules with an alcoholic drink (orange juice and ethanol). The multivariate analysis revealed that the concentration of ethanol used in the in vitro dissolution experiments (47% v/v) can be lowered to less than 20% v/v, reflecting recently found physiological conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Anti-inflammation effects of Sophora flavescens nanoparticles.

PubMed

Han, Chun-Chao; Wang, Yingzi

2012-08-01

The roots of Sophora flavescens was reported to possess many pharmacological activities including anti-inflammatory, antiashmatic, antithelmintic, free radical scavenging and antimicrobial activities. However, the low saturated solubility and dissolution velocity of S. flavescens lead to poor bioavailability. The S. flavescens nanoparticles (SFNP) were prepared by a combination of ultrasound and hydrolysis developed by the authors. The drug dissolution profiles of SFNP in both pH 6.8 and pH 2 media showed complete dissolution within 30 min. The seropharmacology study showed that oral S. flavescens absorption in the SFNP was significantly increased. Anti-inflammation assay revealed the therapeutic efficiency of S. flavescens significantly enhanced upon nanoparticle formation.

Stable amorphous binary systems of glipizide and atorvastatin powders with enhanced dissolution profiles: formulation and characterization.

PubMed

Renuka; Singh, Sachin Kumar; Gulati, Monica; Narang, Rakesh

2017-02-01

The aim of this study was to enhance the dissolution profile of the combination of glipizide and atorvastatin used for simultaneous treatment of hyperglycemia and hyperlipidemia. The strategy to formulate coamorphous glipizide-atorvastatin binary mixture was explored to achieve enhancement in dissolution. The coamorphous glipizide-atorvastatin mixtures (1:1, 1:2 and 2:1) were prepared by cryomilling and characterized with respect to their dissolution profiles, preformulation parameters and physical stability. Amorphization was found to be possible by cryomilling at various tried ratios of the two drugs. The data obtained from glass transition temperatures and from Raman spectroscopy point toward practically no interaction between the two drugs. The dissolution studies revealed the highest enhancement in dissolution profiles of cryomilled coamorphous mixtures containing GPZ:ATV in ratios 1:1 (B-5) and 2:1 (B-7). These two mixtures were, therefore, subjected to studies for the evaluation of precompression parameters in order to find their amenability to satisfactory compression into tablet dosage form. The selected formulation was found to be stable when subjected to accelerated stability testing at 40°. C/75% RH for six months as per ICH guidelines. Based on all these studies, it was concluded that GPZ:ATV (1:1) combination may be able to provide an effective therapy for the comorbidities of hyperglycemia and hyperlipidemia.

Does the stepwave model predict mica dissolution kinetics?

NASA Astrophysics Data System (ADS)

Kurganskaya, Inna; Arvidson, Rolf S.; Fischer, Cornelius; Luttge, Andreas

2012-11-01

The micas are a unique class of minerals because of their layered structure. A frequent question arising in mica dissolution studies is whether this layered structure radically changes the dissolution mechanism. We address this question here, using data from VSI and AFM experiments involving muscovite to evaluate crystallographic controls on mica dissolution. These data provide insight into the dissolution process, and reveal important links to patterns of dissolution observed in framework minerals. Under our experimental conditions (pH 9.4, 155 °C), the minimal global rate of normal surface retreat observed in VSI data was 1.42 × 10-10 mol/m2/s (σ = 27%) while the local rate observed at deep etch pits reached 416 × 10-10 mol/m2/s (σ = 49%). Complementary AFM data clearly show crystallographic control of mica dissolution, both in terms of step advance and the geometric influence of interlayer rotation (stacking periodicity). These observations indicate that basal/edge surface area ratios are highly variable and change continuously over the course of reaction, thus obviating their utility as characteristic parameters defining mica reactivity. Instead, these observations of overall dissolution rate and the influence of screw dislocations illustrate the link between atomic step movement and overall dissolution rate defined by surface retreat normal to the mica surface. Considered in light of similar observations available elsewhere in the literature, these relationships provide support for application of the stepwave model to mica dissolution kinetics. This approach provides a basic mechanistic link between the dissolution kinetics of phyllosilicates, framework silicates, and related minerals, and suggests a resolution to the general problem of mica reactivity.

A reaction limited in vivo dissolution model for the study of drug absorption: Towards a new paradigm for the biopharmaceutic classification of drugs.

PubMed

Macheras, Panos; Iliadis, Athanassios; Melagraki, Georgia

2018-05-30

The aim of this work is to develop a gastrointestinal (GI) drug absorption model based on a reaction limited model of dissolution and consider its impact on the biopharmaceutic classification of drugs. Estimates for the fraction of dose absorbed as a function of dose, solubility, reaction/dissolution rate constant and the stoichiometry of drug-GI fluids reaction/dissolution were derived by numerical solution of the model equations. The undissolved drug dose and the reaction/dissolution rate constant drive the dissolution rate and determine the extent of absorption when high-constant drug permeability throughout the gastrointestinal tract is assumed. Dose is an important element of drug-GI fluids reaction/dissolution while solubility exclusively acts as an upper limit for drug concentrations in the lumen. The 3D plots of fraction of dose absorbed as a function of dose and reaction/dissolution rate constant for highly soluble and low soluble drugs for different "stoichiometries" (0.7, 1.0, 2.0) of the drug-reaction/dissolution with the GI fluids revealed that high extent of absorption was found assuming high drug- reaction/dissolution rate constant and high drug solubility. The model equations were used to simulate in vivo supersaturation and precipitation phenomena. The model developed provides the theoretical basis for the interpretation of the extent of drug's absorption on the basis of the parameters associated with the drug-GI fluids reaction/dissolution. A new paradigm emerges for the biopharmaceutic classification of drugs, namely, a model independent biopharmaceutic classification scheme of four drug categories based on either the fulfillment or not of the current dissolution criteria and the high or low % drug metabolism. Copyright © 2018. Published by Elsevier B.V.

Enhanced dissolution and bioavailability of Nateglinide by microenvironmental pH-regulated ternary solid dispersion: in-vitro and in-vivo evaluation.

PubMed

Wairkar, Sarika; Gaud, Ram; Jadhav, Namdeo

2017-09-01

Nateglinide, an Antidiabetic drug (BCS II), shows pH-dependent solubility and variable bioavailability. The purpose of study was to increase dissolution and bioavailability of Nateglinide by development of its microenvironmental pH-regulated ternary solid dispersion (MeSD). MeSD formulation of Nateglinide, poloxamer-188 and Na 2 CO 3 was prepared by melt dispersion in 1 : 2 : 0.2 w/w ratio and further characterised for solubility, In-vitro dissolution, microenvironmental pH, crystallinity/amorphism, physicochemical interactions, bioavailability in Wistar rats. Solubility of Nateglinide was increased notably in MeSD, and its in-vitro dissolution study showed fourfold increase in the dissolution, particularly in 1.2 pH buffer. Prominent reduction in the peak intensity of X-ray powder diffraction (XRPD) and absence of endotherm in DSC thermogram confirmed the amorphism of Nateglinide in MeSD. Attenuated total reflectance Fourier transform infrared spectra revealed the hydrogen bond interactions between Nateglinide and poloxamer-188. In-vivo study indicated that MeSD exhibited fourfold increase in area under curve over Nateglinide. Tmax of MeSD was observed at 0.25 h, which is beneficial for efficient management of postprandial sugar. Instead of mere transformation of the Nateglinide to its amorphous form as evidenced by DSC and XRPD, formation of a soluble carboxylate compound of Nateglinide in MeSD was predominantly responsible for dissolution and bioavailability enhancement. The study demonstrates the utility of MeSD in achieving pH-independent dissolution, reduced T max and enhanced bioavailability of Nateglinide. © 2017 Royal Pharmaceutical Society.

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

Approaches for Establishing Clinically Relevant Dissolution Specifications for Immediate Release Solid Oral Dosage Forms.

PubMed

Hermans, Andre; Abend, Andreas M; Kesisoglou, Filippos; Flanagan, Talia; Cohen, Michael J; Diaz, Dorys A; Mao, Y; Zhang, Limin; Webster, Gregory K; Lin, Yiqing; Hahn, David A; Coutant, Carrie A; Grady, Haiyan

2017-11-01

This manuscript represents the perspective of the Dissolution Analytical Working Group of the IQ Consortium. The intent of this manuscript is to highlight the challenges of, and to provide a recommendation on, the development of clinically relevant dissolution specifications (CRS) for immediate release (IR) solid oral dosage forms. A roadmap toward the development of CRS for IR products containing active ingredients with a non-narrow therapeutic window is discussed, within the context of mechanistic dissolution understanding, supported by in-human pharmacokinetic (PK) data. Two case studies present potential outcomes of following the CRS roadmap and setting dissolution specifications. These cases reveal some benefits and challenges of pursuing CRS with additional PK data, in light of current regulatory positions, including that of the US Food and Drug Administration (FDA), who generally favor this approach, but with the understanding that both industry and regulatory agency perspectives are still evolving in this relatively new field. The CRS roadmap discussed in this manuscript also describes a way to develop clinically relevant dissolution specifications based primarily on dissolution data for batches used in pivotal clinical studies, acknowledging that not all IR product development efforts need to be supported by additional PK studies, albeit with the associated risk of potentially unnecessarily tight manufacturing controls. Recommendations are provided on what stages during the life cycle investment into in vivo studies may be valuable. Finally, the opportunities for CRS within the context of post-approval changes, Modeling and Simulation (M&S), and the application of biowaivers, are briefly discussed.

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).

Exopolysaccharides regulate calcium flow in cariogenic biofilms

PubMed Central

Varenganayil, Muth M.; Decho, Alan W.

2017-01-01

Caries-associated biofilms induce loss of calcium from tooth surfaces in the presence of dietary carbohydrates. Exopolysaccharides (EPS) provide a matrix scaffold and an abundance of primary binding sites within biofilms. The role of EPS in binding calcium in cariogenic biofilms is only partially understood. Thus, the aim of the present study is to investigate the relationship between the calcium dissolution rates and calcium tolerance of caries-associated bacteria and yeast as well as to examine the properties of EPS to quantify its binding affinity for dissolved calcium. Calcium dissolution was measured by dissolution zones on Pikovskaya’s agar. Calcium tolerance was assessed by isothermal microcalorimetry (IMC) by adding CaCl2 to the bacterial cultures. Acid-base titration and Fourier transform infrared (FTIR) spectroscopy were used to identify possible functional groups responsible for calcium binding, which was assessed by isothermal titration calorimetry (ITC). Lactobacillus spp. and mutans streptococci demonstrated calcium dissolution in the presence of different carbohydrates. All strains that demonstrated high dissolution rates also revealed higher rates of calcium tolerance by IMC. In addition, acidic functional groups were predominantly identified as possible binding sites for calcium ions by acid-base titration and FTIR. Finally, ITC revealed EPS to have a higher binding affinity for calcium compared, for example, to lactic acid. In conclusion, this study illustrates the role of EPS in terms of the calcium tolerance of cariogenic microbiota by determining the ability of EPS to control free calcium concentrations within the biofilms as a self-regulating mode of action in the pathogenesis of dental caries. PMID:29023506

Curcumin phytosomal softgel formulation: Development, optimization and physicochemical characterization.

PubMed

Allam, Ahmed N; Komeil, Ibrahim A; Abdallah, Ossama Y

2015-09-01

Curcumin, a naturally occurring lipophilic molecule can exert multiple and diverse bioactivities. However, its limited aqueous solubility and extensive presystemic metabolism restrict its bioavailability. Curcumin phytosomes were prepared by a simple solvent evaporation method where free flowing powder was obtained in addition to a newly developed semisolid formulation to increase curcumin content in softgels. Phytosomal powder was characterized in terms of drug content and zeta potential. Thirteen different softgel formulations were developed using oils such as Miglyol 812, castor oil and oleic acid, a hydrophilic vehicle such as PEG 400 and bioactive surfactants such as Cremophor EL and KLS P 124. Selected formulations were characterized in terms of curcumin in vitro dissolution. TEM analysis revealed good stability and a spherical, self-closed structure of curcumin phytosomes in complex formulations. Stability studies of chosen formulations prepared using the hydrophilic vehicle revealed a stable curcumin dissolution pattern. In contrast, a dramatic decrease in curcumin dissolution was observed in case of phytosomes formulated in oily vehicles.

Solution behavior of PVP-VA and HPMC-AS-based amorphous solid dispersions and their bioavailability implications.

PubMed

Qian, Feng; Wang, Jennifer; Hartley, Ruiling; Tao, Jing; Haddadin, Raja; Mathias, Neil; Hussain, Munir

2012-10-01

To identify the mechanism behind the unexpected bio-performance of two amorphous solid dispersions: BMS-A/PVP-VA and BMS-A/HPMC-AS. Solubility of crystalline BMS-A in PVP-VA and HPMC-AS was measured by DSC. Drug-polymer interaction parameters were obtained by Flory-Huggins model fitting. Drug dissolution kinetics of spray-dried dispersions were studied under sink and non-sink conditions. BMS-A supersaturation was studied in the presence of pre-dissolved PVP-VA and HPMC-AS. Potency and crystallinity of undissolved solid dispersions were determined by HPLC and DSC. Polymer dissolution kinetics were obtained by mass balance calculation. Bioavailability of solid dispersions was assessed in dogs. In solid state, both polymers are miscible with BMS-A, while PVP-VA solublizes the drug better. BMS-A dissolves similarly from both solid dispersions in vitro regardless of dissolution method, while the HPMC-AS dispersion performed much better in vivo. At the same concentration, HPMC-AS is more effective in prolonging BMS-A supersaturation; this effect was negated by the slow dissolution rate of HPMC-AS. Further study revealed that fast PVP-VA dissolution resulted in elevated drug loading in undissolved dispersions and facilitated drug recrystallization before complete release. In contrast, the hydrophobicity and slower HPMC-AS dissolution prevented BMS-A recrystallization within the HPMC-AS matrix for >24 h. The lower bioavailability of PVP-VA dispersion was attributed to BMS-A recrystallization within the undissolved dispersion, due to hydrophilicity and fast PVP-VA dissolution rate. Polymer selection for solid dispersion development has significant impact on in vivo performance besides physical stability.

Kinetics of cellular dissolution in a Cu-Cd alloy

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

Nakkalil, R.; Gupta, S.P.

1989-07-01

Dissolution of the cellular precipitate by cell boundary migration has been studied in a Cu-2 at.% Cd alloy in the temperature range 777--878 K. Microstructural observations have revealed that the process of dissolution begins at the original position of the grain boundary as well as the cell boundary. The steady state rate of cell boundary migration decreased with decreasing temperature of dissolution and became zero at approximately 770 K, which is about 30 K below the equilibrium solves temperature. The boundary diffusivities were determined at a number of temperatures by using the theory of Petermann and Hornbogen modified for dissolution.more » The diffusivity values calculated from the experimental data are seven orders of magnitude higher than the corresponding volume diffusivities. From the temperature dependence of the diffusivity, an activation energy of 157 kJ mol{sup {minus} 1} is obtained, which is bout three-quarters of the activation energy for the bulk diffusion of Cd into Cu. From the diffusivity and activation energy values, it is concluded that the diffusion of Cd along the migrating grain boundaries control the dissolution of the cellular precipitate in this alloy.« less

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.

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.

Dissolution of Platinum in the Operational Range of Fuel Cells

PubMed Central

Keeley, Gareth P.; Geiger, Simon; Zeradjanin, Aleksandar R.; Hodnik, Nejc; Kulyk, Nadiia

2015-01-01

Abstract One of the most important practical issues in low‐temperature fuel‐cell catalyst degradation is platinum dissolution. According to the literature, it initiates at 0.6–0.9 VRHE, whereas previous time‐ and potential‐resolved inductively coupled plasma mass spectrometry (ICP–MS) experiments, however, revealed dissolution onset at only 1.05 VRHE. In this manuscript, the apparent discrepancy is addressed by investigating bulk and nanoparticulated catalysts. It is shown that, given enough time for accumulation, traces of platinum can be detected at potentials as low as 0.85 VRHE. At these low potentials, anodic dissolution is the dominant process, whereas, at more positive potentials, more platinum dissolves during the oxide reduction after accumulation. Interestingly, the potential and time dissolution dependence is similar for both types of electrode. Dissolution processes are discussed with relevance to fuel‐cell operation and plausible dissolution mechanisms are considered. PMID:27525206

Volume to dissolve applied dose (VDAD) and apparent dissolution rate (ADR): tools to predict in vivo bioavailability from orally applied drug suspensions.

PubMed

Muenster, Uwe; Pelzetter, Christian; Backensfeld, Thomas; Ohm, Andreas; Kuhlmann, Thomas; Mueller, Hartwig; Lustig, Klemens; Keldenich, Jörg; Greschat, Susanne; Göller, Andreas H; Gnoth, Mark Jean

2011-08-01

Low solubility of drug candidates generated in research contributes to their elimination during subsequent development due to insufficient oral bioavailability (BA) of crystalline compound. Therefore, the purpose of the study was to identify critical in vitro solubility and dissolution parameter that would predict critical in vivo dissolution by means of in vitro-in vivo correlation. Thermodynamic solubility and apparent dissolution rate (ADR) were determined using the shake-flask method and mini-flow-through-cell, respectively. Oral BA studies in rats and humans were conducted from drug solution and suspension/tablets. Relative BA was calculated using F(rel) [%]=AUC(suspension)/AUC(solution)*100, representing a measure of in vivo dissolution. Roughly, F(rel) rat >50% translates into F(rel) human of >90%. Both, ADR and log volume to dissolve applied dose (VDAD), when plotted against F(rel) rat, revealed certain threshold levels, (ADR, ∼150-200 μg of compound dissolved under respective assay conditions; VDAD, ∼100-500 ml/kg) which translate into F(rel) in rats of >50%. Thus, assuming that F(rel)>50% in rats is indicative of sufficient in vivo dissolution in humans after oral application, drugs should exhibit a VDAD of ∼100-500 ml/kg or less in aqueous media to avoid insufficient or varying drug absorption. Copyright © 2011 Elsevier B.V. All rights reserved.

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.

Atomic force microscopy of atomic-scale ledges and etch pits formed during dissolution of quartz

NASA Technical Reports Server (NTRS)

Gratz, A. J.; Manne, S.; Hansma, P. K.

1991-01-01

The processes involved in the dissolution and growth of crystals are closely related. Atomic force microscopy (AFM) of faceted pits (called negative crystals) formed during quartz dissolution reveals subtle details of these underlying physical mechanisms for silicates. In imaging these surfaces, the AFM detected ledges less than 1 nm high that were spaced 10 to 90 nm apart. A dislocation pit, invisible to optical and scanning electron microscopy measurements and serving as a ledge source, was also imaged. These observations confirm the applicability of ledge-motion models to dissolution and growth of silicates; coupled with measurements of dissolution rate on facets, these methods provide a powerful tool for probing mineral surface kinetics.

Patterns of entrapped air dissolution in a two-dimensional pilot-scale synthetic aquifer.

PubMed

McLeod, Heather C; Roy, James W; Smith, James E

2015-01-01

Past studies of entrapped air dissolution have focused on one-dimensional laboratory columns. Here the multidimensional nature of entrapped air dissolution was investigated using an indoor tank (180 × 240 × 600 cm(3) ) simulating an unconfined sand aquifer with horizontal flow. Time domain reflectometry (TDR) probes directly measured entrapped air contents, while dissolved gas conditions were monitored with total dissolved gas pressure (PTDG ) probes. Dissolution occurred as a diffuse wedge-shaped front from the inlet downgradient, with preferential dissolution at depth. This pattern was mainly attributed to increased gas solubility, as shown by PTDG measurements. However, compression of entrapped air at greater depths, captured by TDR and leading to lower quasi-saturated hydraulic conductivities and thus greater velocities, also played a small role. Linear propagation of the dissolution front downgradient was observed at each depth, with both TDR and PTDG , with increasing rates with depth (e.g, 4.1 to 5.7× slower at 15 cm vs. 165 cm depth). PTDG values revealed equilibrium with the entrapped gas initially, being higher at greater depth and fluctuating with the barometric pressure, before declining concurrently with entrapped air contents to the lower PTDG of the source water. The observed dissolution pattern has long-term implications for a wide variety of groundwater management issues, from recharge to contaminant transport and remediation strategies, due to the persistence of entrapped air near the water table (potential timescale of years). This study also demonstrated the utility of PTDG probes for simple in situ measurements to detect entrapped air and monitor its dissolution. © 2014 Her Majesty the Queen in Right of Canada Groundwater © 2014, National Ground Water Association.

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.

In situ nanoscale observations of gypsum dissolution by digital holographic microscopy.

PubMed

Feng, Pan; Brand, Alexander S; Chen, Lei; Bullard, Jeffrey W

2017-06-01

Recent topography measurements of gypsum dissolution have not reported the absolute dissolution rates, but instead focus on the rates of formation and growth of etch pits. In this study, the in situ absolute retreat rates of gypsum (010) cleavage surfaces at etch pits, at cleavage steps, and at apparently defect-free portions of the surface are measured in flowing water by reflection digital holographic microscopy. Observations made on randomly sampled fields of view on seven different cleavage surfaces reveal a range of local dissolution rates, the local rate being determined by the topographical features at which material is removed. Four characteristic types of topographical activity are observed: 1) smooth regions, free of etch pits or other noticeable defects, where dissolution rates are relatively low; 2) shallow, wide etch pits bounded by faceted walls which grow gradually at rates somewhat greater than in smooth regions; 3) narrow, deep etch pits which form and grow throughout the observation period at rates that exceed those at the shallow etch pits; and 4) relatively few, submicrometer cleavage steps which move in a wave-like manner and yield local dissolution fluxes that are about five times greater than at etch pits. Molar dissolution rates at all topographical features except submicrometer steps can be aggregated into a continuous, mildly bimodal distribution with a mean of 3.0 µmolm -2 s -1 and a standard deviation of 0.7 µmolm -2 s -1 .

Formulation Predictive Dissolution (fPD) Testing to Advance Oral Drug Product Development: an Introduction to the US FDA Funded '21st Century BA/BE' Project.

PubMed

Hens, Bart; Sinko, Patrick; Job, Nicholas; Dean, Meagan; Al-Gousous, Jozef; Salehi, Niloufar; Ziff, Robert M; Tsume, Yasuhiro; Bermejo, Marival; Paixão, Paulo; Brasseur, James G; Yu, Alex; Talattof, Arjang; Benninghoff, Gail; Langguth, Peter; Lennernäs, Hans; Hasler, William L; Marciani, Luca; Dickens, Joseph; Shedden, Kerby; Sun, Duxin; Amidon, Gregory E; Amidon, Gordon L

2018-06-23

Over the past decade, formulation predictive dissolution (fPD) testing has gained increasing attention. Another mindset is pushed forward where scientists in our field are more confident to explore the in vivo behavior of an oral drug product by performing predictive in vitro dissolution studies. Similarly, there is an increasing interest in the application of modern computational fluid dynamics (CFD) frameworks and high-performance computing platforms to study the local processes underlying absorption within the gastrointestinal (GI) tract. In that way, CFD and computing platforms both can inform future PBPK-based in silico frameworks and determine the GI-motility-driven hydrodynamic impacts that should be incorporated into in vitro dissolution methods for in vivo relevance. Current compendial dissolution methods are not always reliable to predict the in vivo behavior, especially not for biopharmaceutics classification system (BCS) class 2/4 compounds suffering from a low aqueous solubility. Developing a predictive dissolution test will be more reliable, cost-effective and less time-consuming as long as the predictive power of the test is sufficiently strong. There is a need to develop a biorelevant, predictive dissolution method that can be applied by pharmaceutical drug companies to facilitate marketing access for generic and novel drug products. In 2014, Prof. Gordon L. Amidon and his team initiated a far-ranging research program designed to integrate (1) in vivo studies in humans in order to further improve the understanding of the intraluminal processing of oral dosage forms and dissolved drug along the gastrointestinal (GI) tract, (2) advancement of in vitro methodologies that incorporates higher levels of in vivo relevance and (3) computational experiments to study the local processes underlying dissolution, transport and absorption within the intestines performed with a new unique CFD based framework. Of particular importance is revealing the physiological variables determining the variability in in vivo dissolution and GI absorption from person to person in order to address (potential) in vivo BE failures. This paper provides an introduction to this multidisciplinary project, informs the reader about current achievements and outlines future directions. Copyright © 2018. Published by Elsevier B.V.

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.

Predictors of relationship dissolution in lesbian, gay, and heterosexual adoptive parents.

PubMed

Goldberg, Abbie E; Garcia, Randi

2015-06-01

Little work has examined relationship dissolution or divorce in adoptive parents or same-sex parent couples. The current study examined predictors of relationship dissolution across the first 5 years of parenthood among a sample of heterosexual, lesbian, and gay male adoptive couples. Of the 190 couples in the study, 15 (7.9%) dissolved their relationships during the first 5 years of adoptive parenthood. Specifically, 7 of 57 lesbian couples (12.3%), 1 of 49 gay male couples (2.0%), and 7 of 84 heterosexual couples (8.3%) dissolved their unions. Results of our logistic regression analysis revealed that the odds of relationship dissolution were significantly higher for (a) couples who adopted a noninfant (i.e., older child); (b) participants who reported feeling less prepared for the adoption, 3 months postadoptive placement; and (c) couples in which both partners reported very low or very high preadoption levels of relationship maintenance behaviors. Findings have implications for adoption professionals seeking to support same-sex and heterosexual prospective adopters, as well as societal debates and policy regarding same-sex relationships and parenting. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Predictors of Relationship Dissolution in Lesbian, Gay, and Heterosexual Adoptive Parents

PubMed Central

Goldberg, Abbie E.; Garcia, Randi

2015-01-01

Little work has examined relationship dissolution or divorce in adoptive parents or same-sex parent couples. The current study examined predictors of relationship dissolution across the first 5 years of parenthood among a sample of heterosexual, lesbian, and gay male adoptive couples. Of the 190 couples in the study, 15 (7.9%) dissolved their relationships during the first 5 years of adoptive parenthood. Specifically, 7 of 57 lesbian couples (12.3%), 1 of 49 gay male couples (2.0%), and 7 of 84 heterosexual couples (8.3%) dissolved their unions. Results of our logistic regression analysis revealed that the odds of relationship dissolution were significantly higher for (a) couples who adopted a non-infant (i.e., older) child); (b) participants who reported feeling less prepared for the adoption, three months post-adoptive placement; and (c) couples in which both partners reported very low, or very high, pre-adoption levels of relationship maintenance behaviors. Findings have implications for adoption professionals seeking to support same-sex and heterosexual prospective adopters, as well as societal debates and policy regarding same-sex relationships and parenting. PMID:26053348

Investigating Dissolution and Precipitation Phenomena with a Smartphone Microscope

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

Lumetta, Gregg J.; Arcia, Edgar

A novel smartphone microscope can be used to observe the dissolution and crystallization of sodium chloride at a microscopic level. Observation of these seemingly simple phenomena through the microscope at 100× magnification can actually reveal some surprising behavior. These experiments offer the opportunity to discuss some basic concepts such as how the morphological features of the crystals dictates how the dissolution process proceeds, and how materials can be purified by re-crystallization techniques.

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.

Dissolution Processes at Step Edges of Calcite in Water Investigated by High-Speed Frequency Modulation Atomic Force Microscopy and Simulation.

PubMed

Miyata, Kazuki; Tracey, John; Miyazawa, Keisuke; Haapasilta, Ville; Spijker, Peter; Kawagoe, Yuta; Foster, Adam S; Tsukamoto, Katsuo; Fukuma, Takeshi

2017-07-12

The microscopic understanding of the crystal growth and dissolution processes have been greatly advanced by the direct imaging of nanoscale step flows by atomic force microscopy (AFM), optical interferometry, and X-ray microscopy. However, one of the most fundamental events that govern their kinetics, namely, atomistic events at the step edges, have not been well understood. In this study, we have developed high-speed frequency modulation AFM (FM-AFM) and enabled true atomic-resolution imaging in liquid at ∼1 s/frame, which is ∼50 times faster than the conventional FM-AFM. With the developed AFM, we have directly imaged subnanometer-scale surface structures around the moving step edges of calcite during its dissolution in water. The obtained images reveal that the transition region with typical width of a few nanometers is formed along the step edges. Building upon insight in previous studies, our simulations suggest that the transition region is most likely to be a Ca(OH) 2 monolayer formed as an intermediate state in the dissolution process. On the basis of this finding, we improve our understanding of the atomistic dissolution model of calcite in water. These results open up a wide range of future applications of the high-speed FM-AFM to the studies on various dynamic processes at solid-liquid interfaces with true atomic resolution.

Development and evaluation of methods for starch dissolution using asymmetrical flow field-flow fractionation. Part II: Dissolution of amylose.

PubMed

Perez-Rea, Daysi; Bergenståhl, Björn; Nilsson, Lars

2016-02-01

In this paper, we investigate whether dissolution in water under autoclaving conditions (140 °C, 20 min) or in dimethyl sulfoxide, DMSO (100 °C, 1 h), is preferable for characterization of amylose. Two types of amylose, potato and maize, were dissolved either in water using an autoclave or in DMSO. On the aqueous solutions obtained, the extent of molecular dissolution of the sample (referred to as the dissolution yield) was determined by enzymatic analysis as well as the molecular properties, such as molar mass and root-mean-square radius, obtained with asymmetrical flow field-flow fractionation coupled to multi-angle light scattering and differential refractive index detection (AF4-MALS-dRI). The results showed that both dissolution methods are efficient at dissolving amylose. However, AF4-MALS-dRI analysis revealed substantial differences. Amylose aqueous solutions obtained by dissolution in DMSO were relatively stable over time, but the dissolution method in autoclave caused some degradation of the molecules, and their solutions display a high tendency to retrograde.

Hydrodynamics-induced variability in the USP apparatus II dissolution test.

PubMed

Baxter, Jennifer L; Kukura, Joseph; Muzzio, Fernando J

2005-03-23

The USP tablet dissolution test is an analytical tool used for the verification of drug release processes and formulation selection within the pharmaceutical industry. Given the strong impact of this test, it is surprising that operating conditions and testing devices have been selected empirically. In fact, the flow phenomena in the USP test have received little attention in the past. An examination of the hydrodynamics in the USP apparatus II shows that the device is highly vulnerable to mixing problems that can affect testing performance and consistency. Experimental and computational techniques reveal that the flow field within the device is not uniform, and dissolution results can vary dramatically with the position of the tablet within the vessel. Specifically, computations predict sharp variations in the shear along the bottom of the vessel where the tablet is most likely to settle. Experiments in which the tablet location was carefully controlled reveal that the variation of shear within the testing device can affect the measured dissolution rate.

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.

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.

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.

Reaction paths and equilibrium end-points in solid-solution aqueous-solution systems

USGS Publications Warehouse

Glynn, P.D.; Reardon, E.J.; Plummer, Niel; Busenberg, E.

1990-01-01

Equations are presented describing equilibrium in binary solid-solution aqueous-solution (SSAS) systems after a dissolution, precipitation, or recrystallization process, as a function of the composition and relative proportion of the initial phases. Equilibrium phase diagrams incorporating the concept of stoichiometric saturation are used to interpret possible reaction paths and to demonstrate relations between stoichiometric saturation, primary saturation, and thermodynamic equilibrium states. The concept of stoichiometric saturation is found useful in interpreting and putting limits on dissolution pathways, but there currently is no basis for possible application of this concept to the prediction and/ or understanding of precipitation processes. Previously published dissolution experiments for (Ba, Sr)SO4 and (Sr, Ca)C??O3orth. solids are interpreted using equilibrium phase diagrams. These studies show that stoichiometric saturation can control, or at least influence, initial congruent dissolution pathways. The results for (Sr, Ca)CO3orth. solids reveal that stoichiometric saturation can also control the initial stages of incongruent dissolution, despite the intrinsic instability of some of the initial solids. In contrast, recrystallisation experiments in the highly soluble KCl-KBr-H2O system demonstrate equilibrium. The excess free energy of mixing calculated for K(Cl, Br) solids is closely modeled by the relation GE = ??KBr??KClRT[a0 + a1(2??KBr-1)], where a0 is 1.40 ?? 0.02, a1, is -0.08 ?? 0.03 at 25??C, and ??KBr and ??KCl are the mole fractions of KBr and KCl in the solids. The phase diagram constructed using this fit reveals an alyotropic maximum located at ??KBr = 0.676 and at a total solubility product, ???? = [K+]([Cl-] + [Br-]) = 15.35. ?? 1990.

Melt dispersion granules: formulation and evaluation to improve oral delivery of poorly soluble drugs - a case study with valsartan.

PubMed

Chella, Naveen; Tadikonda, Ramarao

2015-06-01

Solid dispersion (SD) technique is a promising strategy to improve the solubility and dissolution of BCS class II drugs. However, only few products are marketed till today based on SD technology due to poor flow properties and stability. The present work was intended to solve these problems by using combination approach, melt dispersion and surface adsorption technologies. The main aim of the present work is to improve the absorption in the stomach (at lower pH) where the absorption window exists for the drug by improving the dissolution, resulting in the enhancement of oral bioavailability of poorly soluble, weakly acidic drug with pH dependant solubility, i.e. valsartan. Melt dispersion granules were prepared in different ratios using different carriers (Gelucire 50/13, PEG 8000 and Pluronic F-68) and lactose as an adsorbent. Similarly, physical mixtures were also prepared at corresponding ratios. The prepared dispersion granules and physical mixtures were characterized by FTIR, DSC and in vitro dissolution studies. DSC studies revealed reduction in the crystallinity with a possibility of presence of amorphous character of drug in the dispersion granules. From dissolution studies, valsartan Gelucire dispersion (GSD4; 1:4 ratio) showed complete drug release in 30 min against the plain drug which showed only 11.31% of drug release in 30 min. Pharmacokinetic studies of optimized formulation in male Wistar rats showed 2.65-fold higher bioavailability and 1.47-fold higher Cmax compared to pure drug. The melt dispersion technology has the potential to improve dissolution and the bioavailability of BCS class II drugs.

Solubility and dissolution performances of spray-dried solid dispersion of Efavirenz in Soluplus.

PubMed

Lavra, Zênia Maria Maciel; Pereira de Santana, Davi; Ré, Maria Inês

2017-01-01

Efavirenz (EFV), a first-line anti-HIV drug largely used as part of antiretroviral therapies, is practically insoluble in water and belongs to BCS class II (low solubility/high permeability). The aim of this study was to improve the solubility and dissolution performances of EFV by formulating an amorphous solid dispersion of the drug in polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus ® ) using spray-drying technique. To this purpose, spray-dried dispersions of EFV in Soluplus ® at different mass ratios (1:1.25, 1:7, 1:10) were prepared and characterized using particle size measurements, SEM, XRD, DSC, FTIR and Raman microscopy mapping. Solubility and dissolution were determined in different media. Stability was studied at accelerated conditions (40 °C/75% RH) and ambient conditions for 12 months. DSC and XRD analyses confirmed the EFV amorphous state. FTIR spectroscopy analyses revealed possible drug-polymer molecular interaction. Solubility and dissolution rate of EFV was enhanced remarkably in the developed spray-dried solid dispersions, as a function of the polymer concentration. Spray-drying was concluded to be a proper technique to formulate a physically stable dispersion of amorphous EFV in Soluplus ® , when protected from moisture.

Investigating Dissolution and Precipitation Phenomena with a Smartphone Microscope

ERIC Educational Resources Information Center

Lumetta, Gregg J.; Arcia, Edgar

2016-01-01

A novel smartphone microscope can be used to observe the dissolution and crystallization of sodium chloride at a microscopic level. Observation of these seemingly simple phenomena through the microscope at 100× magnification can actually reveal some surprising behavior. These experiments offer the opportunity to discuss some basic concepts such as…

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.

Cellulose Crystal Dissolution in Imidazolium-Based Ionic Liquids: A Theoretical Study.

PubMed

Uto, Takuya; Yamamoto, Kazuya; Kadokawa, Jun-Ichi

2018-01-11

The highly crystalline nature of cellulose results in poor processability and solubility, necessitating the search for solvents that can efficiently dissolve this material. Thus, ionic liquids (ILs) have recently been shown to be well suited for this purpose, although the corresponding dissolution mechanism has not been studied in detail. Herein, we adopt a molecular dynamics (MD) approach to study the dissolution of model cellulose crystal structures in imidazolium-based ILs and gain deep mechanistic insights, demonstrating that dissolution involves IL penetration-induced cleavage of hydrogen bonds between cellulose molecular chains. Moreover, we reveal that in ILs with high cellulose dissolving power (powerful solvents, such as 1-allyl-3-methylimidazolium chloride and 1-ethyl-3-methylimidazolium chloride), the above molecular chains are peeled from the crystal phase and subsequently dispersed in the solvent, whereas no significant structural changes are observed in poor-dissolving-power solvents. Finally, we utilize MD trajectory analysis to show that the solubility of microcrystalline cellulose is well correlated with the number of intermolecular hydrogen bonds in cellulose crystals. The obtained results allow us to conclude that both anions and cations of high-dissolving-power ILs contribute to the stepwise breakage of hydrogen bonds between cellulose chains, whereas this breakage does not occur to a sufficient extent in poorly solubilizing ILs.

In Vitro Dissolution of Fluconazole and Dipyridamole in Gastrointestinal Simulator (GIS), Predicting in Vivo Dissolution and Drug-Drug Interaction Caused by Acid-Reducing Agents.

PubMed

Matsui, Kazuki; Tsume, Yasuhiro; Amidon, Gregory E; Amidon, Gordon L

2015-07-06

Weakly basic drugs typically exhibit pH-dependent solubility in the physiological pH range, displaying supersaturation or precipitation along the gastrointestinal tract. Additionally, their oral bioavailabilities may be affected by coadministration of acid-reducing agents that elevate gastric pH. The purpose of this study was to assess the feasibility of a multicompartmental in vitro dissolution apparatus, Gastrointestinal Simulator (GIS), in predicting in vivo dissolution of certain oral medications. In vitro dissolution studies of fluconazole, a BCS class I, and dipyridamole, a BCS class II weak bases (class IIb), were performed in the GIS as well as United States Pharmacopeia (USP) apparatus II and compared with the results of clinical drug-drug interaction (DDI) studies. In both USP apparatus II and GIS, fluconazole completely dissolved within 60 min regardless of pH, reflecting no DDI between fluconazole and acid-reducing agents in a clinical study. On the other hand, seven-fold and 15-fold higher concentrations of dipyridamole than saturation solubility were observed in the intestinal compartments in GIS with gastric pH 2.0. Precipitation of dipyridamole was also observed in the GIS, and the percentage of dipyridamole in solution was 45.2 ± 7.0%. In GIS with gastric pH 6.0, mimicking the coadministration of acid-reducing agents, the concentration of dipyridamole was equal to its saturation solubility, and the percentage of drug in solution was 9.3 ± 2.7%. These results are consistent with the clinical DDI study of dipyridamole with famotidine, which significantly reduced the Cmax and area under the curve. An In situ mouse infusion study combined with GIS revealed that high concentration of dipyridamole in the GIS enhanced oral drug absorption, which confirmed the supersaturation of dipyridamole. In conclusion, GIS was shown to be a useful apparatus to predict in vivo dissolution for BCS class IIb drugs.

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.

Formulation and optimization of mouth dissolve tablets containing rofecoxib solid dispersion.

PubMed

Sammour, Omaima A; Hammad, Mohammed A; Megrab, Nagia A; Zidan, Ahmed S

2006-06-16

The purpose of the present investigation was to increase the solubility and dissolution rate of rofecoxib by the preparation of its solid dispersion with polyvinyl pyrrolidone K30 (PVP K30) using solvent evaporation method. Drug-polymer interactions were investigated using differential scanning calorimetry (DSC), x-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). For the preparation of rofecoxib mouth dissolve tablets, its 1:9 solid dispersion with PVP K30 was used with various disintegrants and sublimable materials. In an attempt to construct a statistical model for the prediction of disintegration time and percentage friability, a 3(2) randomized full and reduced factorial design was used to optimize the influence of the amounts of superdisintegrant and subliming agent. The obtained results showed that dispersion of the drug in the polymer considerably enhanced the dissolution rate. The drug-to-carrier ratio was the controlling factor for dissolution improvement. FTIR spectra revealed no chemical incompatibility between the drug and PVP K30. As indicated from XRD and DSC data, rofecoxib was in the amorphous form, which explains the better dissolution rate of the drug from its solid dispersions. Concerning the optimization study, the multiple regression analysis revealed that an optimum concentration of camphor and a higher percentage of crospovidone are required for obtaining rapidly disintegrating tablets. In conclusion, this investigation demonstrated the potential of experimental design in understanding the effect of the formulation variables on the quality of mouth dissolve tablets containing solid dispersion of a hydrophobic drug.

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.

Determination of the carbonate dissolution mechanism of Lactococcus sp.

NASA Astrophysics Data System (ADS)

Yanmiş, Derya; Orhan, Furkan; Güllüce, Medine; Şahin, Fikrettin

2017-04-01

Magnesite, the main source for magnesium and magnesium derivatives, are also commonly used in the production of caustic, dead-burned and fused magnesia. World magnesite resources are estimated to be at 12 billion tonnes mostly located in China, Russia, North Korea, Australia and Turkey. Turkey is the second producer of the magnesite. Magnesite deposits in Turkey are sedimentary magnesite which have been formed in specific conditions as high concentrations of MgSO4 and CO2 and presence of certain organic salts or created by hot or cold dissolution connected with carbonate rocks mainly with dolomites. According to the genesis of magnesite deposits, they have some impurities as calcium, quartz, iron, etc. Impurities of magnesite, especially CaCO3, reduce its economic value and industrial usability. In our previous study, we have performed biotechnologically enrichment of magnesite by Lactococcus sp., which gave significantly important results. However, we had no information about carbonate dissolution mechanism of bacteria. Therefore, it is aimed to reveal the metabolites of Lactococcus sp. and mechanism leading to the carbonate dissolution (MgCO3 and CaCO3).

Optimized microemulsions and solid microemulsion systems of simvastatin: characterization and in vivo evaluation.

PubMed

Dixit, Rahul P; Nagarsenker, Mangal S

2010-12-01

The study describes development of solid microemulsions (SME) for improved delivery of simvastatin (SMV). Pseudo-ternary phase diagrams were constructed and MEs were optimized for oil and drug content. SMEs were prepared using colloidal silicon dioxide to adsorb the liquid ME. MEs were characterized for mean globule size in aqueous medium and the SMEs were evaluated for powder characteristics, mean globule size after dilution with water, dissolution profile and for in vivo efficacy in rats. X-ray diffraction studies indicated complete amorphization and/or solubilization of SMV in the SMEs. It was supported by scanning electronic microscopic studies, which did not show evidence of precipitation of the drug on the surface of the carrier. Dissolution studies revealed remarkable increase in dissolution of the drug as compared to plain drug. All the formulations provided significant reduction in the total cholesterol levels in hyperlipidemic rats with reference to rats of control group (p < 0.05). The proposed SMEs have potential to deliver water insoluble drugs like SMV by oral route for better efficacy. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association

Imidazole-based deep eutectic solvents for starch dissolution and plasticization.

PubMed

Zdanowicz, Magdalena; Spychaj, Tadeusz; Mąka, Honorata

2016-04-20

Potato starch and high-amylose starch were treated with imidazole-based deep eutectic solvents (DESs) as dissolution and plasticization media. Beside imidazole (IM) for two-component DESs preparation choline chloride (CC), glycerol (G) or carboxylic acids (citric or malic) were used. An influence of water content in starch (as well as an extra water in the starch/DES system) on polymer dissolution and plasticization processes was investigated. Dissolution and gelatinization of starch in DESs were followed via DSC and laser scanning microscopy. A rheometric characteristics revealed an influence of starch/DES system storage time on the plasticization process. The tendency to recrystallization of compression-molded-starch films was evaluated using XRD technique. High dissolution and plasticization effectiveness of CC/IM and G/IM and a low tendency to film retrogradation of thermoplasticized starch were noted. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dissolution and fractionation of nut shells in ionic liquids.

PubMed

Carneiro, Aristides P; Rodríguez, Oscar; Macedo, Eugénia A

2017-03-01

The aim of this work was to study the dissolution of raw peanut and chestnut shells in ionic liquids. Dissolution of raw biomass up to 7wt% was achieved under optimized operatory conditions. Quantification of polysaccharides dissolved through quantitative 13 Cq NMR revealed extractions of the cellulosic material to ionic liquids as high as 87%. Regeneration experiments using an antisolvent mixture allowed to recover the cellulosic material and the ionic liquid. The overall mass balance presented very low loss rates (<8%), recoveries of 75% and 95% of cellulosic material from peanut and chestnut shells, respectively, and the recovery of more than 95% of the ionic liquid in both cases. These results show the high potential of using nut shells and ionic liquids for biorefining purposes. Moreover, high recovery of ionic liquids favors the process from an economical point of view. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dissolution of covalent adaptable network polymers in organic solvent

NASA Astrophysics Data System (ADS)

Yu, Kai; Yang, Hua; Dao, Binh H.; Shi, Qian; Yakacki, Christopher M.

2017-12-01

It was recently reported that thermosetting polymers can be fully dissolved in a proper organic solvent utilizing a bond-exchange reaction (BER), where small molecules diffuse into the polymer, break the long polymer chains into short segments, and eventually dissolve the network when sufficient solvent is provided. The solvent-assisted dissolution approach was applied to fully recycle thermosets and their fiber composites. This paper presents the first multi-scale modeling framework to predict the dissolution kinetics and mechanics of thermosets in organic solvent. The model connects the micro-scale network dynamics with macro-scale material properties: in the micro-scale, a model is developed based on the kinetics of BERs to describe the cleavage rate of polymer chains and evolution of chain segment length during the dissolution. The micro-scale model is then fed into a continuum-level model with considerations of the transportation of solvent molecules and chain segments in the system. The model shows good prediction on conversion rate of functional groups, degradation of network mechanical properties, and dissolution rate of thermosets during the dissolution. It identifies the underlying kinetic factors governing the dissolution process, and reveals the influence of different material and processing variables on the dissolution process, such as time, temperature, catalyst concentration, and chain length between cross-links.

Evaluation of dissolution profile similarity - Comparison between the f2, the multivariate statistical distance and the f2 bootstrapping methods.

PubMed

Paixão, Paulo; Gouveia, Luís F; Silva, Nuno; Morais, José A G

2017-03-01

A simulation study is presented, evaluating the performance of the f 2 , the model-independent multivariate statistical distance and the f 2 bootstrap methods in the ability to conclude similarity between two dissolution profiles. Different dissolution profiles, based on the Noyes-Whitney equation and ranging from theoretical f 2 values between 100 and 40, were simulated. Variability was introduced in the dissolution model parameters in an increasing order, ranging from a situation complying with the European guidelines requirements for the use of the f 2 metric to several situations where the f 2 metric could not be used anymore. Results have shown that the f 2 is an acceptable metric when used according to the regulatory requirements, but loses its applicability when variability increases. The multivariate statistical distance presented contradictory results in several of the simulation scenarios, which makes it an unreliable metric for dissolution profile comparisons. The bootstrap f 2 , although conservative in its conclusions is an alternative suitable method. Overall, as variability increases, all of the discussed methods reveal problems that can only be solved by increasing the number of dosage form units used in the comparison, which is usually not practical or feasible. Additionally, experimental corrective measures may be undertaken in order to reduce the overall variability, particularly when it is shown that it is mainly due to the dissolution assessment instead of being intrinsic to the dosage form. Copyright © 2016. Published by Elsevier B.V.

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

Preparation of amorphous solid dispersions by rotary evaporation and KinetiSol Dispersing: approaches to enhance solubility of a poorly water-soluble gum extract.

PubMed

Bennett, Ryan C; Brough, Chris; Miller, Dave A; O'Donnell, Kevin P; Keen, Justin M; Hughey, Justin R; Williams, Robert O; McGinity, James W

2015-03-01

Acetyl-11-keto-β-boswellic acid (AKBA), a gum resin extract, possesses poor water-solubility that limits bioavailability and a high melting point making it difficult to successfully process into solid dispersions by fusion methods. The purpose of this study was to investigate solvent and thermal processing techniques for the preparation of amorphous solid dispersions (ASDs) exhibiting enhanced solubility, dissolution rates and bioavailability. Solid dispersions were successfully produced by rotary evaporation (RE) and KinetiSol® Dispersing (KSD). Solid state and chemical characterization revealed that ASD with good potency and purity were produced by both RE and KSD. Results of the RE studies demonstrated that AQOAT®-LF, AQOAT®-MF, Eudragit® L100-55 and Soluplus with the incorporation of dioctyl sulfosuccinate sodium provided substantial solubility enhancement. Non-sink dissolution analysis showed enhanced dissolution properties for KSD-processed solid dispersions in comparison to RE-processed solid dispersions. Variances in release performance were identified when different particle size fractions of KSD samples were analyzed. Selected RE samples varying in particle surface morphologies were placed under storage and exhibited crystalline growth following solid-state stability analysis at 12 months in comparison to stored KSD samples confirming amorphous instability for RE products. In vivo analysis of KSD-processed solid dispersions revealed significantly enhanced AKBA absorption in comparison to the neat, active substance.

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.

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.

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.

Development and characterisation of semi-crystalline composite granules: The effect of particle chemistry and the electrostatic charging

NASA Astrophysics Data System (ADS)

Haque, Syed N.; Hussain, Tariq; Chowdhry, Babur Z.; Douroumis, Dennis; Scoutaris, Nikolaos; Nokhodchi, Ali; Maniruzzaman, Mohammed

2017-12-01

This study investigated the surface of semi-crystalline composite granules produced via a novel mechano-chemical process and assessed the effect of electrostatic charging. Ibuprofen (IBU), a model drug with low solubility and known associated processing challenges was loaded in composite granules to improve its processibility and dissolution rates. Synthetic amorphous mesoporous magnesium alumina metasilicate (MAS) was co-processed with hydrophilic HPMC polymer in the presence of polyethylene glycol 2000 (PEG) and deionised water. The solid state analyses conducted by scanning electron microscopy (SEM), X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) revealed the existence of semi-crystalline IBU in the complex composite structures. Dynamic vapour sorption (DVS) study showed the water sorption and desorption profiles of the manufactured composite granules as well as the effect of water on the solid-state stability of IBU in various formulations. Advanced surface analysis conducted via energy dispersive X-ray (EDS) revealed homogenous distribution of the drug/excipients on the surface of the granules while atomic force microscopy (AFM) complemented the findings. The electrostatic charge analysis showed variable charge property which is affected by the size of the particles/granules. As expected, the in vitro dissolution study showed about 5 fold increase in the release rates of IBU compared to that of the bulk drug. The mechanochemical processing has been demonstrated as an efficient technique to develop semi-crystalline composite granules with enhanced dissolution rates of water insoluble drugs.

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.

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.

Development of spray-dried co-precipitate of amorphous celecoxib containing storage and compression stabilizers.

PubMed

Dhumal, Ravindra S; Shimpi, Shamkant L; Paradkar, Anant R

2007-09-01

The purpose of this study was to obtain an amorphous system with minimum unit operations that will prevent recrystallization of amorphous drugs since preparation, during processing (compression) and further storage. Amorphous celecoxib, solid dispersion (SD) of celecoxib with polyvinyl pyrrollidone (PVP) and co-precipitate with PVP and carrageenan (CAR) in different ratios were prepared by the spray drying technique and compressed into tablets. Saturation solubility and dissolution studies were performed to differentiate performance after processing. Differential scanning calorimetry and X-ray powder difraction revealed the amorphous form of celecoxib, whereas infrared spectroscopy revealed hydrogen bonding between celecoxib and PVP. The dissolution profile of the solid dispersion and co-precipitate improved compared to celecoxib and amorphous celecoxib. Amorphous celecoxib was not stable on storage whereas the solid dispersion and co-precipitate powders were stable for 3 months. Tablets of the solid dispersion of celecoxib with PVP and physical mixture with PVP and carrageenan showed better resistance to recrystallization than amorphous celecoxib during compression but recrystallized on storage. However, tablets of co-precipitate with PVP and carageenan showed no evidence of crystallinity during stability studies with comparable dissolution profiles. This extraordinary stability of spray-dried co-precipitate tablets may be attributed to the cushioning action provided by the viscoelastic polymer CAR and hydrogen bonding interaction between celecoxib and PVP. The present study demonstrates the synergistic effect of combining two types of stabilizers, PVP and CAR, on the stability of amorphous drug during compression and storage as compared to their effect when used alone.

Physical stability of micronized powders produced by spray-freezing into liquid (SFL) to enhance the dissolution of an insoluble drug.

PubMed

Rogers, True L; Johnston, Keith P; Williams, Robert O

2003-01-01

The objective of this study was to investigate the physical stability of micronized powders produced by the spray-freezing into liquid (SFL) particle engineeringtechnology. Danazol was formulated with polyvinyl alcohol (MW 22,000), poloxamer 407, and polyvinylpyrrolidone K-15 to form a cosolvent solution that was SFL processed. The dried micronized SFL powders were sealed in glass vials with desiccant and exposed to 25 degrees C/60% RH for 3 and 6 mo, 40 degrees C/75% RH for 1, 2, 3, and 6 mo, and conditions where the temperature was cycled between -5 and +40 degrees C (6 cycles/24 hr) with constant 75% RH for 1, 2, 3 and 4 wk. The samples were characterized by using Karl-Fisher titration, differential scanning calorimetry, x-ray diffraction, specific surface area, scanning electron microscopy, and dissolution testing. Micronized SFL powders consisting of porous aggregates with small-particle domains were characterized as having high surface areas and consisted of amorphous danazol embedded within a hydrophilic excipient matrix. Karl-Fischer titration revealed no moisture absorption over the duration of the stability studies. Differential scanning calorimetry studies demonstrated high degrees of molecular interactions between danazol, PVA, poloxamer, and PVP. Scanning electron microscopy studies confirmed these interactions, especially those between danazol and poloxamer. These interactions facilitated API dissolution in the aqueous media. Powder surface area remained constant during storage at the various stability conditions, and danazol recrystallization did not occur during the entirety of the stability studies. Micronized SFL powders containing danazol dissolved rapidly and completely within 5 min in aqueous media. No differences were observed in the enhanced dissolution profiles of danazol after exposure to the storage conditions investigated. Physically stable micronized powders produced by the SFL particle engineering technology were produced for the purpose of enhancing the dissolution of an insoluble drug. The potential of the SFL particle-engineering technology as a micronization technique for enhancing the dissolution of hydrophobic drugs was demonstrated in this study. The robustness of the micronized SFL powders to withstand stressed storage conditions was shown.

Morphological evolution of dissolving feldspar particles with anisotropic surface kinetics and implications for dissolution rate normalization and grain size dependence: A kinetic modeling study

NASA Astrophysics Data System (ADS)

Zhang, Li; Lüttge, Andreas

2009-11-01

With previous two-dimensional (2D) simulations based on surface-specific feldspar dissolution succeeding in relating the macroscopic feldspar kinetics to the molecular-scale surface reactions of Si and Al atoms ( Zhang and Lüttge, 2008, 2009), we extended our modeling effort to three-dimensional (3D) feldspar particle dissolution simulations. Bearing on the same theoretical basis, the 3D feldspar particle dissolution simulations have verified the anisotropic surface kinetics observed in the 2D surface-specific simulations. The combined effect of saturation state, pH, and temperature on the surface kinetics anisotropy has been subsequently evaluated, found offering diverse options for morphological evolution of dissolving feldspar nanoparticles with varying grain sizes and starting shapes. Among the three primary faces on the simulated feldspar surface, the (1 0 0) face has the biggest dissolution rate across an extensively wide saturation state range and thus acquires a higher percentage of the surface area upon dissolution. The slowest dissolution occurs to either (0 0 1) or (0 1 0) faces depending on the bond energies of Si-(O)-Si ( ΦSi-O-Si/ kT) and Al-(O)-Si ( ΦAl-O-Si/ kT). When the ratio of ΦSi-O-Si/ kT to ΦAl-O-Si/ kT changes from 6:3 to 7:5, the dissolution rates of three primary faces change from the trend of (1 0 0) > (0 1 0) > (0 0 1) to the trend of (1 0 0) > (0 0 1) > (0 1 0). The rate difference between faces becomes more distinct and accordingly edge rounding becomes more significant. Feldspar nanoparticles also experience an increasing degree of edge rounding from far-from-equilibrium to close-to-equilibrium. Furthermore, we assessed the connection between the continuous morphological modification and the variation in the bulk dissolution rate during the dissolution of a single feldspar particle. Different normalization treatments equivalent to the commonly used mass, cube assumption, sphere assumption, geometric surface area, and reactive surface area normalizations have been used to normalize the bulk dissolution rate. For each of the treatments, time consistence and grain size dependence of the normalized dissolution rate have been evaluated and the results revealed significant dependences on the magnitude of surface kinetic anisotropy under differing environmental conditions. In general, the normalized dissolution rates are strongly dependent on grain size. Time-consistent normalization treatment varies with the investigated condition. The modeling results suggest that the sphere-, cube-, and BET-normalized dissolution rates are appropriate under the far-from-equilibrium conditions at low pH where these normalizations are time-consistent and are slightly dependent on grain size.

Pore-scale supercritical CO2 dissolution and mass transfer under imbibition conditions

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

Chang, Chun; Zhou, Quanlin; Kneafsey, Timothy J.

2016-06-01

In modeling of geological carbon storage, dissolution of supercritical CO2 (scCO2) is often assumed to be instantaneous with equilibrium phase partitioning. In contrast, recent core-scale imbibition experiments have shown a prolonged depletion of residual scCO2 by dissolution, implying a non-equilibrium mechanism. In this study, eight pore-scale scCO2 dissolution experiments in a 2D heterogeneous, sandstone-analogue micromodel were conducted at supercritical conditions (9 MPa and 40 °C). The micromodel was first saturated with deionized (DI) water and drained by injecting scCO2 to establish a stable scCO2 saturation. DI water was then injected at constant flow rates after scCO2 drainage was completed. Highmore » resolution time-lapse images of scCO2 and water distributions were obtained during imbibition and dissolution, aided by a scCO2-soluble fluorescent dye introduced with scCO2 during drainage. These images were used to estimate scCO2 saturations and scCO2 depletion rates. Experimental results show that (1) a time-independent, varying number of water-flow channels are created during imbibition and later dominant dissolution by the random nature of water flow at the micromodel inlet, and (2) a time-dependent number of water-flow channels are created by coupled imbibition and dissolution following completion of dominant imbibition. The number of water-flow paths, constant or transient in nature, greatly affects the overall depletion rate of scCO2 by dissolution. The average mass fraction of dissolved CO2 (dsCO2) in water effluent varies from 0.38% to 2.72% of CO2 solubility, indicating non-equilibrium scCO2 dissolution in the millimeter-scale pore network. In general, the transient depletion rate decreases as trapped, discontinuous scCO2 bubbles and clusters within water-flow paths dissolve, then remains low with dissolution of large bypassed scCO2 clusters at their interfaces with longitudinal water flow, and finally increases with coupled transverse water flow and enhanced dissolution of large scCO2 clusters. The three stages of scCO2 depletion, common to experiments with time-independent water-flow paths, are revealed by zoom-in image analysis of individual scCO2 bubbles and clusters. The measured relative permeability of water, affected by scCO2 dissolution and bi-modal permeability, shows a non-monotonic dependence on saturation. The results for experiments with different injection rates imply that the non-equilibrium nature of scCO2 dissolution becomes less important when water flow is relatively low and the time scale for dissolution is large, and more pronounced when heterogeneity is strong.« less

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.

A silica-supported solid dispersion of bifendate using supercritical carbon dioxide method with enhanced dissolution rate and oral bioavailability.

PubMed

Cai, Cuifang; Liu, Muhua; Li, Yun; Guo, Bei; Chang, Hui; Zhang, Xiangrong; Yang, Xiaoxu; Zhang, Tianhong

2016-01-01

In this study, to enhance the dissolution rate and oral bioavailability of bifendate, a silica-supported solid dispersion (SD) of bifendate was prepared using supercritical carbon dioxide (ScCO2) technology. The properties of bifendate-silica SD were characterized by differential scanning calorimetry (DSC), X-ray diffraction (X-RD) and scanning electron microscopy. The pharmacokinetic study was carried out in beagle dogs using commercial bifendate dropping pills as a reference which is a conventional SD formulation of bifendate and PEG6000. A novel method of Ultra Performance Convergence Chromatography-tandem mass spectrometry (UPC(2)™-MS/MS) method was applied to determine bifendate concentration in plasma. The amorphous state of bifendate in bifendate-silica SD was revealed in X-RD and DSC when the ratios of bifendate and silica were 1:15 and 1:19, respectively. In vitro dissolution rate was significantly improved with cumulative release of 67% within 20 min relative to 8% for the physical mixture of bifendate and silica, and which was also higher than the commercial dropping pill of 52%. After storage at 75% relative humidity (RH) for 10 d, no recrystallization was found and reduced dissolution rate was obtained due to the absorption of moisture. In pharmacokinetic study, Cmax and AUC0-t for bifendate-silica SD were 153.1 ng/ml and 979.8 ng h/ml, respectively. AUC0-t of bifendate-silica SDs was ∼1.6-fold higher than that of the commercial dropping pills. These results suggest that adsorbing bifendate onto porous silica via ScCO2 technique could be a feasible method to enhance oral bioavailability together with a higher dissolution rate.

Improving the dissolution and bioavailability of 6-mercaptopurine via co-crystallization with isonicotinamide.

PubMed

Wang, Jian-Rong; Yu, Xueping; Zhou, Chun; Lin, Yunfei; Chen, Chen; Pan, Guoyu; Mei, Xuefeng

2015-03-01

6-Mercaptopurine (6-MP) is a clinically important antitumor drug. The commercially available form was provided as monohydrate and belongs to BCS class II category. Co-crystallization screening by reaction crystallization method (RCM) and monitored by powder X-ray diffraction led to the discovery of a new co-crystal formed between 6-MP and isonicotinamide (co-crystal 1). Co-crystal 1 was thoroughly characterized by X-ray diffraction, FT-IR and Raman spectroscopy, and thermal analysis. Noticeably, the in vitro and in vivo studies revealed that co-crystal 1 possesses improved dissolution rate and superior bioavailability on animal model. Copyright © 2015 Elsevier Ltd. All rights reserved.

Kinetics of brucite dissolution at 25°C in the presence of organic and inorganic ligands and divalent metals

NASA Astrophysics Data System (ADS)

Pokrovsky, Oleg S.; Schott, Jacques; Castillo, Alain

2005-02-01

Brucite (Mg(OH) 2) dissolution rate was measured at 25°C in a mixed-flow reactor at various pH (5 to 11) and ionic strengths (0.01 to 0.03 M) as a function of the concentration of 15 organic and 5 inorganic ligands and 8 divalent metals. At neutral and weakly alkaline pH, the dissolution is promoted by the addition of the following ligands ranked by decreasing effectiveness: EDTA ≥ H 2PO 4- > catechol ≥ HCO 3- > ascorbate > citrate > oxalate > acetate ˜ lactate and it is inhibited by boric acid. At pH >10.5, it decreases in the presence of PO 43-, CO 32-, F -, oxine, salicylate, lactate, acetate, 4-hydroxybenzoate, SO 42- and B(OH) 4- with orthophosphate and borate being the strongest and the weakest inhibitor, respectively. Xylose (up to 0.1 M), glycine (up to 0.05 M), formate (up to 0.3 M) and fulvic and humic acids (up to 40 mg/L DOC) have no effect on brucite dissolution kinetics. Fluorine inhibits dissolution both in neutral and alkaline solutions. From F sorption experiments in batch and flow-through reactors and the analysis of reacted surfaces using X-ray Photoelectron Spectroscopy (XPS), it is shown that fluorine adsorption is followed by its incorporation in brucite lattice likely via isomorphic substitution with OH. The effect of eight divalent metals (Sr, Ba, Ca, Pb, Mn, Fe, Co and Ni) studied at pH 4.9 and 0.01 M concentration revealed brucite dissolution rates to be correlated with the water molecule exchange rates in the first hydration sphere of the corresponding cation. The effect of investigated ligands on brucite dissolution rate can be modelled within the framework of the surface coordination approach taking into account the adsorption of ligands on dissolution-active sites and the molecular structure of the surface complexes they form. The higher the value of the ligand sorption constant, the stronger will be its catalyzing or inhibiting effect. As for Fe and Al oxides, bi- or multidentate mononuclear surface complexes, that labilize Mg-O bonds and water coordination to Mg atoms at the surface, enhance brucite dissolution whereas bi- or polynuclear surface complexes tend to inhibit dissolution by bridging two or more metal centers and extending the cross-linking at the solid surface. Overall, results of this study demonstrate that very high concentrations of organic ligands (0.01-0.1 M) are necessary to enhance or inhibit brucite dissolution. As a result, the effect of extracellular organic products on the weathering rate of Mg-bearing minerals is expected to be weak.

Unraveling the Effect of Thermomechanical Treatment on the Dissolution of Delta Ferrite in Austenitic Stainless Steels

NASA Astrophysics Data System (ADS)

Rezayat, Mohammad; Mirzadeh, Hamed; Namdar, Masih; Parsa, Mohammad Habibi

2016-02-01

Considering the detrimental effects of delta ferrite stringers in austenitic stainless steels and the industrial considerations regarding energy consumption, investigating, and optimizing the kinetics of delta ferrite removal is of vital importance. In the current study, a model alloy prone to the formation of austenite/delta ferrite dual phase microstructure was subjected to thermomechanical treatment using the wedge rolling test aiming to dissolve delta ferrite. The effect of introducing lattice defects and occurrence of dynamic recrystallization (DRX) were investigated. It was revealed that pipe diffusion is responsible for delta ferrite removal during thermomechanical process, whereas when the DRX is dominant, the kinetics of delta ferrite dissolution tends toward that of the static homogenization treatment for delta ferrite removal that is based on the lattice diffusion of Cr and Ni in austenite. It was concluded that the optimum condition for dissolution of delta ferrite can be defined by the highest rolling temperature and strain in which DRX is not pronounced.

Formulation of ternary complexes of glyburide with hydroxypropyl-β-cyclodextrin and other solubilizing agents and their effect on release behavior of glyburide in aqueous and buffered media at different agitation speeds.

PubMed

Singh, Sachin Kumar; Srinivasan, K K; Singare, Dhananjay S; Gowthamarajan, K; Prakash, Dev

2012-11-01

Glyburide, a sulfonylurea derivative, widely used as hypoglycaemic agent. In the present study, an attempt has been made to investigate the most effective third component which can be used with hydroxylpropyl-β-cyclodextrin (HPβCd) to form a ternary complex with glyburide in order to enhance its dissolution rate, as well as reduce the amount of HPβCd used for formulating the binary complex with glyburide. Moreover, the objective of this study was also to develop a discriminatory dissolution media in order to discriminate the effect of the different solubilizing agents used for formulating the ternary complex system. Sodium lauryl sulphate, Poloxamer-188, Polyvinylpyrrolidone K-30, lactose and L-arginine were used to formulate ternary system along with HPβCd and glyburide. The ternary system formulated with glyburide:HPβCd:L-arginine in a proportion of 1:1:0.5 has shown the fastest dissolution rate when compared to other solubilizing agents. Unbuffered aqueous media with stirring speed 50 rpm has produced the most discriminatory dissolution profiles. The DSC thermograms and the powder X-ray analysis revealed the decrease in crystallinity of the drug. This was an indication of amorphous solid dispersion or molecular encapsulation of the drug into the cyclodextrin cavity.

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.

Hypogenic speleogenesis in quartzite: The case of Corona 'e Sa Craba Cave (SW Sardinia, Italy)

NASA Astrophysics Data System (ADS)

Sauro, Francesco; De Waele, Jo; Onac, Bogdan P.; Galli, Ermanno; Dublyansky, Yuri; Baldoni, Eleonora; Sanna, Laura

2014-04-01

The paper presents a detailed study demonstrating the hypogenic origin of the Corona 'e Sa Craba quartzite cave in SW Sardinia (Italy). Although the quartzite host-rock of this cave derived from silicification of Cambrian dolostones and dissolution of carbonate remnants could have had a role in the speleogenesis, detailed morphologic and petrographic investigation revealed clear evidence of quartz dissolution without signs of mechanical erosion by running waters. Thin section microscopy and scanning electron microscope (SEM) images show pervasive dissolution morphologies, such as pits and notches on quartz crystals causing the deep arenization of the cave walls, suggesting that the dissolution of quartz had a primary role in the formation of the void. The study of secondary cave minerals and the sulfur isotopic composition of sulfates and sulfides, coupled with data on fluid inclusions, allowed reconstruction of the peculiar speleogenetic history of this hypogenic hydrothermal quartzite cave. The cave formed by reduced hydrothermal fluids, probably under basic-neutral pH in phreatic conditions. The presence of abundant cations of Ba2 + in reduced Cl-rich fluids enhanced the quartz dissolution rate, allowing the formation of the voids in deep settings. During the Late Oligocene uplift of the area, the hydrothermal fluids in the cave reached oxygen-rich conditions, thus a minerogenetic phase started with the deposition of barite when the temperature of the fluid was ≤ 50 °C. The presence of cinnabar crusts in the lower part of the cave walls and on the boulders suggests a later volcanic phase with Hg-rich vapors ascending from below. Other minerals such as alunite, basaluminite, gypsum and halloysite (typical of an acid sulfate alteration environment), and phosphates were formed in a final, much more recent stage. The δ34S values of the cave sulfate minerals indicate that S is derived from the remobilization of original Precambrian Pb-Zn Mississippi Valley Type ores. These last two stages did not significantly affect the morphology of the cave. The Corona 'e Sa Craba appears to be the world's first example of a hypogenic cave in quartzite where the speleogenetic mechanisms have been studied and reconstructed in detail, using a variety of modern methods. This study confirms that dissolution of quartz by thermal alkaline fluids at depth can produce large dissolutional voids in the apparently poorly soluble quartzite rocks.

Development of Multiple-Unit Floating Drug Delivery System of Clarithromycin: Formulation, in vitro Dissolution by Modified Dissolution Apparatus, in vivo Radiographic Studies in Human Volunteers.

PubMed

Reddy, Arun B; Reddy, Narendar D

2017-07-01

Clarithromycin (CM), a broad spectrum macrolide antibiotic used to eradicate H. pylori in peptic ulcer. Clarithromycin (CM) is well absorbed from the gastrointestinal tract, but has a bioavailability of 50% due to rapid biodegradation. The aim of this investigation was to increase the gastric residence time, and to control the drug release of clarithromycin by formulating into multiple unit floating mini-tablets. Floating tablets were prepared by using direct compression method with HPMC K 4 M and Polyox WSR 1105 as release retarded polymers and sodium bicarbonate as gas generating agent. The prepared mini-tablets were evaluated for thickness, weight variation, friability, hardness, drug content, in vitro buoyancy, swelling studies, in vitro dissolution studies by using modified Rossett-Rice test and in vivo radiographic studies in healthy human volunteers in fasting conditions. DSC analysis revealed that no interaction between drug and excipients. All the physical parameters of the tablets were within the acceptable limits. The optimized formulation (F6) had showed controlled drug release of 99.16±3.22% in 12 h, by zero-order release kinetics, along with floating lag time of 9.5±1.28 s and total floating time of 12±0.14 h. X-ray imaging studies revealed that in vivo gastric residence time of clarithromycin floating mini-tablet in the stomach was about 3.5 h. The results demonstrated that the developed floating mini-tablets of clarithromycin caused significant enhancement in gastric retention time along with sustained effect and increased oral bioavailability. © Georg Thieme Verlag KG Stuttgart · New York.

Impacts of seawater saturation state (ΩA = 0.4-4.6) and temperature (10, 25 °C) on the dissolution kinetics of whole-shell biogenic carbonates

NASA Astrophysics Data System (ADS)

Ries, Justin B.; Ghazaleh, Maite N.; Connolly, Brian; Westfield, Isaac; Castillo, Karl D.

2016-11-01

Anthropogenic increase of atmospheric pCO2 since the Industrial Revolution has caused seawater pH to decrease and seawater temperatures to increase-trends that are expected to continue into the foreseeable future. Myriad experimental studies have investigated the impacts of ocean acidification and warming on marine calcifiers' ability to build protective shells and skeletons. No studies, however, have investigated the combined impacts of ocean acidification and warming on the whole-shell dissolution kinetics of biogenic carbonates. Here, we present the results of experiments designed to investigate the effects of seawater saturation state (ΩA = 0.4-4.6) and temperature (10, 25 °C) on gross rates of whole-shell dissolution for ten species of benthic marine calcifiers: the oyster Crassostrea virginica, the ivory barnacle Balanus eburneus, the blue mussel Mytilus edulis, the conch Strombus alatus, the tropical coral Siderastrea siderea, the temperate coral Oculina arbuscula, the hard clam Mercenaria mercenaria, the soft clam Mya arenaria, the branching bryozoan Schizoporella errata, and the coralline red alga Neogoniolithon sp. These experiments confirm that dissolution rates of whole-shell biogenic carbonates decrease with calcium carbonate (CaCO3) saturation state, increase with temperature, and vary predictably with respect to the relative solubility of the calcifiers' polymorph mineralogy [high-Mg calcite (mol% Mg > 4) ≥ aragonite > low-Mg calcite (mol% Mg < 4)], consistent with prior studies on sedimentary and inorganic carbonates. Furthermore, the severity of the temperature effects on gross dissolution rates also varied with respect to carbonate polymorph solubility, with warming (10-25 °C) exerting the greatest effect on biogenic high-Mg calcite, an intermediate effect on biogenic aragonite, and the least effect on biogenic low-Mg calcite. These results indicate that both ocean acidification and warming will lead to increased dissolution of biogenic carbonates in future oceans, with shells/skeletons composed of the more soluble polymorphs of CaCO3 being the most vulnerable to these stressors. The effects of saturation state and temperature on gross shell dissolution rate were modeled with an exponential asymptotic function (y =B0 -B2 ·e B1 Ω) that appeals to the general Arrhenius-derived rate equation for mineral dissolution [ r = (C ·e -Ea / RT) (1 - Ω)n]. Although the dissolution curves for the investigated biogenic CaCO3 exhibited exponential asymptotic trends similar to those of inorganic CaCO3, the observation that gross dissolution of whole-shell biogenic CaCO3 occurred (albeit at lower rates) even in treatments that were oversaturated (Ω > 1) with respect to both aragonite and calcite reveals fundamental differences between the dissolution kinetics of whole-shell biogenic CaCO3 and inorganic CaCO3. Thus, applying stoichiometric solubility products derived for inorganic CaCO3 to model gross dissolution of biogenic carbonates may substantially underestimate the impacts of ocean acidification on net calcification (gross calcification minus gross dissolution) of systems ranging in scale from individual organisms to entire ecosystems (e.g., net ecosystem calcification). Finally, these experiments permit rough estimation of the impact of CO2-induced ocean acidification on the gross calcification rates of various marine calcifiers, calculated as the difference between net calcification rates derived empirically in prior studies and gross dissolution rates derived from the present study. Organisms' gross calcification responses to acidification were generally less severe than their net calcification response patterns, with aragonite mollusks (bivalves, gastropods) exhibiting the most negative gross calcification response to acidification, and photosynthesizing organisms, including corals and coralline red algae, exhibiting relative resilience.

Trace elements geochemistry of fractured basement aquifer in southern Malawi: A case of Blantyre rural

NASA Astrophysics Data System (ADS)

Mapoma, Harold Wilson Tumwitike; Xie, Xianjun; Nyirenda, Mathews Tananga; Zhang, Liping; Kaonga, Chikumbusko Chiziwa; Mbewe, Rex

2017-07-01

In this study, twenty one (21) trace elements in the basement complex groundwater of Blantyre district, Malawi were analyzed. The majority of the analyzed trace elements in the water were within the standards set by World Health Organization (WHO) and Malawi Standards Board (MSB). But, iron (Fe) (BH16 and 21), manganese (Mn) (BH01) and selenium (Se) (BH02, 13, 18, 19 and 20) were higher than the WHO and MSB standards. Factor analysis (FA) revealed up to five significant factors which accounted for 87.4% of the variance. Factor 1, 2 and 3 suggest evaporite dissolution and silicate weathering processes while the fourth factor may explain carbonate dissolution and pH influence on trace element geochemistry of the studied groundwater samples. According to PHREEQC computed saturation indices, dissolution, precipitation and rock-water-interaction control the levels of trace elements in this aquifer. Elevated concentrations of Fe, Mn and Se in certain boreholes are due to the geology of the aquifer and probable redox status of groundwater. From PHREEQC speciation results, variations in trace element species were observed. Based on this study, boreholes need constant monitoring and assessment for human consumption to avoid health related issues.

Development of self-nanoemulsifying drug delivery system for oral bioavailability enhancement of valsartan in beagle dogs.

PubMed

Li, Zhenbao; Zhang, Wenjuan; Gao, Yan; Xiang, Rongwu; Liu, Yan; Hu, Mingming; Zhou, Mei; Liu, Xiaohong; Wang, Yongjun; He, Zhonggui; Sun, Yinghua; Sun, Jin

2017-02-01

Valsartan, an angiotensin II receptor antagonist, is widely used to treat high blood pressure in the clinical setting. However, its poor water solubility results in the low oral bioavailability. The aim of this study was to improve dissolution rate and oral bioavailability by developing a self-nanoemulsifying drug delivery system. Saturation solubility of valsartan in various oils, surfactants, and cosurfactants was investigated, and the optimized formulation was determined by central composite design-response surface methodology. The shape of resultant VAL-SNEDDS was spherical with an average diameter of about 27 nm. And the drug loading efficiency is approximately 14 wt%. Differential scanning calorimetry and XRD studies disclosed the molecular or amorphous state of valsartan in VAL-SNEDDS. The dissolution study indicated that the self-nanoemulsifying drug delivery systems (SNEDDS) exhibited significantly enhanced dissolution compared with market capsules (Diovan®) in various media. Furthermore, the stability of formulation revealed that valsartan SNEDDS was stable under low temperature and accelerated test condition. Furthermore, the pharmacokinetics demonstrated that C max and AUC (0-∞) of SNEDDS capsules were about three- and twofold higher than Diovan® in beagle dogs, respectively. Meanwhile, the safety evaluation implied that VAL-SNEDDS was innocuous to beagle dogs during 15 days of continuous administration. Our results suggested that VAL-SNEDDS was a potential and safe delivery system with enhanced dissolution rate and oral bioavailability, as well as offered a strategy for the engineering of poorly water-soluble drugs in the clinical setting.

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.

Probing interfacial reactions with x-ray reflectivity and x-ray reflection interface microscopy : influence of NaCl on the dissolution of orthoclase at pOH2 and 85 {degree} C.

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

Fenter, P.; Lee, S. S.; Park, C.

2010-01-01

The role of electrolyte ions in the dissolution of orthoclase (0 0 1) in 0.01 m NaOH (pOH {approx} 2) at 84 {+-} 1 C is studied using a combination of in-situ X-ray reflectivity (XR) and ex-situ X-ray reflection interface microscopy (XRIM). The real-time XR measurements show characteristic intensity oscillations as a function of time indicative of the successive removal of individual layers. The dissolution rate in 0.01 m NaOH increases approximately linearly with increasing NaCl concentration up to 2 m NaCl. XRIM measurements of the lateral interfacial topography/structure were made for unreacted surfaces and those reacted in 0.01 mmore » NaOH/1.0 m NaCl solution for 15, 30 and 58 min. The XRIM images reveal that the dissolution reaction leads to the formation of micron-scale regions that are characterized by intrinsically lower reflectivity than the unreacted regions, and appears to be nucleated at steps and defect sites. The reflectivity signal from these reacted regions in the presence of NaCl in solution is significantly lower than that calculated from an idealized layer-by-layer dissolution process, as observed previously in 0.1 m NaOH in the absence of added electrolyte. This difference suggests that dissolved NaCl results in a higher terrace reactivity leading to a more three-dimensional process, consistent with the real-time XR measurements. These observations demonstrate the feasibility of XRIM to gain new insights into processes that control interfacial reactivity, specifically the role of electrolytes in feldspar dissolution at alkaline conditions.« less

Energetics of the molecular interactions of L-cysteine, L-serine, and L-asparagine in aqueous propylene glycol solutions at 298.15 K

NASA Astrophysics Data System (ADS)

Mezhevoi, I. N.; Badelin, V. G.

2015-03-01

Integral enthalpies of dissolution Δsol H m of L-cysteine, L-serine, and L-asparagine in aqueous solutions of 1,3-propylene glycol at organic solvent concentrations of up to 0.26 mole fraction are measured via the thermochemistry of dissolution. Standard enthalpies of dissolution (Δsol H ○) and transfer (Δtr H ○) of amino acids from water to a mixed solvent are calculated. It is found that the calculated enthalpy coefficients of pair interactions of the amino acids with polyhydric alcohol molecules have positive values. The effect the arrangement of the hydroxyl group in the structure of polyhydric alcohols has on the enthalpy of interaction of amino acids in aqueous solutions is revealed. The effect of different types of interactions in solutions and the structural features of biomolecules and cosolvents on the enthalpy of dissolution of amino acids is analyzed.

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.

[Study on Xinyueshu spray drying assisted with copovidone and its effect on powder property].

PubMed

Jiang, Yan-Rong; Zhang, Zhen-Hai; Ding, Dong-Mei; Yan, Hong-Mei; Hu, Shao-Ying; Jia, Xiao-Bin

2013-12-01

To study the application characteristics of copovidone (PVP-S630) in Xinyueshu extracts during the spray drying process, and its effect on such pharmaceutical properties as micromeritics and drug release behavior. PVP-S630 was added into Xinyueshu extracts to study on the spray drying, the effect of different dosages of PVP-S630 against the wall sticking effect of the spray drying, as well as the power property of Xinyueshu spray drying power and the dissolution in vitro behavior of the effective component of hyperoside. The results showed that PVP-S630 revealed a significant anti-wall sticking effect, with no notable change in the grain size of the spray drying power, increase in the fluidity, improvement in the moisture absorption and remarkable rise in the dissolution in vitro behavior of hyperoside. It was worth further studying the application of PVP-S630 in spray drying power of traditional Chinese medicine.

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.

Impact of formulation and process variables on solid-state stability of theophylline in controlled release formulations.

PubMed

Korang-Yeboah, Maxwell; Rahman, Ziyaur; Shah, Dhaval; Mohammad, Adil; Wu, Suyang; Siddiqui, Akhtar; Khan, Mansoor A

2016-02-29

Understanding the impact of pharmaceutical processing, formulation excipients and their interactions on the solid-state transitions of pharmaceutical solids during use and in storage is critical in ensuring consistent product performance. This study reports the effect of polymer viscosity, diluent type, granulation and granulating fluid (water and isopropanol) on the pseudopolymorphic transition of theophylline anhydrous (THA) in controlled release formulations as well as the implications of this transition on critical quality attributes of the tablets. Accordingly, 12 formulations were prepared using a full factorial screening design and monitored over a 3 month period at 40 °C and 75%. Physicochemical characterization revealed a drastic drop in tablet hardness accompanied by a very significant increase in moisture content and swelling of all formulations. Spectroscopic analysis (ssNMR, Raman, NIR and PXRD) indicated conversion of THA to theophylline monohydrate (TMO) in all formulations prepared by aqueous wet granulation in as early as two weeks. Although all freshly prepared formulations contained THA, the hydration-dehydration process induced during aqueous wet granulation hastened the pseudopolymorphic conversion of theophylline during storage through a cascade of events. On the other hand, no solid state transformation was observed in directly compressed formulations and formulations in which isopropanol was employed as a granulating fluid even after the twelve weeks study period. The transition of THA to TMO resulted in a decrease in dissolution while an increase in dissolution was observed in directly compressed and IPA granulated formulation. Consequently, the impact of pseudopolymorphic transition of theophylline on dissolution in controlled release formulations may be the net result of two opposing factors: swelling and softening of the tablets which tend to favor an increase in drug dissolution and hydration of theophylline which decreases the drug dissolution. Published by Elsevier B.V.

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

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.

Outer organic layer and internal repair mechanism protects pteropod Limacina helicina from ocean acidification

NASA Astrophysics Data System (ADS)

Peck, Victoria L.; Tarling, Geraint A.; Manno, Clara; Harper, Elizabeth M.; Tynan, Eithne

2016-05-01

Scarred shells of polar pteropod Limacina helicina collected from the Greenland Sea in June 2012 reveal a history of damage, most likely failed predation, in earlier life stages. Evidence of shell fracture and subsequent re-growth is commonly observed in specimens recovered from the sub-Arctic and further afield. However, at one site within sea-ice on the Greenland shelf, shells that had been subject to mechanical damage were also found to exhibit considerable dissolution. It was evident that shell dissolution was localised to areas where the organic, periostracal sheet that covers the outer shell had been damaged at some earlier stage during the animal's life. Where the periostracum remained intact, the shell appeared pristine with no sign of dissolution. Specimens which appeared to be pristine following collection were incubated for four days. Scarring of shells that received periostracal damage during collection only became evident in specimens that were incubated in waters undersaturated with respect to aragonite, ΩAr≤1. While the waters from which the damaged specimens were collected at the Greenland Sea sea-ice margin were not ΩAr≤1, the water column did exhibit the lowest ΩAr values observed in the Greenland and Barents Seas, and was likely to have approached ΩAr≤1 during the winter months. We demonstrate that L. helicina shells are only susceptible to dissolution where both the periostracum has been breached and the aragonite beneath the breach is exposed to waters of ΩAr≤1. Exposure of multiple layers of aragonite in areas of deep dissolution indicate that, as with many molluscs, L. helicina is able to patch up dissolution damage to the shell by secreting additional aragonite internally and maintain their shell. We conclude that, unless breached, the periostracum provides an effective shield for pteropod shells against dissolution in waters ΩAr≤1, and when dissolution does occur the animal has an effective means of self-repair. We suggest that future studies of pteropod shell condition are undertaken on specimens from which the periostracum has not been removed in preparation.

Hydrothermal alteration of deep fractured granite: Effects of dissolution and precipitation

NASA Astrophysics Data System (ADS)

Nishimoto, Shoji; Yoshida, Hidekazu

2010-03-01

This paper investigates the mineralogical effects of hydrothermal alteration at depth in fractures in granite. A fracture accompanied by an alteration halo and filled with clay was found at a depth of 200 m in a drill core through Toki granite, Gifu, central Japan. Microscopic observation, XRD, XRF, EPMA and SXAM investigations revealed that the microcrystalline clays consist of illite, quartz and pyrite and that the halo round the fracture can be subdivided into a phyllic zone adjacent to the fracture, surrounded by a propylitic zone in which Fe-phyllosilicates are present, and a distinctive outer alteration front characterized by plagioclase breakdown. The processes that result in these changes took place in three successive stages: 1) partial dissolution of plagioclase with partial chloritization of biotite; 2) biotite dissolution and precipitation of Fe-phyllosilicate in the dissolution pores; 3) dissolution of K-feldspar and Fe-phyllosilicate, and illite precipitation associated with development of microcracks. These hydrothermal alterations of the granite proceed mainly by a dissolution-precipitation process resulting from the infiltration of hydrothermal fluid along microcracks. Such infiltration causes locally high mobility of Al and increases the ratio of fluid to rock in the alteration halo. These results contribute to an understanding of how granitic rock becomes altered in orogenic fields such as the Japanese island arc.

Physicochemical characterization of atorvastatin calcium/ezetimibe amorphous nano-solid dispersions prepared by electrospraying method.

PubMed

Jahangiri, Azin; Barzegar-Jalali, Mohammad; Javadzadeh, Yousef; Hamishehkar, Hamed; Adibkia, Khosro

2017-09-01

In the present study, electrospraying was applied as a novel method for the fabrication of amorphous nano-solid dispersions (N-SDs) of atorvastatin calcium (ATV), ezetimibe (EZT), and ATV/EZT combination as poorly water-soluble drugs. N-SDs were prepared using polyvinylpyrrolidone K30 as an amorphous carrier in 1:1 and 1:5 drug to polymer ratios and the total solid (including drug and polymer) concentrations of 10 and 20% (w/v). The prepared formulations were further investigated for their morphological, physicochemical, and dissolution properties. Scanning electron microscopy studies indicated that the morphology and diameter of the electrosprayed samples (ESs) were influenced by the solution concentration and drug:polymer ratio, so that an increase in the solution concentration resulted in fiber formation while an increase in the polymer ratio led to enhancement of the particle diameter. Differential scanning calorimetry and X-ray powder diffraction studies together with in vitro dissolution test revealed that the ESs were present in an amorphous form with improved dissolution properties. Infrared spectroscopic studies showed hydrogen-bonding interaction between the drug and polymer in ESs. Since the electrospraying method benefits from the both amorphization and nanosizing effect, this novel approach seems to be an efficient method for the fabrication of N-SDs of poorly water-soluble drugs.

Looking for the Self: Phenomenology, Neurophysiology and Philosophical Significance of Drug-induced Ego Dissolution.

PubMed

Millière, Raphaël

2017-01-01

There is converging evidence that high doses of hallucinogenic drugs can produce significant alterations of self-experience, described as the dissolution of the sense of self and the loss of boundaries between self and world. This article discusses the relevance of this phenomenon, known as "drug-induced ego dissolution (DIED)", for cognitive neuroscience, psychology and philosophy of mind. Data from self-report questionnaires suggest that three neuropharmacological classes of drugs can induce ego dissolution: classical psychedelics, dissociative anesthetics and agonists of the kappa opioid receptor (KOR). While these substances act on different neurotransmitter receptors, they all produce strong subjective effects that can be compared to the symptoms of acute psychosis, including ego dissolution. It has been suggested that neuroimaging of DIED can indirectly shed light on the neural correlates of the self. While this line of inquiry is promising, its results must be interpreted with caution. First, neural correlates of ego dissolution might reveal the necessary neurophysiological conditions for the maintenance of the sense of self, but it is more doubtful that this method can reveal its minimally sufficient conditions. Second, it is necessary to define the relevant notion of self at play in the phenomenon of DIED. This article suggests that DIED consists in the disruption of subpersonal processes underlying the "minimal" or "embodied" self, i.e., the basic experience of being a self rooted in multimodal integration of self-related stimuli. This hypothesis is consistent with Bayesian models of phenomenal selfhood, according to which the subjective structure of conscious experience ultimately results from the optimization of predictions in perception and action. Finally, it is argued that DIED is also of particular interest for philosophy of mind. On the one hand, it challenges theories according to which consciousness always involves self-awareness. On the other hand, it suggests that ordinary conscious experience might involve a minimal kind of self-awareness rooted in multisensory processing, which is what appears to fade away during DIED.

Dynamics of altered surface layer formation on dissolving silicates

NASA Astrophysics Data System (ADS)

Daval, Damien; Bernard, Sylvain; Rémusat, Laurent; Wild, Bastien; Guyot, François; Micha, Jean Sébastien; Rieutord, François; Magnin, Valérie; Fernandez-Martinez, Alejandro

2017-07-01

The extrapolation of mineral dissolution kinetics experiments to geological timescales has frequently been challenged by the observation that mineral dissolution rates decrease with time. In the present study, we report a detailed investigation of the early stages of wollastonite dissolution kinetics, linking time-resolved measurements of wollastonite dissolution rate as a function of crystallographic orientation to the evolution of physicochemical properties (i.e., diffusivity, density, and thickness) of amorphous silica-rich layers (ASSLs) that developed on each surface. Batch dissolution experiments conducted at room temperature and at far-from-equilibrium conditions revealed that the initial (i.e., ASSL-free) dissolution rate of wollastonite (R(hkl)) based on Ca release observe the following trend: R(010) ≈R(100) >R(101) >R(001) . A gradual decrease of the dissolution rate of some faces by up to one order of magnitude resulted in a modification of this trend after two days: R(010) ≫R(100) ⩾R(101) ≈R(001) . In parallel, the diffusivity of ASSLs developed on each face was estimated based on the measurement of the concentration profile of a conservative tracer (methylene blue) across the ASSL using nanoSIMS. The apparent diffusion coefficients of methylene blue as a function of the crystallographic orientation (Dapp(hkl)) observe the following trend: Dapp(010) ⩾Dapp(100) >Dapp(101) ≫Dapp(001) , and decreases as a function of time for the (1 0 0) and (1 0 1) faces. Finally, the density of ASSL was estimated based on the modeling of X-ray reflectivity patterns acquired as a function of time. The density of ASSLs developed on the (0 1 0) faces remains low and constant, whereas it increases for the ASSLs developed on the (0 0 1) faces. On the whole, our results suggest that the impact of the formation of ASSLs on the wollastonite dissolution rate is anisotropic: while some crystal faces are weakly affected by the formation of non-passivating ASSLs (e.g., the (0 1 0) face), the dissolution of other faces is hampered by passivating ASSLs within a few hours. The observed passivation is suggested to originate from the progressive densification of the ASSL, which limits the transport of reactive species from and to the dissolving wollastonite surface, as evidenced by the estimated diffusivity of the ASSLs. Because the apparent face-specific diffusivity of the ASSLs is correlated with the face-specific initial (i.e., ASSL-free) dissolution rate of wollastonite, we propose that the extent of ASSL densification (and the resulting impact on ion transport) is (at least partly) controlled by the absolute mineral dissolution rate. Overall, this study argues that the formation and microstructural evolution of ASSLs are likely candidates for mineral ageing, highlighting the need for determining the parameters controlling the spontaneous changes of ASSL diffusivity as a function of the reaction progress.

Rapid dissolution of ZnO nanocrystals in acidic cancer microenvironment leading to preferential apoptosis

NASA Astrophysics Data System (ADS)

Sasidharan, Abhilash; Chandran, Parwathy; Menon, Deepthy; Raman, Sreerekha; Nair, Shantikumar; Koyakutty, Manzoor

2011-09-01

The microenvironment of cancer plays a very critical role in the survival, proliferation and drug resistance of solid tumors. Here, we report an interesting, acidic cancer microenvironment-mediated dissolution-induced preferential toxicity of ZnO nanocrystals (NCs) against cancer cells while leaving primary cells unaffected. Irrespective of the size-scale (5 and 200 nm) and surface chemistry differences (silica, starch or polyethylene glycol coating), ZnO NCs exhibited multiple stress mechanisms against cancer cell lines (IC50 ~150 μM) while normal human primary cells (human dermal fibroblast, lymphocytes, human umbilical vein endothelial cells) remain less affected. Flow cytometry and confocal microscopy studies revealed that ZnO NCs undergo rapid preferential dissolution in acidic (pH ~5-6) cancer microenvironment causing elevated ROS stress, mitochondrial superoxide formation, depolarization of mitochondrial membrane, and cell cycle arrest at S/G2 phase leading to apoptosis. In effect, by elucidating the unique toxicity mechanism of ZnO NCs, we show that ZnO NCs can destabilize cancer cells by utilizing its own hostile acidic microenvironment, which is otherwise critical for its survival.The microenvironment of cancer plays a very critical role in the survival, proliferation and drug resistance of solid tumors. Here, we report an interesting, acidic cancer microenvironment-mediated dissolution-induced preferential toxicity of ZnO nanocrystals (NCs) against cancer cells while leaving primary cells unaffected. Irrespective of the size-scale (5 and 200 nm) and surface chemistry differences (silica, starch or polyethylene glycol coating), ZnO NCs exhibited multiple stress mechanisms against cancer cell lines (IC50 ~150 μM) while normal human primary cells (human dermal fibroblast, lymphocytes, human umbilical vein endothelial cells) remain less affected. Flow cytometry and confocal microscopy studies revealed that ZnO NCs undergo rapid preferential dissolution in acidic (pH ~5-6) cancer microenvironment causing elevated ROS stress, mitochondrial superoxide formation, depolarization of mitochondrial membrane, and cell cycle arrest at S/G2 phase leading to apoptosis. In effect, by elucidating the unique toxicity mechanism of ZnO NCs, we show that ZnO NCs can destabilize cancer cells by utilizing its own hostile acidic microenvironment, which is otherwise critical for its survival. Electronic supplementary information (ESI) available: FTIR data, MTT assay and zinc ion release. See DOI: 10.1039/c1nr10272a

Dissolution of lead matte and copper slag upon exposure to rhizosphere-like conditions

NASA Astrophysics Data System (ADS)

Potysz, Anna; Kierczak, Jakub

2017-12-01

Metallurgical wastes displaying various chemical and mineralogical properties may reveal different behaviour under exposure to weathering conditions. The latter impact the stability of the wastes, which often results in metal release and subsequent pollution problems. The aim of this study was to compare the weathering of two types of metallurgical wastes (i.e., copper slag and lead matte) exposed to artificial root exudates organic solutions and demineralized water. The results of experimental weathering demonstrated that the extent of waste dissolution depends on the composition of weathering solution as well as on the waste properties. Artificial root exudates rich in organic acids were found to enhance elements release from sulphide rich lead matte and copper glassy slag relative to demineralized water control. The release of elements from the wastes exposed to artificial root exudates for 7 weeks reached 17.8% of Pb and 4.97% of Cu, for lead matte and granulated slag respectively. The most leachable elements may result from the dissolution of intermetallic phases hosting these elements. The fraction size ranging from 0.25-0.5 mm to 1-2 mm was found to be a minor factor in elements release under studied conditions.

Glass-water interaction: Effect of high-valence cations on glass structure and chemical durability

NASA Astrophysics Data System (ADS)

Hopf, J.; Kerisit, S. N.; Angeli, F.; Charpentier, T.; Icenhower, J. P.; McGrail, B. P.; Windisch, C. F.; Burton, S. D.; Pierce, E. M.

2016-05-01

Borosilicate glass is a durable solid, but it dissolves when in contact with aqueous fluids. The dissolution mechanism, which involves a variety of sequential reactions that occur at the solid-fluid interface, has important implications for the corrosion resistance of industrial and nuclear waste glasses. In this study, spectroscopic measurements, dissolution experiments, and Monte Carlo simulations were performed to investigate the effect of high-valence cations (HVC) on the mechanisms of glass dissolution under dilute and near-saturated conditions. Raman and NMR spectroscopy were used to determine the structural changes that occur in glass, specifically network formers (e.g., Al, Si, and B), with the addition of the HVC element hafnium in the Na2O-Al2O3-B2O3-HfO2-SiO2 system (e.g., Na/[Al + B] = 1.0 and HfO2/SiO2 from 0.0 to 0.42). Spectroscopic measurements revealed that increasing hafnium content decreases N4 (tetrahedral boron/total boron) and increases the amount of Si-O-Hf moieties in the glass. Results from flow-through experiments conducted under dilute and near-saturated conditions show a decrease of approximately 100× or more in the dissolution rate over the series from 0 to 20 mol% HfO2. Comparing the average steady-state rates obtained under dilute conditions to the rates obtained for near-saturated conditions reveals a divergence in the magnitude between the average steady state rates measured in these different conditions. The reason for this divergence was investigated more thoroughly using Monte Carlo simulations. Simulations indicate that the divergence in glass dissolution behavior under dilute and near-saturated conditions result from the stronger binding of Si sites that deposit on the surface from the influent when Hf is present in the glass. As a result, the residence time at the glass surface of these newly-formed Si sites is longer in the presence of Hf, which increases the density of anchor sites from which altered layers with higher Si densities can form. These results illustrate the importance of understanding solid-water/solid-fluid interactions by linking macroscopic reaction kinetics to nanometer scale interfacial processes.

Thermodynamics of cellulose solvation in water and the ionic liquid 1-butyl-3-methylimidazolim chloride.

PubMed

Gross, Adam S; Bell, Alexis T; Chu, Jhih-Wei

2011-11-24

Cellulose is present in biomass as crystalline microfibrils held together by a complex network of intermolecular interactions making it difficult to initiate its hydrolysis and conversion to fuels. While cellulose is insoluble in water and most organic solvents, complete dissolution of cellulose can be achieved in certain classes of ionic liquids (ILs). The present study was undertaken to analyze the thermodynamic driving forces of this process and to understand how the anions and cations comprising an IL interact with the different moieties of glucose residues to cause dissolution. All-atom molecular dynamics (MD) simulations were performed at two extreme states of cellulose dissolution: a crystalline microfibril and a dissociated state in which all the glucan chains of the microfibril are fully separated from each other by at least four solvation shells. MD simulations of the two states were carried out in water and in the IL 1-butyl-3-methylimidazolium chloride (BmimCl) to provide a comprehensive analysis of solvent effects on cellulose dissolution. The results reveal two important molecular aspects of the mechanism of cellulose dissolution. The first is that the perturbation of solvent structures by the dissolved glucan chains can be a crucial factor in determining solubility, particularly for the insolubility of cellulose in water at 300 K. Second, both the Cl(-) and the Bmim(+) ions of BmimCl interact with the moieties of glucan residues that form intersheet contacts, the most robust component of the interaction network of crystalline cellulose. Cl(-) anions can form hydrogen bonds (HBs) with the hydroxyl groups of glucan chains from either the equatorial or the axial directions. For Bmim(+) cations, the calculated density profiles reveal that the contacts with glucan chains along the axial directions are closer than those along the equatorial directions. On the basis of the results of atomistic MD simulations, we propose that interacting with glucan chains along axial directions and disrupting the intersheet contacts of cellulose is an important ability of cellulose pretreatment solvents. © 2011 American Chemical Society

Increase of apatite dissolution rate by Scots pine roots associated or not with Burkholderia glathei PML1(12)Rp in open-system flow microcosms

NASA Astrophysics Data System (ADS)

Calvaruso, Christophe; Turpault, Marie-Pierre; Frey-Klett, Pascale; Uroz, Stéphane; Pierret, Marie-Claire; Tosheva, Zornitza; Kies, Antoine

2013-04-01

The release of nutritive elements through apatite dissolution represents the main source of phosphorus, calcium, and several micronutrients (e.g., Zn, Cu) for organisms in non-fertilized forest ecosystems. The aim of this study was to quantify, for the first time, the dissolution rate of apatite grains by tree roots that were or were not associated with a mineral weathering bacterial strain, and by various acids known to be produced by tree roots and soil bacterial strains in open-system flow microcosms. In addition, we explored whether the mobilization of trace elements (including rare earth elements) upon apatite dissolution was affected by the presence of trees and associated microorganisms. The dissolution rate of apatite by Scots pine plants that were or were not inoculated with the strain Burkholderia glathei PML1(12)Rp, and by inorganic (nitric) and organic (citric, oxalic and gluconic) acids at pH 5.5, 4.8, 3.8, 3.5, 3.0, and 2.0 was monitored in two controlled experiments: "plant-bacteria interaction" and "inorganic and organic acids". Analyses of the outlet solutions in the "plant-bacteria interaction" experiment showed that Scots pine roots and B. glathei PML1(12)Rp produced protons and organic acids such as gluconate, oxalate, acetate, and lactate. The weathering budget calculation revealed that Scots pines (with or without PML1(12)Rp) significantly increased (factor > 10) the release of Ca, P, As, Sr, Zn, U, Y, and rare earth elements such as Ce, La, Nd from apatite, compared to control abiotic treatment. Scanning electron microscopy observation confirmed traces of apatite dissolution in contact of roots. Most dissolved elements were taken up by Scots pine roots, i.e., approximately 50% of Ca, 70% of P, 30% of As, 70% of Sr, 90% of Zn, and 100% of U, Y, and rare earth elements. Interestingly, no significant additional effect due to the bacterial strain PML1(12)Rp on apatite dissolution and Scots pine nutrition and growth was observed. The "inorganic and organic acids" experiment demonstrated that the apatite dissolution efficacy of organic acids was higher than for the inorganic acid and varied in function of the acids: oxalic acid > citric acid > gluconic acid > nitric acid for pH ⩽3.5. In addition, apatite dissolution increased with increasing acidity for each acid. Only oxalic acid generated non-stoichiometric release of calcium and phosphorus from apatite in the solution at pH ⩽3.5, due to the precipitation of Ca-oxalate crystals at apatite surfaces. Comparison of the experiments revealed that the apatite dissolution rate by Scots pines supplied with nutritive solution at pH 5.5 reached 2.0 × 10-13 mol cm-2 s-1 and was equivalent to rates with nitric acid at pH 3.2, gluconic acid at pH 3.5, citric acid at pH 3.7, and oxalic acid at pH 3.8. Altogether our results highlight that, through the production of weathering agents, notably protons and organic acids, tree roots and root-associated microorganisms are able to significantly increase the release of macro- and micro-nutrients from apatite, thus maintaining high-nutrient conditions to support their growth.

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.

Evaluation of extemporaneous oral itraconazole suspensions by dissolution profiles mapping.

PubMed

Tong, Henry H Y; Chan, Hokman; Du, Zhen; Zheng, Ying

2010-01-01

The objective of this study was to evaluate by dissolution profiles mapping five extemporaneous oral itraconazole suspensions reported in the literature. Dissolution profiles of the extemporaneous oral itraconazole preparations were mapped and correlated with their reported clinical data therein. Four out of five extemporaneous preparations had either too early or insufficient release of itraconazole during the dissolution study, potentially limiting the in vivo oral bioavailability in patients. Dissolution profiles in the remaining extemporaneous preparation was closely similar to that in commercial itraconazole capsules. Based on the reported clinical data and dissolution results in this study, the extemporaneous preparation proposed in a study by Ong and Fobes seems to be the most reasonable choice for our patients. Dissolution profile evaluation is an important quality-control parameter during the evaluation of extemporaneous preparations by pharmacists.

Characterization and taste-masking evaluation of acetaminophen granules: comparison between different preparation methods in a high-shear mixer.

PubMed

Albertini, Beatrice; Cavallari, Cristina; Passerini, Nadia; Voinovich, Dario; González-Rodríguez, Marisa L; Magarotto, Lorenzo; Rodriguez, Lorenzo

2004-02-01

The aim of this study was to prepare and to investigate acetaminophen taste-masked granules obtained in a high-shear mixer using three different wet granulation methods (method A: water granulation, method B: granulation with a polyvinylpyrrolidone (PVP) binding solution and method C: steam granulation). The studied formulation was: acetaminophen 15%, alpha-lactose monohydrate 30%, cornstarch 45%, polyvinylpyrrolidone K30 5% and orange flavour 5% (w/w). In vitro dissolution studies, performed at pH 6.8, showed that steam granules enabled the lower dissolution rate in comparison to the water and binding solution granules; these results were then confirmed by their lower surface reactivity (D(R)) during the dissolution process. Moreover, the results of the gustatory sensation test performed by six volunteers confirmed the taste-masking effects of the granules, especially steam granules (P<0.001). Morphological, fractal and porosity analysis were then performed to explain the dissolution profiles and the results of the gustatory sensation test. Scanning electron microscopy (SEM) analysis revealed the smoother and the more regular surface of steam granules with respect to the samples obtained using methods A and B; these results were also confirmed by their lower fractal dimension (D(s)) and porosity values. Finally, differential scanning calorimetry (DSC) results showed a shift of the melting point of the drug, which was due to the simple mixing of the components and not to the granulation processes. In conclusion, the steam granulation technique resulted a suitable method to comply the purpose of this work, without modifying the availability of the drug.

Preparation of theophylline-hydroxypropylmethylcellulose matrices using supercritical antisolvent precipitation: a preliminary study.

PubMed

Moneghini, M; Perissutti, B; Kikic, I; Grassi, M; Cortesi, A; Princivalle, F

2006-01-01

Several controlled release systems of drugs have been elaborated using a supercritical fluid process. Indeed, recent techniques using a supercritical fluid as a solvent or as an antisolvent are considered to be useful alternatives to produce fine powders. In this preliminary study, the effect of Supercritical Anti Solvent process (SAS) on the release of theophylline from matrices manufactured with hydroxypropylmethylcellulose (HPMC) was investigated. Two grades of HPMC (HPMC E5 and K100) as carriers were considered in order to prepare a sustained delivery system for theophylline which was used as a model drug. The characterization of the drug before and after SAS treatment, and the coprecipitates with carriers, was performed by X-ray Diffraction (XRD) and Differential Scanning Calorimetry (DSC). The dissolution rate of theophylline, theophylline-coprecipitates, and matricial tablets prepared with coprecipitates were determined. The physical characterizations revealed a substantial correspondence of the drug solid state before and after supercritical fluid treatment while drug-polymer interactions in the SAS-coprecipitates were attested. The dissolution studies of the matrices prepared compressing the coprecipitated systems showed that the matrices based on HPMC K100 were able to promote a sustained release of the drug. Further, this advantageous dissolution performance was found to be substantially independent of the pH of the medium. The comparison with the matrices prepared with untreated substances demonstrated that matrices obtained with SAS technique can provide a slower theophylline release rate. A new mathematical model describing the in vitro dissolution kinetics was proposed and successfully tested on these systems.

Dissolution and degradation of Fmoc-diphenylalanine self-assembled gels results in necrosis at high concentrations in vitro.

PubMed

Truong, Warren Ty; Su, Yingying; Gloria, Danmar; Braet, Filip; Thordarson, Pall

2015-02-01

Herein we report an approach to assess in vitro cellular responses to the dissolution or degradation products from Fmoc-diphenylalanine (Fmoc-FF) self-assembled hydrogels. Three cell lines were used in these studies and two-way ANOVA was used to assess (i) the age of gel dissolution and degradation products and (ii) exposure time on cell fate and state, using viability assays in conjunction with time-lapse fluorescence and high-resolution scanning electron microscopy investigation. The studies show that leaching time but not the exposure time affects the overall cell viability. The cytotoxic effect was only observed once the gel is completely dissolved. Further analysis revealed that the principal mechanism of cell death is necrosis. In addition, the effect of chemotherapeutics (5-fluorouracil and paclitaxel) released from the Fmoc-FF gel (with addition before and after gelation) on colorectal cancer cells were investigated using this methodology, demonstrating enhanced activity of these drugs compared to bulk control. This enhanced activity, however, appears to be a combination of the apoptosis caused by the cancer drugs and necrosis caused by gel dissolution and degradation products. Given that in vivo studies by others on Fmoc-peptides that this material is not harmful to animals, our work highlights that conventional in vitro cellular assays may yield conflicting messages when used for the evaluation of cytotoxicity and drug release from self-assembled gels such as Fmoc-FF and that better in vitro models, (e.g. 3D cell culture systems) need to be developed to evaluate these materials for biomedical applications.

Ionic solutions of two-dimensional materials

NASA Astrophysics Data System (ADS)

Cullen, Patrick L.; Cox, Kathleen M.; Bin Subhan, Mohammed K.; Picco, Loren; Payton, Oliver D.; Buckley, David J.; Miller, Thomas S.; Hodge, Stephen A.; Skipper, Neal T.; Tileli, Vasiliki; Howard, Christopher A.

2017-03-01

Strategies for forming liquid dispersions of nanomaterials typically focus on retarding reaggregation, for example via surface modification, as opposed to promoting the thermodynamically driven dissolution common for molecule-sized species. Here we demonstrate the true dissolution of a wide range of important 2D nanomaterials by forming layered material salts that spontaneously dissolve in polar solvents yielding ionic solutions. The benign dissolution advantageously maintains the morphology of the starting material, is stable against reaggregation and can achieve solutions containing exclusively individualized monolayers. Importantly, the charge on the anionic nanosheet solutes is reversible, enables targeted deposition over large areas via electroplating and can initiate novel self-assembly upon drying. Our findings thus reveal a unique solution-like behaviour for 2D materials that enables their scalable production and controlled manipulation.

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.

Influence of calcium on microbial reduction of solid phase uranium(VI).

PubMed

Liu, Chongxuan; Jeon, Byong-Hun; Zachara, John M; Wang, Zheming

2007-08-15

The effect of calcium on the dissolution and microbial reduction of a representative solid phase uranyl [U(VI)], sodium boltwoodite (NaUO(2)SiO(3)OH . 1.5H(2)O), was investigated to evaluate the rate-limiting step of microbial reduction of the solid phase U(VI). Microbial reduction experiments were performed in a culture of a dissimilatory metal-reducing bacterium (DMRB), Shewanella oneidensis strain MR-1, in a bicarbonate medium with lactate as electron donor at pH 6.8 buffered with PIPES. Calcium increased the rate of Na-boltwoodite dissolution and U(VI) bioavailability by increasing its solubility through the formation of a ternary aqueous calcium-uranyl-carbonate species. The ternary species, however, decreased the rates of microbial reduction of aqueous U(VI). Laser-induced fluorescence spectroscopy (LIFS) and transmission electron microscopy (TEM) collectively revealed that microbial reduction of solid phase U(VI) was a sequentially coupled process of Na-boltwoodite dissolution, U(VI) aqueous speciation, and microbial reduction of dissolved U(VI) to U(IV) that accumulated on bacterial surfaces/periplasm. Under studied experimental conditions, the overall rate of microbial reduction of solid phase U(VI) was limited by U(VI) dissolution reactions in solutions without calcium and limited by microbial reduction in solutions with calcium. Generally, the overall rate of microbial reduction of solid phase U(VI) was determined by the coupling of solid phase U(VI) dissolution, U(VI) aqueous speciation, and microbial reduction of dissolved U(VI) that were all affected by calcium. (c) 2007 Wiley Periodicals, Inc.

The initial stages of NaCl dissolution: Ion or ion pair solvation?

NASA Astrophysics Data System (ADS)

Klimes, Jiri; Michaelides, Angelos

2009-03-01

The interaction of water with rock salt (NaCl) is important in a wide variety of natural processes and human activities. A lot is known about NaCl dissolution at the macroscopic level but we do not yet have a detailed atomic scale picture of how salt crystals dissolve. Here we report an extensive series of density functional theory, forcefield and molecular dynamics studies of water clusters at flat and defective NaCl surfaces and NaCl clusters. The focus is on answering seemingly elementary questions such as how many water molecules are needed before it becomes favorable to extract an ion or a pair of ions from the crystal or the cluster. It turns out, however, that the answers to these questions are not so straightforward: below a certain number of water molecules (˜ 12) solvation of individual ions is less costly and above this number solvation of ion pairs is favored. These results reveal a hitherto unknown complexity in the NaCl dissolution process born out of a subtle interplay between water-water and water-ion interactions.

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.

Pore scale study of multiphase multicomponent reactive transport during CO 2 dissolution trapping

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

Chen, Li; Wang, Mengyi; Kang, Qinjun

Solubility trapping is crucial for permanent CO 2 sequestration in deep saline aquifers. For the first time, a pore-scale numerical method is developed to investigate coupled scCO 2-water two-phase flow, multicomponent (CO 2(aq), H +, HCO 3 –, CO 3 2 – and OH –) mass transport, heterogeneous interfacial dissolution reaction, and homogeneous dissociation reactions. Pore-scale details of evolutions of multiphase distributions and concentration fields are presented and discussed. Time evolutions of several variables including averaged CO 2(aq) concentration, scCO 2 saturation, and pH value are analyzed. Specific interfacial length, an important variable which cannot be determined but is requiredmore » by continuum models, is investigated in detail. Mass transport coefficient or efficient dissolution rate is also evaluated. The pore-scale results show strong non-equilibrium characteristics during solubility trapping due to non-uniform distributions of multiphase as well as slow mass transport process. Complicated coupling mechanisms between multiphase flow, mass transport and chemical reactions are also revealed. Lastly, effects of wettability are also studied. The pore-scale studies provide deep understanding of non-linear non-equilibrium multiple physicochemical processes during CO 2 solubility trapping processes, and also allow to quantitatively predict some important empirical relationships, such as saturation-interfacial surface area, for continuum models.« less

Pore scale study of multiphase multicomponent reactive transport during CO 2 dissolution trapping

DOE PAGES

Chen, Li; Wang, Mengyi; Kang, Qinjun; ...

2018-04-26

Solubility trapping is crucial for permanent CO 2 sequestration in deep saline aquifers. For the first time, a pore-scale numerical method is developed to investigate coupled scCO 2-water two-phase flow, multicomponent (CO 2(aq), H +, HCO 3 –, CO 3 2 – and OH –) mass transport, heterogeneous interfacial dissolution reaction, and homogeneous dissociation reactions. Pore-scale details of evolutions of multiphase distributions and concentration fields are presented and discussed. Time evolutions of several variables including averaged CO 2(aq) concentration, scCO 2 saturation, and pH value are analyzed. Specific interfacial length, an important variable which cannot be determined but is requiredmore » by continuum models, is investigated in detail. Mass transport coefficient or efficient dissolution rate is also evaluated. The pore-scale results show strong non-equilibrium characteristics during solubility trapping due to non-uniform distributions of multiphase as well as slow mass transport process. Complicated coupling mechanisms between multiphase flow, mass transport and chemical reactions are also revealed. Lastly, effects of wettability are also studied. The pore-scale studies provide deep understanding of non-linear non-equilibrium multiple physicochemical processes during CO 2 solubility trapping processes, and also allow to quantitatively predict some important empirical relationships, such as saturation-interfacial surface area, for continuum models.« less

Pore scale study of multiphase multicomponent reactive transport during CO2 dissolution trapping

NASA Astrophysics Data System (ADS)

Chen, Li; Wang, Mengyi; Kang, Qinjun; Tao, Wenquan

2018-06-01

Solubility trapping is crucial for permanent CO2 sequestration in deep saline aquifers. For the first time, a pore-scale numerical method is developed to investigate coupled scCO2-water two-phase flow, multicomponent (CO2(aq), H+, HCO3-, CO32- and OH-) mass transport, heterogeneous interfacial dissolution reaction, and homogeneous dissociation reactions. Pore-scale details of evolutions of multiphase distributions and concentration fields are presented and discussed. Time evolutions of several variables including averaged CO2(aq) concentration, scCO2 saturation, and pH value are analyzed. Specific interfacial length, an important variable which cannot be determined but is required by continuum models, is investigated in detail. Mass transport coefficient or efficient dissolution rate is also evaluated. The pore-scale results show strong non-equilibrium characteristics during solubility trapping due to non-uniform distributions of multiphase as well as slow mass transport process. Complicated coupling mechanisms between multiphase flow, mass transport and chemical reactions are also revealed. Finally, effects of wettability are also studied. The pore-scale studies provide deep understanding of non-linear non-equilibrium multiple physicochemical processes during CO2 solubility trapping processes, and also allow to quantitatively predict some important empirical relationships, such as saturation-interfacial surface area, for continuum models.

Applications of supercritical fluids to enhance the dissolution behaviors of Furosemide by generation of microparticles and solid dispersions.

PubMed

De Zordi, Nicola; Moneghini, Mariarosa; Kikic, Ireneo; Grassi, Mario; Del Rio Castillo, Antonio Esau; Solinas, Dario; Bolger, Michael B

2012-05-01

The 'classical' loop diuretic drug Furosemide has been used as a model compound to investigate the possibility of enhancing the dissolution rate of poorly water-soluble drugs using supercritical anti-solvent techniques (SASs). In the present study we report upon the in vitro bioavailability improvement of Furosemide through particle size reduction as well as formation of solid dispersions (SDs) using the hydrophilic polymer Crospovidone. Supercritical carbon dioxide was used as the processing medium for these experiments. In order to successfully design a CO(2) antisolvent process, preliminary studies of Furosemide microparticles generation were conducted using Peng Robinson's Equation of State. These preliminary studies indicated using acetone as a solvent with pressures of 100 and 200bar and a temperature of 313K would yield optimum results. These operative conditions were then adopted for the SDs. Micronization by means of SAS at 200bar resulted in a significant reduction of crystallites, particle size, as well as improved dissolution rate in comparison with untreated drug. Furosemide recrystallized by SAS at 100bar and using traditional solvent evaporation. Moreover, changes in polymorphic form were observed in the 200bar samples. The physicochemical characterization of Furosemide:crospovidone SDs (1:1 and 1:2 w/w, respectively) generated by SAS revealed the presence of the drug amorphously dispersed in the 1:2 w/w sample at 100bar still remaining stable after 6months. This sample exhibits the best in vitro dissolution performance in the simulated gastric fluid (pH 1.2), in comparison with the same SD obtained by traditional method. No interactions between drug and polymer were observed. These results, together with the presence of the selected carrier, confirm that the use of Supercritical fluids antisolvent technology is a valid mean to increase the dissolution rate of poorly soluble drugs. Theoretical in vivo-in vitro relation was predicted by means of a pharmacokinetics mathematical model. Copyright © 2012 Elsevier B.V. All rights reserved.

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.

In vitro dissolution of uranium oxide by baboon alveolar macrophages.

PubMed Central

Poncy, J L; Metivier, H; Dhilly, M; Verry, M; Masse, R

1992-01-01

In vitro cellular dissolution tests for insoluble forms of uranium oxide are technically difficult with conventional methodology using adherent alveolar macrophages. The limited number of cells per flask and the slow dissolution rate in a large volume of nutritive medium are obvious restricting factors. Macrophages in suspension cannot be substituted because they represent different and poorly reproducible functional subtypes with regard to activation and enzyme secretion. Preliminary results on the dissolution of uranium oxide using immobilized alveolar macrophages are promising because large numbers of highly functional macrophages can be cultured in a limited volume. Cells were obtained by bronchoalveolar lavages performed on baboons (Papio papio) and then immobilized after the phagocytosis of uranium octoxide (U3O8) particles in alginate beads linked with Ca2+. The dissolution rate expressed as percentage of initial uranium content in cells was 0.039 +/- 0.016%/day for particles with a count median geometric diameter of 3.84 microns(sigma g = 1.84). A 2-fold increase in the dissolution rate was observed when the same number of particles was immobilized without macrophages. These results, obtained in vitro, suggest that the U3O8 preparation investigated should be assigned to inhalation class Y as recommended by the International Commission on Radiological Protection. Future experiments are intended to clarify this preliminary work and to examine the dissolution characteristics of other particles such as uranium dioxide. It is recommended that the dissolution rate should be measured over an interval of 3 weeks, which is compatible with the survival time of immobilized cells in culture and may reveal transformation states occurring with aging of the particles. PMID:1396447

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.

Suppressing Manganese Dissolution from Lithium Manganese Oxide Spinel Cathodes with Single-Layer Graphene

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

Jaber-Ansari, Laila; Puntambekar, Kanan P.; Kim, Soo

2015-06-24

Spinel-structured LiMn 2 O 4 (LMO) is a desirable cathode material for Li-ion batteries due to its low cost, abundance, and high power capability. However, LMO suffers from limited cycle life that is triggered by manganese dissolution into the electrolyte during electrochemical cycling. Here, it is shown that single-layer graphene coatings suppress manganese dissolution, thus enhancing the performance and lifetime of LMO cathodes. Relative to lithium cells with uncoated LMO cathodes, cells with graphene-coated LMO cathodes provide improved capacity retention with enhanced cycling stability. X-ray photoelectron spectroscopy reveals that graphene coatings inhibit manganese depletion from the LMO surface. Additionally, transmissionmore » electron microscopy demonstrates that a stable solid electrolyte interphase is formed on graphene, which screens the LMO from direct contact with the electrolyte. Density functional theory calculations provide two mechanisms for the role of graphene in the suppression of manganese dissolution. First, common defects in single-layer graphene are found to allow the transport of lithium while concurrently acting as barriers for manganese diffusion. Second, graphene can chemically interact with Mn 3+ at the LMO electrode surface, promoting an oxidation state change to Mn 4+ , which suppresses dissolution.« less

Effects of mining activities on evolution of water chemistry in coal-bearing aquifers in karst region of Midwestern Guizhou, China: evidences from δ13C of dissolved inorganic carbon and δ34S of sulfate.

PubMed

Li, Qingguang; Wu, Pan; Zha, Xuefang; Li, Xuexian; Wu, Linna; Gu, Shangyi

2018-04-24

The generation of acid mine drainage (AMD) may accelerate watershed erosion and promote the migration of heavy metals, then threaten local ecosystems such as aquatic life and even human health. Previous studies have focused primarily on influence of AMD in surface environment. In order to reveal the acidizing processes in karst high-sulfur coalfield in Southwest China, this study, by contrast, focused on the hydrogeochemical evolution process and acidification mechanism of mine water in Zhijin coalfield, western Guizhou Province. The oxidation of pyrite and other sulfides induced strong acidification of mine water according to the water chemical analysis. As a result, a series of geochemical processes such as dissolution of carbonates and silicates, hydrolysis of metal ions, and degassing of CO 2 complicated water chemical evolution. The dissolution of silicates controlled the chemical composition of mine water, but more carbonates might be dissolved during the acidification of mine water. The sources of sulfate are quite different in water samples collected from the two selected mine. According to sulfur isotope analysis, the dissolution of gypsum is the primary source of sulfate in samples from Hongfa mine, whereas sulfide oxidation contributed a large amount of sulfate to the mine water in Fenghuangshan mine. The dissolution of carbonates should be an important source of DIC in mine water and CO 2 originating from organic mineralization might also have a certain contribution. This study elucidated the groundwater chemical evolution processes in high-sulfur coal-bearing strata and provided a foundation for further study of carbonates erosion and carbon emission during acidification of mine water.

Mechanisms by which moisture generates cocrystals.

PubMed

Jayasankar, Adivaraha; Good, David J; Rodríguez-Hornedo, Naír

2007-01-01

The purpose of this study is to determine the mechanisms by which moisture can generate cocrystals when solid particles of cocrystal reactants are exposed to deliquescent conditions (when moisture sorption forms an aqueous solution). It is based on the hypothesis that cocrystallization behavior during water uptake can be derived from solution chemistry using models that describe cocrystal solubility and reaction crystallization of molecular complexes. Cocrystal systems were selected with active pharmaceutical ingredients (APIs) that form hydrates and include carbamazepine, caffeine, and theophylline. Moisture uptake and crystallization behavior were studied by gravimetric vapor sorption, X-ray powder diffraction, and on-line Raman spectroscopy. Results indicate that moisture uptake generates cocrystals of carbamazepine-nicotinamide, carbamazepine-saccharin, and caffeine or theophylline with dicarboxylic acid ligands (oxalic acid, maleic acid, glutaric acid, and malonic acid) when solid mixtures with cocrystal reactants deliquesce. Microscopy studies revealed that the transformation mechanism to cocrystal involves (1) moisture uptake, (2) dissolution of reactants, and (3) cocrystal nucleation and growth. Studies of solid blends of reactants in a macro scale show that the rate and extent of cocrystal formation are a function of relative humidity, moisture uptake, deliquescent material, and dissolution rates of reactants. It is shown that the interplay between moisture uptake and dissolution determines the liquid phase composition, supersaturation, and cocrystal formation rates. Differences in the behavior of deliquescent additives (sucrose and fructose) are associated with moisture uptake and composition of the deliquesced solution. Our results show that deliquescence can transform API to cocrystal or reverse the reaction given the right conditions. Key indicators of cocrystal formation and stability are (1) moisture uptake, (2) cocrystal aqueous solubility, (3) solubility and dissolution of cocrystal reactants, and (4) transition concentration.

In vitro and in vivo evaluation of silybin nanosuspensions for oral and intravenous delivery

NASA Astrophysics Data System (ADS)

Wang, Yancai; Zhang, Dianrui; Liu, Zhaoping; Liu, Guangpu; Duan, Cunxian; Jia, Lejiao; Feng, Feifei; Zhang, Xiaoyu; Shi, Yanqiu; Zhang, Qiang

2010-04-01

In this study, we evaluate the effect of particle sizes on the physicochemical properties of silybin and identify the influence of silybin nanosuspensions on its permeation across the Caco-2 cell monolayer. In vivo pharmacokinetic evaluation of silybin nanosuspensions was also carried out in beagle dogs. TEM, AFM and SEM analyses revealed the effect of homogenization pressure on particle size and morphology, and confirmed the existence of a surfactant-stabilizer film on the surface of nanoparticles. DSC and XRPD experiments manifested that the crystalline state was maintained as particle size was reduced and the enhanced dissolution property was due to the increased surface area. Nanosuspensions had a significant influence on drug transport across the Caco-2 cell monolayer and the enhanced dissolution velocity was responsible for the increased permeability. A pharmacokinetics study in beagle dogs further confirmed the in vitro results and demonstrated that oral administration of silybin nanosuspensions significantly increase its bioavailability compared to the coarse powder. Nanosuspensions of silybin with smaller particle size reveal a higher potential to increase their oral bioavailability; while for intravenous infusion the lower pressure produced silybin nanosuspensions appeared to maintain a more sustained drug release profile.

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.

Dissolution-Driven Permeability Reduction of a Fractured Carbonate Caprock

PubMed Central

Ellis, Brian R.; Fitts, Jeffrey P.; Bromhal, Grant S.; McIntyre, Dustin L.; Tappero, Ryan; Peters, Catherine A.

2013-01-01

Abstract Geochemical reactions may alter the permeability of leakage pathways in caprocks, which serve a critical role in confining CO2 in geologic carbon sequestration. A caprock specimen from a carbonate formation in the Michigan sedimentary Basin was fractured and studied in a high-pressure core flow experiment. Inflowing brine was saturated with CO2 at 40°C and 10 MPa, resulting in an initial pH of 4.6, and had a calcite saturation index of −0.8. Fracture permeability decreased during the experiment, but subsequent analyses did not reveal calcite precipitation. Instead, experimental observations indicate that calcite dissolution along the fracture pathway led to mobilization of less soluble mineral particles that clogged the flow path. Analyses of core sections via electron microscopy, synchrotron-based X-ray diffraction imaging, and the first application of microbeam Ca K-edge X-ray absorption near edge structure, provided evidence that these occlusions were fragments from the host rock rather than secondary precipitates. X-ray computed tomography showed a significant loss of rock mass within preferential flow paths, suggesting that dissolution also removed critical asperities and caused mechanical closure of the fracture. The decrease in fracture permeability despite a net removal of material along the fracture pathway demonstrates a nonintuitive, inverse relationship between dissolution and permeability evolution in a fractured carbonate caprock. PMID:23633894

Co-grinding Effect on Crystalline Zaltoprofen with β-cyclodextrin/Cucurbit[7]uril in Tablet Formulation

PubMed Central

Li, Shanshan; Lin, Xiang; Xu, Kailin; He, Jiawei; Yang, Hongqin; Li, Hui

2017-01-01

This work aimed to investigate the co-grinding effects of β-cyclodextrin (β-CD) and cucurbit[7]uril (CB[7]) on crystalline zaltoprofen (ZPF) in tablet formulation. Crystalline ZPF was prepared through anti-solvent recrystallization and fully analyzed through single-crystal X-ray diffraction. Co-ground dispersions and mono-ground ZPF were prepared using a ball grinding process. Results revealed that mono-ground ZPF slightly affected the solid state, solubility, and dissolution of crystalline ZPF. Co-ground dispersions exhibited completely amorphous states and elicited a significant reinforcing effect on drug solubility. UV-vis spectroscopy, XRPD, FT-IR, DSC, ssNMR, and molecular docking demonstrated the interactions in the amorphous product. Hardness tests on blank tablets with different β-CD and CB[7] contents suggested the addition of β-CD or CB[7] could enhance the compressibility of the powder mixture. Disintegration tests showed that CB[7] could efficiently shorten the disintegrating time. Dissolution tests indicated that β-CD and CB[7] could accelerate the drug dissolution rate via different mechanisms. Specifically, CB[7] could accelerate the dissolution rate by improving disintegration and β-CD showed a distinct advantage in solubility enhancement. Based on the comparative study on β-CD and CB[7] for tablet formulation combined with co-grinding, we found that CB[7] could be considered a promising drug delivery, which acted as a disintegrant. PMID:28368030

Co-grinding Effect on Crystalline Zaltoprofen with β-cyclodextrin/Cucurbit[7]uril in Tablet Formulation.

PubMed

Li, Shanshan; Lin, Xiang; Xu, Kailin; He, Jiawei; Yang, Hongqin; Li, Hui

2017-04-03

This work aimed to investigate the co-grinding effects of β-cyclodextrin (β-CD) and cucurbit[7]uril (CB[7]) on crystalline zaltoprofen (ZPF) in tablet formulation. Crystalline ZPF was prepared through anti-solvent recrystallization and fully analyzed through single-crystal X-ray diffraction. Co-ground dispersions and mono-ground ZPF were prepared using a ball grinding process. Results revealed that mono-ground ZPF slightly affected the solid state, solubility, and dissolution of crystalline ZPF. Co-ground dispersions exhibited completely amorphous states and elicited a significant reinforcing effect on drug solubility. UV-vis spectroscopy, XRPD, FT-IR, DSC, ssNMR, and molecular docking demonstrated the interactions in the amorphous product. Hardness tests on blank tablets with different β-CD and CB[7] contents suggested the addition of β-CD or CB[7] could enhance the compressibility of the powder mixture. Disintegration tests showed that CB[7] could efficiently shorten the disintegrating time. Dissolution tests indicated that β-CD and CB[7] could accelerate the drug dissolution rate via different mechanisms. Specifically, CB[7] could accelerate the dissolution rate by improving disintegration and β-CD showed a distinct advantage in solubility enhancement. Based on the comparative study on β-CD and CB[7] for tablet formulation combined with co-grinding, we found that CB[7] could be considered a promising drug delivery, which acted as a disintegrant.

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.

Co-grinding Effect on Crystalline Zaltoprofen with β-cyclodextrin/Cucurbit[7]uril in Tablet Formulation

NASA Astrophysics Data System (ADS)

Li, Shanshan; Lin, Xiang; Xu, Kailin; He, Jiawei; Yang, Hongqin; Li, Hui

2017-04-01

This work aimed to investigate the co-grinding effects of β-cyclodextrin (β-CD) and cucurbit[7]uril (CB[7]) on crystalline zaltoprofen (ZPF) in tablet formulation. Crystalline ZPF was prepared through anti-solvent recrystallization and fully analyzed through single-crystal X-ray diffraction. Co-ground dispersions and mono-ground ZPF were prepared using a ball grinding process. Results revealed that mono-ground ZPF slightly affected the solid state, solubility, and dissolution of crystalline ZPF. Co-ground dispersions exhibited completely amorphous states and elicited a significant reinforcing effect on drug solubility. UV-vis spectroscopy, XRPD, FT-IR, DSC, ssNMR, and molecular docking demonstrated the interactions in the amorphous product. Hardness tests on blank tablets with different β-CD and CB[7] contents suggested the addition of β-CD or CB[7] could enhance the compressibility of the powder mixture. Disintegration tests showed that CB[7] could efficiently shorten the disintegrating time. Dissolution tests indicated that β-CD and CB[7] could accelerate the drug dissolution rate via different mechanisms. Specifically, CB[7] could accelerate the dissolution rate by improving disintegration and β-CD showed a distinct advantage in solubility enhancement. Based on the comparative study on β-CD and CB[7] for tablet formulation combined with co-grinding, we found that CB[7] could be considered a promising drug delivery, which acted as a disintegrant.

UV-vis Imaging of Piroxicam Supersaturation, Precipitation, and Dissolution in a Flow-Through Setup.

PubMed

Sun, Yu; Chapman, Alex; Larsen, Susan W; Jensen, Henrik; Petersen, Nickolaj J; Goodall, David M; Østergaard, Jesper

2018-06-05

Evaluation of drug precipitation is important in order to address challenges regarding low and variable bioavailability of poorly water-soluble drugs, to assess potential risk of patient safety with infusion therapy, and to explore injectable in situ suspension-forming drug delivery systems. Generally, drug precipitation is assessed in vitro through solution concentration analysis methods. Dual-wavelength UV-vis imaging is a novel imaging technique that may provide an opportunity for simultaneously monitoring changes in both solution and solid phases during precipitation. In the present study, a multimodal approach integrating UV-vis imaging, light microscopy, and Raman spectroscopy was developed for characterization of piroxicam supersaturation, precipitation, and dissolution in a flow-through setup. A solution of piroxicam dissolved in 1-methyl-2-pyrrolidinone was injected into a flowing aqueous environment (pH 7.4), causing piroxicam to precipitate. Imaging at 405 and 280 nm monitored piroxicam concentration distributions during precipitation and revealed different supersaturation levels dependent on the initial concentration of the piroxicam solution. The combination with imaging at 525 nm, light microscopy, and Raman spectroscopy measurements demonstrated concentration-dependent precipitation and the formation, growth, and dissolution of individual particles. Results emphasize the importance of the specific hydrodynamic conditions on the piroxicam precipitation. The approach used may facilitate comprehensive understanding of drug precipitation and dissolution processes and may be developed further into a basic tool for formulation screening and development.

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

Effect of micro-environment modification and polymer type on the in-vitro dissolution behavior and in-vivo performance of amorphous solid dispersions.

PubMed

Sun, Weiwei; Pan, Baoliang

2017-06-15

This study investigates the effects of micro-environment modification and polymer type on the in-vitro dissolution behavior and in-vivo performance of micro-environment pH modifying solid dispersions (pH M -SD) for the poorly water-soluble model drug Toltrazuril (TOL). Various pH M -SDs were prepared using Ca(OH) 2 as a pH-modifier in hydrophilic polymers, including polyethylene glycol 6000 (PEG6000), polyvinylpyrrolidone k30 (PVPk30) and hydroxypropyl methylcellulose (HPMC). Based on the results of physicochemical characterizations and in-vitro dissolution testing, the representative ternary (Ca(OH) 2 :TOL:PEG6000/HPMC/PVPk30=1:8:24, w/w/w) and binary (TOL:PVPk30=1:3, w/w) solid dispersions were selected and optimized to perform in-vivo pharmacokinetic study. The micro-environment pH modification improved the in-vitro water-solubility and in-vivo bioavailability of parent drug TOL. Furthermore, the addition of alkalizers not only enhanced the release and absorption of prototype drug, but also promoted the generation of active metabolites, including toltrazuril sulfoxide (TOLSO) and toltrazuril sulfone (TOLSO 2 ). The in-vitro dissolution profiles and in-vivo absorption, distribution and metabolism behaviors of the pH M -SDs varied with polymer type. Moreover, in-vivo bioavailability of three active pharmaceutical ingredients increased with an increase in in-vitro dissolution rates of the drug from the pH M -SDs prepared with various polymers. Therefore, a non-sink in-vitro dissolution method can be used to predict the in-vivo performance of pH M -SDs formulated with various polymers with trend consistency. In-vitro and in-vivo screening procedures revealed that the pH M -SD composed of Ca(OH) 2 , TOL and PVPk30 at a weight ratio of 1:8:24, of which the safety was adequately proved via histopathological examination, may be a promising candidate for providing better clinical outcomes. Copyright © 2017. Published by Elsevier B.V.

Surface potential driven dissolution phenomena of [0 0 0 1]-oriented ZnO nanorods grown from ZnO and Pt seed layers

NASA Astrophysics Data System (ADS)

Seo, Youngmi; Kim, Jung Hyeun

2011-06-01

Highly oriented ZnO nanorods are synthesized hydrothermally on ZnO and Pt seed layers, and they are dissolved in KOH solution. The rods grown on ZnO seed layer show uniform dissolution, but those grown on Pt seed layer are rod-selectively dissolved. The ZnO nanorods from both seed layers show the same crystalline structure through XRD and Raman spectrometer data. However, the surface potential analysis reveals big difference for ZnO and Pt seed cases. The surface potential distribution is very uniform for the ZnO seed case, but it is much fluctuated on the Pt seed case. It suggests that the rod-selective dissolution phenomena on Pt seed case are likely due to the surface energy difference.

Mechanistic understanding of the link between Sodium Starch Glycolate properties and the performance of tablets made by wet granulation.

PubMed

Wren, S A C; Alhusban, F; Barry, A R; Hughes, L P

2017-08-30

The impact of varying Sodium Starch Glycolate (SSG) grade and wet granulation intensity on the mechanism of disintegration and dissolution of mannitol-based Immediate Release (IR) placebo tablets was investigated. MRI and 1 H NMR provided mechanistic insight, and revealed a four-fold range in both tablet disintegration and dissolution rates. MRI was used to quantify the rates of change in tablet volumes and the data fitted to a hydration/erosion model. Reduced levels of cross-linking change SSG from a swelling to a gelling matrix. The tablet hydration and dissolution rates are related to the viscosity at the tablet-solution interface, with high viscosities limiting mass transport. Copyright © 2017 Elsevier B.V. All rights reserved.

Experimental and theoretical investigation of the inhibitory effect of new pyridazine derivatives for the corrosion of mild steel in 1 M HCl

NASA Astrophysics Data System (ADS)

Mashuga, Motsie E.; Olasunkanmi, Lukman O.; Ebenso, Eno E.

2017-05-01

The effects of four pyridazine derivatives namely, 2-(6-chloropyridazin-3-yl)-2-phenylacetonitrile (P1), 3-(6-chloro-3-pyridazinyl)-1H-indole (P2), 4-(6-chloropyridazin-3-yl)benzoic acid (P3) and 3-(6-chloropyridazin-3-yl)benzoic acid (P4) on electrochemical dissolution of mild steel in 1 M HCl were studied using electrochemical, spectroscopic, and theoretical computational chemistry techniques. The inhibition efficiency increases with increasing concentration of the inhibitors and the shift in corrosion potentials obtained revealed that the compounds are mixed-type inhibitors and steel dissolution was found to be a charge transfer process with the steel/electrolyte interface showed pseudo-capacitive behaviour. P1 and P2 showed the best protection performances for mild steel in the studied medium, attributable to the presence of more nitrogen atoms and unsaturated groups in their molecules compared to P3 and P4. The experimental adsorption data obeyed the Langmuir and Temkin isotherm models and was found to involve both physisorption and chemisorption. Spectroscopic studies revealed that the inhibitor molecules interact chemically with mild steel and the pyridazine ring is actively involved in these interactions. Quantum chemical calculations also showed that pyridazine ring has the tendency of interacting with metallic atoms via both forward and backward donations. Molecular dynamic simulation revealed that the molecules can adsorb strongly onto the surface of iron in a near flat orientation.

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.

Colloid-associated plutonium aged at room temperature: evaluating its transport velocity in saturated coarse-grained granites

NASA Astrophysics Data System (ADS)

Xie, Jinchuan; Lin, Jianfeng; Wang, Yu; Li, Mei; Zhang, Jihong; Zhou, Xiaohua; He, Yifeng

2015-01-01

The fate and transport of colloidal contaminants in natural media are complicated by physicochemical properties of the contaminants and heterogeneous characteristics of the media. Size and charge exclusion are two key microscopic mechanisms dominating macroscopic transport velocities. Faster velocities of colloid-associated actinides than that of 3H2O were consistently indicated in many studies. However, dissociation/dissolution of these sorbed actinides (e.g., Pu and Np), caused by their redox reactions on mineral surfaces, possibly occurred under certain chemical conditions. How this dissolution is related to transport velocities remains unanswered. In this study, aging of the colloid-associated Pu (pseudo-colloid) at room temperature and transport through the saturated coarse-grained granites were performed to study whether Pu could exhibit slower velocity than that of 3H2O (UPu/UT < 1). The results show that oxidative dissolution of Pu(IV) associated with the surfaces of colloidal granite particles took place during the aging period. The relative velocity of UPu/UT declined from 1.06 (unaged) to 0.745 (135 d) over time. Size exclusion limited to the uncharged nano-sized particles could not explain such observed UPu/UT < 1. Therefore, the decline in UPu/UT was ascribed to the presence of electrostatic attraction between the negatively charged wall of granite pore channels and the Pu(V)O2+, as evidenced by increasing Pu(V)O2+ concentrations in the suspensions aged in sealed vessels. As a result of this attraction, Pu(V)O2+ was excluded from the domain closer to the centerline of pore channels. This reveals that charge exclusion played a more important role in dominating UPu than the size exclusion under the specific conditions, where oxidative dissolution of colloid-associated Pu(IV) was observed in the aged suspensions.

Dissolution of bovine pulp tissue in solutions consisting of varying NaOCl concentrations and combined with EDTA.

PubMed

Irala, Luis Eduardo Duarte; Grazziotin-Soares, Renata; Salles, Alexandre Azevedo; Munari, Aline Zen; Pereira, Joseani Santos

2010-01-01

This in vitro study evaluated (1) the dissolution of bovine pulp tissue in solutions consisting of varying NaOCl concentrations and combined with EDTA; and (2) the pH of these solutions before and after the experiment. The independent variables were the concentration and the volume of the solution. Thirty bovine pulps were divided in equal fragments, resulting in 90 fragments of pulp tissue. Each fragment was immersed in one of the following solutions: 1% NaOCl (4 ml), 2.5% NaOCl (4 ml), 1% NaOCl + 17% EDTA (2 ml : 2 ml), 1% NaOCl + 17% EDTA (1 ml : 3 ml), 2.5% NaOCl + 17% EDTA (2 ml : 2 ml), and 2.5% NaOCl + 17% EDTA (1 ml : 3 ml). The test solutions were dichotomized as either able or not able to dissolve the tissue, the latter being attributed when the dissolution of the pulp tissue was not complete within 48 hours. When the samples were able to dissolve the tissue, the time required for complete tissue dissolution was submitted to statistical analysis. The pH of the solutions was measured before and after the experiment. The pH variable was dichotomized as either changed or unchanged. The results demonstrated that the NaOCl solutions combined with 17% EDTA were not able to dissolve the tissue. The t-test revealed that the 2.5% NaOCl solution presented a lower mean dissolution time than the 1% NaOCl solution (p < 0.001). The pH of the solutions with equal volumes of NaOCl and EDTA decreased in 48 hours.

Audio-magnetotelluric surveys to constrain the origin of a network of narrow synclines in Eocene limestone, Western Desert, Egypt

NASA Astrophysics Data System (ADS)

Tarabees, Elhamy A.; Tewksbury, Barbara J.; Mehrtens, Charlotte J.; Younis, Abdellatif

2017-12-01

Recent work with high resolution satellite imagery has revealed a network of narrow synclines developed during the Oligocene or Miocene over tens of thousands of square kilometers in Eocene limestone of the Thebes Group in the Western Desert of Egypt. The synclines are non-tectonic, and their scale and geometry strongly resemble sag synclines in Qatar that were produced by dissolution of subsurface evaporites and resulting sag of overlying layers. Evaporite dissolution cannot explain the Egypt synclines, because subsurface evaporites of any significance have never been reported in this part of Egypt. In this study, we use audio-magnetotelluric surveys to illuminate the subsurface under the synclines in order to constrain possible models for their formation. We suspected karst dissolution at depth, and, given a modern water table depth of over 400 m, we expected that dry fracture networks and void spaces under the synclines might result in higher electrical resistivities than surrounding coherent limestone. We also anticipated a significant change from high to low resistivity at the contact between the Thebes Group and the underlying Esna Shale at depths of 400 m or more. Instead, we found localized low resistivity zones extending from about 50-100 m below the surface to depths of more than 400 m that are strongly correlated with synclines. We suggest that these localized low resistivity zones are filled with artesian groundwater that has insufficient hydraulic head to rise to the modern topographic surface and that is localized in subsurface voids and collapse breccias produced by dissolution. Sag of overlying limestone layers is a reasonable model for syncline formation but, given the Oligocene/Miocene age of the synclines, dissolution and sag would be unrelated to young groundwater processes.

Indomethacin nanocrystals prepared by different laboratory scale methods: effect on crystalline form and dissolution behavior

NASA Astrophysics Data System (ADS)

Martena, Valentina; Censi, Roberta; Hoti, Ela; Malaj, Ledjan; Di Martino, Piera

2012-12-01

The objective of this study is to select very simple and well-known laboratory scale methods able to reduce particle size of indomethacin until the nanometric scale. The effect on the crystalline form and the dissolution behavior of the different samples was deliberately evaluated in absence of any surfactants as stabilizers. Nanocrystals of indomethacin (native crystals are in the γ form) (IDM) were obtained by three laboratory scale methods: A (Batch A: crystallization by solvent evaporation in a nano-spray dryer), B (Batch B-15 and B-30: wet milling and lyophilization), and C (Batch C-20-N and C-40-N: Cryo-milling in the presence of liquid nitrogen). Nanocrystals obtained by the method A (Batch A) crystallized into a mixture of α and γ polymorphic forms. IDM obtained by the two other methods remained in the γ form and a different attitude to the crystallinity decrease were observed, with a more considerable decrease in crystalline degree for IDM milled for 40 min in the presence of liquid nitrogen. The intrinsic dissolution rate (IDR) revealed a higher dissolution rate for Batches A and C-40-N, due to the higher IDR of α form than γ form for the Batch A, and the lower crystallinity degree for both the Batches A and C-40-N. These factors, as well as the decrease in particle size, influenced the IDM dissolution rate from the particle samples. Modifications in the solid physical state that may occur using different particle size reduction treatments have to be taken into consideration during the scale up and industrial development of new solid dosage forms.

Evaluating the role of re-adsorption of dissolved Hg 2+ during cinnabar dissolution using isotope tracer technique

DOE PAGES

Jiang, Ping; Li, Yanbin; Liu, Guangliang; ...

2016-06-02

Cinnabar dissolution is an important factor controlling mercury (Hg) cycling. Recent studies have suggested the co-occurrence of re-adsorption of the released Hg during the course of cinnabar dissolution. However, there is a lack of feasible techniques that can quantitatively assess the amount of Hg re-adsorbed on cinnabar when investigating cinnabar dissolution. In this study, a new method, based on isotope tracing and dilution techniques, was developed to study the role of Hg re-adsorption in cinnabar dissolution. The developed method includes two key components: (1) accurate measurement of both released and spiked Hg in aqueous phase and (2) estimation of re-adsorbedmore » Hg on cinnabar surface via the reduction in spiked 202Hg 2+. By adopting the developed method, it was found that the released Hg for trials purged with oxygen could reach several hundred g L –1, while no significant cinnabar dissolution was detected under anaerobic condition. Cinnabar dissolution rate when considering Hg re-adsorption was approximately 2 times the value calculated solely with the Hg detected in the aqueous phase. Lastly, these results suggest that ignoring the Hg re-adsorption process can significantly underestimate the importance of cinnabar dissolution, highlighting the necessity of applying the developed method in future cinnabar dissolution studies.« less

Electrochemical Dissolution of Iridium and Iridium Oxide Particles in Acidic Media: Transmission Electron Microscopy, Electrochemical Flow Cell Coupled to Inductively Coupled Plasma Mass Spectrometry, and X-ray Absorption Spectroscopy Study.

PubMed

Jovanovič, Primož; Hodnik, Nejc; Ruiz-Zepeda, Francisco; Arčon, Iztok; Jozinović, Barbara; Zorko, Milena; Bele, Marjan; Šala, Martin; Šelih, Vid Simon; Hočevar, Samo; Gaberšček, Miran

2017-09-13

Iridium-based particles, regarded as the most promising proton exchange membrane electrolyzer electrocatalysts, were investigated by transmission electron microscopy and by coupling of an electrochemical flow cell (EFC) with online inductively coupled plasma mass spectrometry. Additionally, studies using a thin-film rotating disc electrode, identical location transmission and scanning electron microscopy, as well as X-ray absorption spectroscopy have been performed. Extremely sensitive online time-and potential-resolved electrochemical dissolution profiles revealed that Ir particles dissolve well below oxygen evolution reaction (OER) potentials, presumably induced by Ir surface oxidation and reduction processes, also referred to as transient dissolution. Overall, thermally prepared rutile-type IrO 2 particles are substantially more stable and less active in comparison to as-prepared metallic and electrochemically pretreated (E-Ir) analogues. Interestingly, under OER-relevant conditions, E-Ir particles exhibit superior stability and activity owing to the altered corrosion mechanism, where the formation of unstable Ir(>IV) species is hindered. Due to the enhanced and lasting OER performance, electrochemically pre-oxidized E-Ir particles may be considered as the electrocatalyst of choice for an improved low-temperature electrochemical hydrogen production device, namely a proton exchange membrane electrolyzer.

Looking for the Self: Phenomenology, Neurophysiology and Philosophical Significance of Drug-induced Ego Dissolution

PubMed Central

Millière, Raphaël

2017-01-01

There is converging evidence that high doses of hallucinogenic drugs can produce significant alterations of self-experience, described as the dissolution of the sense of self and the loss of boundaries between self and world. This article discusses the relevance of this phenomenon, known as “drug-induced ego dissolution (DIED)”, for cognitive neuroscience, psychology and philosophy of mind. Data from self-report questionnaires suggest that three neuropharmacological classes of drugs can induce ego dissolution: classical psychedelics, dissociative anesthetics and agonists of the kappa opioid receptor (KOR). While these substances act on different neurotransmitter receptors, they all produce strong subjective effects that can be compared to the symptoms of acute psychosis, including ego dissolution. It has been suggested that neuroimaging of DIED can indirectly shed light on the neural correlates of the self. While this line of inquiry is promising, its results must be interpreted with caution. First, neural correlates of ego dissolution might reveal the necessary neurophysiological conditions for the maintenance of the sense of self, but it is more doubtful that this method can reveal its minimally sufficient conditions. Second, it is necessary to define the relevant notion of self at play in the phenomenon of DIED. This article suggests that DIED consists in the disruption of subpersonal processes underlying the “minimal” or “embodied” self, i.e., the basic experience of being a self rooted in multimodal integration of self-related stimuli. This hypothesis is consistent with Bayesian models of phenomenal selfhood, according to which the subjective structure of conscious experience ultimately results from the optimization of predictions in perception and action. Finally, it is argued that DIED is also of particular interest for philosophy of mind. On the one hand, it challenges theories according to which consciousness always involves self-awareness. On the other hand, it suggests that ordinary conscious experience might involve a minimal kind of self-awareness rooted in multisensory processing, which is what appears to fade away during DIED. PMID:28588463

Influence of oxalic acid on the dissolution kinetics of manganese oxide

NASA Astrophysics Data System (ADS)

Godunov, E. B.; Artamonova, I. V.; Gorichev, I. G.; Lainer, Yu. A.

2012-11-01

The kinetics and electrochemical processes of the dissolution of manganese oxides with various oxidation states in sulfuric acid solutions containing oxalate ion additives is studied under variable conditions (concentration, pH, temperature). The parameters favoring a higher degree of the dissolution of manganese oxides in acidic media are determined. The optimal conditions are found for the dissolution of manganese oxides in acidic media in the presence of oxalate ions. The mechanism proposed for the dissolution of manganese oxides in sulfuric acid solutions containing oxalic acid is based on the results of kinetic and electrochemical studies. The steps of the dissolution mechanism are discussed.

Influence of Heterogamy by Religion on Risk of Marital Dissolution: A Cohort Study of 20,000 Couples.

PubMed

Wright, David M; Rosato, Michael; O'Reilly, Dermot

2017-01-01

Heterogamous marriages, in which partners have dissimilar attributes (e.g. by socio-economic status or ethnicity), are often at elevated risk of dissolution. We investigated the influences of heterogamy by religion and area of residence on risk of marital dissolution in Northern Ireland, a country with a history of conflict and residential segregation along Catholic-Protestant lines. We expected Catholic-Protestant marriages to have elevated risks of dissolution, especially in areas with high concentrations of a single religious group where opposition to intermarriage was expected to be high. We estimated risks of marital dissolution from 2001 to 2011 for 19,791 couples drawn from the Northern Ireland Longitudinal Study (a record linkage study), adjusting for a range of compositional and contextual factors using multilevel logistic regression. Dissolution risk decreased with increasing age and higher socio-economic status. Catholic-Protestant marriages were rare (5.9 % of the sample) and were at increased risk of dissolution relative to homogamous marriages. We found no association between local population composition and dissolution risk for Catholic-Protestant couples, indicating that partner and household characteristics may have a greater influence on dissolution risk than the wider community.

Dissolution enhancement of tadalafil by liquisolid technique.

PubMed

Lu, Mei; Xing, Haonan; Yang, Tianzhi; Yu, Jiankun; Yang, Zhen; Sun, Yanping; Ding, Pingtian

2017-02-01

This study aimed to enhance the dissolution of tadalafil, a poorly water-soluble drug by applying liquisolid technique. The effects of two critical formulation variables, namely drug concentration (17.5% and 35%, w/w) and excipients ratio (10, 15 and 20) on dissolution rates were investigated. Pre-compression tests, including particle size distribution, flowability determination, Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and scanning electron microscopy (SEM), were carried out to investigate the mechanism of dissolution enhancement. Tadalafil liquisolid tablets were prepared and their quality control tests, dissolution study, contact angle measurement, Raman mapping, and storage stability test were performed. The results suggested that all the liquisolid tablets exhibited significantly higher dissolution rates than the conventional tablets and pure tadalafil. FT-IR spectrum reflected no drug-excipient interactions. DSC and XRD studies indicated reduction in crystallinity of tadalafil, which was further confirmed by SEM and Raman mapping outcomes. The contact angle measurement demonstrated obvious increase in wetting property. Taken together, the reduction of particle size and crystallinity, and the improvement of wettability were the main mechanisms for the enhanced dissolution rate. No significant changes were observed in drug crystallinity and dissolution behavior after storage based on XRD, SEM and dissolution results.

The effects of physicochemical properties of CeO2 nanoparticles on toxicity to soil denitrification processes

NASA Astrophysics Data System (ADS)

Dahle, Jessica Teague

The studies presented in this thesis identify the impact of NP CeO 2 on soil denitrifying microbial communities and reveal that physical and chemical characteristics including particle size, speciation, concentration, pH, and presence of ligands are key to predicting environmental fate and reactivity of NP CeO2 in the soil. A review of the literature in Chapter 1 revealed a widespread lack of toxicological information for soil exposures to NP CeO2. Soil denitrifying bacteria are a keystone species because they serve an important role in the global nitrogen cycle controlling the atmospheric nitrogen input. Soil denitrifiers are important to this study because the reducing conditions during denitrification could induce phase transformation of Ce(IV) to Ce(III), potentially influencing the toxicity of Ce. Cerium is well known for being the only lanthanide that is thermodynamically stable in both the trivalent and tetravalent state in low temperature geochemical environments. Using well characterized NP Ce(IV)O 2 as well as bulk soluble Ce(III), batch denitrification experiments were conducted to evaluate the toxicity of Ce species to the denitrifying community in a Toccoa sandy loam soil. The statistical analysis on the antimicrobial effect on soil denitrifiers was conducted using both steady-state evaluation and zero-order kinetic models in order to compare the toxicity of the Ce(III) species to the NPs. These studies, presented in Chapter 3, show that soluble Ce(III) is far more toxic than Ce(IV)O2 NPs when an equal total concentration of Ce is used, though both species exhibit toxicity to the denitrifiers via statistically significant inhibition of soil denitrification processes. Particle-size dependent toxicity, species-dependent toxicity, and concentration-dependent toxicity were all observed in this study for both the steady-state and the kinetic evaluations. The possibility of toxicity enhancement and diminishment via dissolution and ligand complexation pathways was investigated thoroughly in Chapter 2. In addition to the equilibrium and kinetic-based toxicological assessments presented in Chapter 1, dissolution and sorption experiments were performed to gain an overall understanding of Ce biogeochemistry in the terrestrial environment post-release and reveal possible geochemical controls on toxicity. It was shown that dissolution of bioavailable Ce is pH-dependent; dissolution is only detectable at acidic pH values (< pH 5) and increases with increasing acidity. Dissolution of Ce from NP CeO2 was identified to be almost 100% Ce(III). It was also demonstrated that this dissolution is suppressed by the addition of phosphate ligand, which is largely bioavailable in soils, especially in agricultural lands. This suppression was explained by the strong sorption of phosphate ligand to NP CeO2. The elimination of bioavailable Ce(III) release from NP CeO2 by phosphate ligand is likely one of the most important controls on toxicity effects and should be a large consideration in determining the fate and transport of NP CeO2 in the aquatic and terrestrial environment. It was also demonstrated that both Ce(III) and NP CeO2 have extremely strong affinity for sorption to soil matter, which could serve as another controlling pathway. Experiments indicated that factors such as reductive transformation of NP CeO2 in soils and exchangeable Ce(III) impurity in the NPs could contribute to controls on toxicity as well. In conclusion, the studies presented in this thesis indicate that the toxicity effects of the studied Ce species to soil denitrifiers are strongly affected by physical and chemical characteristics such as speciation, pH, and bioavailable ligands. As the global market for nanomaterials rapidly expands, so does the need of the scientific community for an understanding of how these influences in environmental fate and reactivity may be key in assessing toxicological risks associated with environmental exposures to NP CeO2 as well as other engineered metal oxide nanoparticles. (Abstract shortened by UMI.)

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.

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

Jiang, Ping; Li, Yanbin; Liu, Guangliang

Cinnabar dissolution is an important factor controlling mercury (Hg) cycling. Recent studies have suggested the co-occurrence of re-adsorption of the released Hg during the course of cinnabar dissolution. However, there is a lack of feasible techniques that can quantitatively assess the amount of Hg re-adsorbed on cinnabar when investigating cinnabar dissolution. In this study, a new method, based on isotope tracing and dilution techniques, was developed to study the role of Hg re-adsorption in cinnabar dissolution. The developed method includes two key components: (1) accurate measurement of both released and spiked Hg in aqueous phase and (2) estimation of re-adsorbedmore » Hg on cinnabar surface via the reduction in spiked 202Hg 2+. By adopting the developed method, it was found that the released Hg for trials purged with oxygen could reach several hundred g L –1, while no significant cinnabar dissolution was detected under anaerobic condition. Cinnabar dissolution rate when considering Hg re-adsorption was approximately 2 times the value calculated solely with the Hg detected in the aqueous phase. Lastly, these results suggest that ignoring the Hg re-adsorption process can significantly underestimate the importance of cinnabar dissolution, highlighting the necessity of applying the developed method in future cinnabar dissolution studies.« less

Improvement of Physico-mechanical Properties of Partially Amorphous Acetaminophen Developed from Hydroalcoholic Solution Using Spray Drying Technique

PubMed Central

Sadeghi, Fatemeh; Torab, Mansour; Khattab, Mostafa; Homayouni, Alireza; Afrasiabi Garekani, Hadi

2013-01-01

Objective(s): This study was performed aiming to investigate the effect of particle engineering via spray drying of hydroalcoholic solution on solid states and physico-mechanical properties of acetaminophen. Materials and Methods: Spray drying of hydroalcoholic solution (25% v/v ethanol/water) of acetaminophen (5% w/v) in the presence of small amounts of polyninylpyrrolidone K30 (PVP) (0, 1.25, 2.5 and 5% w/w based on acetaminophen weight) was carried out. The properties of spray dried particles namely morphology, surface characteristics, particle size, crystallinity, dissolution rate and compactibility were evaluated. Results: Spray drying process significantly changed the morphology of acetaminophen crystals from acicular (rod shape) to spherical microparticle. Differential scanning calorimetery (DSC) and x-ray powder diffraction (XRPD) studies ruled out any polymorphism in spray dried samples, however, a major reduction in crystallinity up to 65%, especially for those containing 5% w/w PVP was observed. Spray dried acetaminophen particles especially those obtained in the presence of PVP exhibited an obvious improvement of the dissolution and compaction properties. Tablets produced from spray dried samples exhibited excellent crushing strengths and no tendency to cap. Conclusions: The findings of this study revealed that spray drying of acetaminophen from hydroalcoholic solution in the presence of small amount of PVP produced partially amorphous particles with improved dissolution and excellent compaction properties. PMID:24379968

Glass–water interaction: Effect of high-valence cations on glass structure and chemical durability

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

Hopf, J.; Kerisit, Sebastien N.; Angeli, F.

2016-05-15

Borosilicate glass is a durable solid, but it dissolves when in contact with aqueous fluids. The dissolution mechanism, which involves a variety of sequential reactions that occur at the solid-fluid interface, has important implications for the corrosion resistance of industrial and nuclear waste glasses. In this study, spectroscopic measurements, dissolution experiments, and Monte Carlo simulations were performed to investigate the effect of high–valence cations (HVC) on the mechanisms of glass dissolution under dilute and near-saturated conditions. Raman and NMR spectroscopy were used to determine the structural changes that occur in glass, specifically network formers (e.g., Al, Si, and B), withmore » the addition of the HVC element hafnium in the Na2O–Al2O3–B2O3–HfO2–SiO2 system (e.g., Na/[Al+B] = 1.0 and HfO2/SiO2 from 0.0 to 0.42). Spectroscopic measurements revealed that increasing hafnium content decreases N4 (tetrahedral boron/total boron) and increases the amount of Si—O—Hf moieties in the glass. Results from flow–through experiments conducted under dilute and near–saturated conditions show a decrease of approximately 100× or more in the dissolution rate over the series from 0 to 20 mol% HfO2. Comparing the average steady-state rates obtained under dilute conditions to the rates obtained for near-saturated conditions reveals a divergence in the magnitude between the average steady state rates measured in these different conditions. The reason for this divergence was investigated more thoroughly using Monte Carlo simulations. Simulations indicate that the divergence in glass dissolution behavior under dilute and near-saturated conditions result from the stronger binding of Si sites that deposit on the surface from the influent when Hf is present in the glass. As a result, the residence time at the glass surface of these newly-formed Si sites is longer in the presence of Hf, which increases the density of anchor sites from which altered layers with higher Si densities can form. These results illustrate the importance of understanding solid–water/solid-fluid interactions by linking macroscopic reaction kinetics to nanometer scale interfacial processes.« less

Dissolution of man-made vitreous fibers in rat alveolar macrophage culture and Gamble's saline solution: influence of different media and chemical composition of the fibers.

PubMed Central

Luoto, K; Holopainen, M; Karppinen, K; Perander, M; Savolainen, K

1994-01-01

The effect of different chemical compositions of man-made vitreous fibers (MMVF) on their dissolution by alveolar macrophages (AM) in culture and in Gamble's solution was studied. The fibers were exposed to cultured rat AMs, culture medium alone; or Gamble's saline solution for 2, 4, or 8 days. The dissolution of the fibers was studied by measuring the amount of silicon (Si), iron (Fe), and aluminum (Al) in each medium. The AMs in culture dissolved Fe and Al from the fibers but the dissolution of Si was more marked in the cell culture medium without cells and in the Gamble's solution. The dissolution of Si, Fe, and Al was different for different fibers, and increased as a function of time. The Fe and Al content of the fibers correlated negatively with the dissolution of Si by AMs from the MMVF, i.e., when the content of Fe and Al of the fibers increased the dissolution of Si decreased. These results suggest that the chemical composition of MMVFs has a marked effect on their dissolution. AMs seem to affect the dissolution of Fe and Al from the fibers. This suggests that in vitro models with cells in the media rather than only culture media or saline solutions would be preferable in dissolution studies of MMVFs. PMID:7882911

Viewing Molecular and Interface Interactions of Curcumin Amorphous Solid Dispersions for Comprehending Dissolution Mechanisms.

PubMed

Li, Jing; Wang, Xin; Li, Chang; Fan, Na; Wang, Jian; He, Zhonggui; Sun, Jin

2017-08-07

Tautomeric curcumin amorphous solid dispersions (Cur ASDs) formulated with various typical polymers (polyethylene glycol 6000 (PEG), polyvinylpyrrolidone K30 (PVP), Eudragit EPO (EuD), EuD/hydroxypropylmethyl cellulose E50 (HPMC), and PVP/EuD) were probed using in situ Raman imaging plus spectroscopy and molecular modeling techniques, and dissolution mechanism of Cur ASDs were revealed mainly through molecular and interfacial interactions formed between Cur and polymer. The results demonstrated that Cur of keto form existed in Cur-PEG, Cur of enol form was shown in Cur-PVP, while Cur-EuD or Cur ASDs formulated with EuD as component had Cur of keto form and enol form. Hydrogen bond interactions were formed between OH group (PEG, HPMC) with C═O (Cur), and C═O (PVP or EuD) with the OH group (Cur). For Cur ASDs formulated with single polymer, the existed form of Cur was possibly related with the molecular interactions formed between drug and polymer. The wetting effect of excipient and Cur ASDs as well as their fitting equations of contact angle profiles should be seriously considered when analyzing the dissolution mechanism of Cur ASDs. Furthermore, dissolution of Cur-EuD with erosion dissolution pattern was higher than Cur-PVP with diffusion mechanism, and their crystallization pathway can ascribe to solution pathway and solid matrix pathway, respectively. Last but not least, turbidimetry method was effective in determining which excipient was superior and evaluating the function of polymers, including their abilities to improve amorphous Cur loading, drug dissolution, and supersaturation levels. Therefore, both the probing of tautomeric Cur in ASDs at intermolecular level and elucidation of its dissolution mechanism has tremendous value.

Karst landforms revealed at various scales using LiDAR and UAV in semi-arid Brazil: Consideration on karstification processes and methodological constraints

NASA Astrophysics Data System (ADS)

Silva, Orildo L.; Bezerra, Francisco H. R.; Maia, Rubson P.; Cazarin, Caroline L.

2017-10-01

This paper analyzes different types of karst landforms and their relationships with fracture systems, sedimentary bedding, and fluvial processes. We mapped karst features in the Cretaceous carbonates of the Jandaíra Formation in the Potiguar Basin, Brazil. We used high-resolution digital elevation models acquired using LiDAR and aerial orthophotographs acquired using an unmanned aerial vehicle (UAV). We grouped and described karst evolution according to scale and degree of karstification. These degrees of karst evolution are coeval. Fractures are opened by dissolution, forming vertical fluid conduits, whereas coeval dissolution occurs along horizontal layers. This conduit system acts as pathways for water flow. The enlargement of conduits contributes to the collapse of blocks in sinkholes and expansion of caves during an intermediate degree of karstification. Propagation of dissolution can cause the coalescence of sinkholes and the capture of small streams. Fluvial processes dominate karst dissolution at an advanced degree of karstification. Comparisons with previously published ground-penetrating radar (GPR), borehole and seismic surveys in sedimentary basins indicate that these structures can be partially preserved during burial.

Anion-Dependent Potential Precycling Effects on Lithium Deposition/Dissolution Reaction Studied by an Electrochemical Quartz Crystal Microbalance.

PubMed

Smaran, Kumar Sai; Shibata, Sae; Omachi, Asami; Ohama, Ayano; Tomizawa, Eika; Kondo, Toshihiro

2017-10-19

The electrochemical quartz crystal microbalance technique was employed to study the initial stage of the electrodeposition and dissolution of lithium utilizing three kinds of electrolyte solutions such as LiPF 6 , LiTFSI, or LiFSI in tetraglyme. The native-SEI (solid-electrolyte interphase) formed by a potential prescan before lithium deposition/dissolution in all three solutions. Simultaneous additional SEI (add-SEI) deposition and its dissolution with lithium deposition and dissolution, respectively, were observed in LiPF 6 and LiTFSI. Conversely, the add-SEI dissolution with lithium deposition and its deposition with lithium dissolution were observed in LiFSI. Additional potential precycling resulted in the accumulation of a "pre-SEI" layer over the native-SEI layer in all of the solutions. With the pre-SEI, only lithium deposition/dissolution were significantly observed in LiTFSI and LiFSI. On the basis of the potential dependences of the mass and resistance changes, the anion-dependent effects of such a pre-SEI layer presence/absence on the lithium deposition/dissolution processes were discussed.

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.

Dissolution behavior of MgO based inert matrix fuel for the transmutation of minor actinides

NASA Astrophysics Data System (ADS)

Mühr-Ebert, E. L.; Lichte, E.; Bukaemskiy, A.; Finkeldei, S.; Klinkenberg, M.; Brandt, F.; Bosbach, D.; Modolo, G.

2018-07-01

This study explores the dissolution properties of magnesia-based inert matrix nuclear fuel (IMF) containing transuranium elements (TRU). Pure MgO pellets as well as MgO pellets containing CeO2, as surrogate for TRU oxides, and are considered as model systems for genuine magnesia based inert matrix fuel were fabricated. The aim of this study is to identify conditions at which the matrix material can be selectively dissolved during the head-end reprocessing step, allowing a separation of MgO from the actinides, whereas the actinides remain undissolved. The dissolution behavior was studied in macroscopic batch experiments as a function of nitric acid concentration, dissolution medium volume, temperature, stirring velocity, and pellet density (85, 90, 96, and 99%TD). To mimic pellets with various burn-ups the density of the here fabricated pellets was varied. MgO is soluble even under mild conditions (RT, 2.5 mol/L HNO3). The dissolution rates of MgO at different acid concentrations are rather similar, whereas the dissolution rate is strongly dependent on the temperature. Via a microscopic approach, a model was developed to describe the evolution of the pellet surface area during dissolution and determine a surface normalized dissolution rate. Moreover, dissolution rates of the inert matrix fuel containing CeO2 were determined as a function of the acid concentration and temperature. During the dissolution of MgO/CeO2 pellets the MgO dissolves completely, while CeO2 (>99%) remains undissolved. This study intends to provide a profound understanding of the chemical performance of magnesia based IMF containing fissile material. The feasibility of the dissolution of magnesia based IMF with nitric acid is discussed.

Arsenic mineral dissolution and possible mobilization in mineral-microbe-groundwater environment.

PubMed

Islam, A B M R; Maity, Jyoti Prakash; Bundschuh, Jochen; Chen, Chien-Yen; Bhowmik, Bejon Kumar; Tazaki, Kazue

2013-11-15

Arsenic (As) is widely distributed in the nature as ores or minerals. It has been attracted much attention for the global public health issue, especially for groundwater As contamination. The aim of this study was to elucidate the characteristics of microbes in groundwater where As-minerals were dissolved. An ex situ experiment was conducted with 7 standard As-minerals in bacteria-free groundwater and stored in experimental vessels for 1 year without supplementary nutrients. The pH (6.7-8.4) and EhS.H.E. (24-548 mV) changed between initial (0 day) and final stages (365 days) of experiment. The dissolution of As was detected higher from arsenolite (4240 ± 8.69 mg/L) and native arsenic (4538 ± 9.02 mg/L), whereas moderately dissolved from orpiment (653 ± 3.56 mg/L) and realgar (319 ± 2.56 mg/L) in compare to arsenopyrite (85 ± 1.25mg/L) and tennantite (3 ± 0.06 mg/L). Optical microscopic, scanning electron microscopic observations and flurometric enumeration revealed the abundance of As-resistant bacillus, coccus and filamentous types of microorganisms on the surface of most of As-mineral. 4'-6-Diamidino-2-phenylindole (DAPI)-stained epifluorescence micrograph confirmed the presence of DNA and carboxyfluorescein diacetate (CFDA) staining method revealed the enzymatically active bacteria on the surface of As-minerals such as in realgar (As4S4). Therefore, the microbes enable to survive and mobilize the As in groundwater by dissolution/bioweathering of As-minerals. Copyright © 2012. Published by Elsevier B.V.

Evaluating the role of re-adsorption of dissolved Hg(2+) during cinnabar dissolution using isotope tracer technique.

PubMed

Jiang, Ping; Li, Yanbin; Liu, Guangliang; Yang, Guidi; Lagos, Leonel; Yin, Yongguang; Gu, Baohua; Jiang, Guibin; Cai, Yong

2016-11-05

Cinnabar dissolution is an important factor controlling mercury (Hg) cycling. Recent studies have suggested the co-occurrence of re-adsorption of the released Hg during the course of cinnabar dissolution. However, there is a lack of feasible techniques that can quantitatively assess the amount of Hg re-adsorbed on cinnabar when investigating cinnabar dissolution. In this study, a new method, based on isotope tracing and dilution techniques, was developed to study the role of Hg re-adsorption in cinnabar dissolution. The developed method includes two key components: (1) accurate measurement of both released and spiked Hg in aqueous phase and (2) estimation of re-adsorbed Hg on cinnabar surface via the reduction in spiked (202)Hg(2+). By adopting the developed method, it was found that the released Hg for trials purged with oxygen could reach several hundred μgL(-1), while no significant cinnabar dissolution was detected under anaerobic condition. Cinnabar dissolution rate when considering Hg re-adsorption was approximately 2 times the value calculated solely with the Hg detected in the aqueous phase. These results suggest that ignoring the Hg re-adsorption process can significantly underestimate the importance of cinnabar dissolution, highlighting the necessity of applying the developed method in future cinnabar dissolution studies. Copyright © 2016 Elsevier B.V. All rights reserved.

The Labrador Sea during the Last Glacial Maximum: Calcite dissolution or low biogenic carbonate fluxes?

NASA Astrophysics Data System (ADS)

Marshall, Nicole; de Vernal, Anne; Mucci, Alfonso; Filippova, Alexandra; Kienast, Markus

2017-04-01

Low concentrations of biogenic carbonate characterize the sediments deposited in the Labrador Sea during the last glaciation. This may reflect poor calcite preservation and/or low biogenic carbonate productivity and fluxes. Regional bottom water ventilation was reduced during the Last Glacial Maximum (LGM), so the calcite lysocline might have been shallower than at present in the deep Labrador Sea making dissolution of calcite shells in the deep Labrador Sea possible. To address the issue, a multi-proxy approach based on micropaleontological counts (coccoliths, foraminifers, palynomorphs) and biogeochemical analyses (alkenones) was applied in the investigation of core HU2008-029-004-PC recovered in the northwestern Labrador Sea. Calcite dissolution indices based on the relative abundance benthic foraminifera shells to their organic linings as well as on fragmentation of planktonic foraminifera shells were used to evaluate changes in calcite dissolution/ preservation since the LGM. In addition, the ratio of the concentrations of coccoliths, specifically of the alkenone-producer Emiliania huxleyi, and alkenones (Emiliania huxleyi: alkenones) was explored as a potential new proxy of calcite dissolution. A sharp increase in coccoliths, foraminifers and organic linings from nearly none to substantial concentrations at 12 ka, reflect a jump to significantly greater biogenic fluxes at the glacial-interglacial transition. Furthermore, conventional dissolution indices (shells/linings of benthic foraminifera and fragmentation of planktic foraminifers) reveal that dissolution is not likely responsible for the lower glacial abundances of coccoliths and foraminifers. Only the low Emiliania huxleyi: alkenones ratios in glacial sediments could be interpreted as evidence of increased dissolution during the LGM. Given the evidence of allochthonous alkenone input into the glacial Labrador Sea, the latter observations must be treated with caution. Overall, the records indicate that low biogenic fluxes during the LGM were the most likely cause of the decreased biogenic carbonate concentrations.

Simultaneous in vitro and in vivo evaluation of both trimethoprim and sulfamethoxazole from certain dosage forms.

PubMed

Meshali, M; El-Sabbagh, H; Ghanem, A; Foda, A

1983-06-01

The dissolution rates of trimethoprim (T), and sulphamethoxazole (S), from different brands of tablets and suspensions were studied at pH = 1.1 and 7.2. The bioavailabilities of both drugs in humans were studied by the urine excretion method. The dissolution rates were dependent on the pH of the dissolution medium, the solubilities of the drugs at the pH involved, the dosage form and the brand studied. While the dissolution rates of T from all brands studied were consistent with their pH-dependent solubility, those of S were not. The dissolution rates of S from suspensions were found to be equal at pH = 7.2, but different at pH = 1.1. A correlation existed between the dissolution rate of T at pH = 1.1 from tablets and the excretion rate in humans. With S, however, no such correlation was observed at either pH.

In-vitro Drug Dissolution Studies in Medicinal Compounds.

PubMed

Bozal-Palabiyik, Burcin; Uslu, Bengi; Ozkan, Yalcin; Ozkan, Sibel A

2018-03-22

After oral administration, drug absorption from solid dosage forms depend on the release of the drug active compounds from the dosage form, the dissolution or solubilization of the drug under physiological conditions, and the permeability across the gastrointestinal tract. Dissolution testing is an essential part of designing more effective solid dosage forms in pharmaceutical industry. Moreover dissolution testing contributes to the selection of appropriate formulation excipients for improving the dosage form efficiency. This study aims to analyze in-vitro drug dissolution testing in solid dosage forms since 2010 in order to present a comprehensive outlook of recent trends. In doing that the previous studies in the literature are summarized in the form of a table to demonstrate the apparatuses used for dissolution testing, the media in which the solid dosage form is dissolved, the method preferred for analysis from dissolution media, the conditions of analyses and the results obtained. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effects of Low-Molecular-Weight Organic Acids on the Dissolution of Hydroxyapatite Nanoparticles in Batch and Column Experiments: A Perspective from Phosphate Oxygen Isotope Fractionation

NASA Astrophysics Data System (ADS)

Wang, D.; Jaisi, D. P.; Jin, Y.

2015-12-01

Hydroxyapatite nanoparticles (HANPs) are increasingly being advocated as an efficient and environment-friendly "green" phosphorus nanofertilizer attributed to their nanoscale dimension, large reactive surface area, and low leaching potential. However, knowledge of how naturally occurring low-molecular-weight organic acids (LMWOAs) that are secreted by plant roots mediate the dissolution of HANPs (releasing PO43- ion for plant growth) is nonexistent. Here three most commonly encountered LMWOAs (acetic acid, oxalic acid, and citric acid) at environmentally relevant concentration (1 mM) were evaluated for their effects on HANPs' dissolution in static batch and dynamic column systems. Particularly, phosphate oxygen isotope fractionation of HANPs during dissolution was examined to disentangle mechanisms controlling the evolution of O-isotopic composition of dissolved PO43- ion. Our results reveal that in batch experiments the dissolution of HANPs was fast but the overall dissolution efficiency of HANPs was limited (≤30%). In contrast, ~100% HANPs were dissolved in columns where LMWOAs were continuously injected. The limited dissolution of HANPs in static batch systems was due primarily to pH buffer effect (pH increased sharply when LMWOA was added in HANPs suspension), whereas in dynamic column systems the HANPs were continuously dissolved by low pH LMWOAs and leached away. Regardless of LMWOA type and experimental system, the isotopically light phosphate (P16O4) was preferentially released during dissolution and the O-isotopic composition of dissolved PO43- ion increased gradually with increasing dissolution due to equilibrium isotope effect between dissolved PO43- ion and HANPs. However, the overall magnitude of O-isotopic fractionation of dissolved PO43- ion was less in batch than in column systems, due to less mass transfer between dissolved PO43- ions and HANPs in batch relative to column experiments. Our findings provide new insights into bioavailability, transformation, and evolution of O-isotopic signatures of phosphate-based nanoparticles in agricultural soils particularly in the rhizosphere where such LMWOAs are ubiquitous.

Ferrihydrite dissolution by pyridine-2,6-bis(monothiocarboxylic acid) and hydrolysis products

NASA Astrophysics Data System (ADS)

Dhungana, Suraj; Anthony, Charles R.; Hersman, Larry E.

2007-12-01

Pyridine-2,6-bis(monothiocarboxylate) (pdtc), a metabolic product of microorganisms, including Pseudomonas putida and Pseudomonas stutzeri was investigated for its ability of dissolve Fe(III)(hydr)oxides at pH 7.5. Concentration dependent dissolution of ferrihydrite under anaerobic environment showed saturation of the dissolution rate at the higher concentration of pdtc. The surface controlled ferrihydrite dissolution rate was determined to be 1.2 × 10 -6 mol m -2 h -1. Anaerobic dissolution of ferrihydrite by pyridine-2,6-dicarboxylic acid or dipicolinic acid (dpa), a hydrolysis product of pdtc, was investigated to study the mechanism(s) involved in the pdtc facilitated ferrihydrite dissolution. These studies suggest that pdtc dissolved ferrihydrite using a reduction step, where dpa chelates the Fe reduced by a second hydrolysis product, H 2S. Dpa facilitated dissolution of ferrihydrite showed very small increase in the Fe dissolution when the concentration of external reductant, ascorbate, was doubled, suggesting the surface dynamics being dominated by the interactions between dpa and ferrihydrite. Greater than stoichiometric amounts of Fe were mobilized during dpa dissolution of ferrihydrite assisted by ascorbate and cysteine. This is attributed to the catalytic dissolution of Fe(III)(hydr)oxides by the in situ generated Fe(II) in the presence of a complex former, dpa.

Lyophilic matrix method for dissolution and release studies of nanoscale particles.

PubMed

Pessi, Jenni; Svanbäck, Sami; Lassila, Ilkka; Hæggström, Edward; Yliruusi, Jouko

2017-10-25

We introduce a system with a lyophilic matrix to aid dissolution studies of powders and particulate systems. This lyophilic matrix method (LM method) is based on the ability to discriminate between non-dissolved particles and the dissolved species. In the LM method the test substance is embedded in a thin lyophilic core-shell matrix. This permits rapid contact with the dissolution medium while minimizing dispersion of non-dissolved particles without presenting a substantial diffusion barrier. The method produces realistic dissolution and release results for particulate systems, especially those featuring nanoscale particles. By minimizing method-induced effects on the dissolution profile of nanopowders, the LM method overcomes shortcomings associated with current dissolution tests. Copyright © 2017 Elsevier B.V. All rights reserved.

Microenvironmental pH measurement during sodium naproxenate dissolution in acidic medium by UV/vis imaging.

PubMed

Østergaard, Jesper; Jensen, Henrik; Larsen, Susan W; Larsen, Claus; Lenke, Jim

2014-11-01

Variable dissolution from sodium salts of drugs containing a carboxylic acid group after passing the acidic environment of the stomach may affect oral bioavailability. The aim of the present proof of concept study was to investigate pH effects in relation to the dissolution of sodium naproxenate in 0.01M hydrochloric acid. For this purpose a UV/vis imaging-based approach capable of measuring microenvironmental pH in the vicinity of the solid drug compact as well as monitoring drug dissolution was developed. Using a pH indicating dye real-time spatially resolved measurement of pH was achieved. Sodium naproxenate, can significantly alter the local pH of the dissolution medium, is eventually neutralized and precipitates as the acidic species naproxen. The developed approach is considered useful for detailed studies of pH dependent dissolution phenomena in dissolution testing. Copyright © 2014 Elsevier B.V. All rights reserved.

Diblock Terpolymers Are Tunable and pH Responsive Vehicles To Increase Hydrophobic Drug Solubility for Oral Administration.

PubMed

Tale, Swapnil; Purchel, Anatolii A; Dalsin, Molly C; Reineke, Theresa M

2017-11-06

Synthetic polymers offer tunable platforms to create new oral drug delivery vehicles (excipients) to increase solubility, supersaturation maintenance, and bioavailability of poorly aqueous soluble pharmaceutical candidates. Five well-defined diblock terpolymers were synthesized via reversible addition-fragmentation chain transfer polymerization (RAFT) and consist of a first block of either poly(ethylene-alt-propylene) (PEP), poly(N-isopropylacrylamide) (PNIPAm), or poly(N,N-diethylaminoethyl methacrylate) (PDEAEMA) and a second hydrophilic block consisting of a gradient copolymer of N,N-dimethylacrylamide (DMA) and 2-methacrylamidotrehalose (MAT). This family of diblock terpolymers offers hydrophobic, hydrophilic, or H-bonding functionalities to serve as noncovalent sites of drug binding. Drug-polymer spray dried dispersions (SDDs) were created with a model drug, probucol, and characterized by differential scanning calorimetry (DSC). These studies revealed that probucol crystallinity decreased with increasing H-bonding sites available in the polymer. The PNIPAm-b-P(DMA-grad-MAT) systems revealed the best performance at pH 6.5, where immediate probucol release and effective maintenance of 100% supersaturation was found, which is important for facilitating drug solubility in more neutral conditions (intestinal environment). However, the PDEAEMA-b-P(DMA-grad-MAT) system revealed poor probucol dissolution at pH 6.5 and 5.1. Alternatively, at an acidic pH of 3.1, a rapid and high dissolution profile and effective supersaturation maintenance of up to 90% of the drug was found, which could be useful for triggering drug release in acidic environments (stomach). The PEP-b-P(DMA-grad-MAT) system showed poor performance (only ∼20% of drug solubility at pH 6.5), which was attributed to the low solubility of the polymers in the dissolution media. This work demonstrates the utility of diblock terpolymers as a potential new excipient platform to optimize design parameters for triggered release and solubilizing hydrophobic drug candidates for oral delivery.

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.

Kinetics and mechanism of hydroxyapatite crystal dissolution in weak acid buffers using the rotating disk method.

PubMed

Wu, M S; Higuchi, W I; Fox, J L; Friedman, M

1976-01-01

The model given in this report and the rotating disk method provide a useful combination in the study of dental enamel and hydroxyapatite dissolution kinetics. The present approach is a significant improvement over earlier studies, and both the ionic activity product that governs the dissolution reaction and the apparent surface dissolution reaction rate constant may be simultaneously obtained. Thus, these investigations have established the baseline for the dissolution rate studies under sink conditions. Concurrent studies, under conditions where the acidic buffer mediums are partially saturated with respect to hydroxyapatite have shown another dissolution site for hydroxyapatite that operates at a higher ionic activity product but has a much smaller apparent surface reaction rate constant. This has raised the question of whether the presence of this second site may interfere with the proper theoretical analysis of the experimental results obtained under sink conditions. A preliminary analysis of the two-site model has shown that the dissolution kinetics of hydroxyapatite under sink conditions is almost completely governed by the sink condition site (KHAP = 10(-124.5), k' = 174) established in this report. The difference between the predicted dissolution rate for the one-site model and the two-site model are generally of the order of 4 to 5% where the experiments are conducted under sink conditions and over the range of variables covered in the present study.

Pharmaceutical Cocrystal of Piroxicam: Design, Formulation and Evaluation

PubMed Central

Panzade, Prabhakar; Shendarkar, Giridhar; Shaikh, Sarfaraj; Balmukund Rathi, Pavan

2017-01-01

Purpose: Cocrystallisation of drug with coformers is a promising approach to alter the solid sate properties of drug substances like solubility and dissolution. The objective of the present work was to prepare, formulate and evaluate the piroxicam cocrystal by screening various coformers. Methods: Cocrystals of piroxicam were prepared by dry grinding method. The melting point and solubility of crystalline phase was determined. The potential cocrystal was characterized by DSC, IR, XRPD. Other pharmaceutical properties like solubility and dissolution rate were also evaluated. Orodispersible tablets of piroxicam cocrystal were formulated, optimized and evaluated using 32 factorial design. Results: Cocrystals of piroxicam-sodium acetate revealed the variation in melting points and solubility. The cocrystals were obtained in 1:1 ratio with sodium acetate. The analysis of Infrared explicitly indicated the shifting of characteristic bands of piroxicam. The X-Ray Powder Diffraction pattern denoted the crystallinity of cocrystals and noteworthy difference in 2θ value of intense peaks. Differential scanning calorimetry spectra of cocrystals indicated altered endotherms corresponding to melting point. The pH solubility profile of piroxicam showed sigmoidal curve, which authenticated the pKa-dependent solubility. Piroxicam cocrystals also exhibited a similar pH-solubility profile. The cocrystals exhibited faster dissolution rate owing to cocrystallization as evident from 30% increase in the extent of dissolution. The orodispersible tablets of piroxicam cocrystals were successfully prepared by direct compression method using crosscarmelose sodium as superdisintegrant with improved disintegration time (30 sec) and dissolution rate. Conclusion: The piroxicam cocrystal with modified properties was prepared with sodium acetate and formulated as orodispersible tablets having faster disintegration and greater dissolution rate. PMID:29071222

Pharmaceutical Cocrystal of Piroxicam: Design, Formulation and Evaluation.

PubMed

Panzade, Prabhakar; Shendarkar, Giridhar; Shaikh, Sarfaraj; Balmukund Rathi, Pavan

2017-09-01

Purpose: Cocrystallisation of drug with coformers is a promising approach to alter the solid sate properties of drug substances like solubility and dissolution. The objective of the present work was to prepare, formulate and evaluate the piroxicam cocrystal by screening various coformers. Methods: Cocrystals of piroxicam were prepared by dry grinding method. The melting point and solubility of crystalline phase was determined. The potential cocrystal was characterized by DSC, IR, XRPD. Other pharmaceutical properties like solubility and dissolution rate were also evaluated. Orodispersible tablets of piroxicam cocrystal were formulated, optimized and evaluated using 3 2 factorial design. Results: Cocrystals of piroxicam-sodium acetate revealed the variation in melting points and solubility. The cocrystals were obtained in 1:1 ratio with sodium acetate. The analysis of Infrared explicitly indicated the shifting of characteristic bands of piroxicam. The X-Ray Powder Diffraction pattern denoted the crystallinity of cocrystals and noteworthy difference in 2θ value of intense peaks. Differential scanning calorimetry spectra of cocrystals indicated altered endotherms corresponding to melting point. The pH solubility profile of piroxicam showed sigmoidal curve, which authenticated the pKa-dependent solubility. Piroxicam cocrystals also exhibited a similar pH-solubility profile. The cocrystals exhibited faster dissolution rate owing to cocrystallization as evident from 30% increase in the extent of dissolution. The orodispersible tablets of piroxicam cocrystals were successfully prepared by direct compression method using crosscarmelose sodium as superdisintegrant with improved disintegration time (30 sec) and dissolution rate. Conclusion: The piroxicam cocrystal with modified properties was prepared with sodium acetate and formulated as orodispersible tablets having faster disintegration and greater dissolution rate.

Characterization of solid dispersions of itraconazole and hydroxypropylmethylcellulose prepared by melt extrusion, Part II.

PubMed

Six, Karel; Berghmans, Hugo; Leuner, Christian; Dressman, Jennifer; Van Werde, Kristof; Mullens, Jules; Benoist, Luc; Thimon, Mireille; Meublat, Laurent; Verreck, Geert; Peeters, Jef; Brewster, Marcus; Van den Mooter, Guy

2003-07-01

This study was done to elucidate the physical and pharmaceutical properties of itraconazole-HPMC dispersions and the influence of water on the phase separation. Extrudates were prepared using a corotating twin-screw hot-stage extruder with fixed process parameters. Modulated-temperature differential scanning calorimetry (MTDSC) and DSC 111 were used to examine the mixing behavior of itraconazole and the carrier by evaluation of the glass transition region. High temperature diffuse reflectance infrared transform spectroscopy (HT-DRIFT) was performed to reveal interactions between itraconazole and HPMC. Dissolution was performed to investigate the pharmaceutical performance of the dispersions. Although the dissolution rate of itraconazole significantly increased, we found that the solid dispersions do not form a homogeneous system. A different picture was obtained depending on the way MTDSC analysis was performed, i.e., using open or closed sample pans. Water can evaporate in open pans, which allows itraconazole to interact with HPMC and leads to a partially mixed phase. Analysis in hermetically closed pans revealed a further phase separation as water remains on the sample and impedes the interaction between drug and polymer. Solid dispersions of itraconazole and HPMC do not form a homogeneous phase.

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.

CALCIUM CARBONATE DISSOLUTION RATE IN LIMESTONE CONTACTORS

EPA Science Inventory

The rate of carbonate mineral dissolution from limestone was studied using a rotating disk apparatus and samples of limestone of varied composition. The purpose of this study was to determine the effect of limestone composition on the kinetics of carbonate mineral dissolution. Th...

Effects of pretreatment processes for Zr electrorefining of oxidized Zircaloy-4 cladding tubes

NASA Astrophysics Data System (ADS)

Hwa Lee, Chang; Lee, Yoo Lee; Jeon, Min Ku; Choi, Yong Taek; Kang, Kweon Ho; Park, Geun Il

2014-06-01

The effect of pretreatment processes for the Zr electrorefining of oxidized Zircaloy-4 cladding tubes is examined in LiCl-KCl-ZrCl4 molten salts at 500 °C. The cyclic voltammetries reveal that the Zr dissolution kinetics is highly dependent on the thickness of a Zr oxide layer formed at 500 °C under air atmosphere. For the Zircaloy-4 tube covered with a 1 μm thick oxide layer, the Zr dissolution process is initiated from a non-stoichiometric Zr oxide surface through salt treatment at an open circuit potential in the molten salt electrolyte. The Zr dissolution of the samples in the middle range of oxide layer thickness appears to be more effectively derived by the salt treatment coupled with an anodic potential application at an oxidation potential of Zr. A modification of the process scheme offers an applicability of Zr electrorefining for the treatment of oxidized cladding hull wastes.

Understanding cellulose dissolution: energetics of interactions of ionic liquids and cellobiose revealed by solution microcalorimetry.

PubMed

de Oliveira, Heitor Fernando Nunes; Rinaldi, Roberto

2015-05-11

In this report, the interactions between fifteen selected ionic liquids (ILs) and cellobiose (CB) are examined by high-precision solution microcalorimetry. The heat of mixing (Δmix H) of CB and ILs, or CB and IL/molecular solvent (MS) solutions, provides the first ever-published measure of the affinity of CB with ILs. Most importantly, we found that there is a very good correlation between the nature of the results found for Δmix H(CB) and the solubility behavior of cellulose. This correlation suggests that Δmix H(CB) offers a good estimate of the enthalpy of dissolution of cellulose even in solvents in which cellulose is insoluble. Therefore, the current findings open up new horizons for unravelling the intricacies of the thermodynamic factors accounting for the spontaneity of cellulose dissolution in ILs or IL/MS solutions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Parental Education and Family Dissolution: A Cross‐National and Cohort Comparison

PubMed Central

Härkönen, Juho

2018-01-01

This is the first study to systematically analyze whether the association between parental education and family dissolution varies cross‐nationally and over time. The authors use meta‐analytic tools to study cross‐national variation between 17 countries with data from the Generations and Gender Study and Harmonized Histories. The association shows considerable cross‐national variation, but is positive in most countries. The association between parental education and family dissolution has become less positive or even negative in six countries. The findings show that the association between parental education and family dissolution is generally positive or nil, even if the association between own education and family dissolution is in many countries increasingly negative. The authors find suggestive evidence that the association is related to the crude divorce rate, but not to the generosity of the welfare state in these countries. The implications of these findings for understanding the stratification in family dissolution are discussed. PMID:29657335

The Relationship Between the Evolution of an Internal Structure and Drug Dissolution from Controlled-Release Matrix Tablets.

PubMed

Kulinowski, Piotr; Hudy, Wiktor; Mendyk, Aleksander; Juszczyk, Ewelina; Węglarz, Władysław P; Jachowicz, Renata; Dorożyński, Przemysław

2016-06-01

In the last decade, imaging has been introduced as a supplementary method to the dissolution tests, but a direct relationship of dissolution and imaging data has been almost completely overlooked. The purpose of this study was to assess the feasibility of relating magnetic resonance imaging (MRI) and dissolution data to elucidate dissolution profile features (i.e., kinetics, kinetics changes, and variability). Commercial, hydroxypropylmethyl cellulose-based quetiapine fumarate controlled-release matrix tablets were studied using the following two methods: (i) MRI inside the USP4 apparatus with subsequent machine learning-based image segmentation and (ii) dissolution testing with piecewise dissolution modeling. Obtained data were analyzed together using statistical data processing methods, including multiple linear regression. As a result, in this case, zeroth order release was found to be a consequence of internal structure evolution (interplay between region's areas-e.g., linear relationship between interface and core), which eventually resulted in core disappearance. Dry core disappearance had an impact on (i) changes in dissolution kinetics (from zeroth order to nonlinear) and (ii) an increase in variability of drug dissolution results. It can be concluded that it is feasible to parameterize changes in micro/meso morphology of hydrated, controlled release, swellable matrices using MRI to establish a causal relationship between the changes in morphology and drug dissolution. Presented results open new perspectives in practical application of combined MRI/dissolution to controlled-release drug products.

Disintegration of highly soluble immediate release tablets: a surrogate for dissolution.

PubMed

Gupta, Abhay; Hunt, Robert L; Shah, Rakhi B; Sayeed, Vilayat A; Khan, Mansoor A

2009-01-01

The purpose of the work was to investigate correlation between disintegration and dissolution for immediate release tablets containing a high solubility drug and to identify formulations where disintegration test, instead of the dissolution test, may be used as the acceptance criteria based on International Conference on Harmonization Q6A guidelines. A statistical design of experiments was used to study the effect of filler, binder, disintegrating agent, and tablet hardness on the disintegration and dissolution of verapamil hydrochloride tablets. All formulation variables, i.e., filler, binder, and disintegrating agent, were found to influence tablet dissolution and disintegration, with the filler and disintegrating agent exerting the most significant influence. Slower dissolution was observed with increasing disintegration time when either the filler or the disintegrating agent was kept constant. However, no direct corelationship was observed between the disintegration and dissolution across all formulations due to the interactions between different formulation components. Although all tablets containing sodium carboxymethyl cellulose as the disintegrating agent, disintegrated in less than 3 min, half of them failed to meet the US Pharmacopeia 30 dissolution criteria for the verapamil hydrochloride tablets highlighting the dependence of dissolution process on the formulation components other than the disintegrating agent. The results identified only one formulation as suitable for using the disintegration test, instead of the dissolution test, as drug product acceptance criteria and highlight the need for systematic studies before using the disintegration test, instead of the dissolution test as the drug acceptance criteria.

Preventing Small Molecule Nucleation and Crystallization by Sequestering in a Micelle Corona

NASA Astrophysics Data System (ADS)

Li, Ziang; Johnson, Lindsay; Ricarte, Ralm; Yao, Letitia; Hillmyer, Marc; Bates, Frank; Lodge, Timothy

We exploited a blend of hydroxypropyl methylcellulose acetate succinate and poly(N-isopropylacrylamide) (PNIPAm) to improve the solubility and dissolution of a rapidly crystallizing model drug molecule phenytoin and observed synergistic effect in vitro at constant drug loading by varying the blending ratio. Dynamic and static light scattering experiments showed that PNIPAm self-assembled into micelles in aqueous solution. We believe that adding these PNIPAm micelles inhibited both nucleation and crystal growth of phenytoin based on the polarized light micrographs taken from the dissolution media. The drug-polymer intermolecular interaction was revealed by nuclear Overhauser effect spectroscopy and further quantified by diffusion ordered spectroscopy. We found that the phenytoin molecules were sequestered in aqueous solution by partitioning into the corona of the micelle. The blend strategy through the use of self-assembled micelles showcased in this study offers a new platform for designing advanced excipients for oral drug delivery. This study was funded by The Dow Chemical Company through Agreement 224249AT with the University of Minnesota.

Preparation of delayed release tablet dosage forms by compression coating: effect of coating material on theophylline release.

PubMed

El-Malah, Yasser; Nazzal, Sami

2010-06-01

In this study, compression-coated tablets were prepared and examined by real-time swelling/erosion analysis and dissolution studies. Of the coating materials, PVP showed no swelling behavior and had no impact on theophylline release. Polyox(®) exhibited swelling behavior of an entangled polymer, which was reflected in its > 14-hour delayed-release profile. Hydroxypropyl methylcellulose (HPMC), which revealed the characteristics of a disentangled polymer, caused a 2-h delay in theophylline release. Based on preliminary texture analysis data, Polyox(®)/PVP blends were used as coating materials to manipulate the onset of drug release from the compression-coated tablets. Of the blends, at a 1:1 ratio, for example, resulted in a burst release after 10 h, which demonstrated the feasibility of preparing delayed release dosage forms by compression coating. Furthermore, it was feasible to predict the dissolution behavior of polymers from their swelling/erosion data, which were generated from texture analysis.

Examining Two Types of Best Friendship Dissolution during Early Adolescence

ERIC Educational Resources Information Center

Bowker, Julie C.

2011-01-01

This study examined young adolescents' experiences with best friendship dissolution. Participants were 77 sixth-grade students (M age = 11.63 years, SD = 0.36; 11.00-12.69 age range) who reported on past experiences with (1) "complete dissolutions" (when friendship ties are completely severed), and (2) "downgrade dissolutions"…

In vitro dissolution kinetic study of theophylline from hydrophilic and hydrophobic matrices.

PubMed

Maswadeh, Hamzah M; Semreen, Mohammad H; Abdulhalim, Abdulatif A

2006-01-01

Oral dosage forms containing 300 mg theophylline in matrix type tablets, were prepared by direct compression method using two kinds of matrices, glycerylbehenate (hydrophobic), and (hydroxypropyl)methyl cellulose (hydrophilic). The in vitro release kinetics of these formulations were studied at pH 6.8 using the USP dissolution apparatus with the paddle assemble. The kinetics of the dissolution process were studied by analyzing the dissolution data using four kinetic equations, the zero-order equation, the first-order equation, the Higuchi square root equation and the Hixson-Crowell cube root law. The analysis of the dissolution kinetic data for the theophylline preparations in this study shows that it follows the first order kinetics and the release process involves erosion / diffusion and an alteration in the surface area and diameter of the matrix system, as well as in the diffusion path length from the matrix drug load during the dissolution process. This relation is best described by the use of both the first-order equation and the Hixson-Crowell cube root law.

Terahertz Pulsed Imaging and Magnetic Resonance Imaging as Tools to Probe Formulation Stability

PubMed Central

Zhang, Qilei; Gladden, Lynn F.; Avalle, Paolo; Zeitler, J. Axel; Mantle, Michael D.

2013-01-01

Dissolution stability over the entire shelf life duration is of critical importance to ensure the quality of solid dosage forms. Changes in the drug release profile during storage may affect the bioavailability of drug products. This study investigated the stability of a commercial tablet (Lescol® XL) when stored under accelerated conditions (40 °C/75% r.h.). Terahertz pulsed imaging (TPI) was used to investigate the structure of the tablet coating before and after the accelerated aging process. The results indicate that the coating was reduced in thickness and exhibited a higher density after being stored under accelerated conditions for four weeks. In situ magnetic resonance imaging (MRI) of the water penetration processes during tablet dissolution in a USP-IV dissolution cell equipped with an in-line UV-vis analyzer was carried out to study local differences in water uptake into the tablet matrix between the stressed and unstressed state. The drug release profiles of the Lescol® XL tablet before and after the accelerated storage stability testing were compared using a “difference” factor f1 and a “similarity” factor f2. The results reveal that even though the physical properties of the coating layers changed significantly during the stress testing, the coating protected the tablet matrix and the densification of the coating polymer had no adverse effect on the drug release performance. PMID:24300564

In-life pteropod shell dissolution as an indicator of past ocean carbonate saturation

NASA Astrophysics Data System (ADS)

Wall-Palmer, Deborah; Smart, Christopher W.; Hart, Malcolm B.

2013-12-01

Recent concern over the effects of ocean acidification upon calcifying organisms has highlighted the aragonitic shelled thecosomatous pteropods as being at a high risk. Both in-situ and laboratory studies have shown that an increased dissolved CO2 concentration, leading to decreased water pH and low carbonate concentration, causes reduced calcification rates and enhanced dissolution in the shells of living pteropods. In fossil records unaffected by post-depositional dissolution, this in-life shell dissolution can be detected. Here we present the first evidence of variations of in-life pteropod shell dissolution due to variations in surface water carbonate concentration during the Late Pleistocene by analysing the surface layer of pteropod shells in marine sediment cores from the Caribbean Sea and Indian Ocean. In-life shell dissolution was determined by applying the Limacina Dissolution Index (LDX) to the sub-tropical pteropod Limacina inflata. Average shell size information shows that high in-life dissolution is accompanied by smaller shell sizes in L. inflata, which may indicate a reduction in calcification rate. Comparison of the LDX profile to Late Pleistocene Vostok atmospheric CO2 concentrations, shows that in-life pteropod dissolution is closely associated to variations in past ocean carbonate saturation. This study confirms the findings of laboratory studies, showing enhanced shell dissolution and reduced calcification in living pteropods when surface ocean carbonate concentrations were lower. Results also demonstrate that oceanic pH levels that were less acidic and changing less rapidly than those predicted for the 21st Century, negatively affected pteropods during the Late Pleistocene.

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.

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.

Kinetics Study on the Effect of NaCl on the CaSO4 Dissolution Behavior

NASA Astrophysics Data System (ADS)

Song, Jingyao; Shi, Peiyang; Wang, Yeguang; Jiang, Maofa

2018-01-01

The study of the dissolution kinetics of CaSO4 is essential for the control of the dissolution and recrystallization behavior of CaSO4. In this work, the kinetic behavior of CaSO4 dissolved in NaCl solution was investigated by means of conductivity meter. The results show that with the increase of concentration of NaCl, the temperature rise and the time prolonged, the dissolution rate of dihydrate CaSO4 gradually increases, and the dissolved apparent activation energy is gradually decreased. When the NaCl concentration is 1.8%, the dissolution kinetic equation is 1-(1-α) 1/3=5.46*10-4exp (-9147/RT) t; When the NaCl concentration is 3.0%, the dissolution kinetic equation is 1-(1-α) 1/3=2.81×10-4 exp (-6753/RT)t; When the NaCl concentration is 3.6%, the dissolution kinetic equation is 1-(1-α) 1/3=3.07×l0-4exp(-6103/RT)t.

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.

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.

Dissolution Failure of Solid Oral Drug Products in Field Alert Reports.

PubMed

Sun, Dajun; Hu, Meng; Browning, Mark; Friedman, Rick L; Jiang, Wenlei; Zhao, Liang; Wen, Hong

2017-05-01

From 2005 to 2014, 370 data entries of dissolution failures of solid oral drug products were assessed with respect to the solubility of drug substances, dosage forms [immediate release (IR) vs. modified release (MR)], and manufacturers (brand name vs. generic). The study results show that the solubility of drug substances does not play a significant role in dissolution failures; however, MR drug products fail dissolution tests more frequently than IR drug products. When multiple variables were analyzed simultaneously, poorly water-soluble IR drug products failed the most dissolution tests, followed by poorly soluble MR drug products and very soluble MR drug products. Interestingly, the generic drug products fail dissolution tests at an earlier time point during a stability study than the brand name drug products. Whether the dissolution failure of these solid oral drug products has any in vivo implication will require further pharmacokinetic, pharmacodynamic, clinical, and drug safety evaluation. Food and Drug Administration is currently conducting risk-based assessment using in-house dissolution testing, physiologically based pharmacokinetic modeling and simulation, and post-market surveillance tools. At the meantime, this interim report will outline a general scheme of monitoring dissolution failures of solid oral dosage forms as a pharmaceutical quality indicator. Published by Elsevier Inc.

In-situ early-age hydration study of sulfobelite cements by synchrotron powder diffraction

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

Álvarez-Pinazo, G.; Cuesta, A.; García-Maté, M.

Eco-friendly belite calcium sulfoaluminate (BCSA) cement hydration behavior is not yet well understood. Here, we report an in-situ synchrotron X-ray powder diffraction study for the first hours of hydration of BCSA cements. Rietveld quantitative phase analysis has been used to establish the degree of reaction (α). The hydration of a mixture of ye'elimite and gypsum revealed that ettringite formation (α ∼ 70% at 50 h) is limited by ye'elimite dissolution. Two laboratory-prepared BCSA cements were also studied: non-active-BCSA and active-BCSA cements, with β- and α′{sub H}-belite as main phases, respectively. Ye'elimite, in the non-active-BCSA system, dissolves at higher pace (αmore » ∼ 25% at 1 h) than in the active-BCSA one (α ∼ 10% at 1 h), with differences in the crystallization of ettringite (α ∼ 30% and α ∼ 5%, respectively). This behavior has strongly affected subsequent belite and ferrite reactivities, yielding stratlingite and other layered phases in non-active-BCSA. The dissolution and crystallization processes are reported and discussed in detail. -- Highlights: •Belite calcium sulfoaluminate cements early hydration mechanism has been determined. •Belite hydration strongly depends on availability of aluminum hydroxide. •Orthorhombic ye’elimite dissolved at a higher pace than cubic one. •Ye’elimite larger reaction degree yields stratlingite formation by belite reaction. •Rietveld method quantified gypsum, anhydrite and bassanite dissolution rates.« less

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.

Template occluded SBA-15: An effective dissolution enhancer for poorly water-soluble drug

NASA Astrophysics Data System (ADS)

Tingming, Fu; Liwei, Guo; Kang, Le; Tianyao, Wang; Jin, Lu

2010-09-01

The aim of the present work was to improve the dissolution rate of piroxicam by inclusion into template occluded SBA-15. Our strategy involves directly introducing piroxicam into as-prepared SBA-15 occluded with P123 (EO 20PO 70EO 20) by self assembling method in acetonitrile/methylene chloride mixture solution. Ultraviolet spectrometry experiment and thermogravimetric analysis-differential scanning calorimetry (TG-DSC) profiles show that the piroxicam and P123 contents in the inclusion compound are 12 wt% and 28 wt%, respectively. X-ray powder diffraction and DSC analysis reveal that the included piroxicam is arranged in amorphous form. N 2 adsorption-desorption experiment indicates that the piroxicam has been introduced to the mesopores instead of precipitating at the outside of the silica material. The inclusion compound was submitted to in vitro dissolution tests, the results show that the piroxicam dissolve from template occluded inclusion compound more rapidly, than these from the piroxicam crystalline and template removed samples in all tested conditions. Thus a facile method to improve the dissolution rate of poorly water-soluble drug was established, and this discovery opens a new avenue for the utilization of templates used for the synthesis of mesoporous materials.

Comparison on Response and Dissolution Rates Between Ursodeoxycholic Acid Alone or in Combination With Chenodeoxycholic Acid for Gallstone Dissolution According to Stone Density on CT Scan: Strobe Compliant Observation Study.

PubMed

Lee, Jae Min; Hyun, Jong Jin; Choi, In Young; Yeom, Suk Keu; Kim, Seung Young; Jung, Sung Woo; Jung, Young Kul; Koo, Ja Seol; Yim, Hyung Joon; Lee, Hong Sik; Lee, Sang Woo; Kim, Chang Duck

2015-12-01

Medical dissolution of gallstone is usually performed on radiolucent gallstones in a functioning gallbladder. However, absence of visible gallstone on plain abdominal x-ray does not always preclude calcification. This study aims to compare the response and dissolution rates between ursodeoxycholic acid (UDCA) alone or in combination with chenodeoxycholic acid (CDCA) according to stone density on computed tomography (CT) scan. A total of 126 patients underwent dissolution therapy with either UDCA alone or combination of CDCA and UDCA (CNU) from December 2010 to March 2014 at Korea University Ansan Hospital. In the end, 81 patients (CNU group = 44, UDCA group = 37) completed dissolution therapy for 6 months. Dissolution rate (percentage reduction in the gallstone volume) and response to therapy (complete dissolution or partial dissolution defined as reduction in stone volume of >50%) were compared between the 2 groups. Dissolution and response rates of sludge was also compared between the 2 groups. The overall response rate was 50.6% (CNU group 43.2% vs UDCA group 59.5%, P = 0.14), and the overall dissolution rate was 48.34% (CNU group 41.5% vs UDCA group 56.5%, P = 0.13). When analyzed according to stone density, response rate was 33.3%, 87.1%, 30.0%, and 6.2% for hypodense, isodense, hyperdense, and calcified stones, respectively. Response rate (85.7% vs 88.2%, P = 0.83) and dissolution rate (81.01% vs 85.38%, P = 0.17) of isodense stones were similar between CNU and UDCA group. When only sludge was considered, the overall response rate was 87.5% (CNU group 71.4% vs UDCA group 94.1%, P = 0.19), and the overall dissolution rate was 85.42% (CNU group 67.9% vs UDCA group 92.7%, P = 0.23). Patients with isodense gallstones and sludge showed much better response to dissolution therapy with CNU and UDCA showing comparable efficacy. Therefore, CT scan should be performed before medication therapy if stone dissolution is intended.

Preparation and characterization of fast dissolving pullulan films containing BCS class II drug nanoparticles for bioavailability enhancement.

PubMed

Krull, Scott M; Ma, Zhelun; Li, Meng; Davé, Rajesh N; Bilgili, Ecevit

2016-01-01

The aim of this study is to assess pullulan as a novel steric stabilizer during the wet-stirred media milling (WSMM) of griseofulvin, a model poorly water-soluble drug, and as a film-former in the preparation of strip films via casting-drying the wet-milled drug suspensions for dissolution and bioavailability enhancement. To this end, pullulan films, with xanthan gum (XG) as thickening agent and glycerin as plasticizer, were loaded with griseofulvin nanoparticles prepared by WSMM using pullulan in combination with sodium dodecyl sulfate (SDS) as an ionic stabilizer. The effects of drug loading and milling time on the particle size and suspension stability were investigated, as well as XG concentration and casting thickness on film properties and dissolution rate. The nanosuspensions prepared with pullulan-SDS combination were relatively stable over 7 days; hence, this combination was used for the film preparation. All pullulan-based strip films exhibited excellent content uniformity (most <3% RSD) despite containing only 0.3-1.3 mg drug, which was ensured by the use of precursor suspensions with >5000 cP viscosity. USP IV dissolution tests revealed fast/immediate drug release (t80 < 30 min) from films <120 μm thick. Thinner films, films with lower XG loading, or smaller drug particles led to faster drug dissolution, while drug loading had no discernible effect. Overall, these results suggest that pullulan may serve as an acceptable stabilizer for media milling in combination with surfactant as well as a fast-dissolving film former for the fast release of poorly water-soluble drug nanoparticles.

Impact of dual energy characterization of urinary calculus on management.

PubMed

Habashy, David; Xia, Ryan; Ridley, William; Chan, Lewis; Ridley, Lloyd

2016-10-01

Dual energy CT (DECT) is a recent technique that is increasingly being used to differentiate between calcium and uric acid urinary tract calculi. The aim of this study is to determine if urinary calculi composition analysis determined by DECT scanning results in a change of patient management. All patients presenting with symptoms of renal colic, who had not previously undergone DECT scanning underwent DECT KUB. DECT data of all patients between September 2013 and July 2015 were reviewed. Urinary calculi composition based on dual energy characterization was cross-matched with patient management and outcome. A total of 585 DECT KUB were performed. 393/585 (67%) DECT scans revealed urinary tract calculi. After excluding those with isolated bladder or small asymptomatic renal stones, 303 patients were found to have symptomatic stone(s) as an explanation for their presentation. Of these 303 patients, there were 273 (90.1%) calcium calculi, 19 (6.3%) uric acid calculi and 11 (3.4%) mixed calculi. Of those with uric acid calculi, 15 were commenced on dissolution therapy. Twelve of those commenced on dissolution therapy had a successful outcome, avoiding need for surgical intervention (lithotripsy or stone retrieval). Three patients failed dissolution therapy and required operative intervention for definitive management of the stone. Predicting urinary tract calculi composition by DECT plays an important role in identifying patients who may be managed with dissolution therapy. Identification of uric acid stone composition altered management in 15 of 303 (5.0%) patients, and was successful in 12, thereby avoiding surgery and its attendant risks. © 2016 The Royal Australian and New Zealand College of Radiologists.

Kozeny-Carman permeability relationship with disintegration process predicted from early dissolution profiles of immediate release tablets.

PubMed

Kumari, Parveen; Rathi, Pooja; Kumar, Virender; Lal, Jatin; Kaur, Harmeet; Singh, Jasbir

2017-07-01

This study was oriented toward the disintegration profiling of the diclofenac sodium (DS) immediate-release (IR) tablets and development of its relationship with medium permeability k perm based on Kozeny-Carman equation. Batches (L1-L9) of DS IR tablets with different porosities and specific surface area were prepared at different compression forces and evaluated for porosity, in vitro dissolution and particle-size analysis of the disintegrated mass. The k perm was calculated from porosities and specific surface area, and disintegration profiles were predicted from the dissolution profiles of IR tablets by stripping/residual method. The disintegration profiles were subjected to exponential regression to find out the respective disintegration equations and rate constants k d . Batches L1 and L2 showed the fastest disintegration rates as evident from their bi-exponential equations while the rest of the batches L3-L9 exhibited the first order or mono-exponential disintegration kinetics. The 95% confidence interval (CI 95% ) revealed significant differences between k d values of different batches except L4 and L6. Similar results were also spotted for dissolution profiles of IR tablets by similarity (f 2 ) test. The final relationship between k d and k perm was found to be hyperbolic, signifying the initial effect of k perm on the disintegration rate. The results showed that disintegration profiling is possible because a relationship exists between k d and k perm . The later being relatable with porosity and specific surface area can be determined by nondestructive tests.

Comparison of Dissolution Similarity Assessment Methods for Products with Large Variations: f2 Statistics and Model-Independent Multivariate Confidence Region Procedure for Dissolution Profiles of Multiple Oral Products.

PubMed

Yoshida, Hiroyuki; Shibata, Hiroko; Izutsu, Ken-Ichi; Goda, Yukihiro

2017-01-01

The current Japanese Ministry of Health Labour and Welfare (MHLW)'s Guideline for Bioequivalence Studies of Generic Products uses averaged dissolution rates for the assessment of dissolution similarity between test and reference formulations. This study clarifies how the application of model-independent multivariate confidence region procedure (Method B), described in the European Medical Agency and U.S. Food and Drug Administration guidelines, affects similarity outcomes obtained empirically from dissolution profiles with large variations in individual dissolution rates. Sixty-one datasets of dissolution profiles for immediate release, oral generic, and corresponding innovator products that showed large variation in individual dissolution rates in generic products were assessed on their similarity by using the f 2 statistics defined in the MHLW guidelines (MHLW f 2 method) and two different Method B procedures, including a bootstrap method applied with f 2 statistics (BS method) and a multivariate analysis method using the Mahalanobis distance (MV method). The MHLW f 2 and BS methods provided similar dissolution similarities between reference and generic products. Although a small difference in the similarity assessment may be due to the decrease in the lower confidence interval for expected f 2 values derived from the large variation in individual dissolution rates, the MV method provided results different from those obtained through MHLW f 2 and BS methods. Analysis of actual dissolution data for products with large individual variations would provide valuable information towards an enhanced understanding of these methods and their possible incorporation in the MHLW guidelines.

Development of a biphasic dissolution test for Deferasirox dispersible tablets and its application in establishing an in vitro-in vivo correlation.

PubMed

Al Durdunji, Amal; AlKhatib, Hatim S; Al-Ghazawi, Mutasim

2016-05-01

In a biphasic dissolution medium, the integration of the in vitro dissolution of a drug in an aqueous phase and its subsequent partitioning into an organic phase is hypothesized to simulate the in vivo drug absorption. Such a methodology is expected to improve the probability of achieving a successful in vitro-in vivo correlation. Dissolution of Dispersible tablets of Deferasirox, a biopharmaceutics classification system type II compound, was studied in a biphasic dissolution medium using a flow-through dissolution apparatus coupled to a paddle apparatus. The experimental parameters associated with dissolution were optimized to discriminate between Deferasirox dispersible tablets of different formulations. The dissolution profiles obtained from this system were subsequently used to construct a level A in vitro-in vivo correlation. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Investigating the structural transitions of proteins during dissolution by mass spectrometry.

PubMed

Gong, Xiaoyun; Xiong, Xingchuang; Qi, Lin; Fang, Xiang

2017-03-01

An appropriate solvent environment is essential for the implementation of biological functions of proteins. Interactions between protein residues and solvent molecules are of great importance for proteins to maintain their active structure and catalyze biochemical reactions. In this study, we investigated such interactions and studied the structural transitions of proteins during their dissolution process. Our previously developed technique, namely solvent assisted electric field induced desorption/ionization, was used for the dissolution and immediate ionization of proteins. Different solvents and proteins were involved in the investigation. According to the results, cytochrome c underwent significant unfolding during dissolution in the most commonly used NH 4 Ac buffer. The unfolding got more serious when the concentration of NH 4 Ac was further increased. Extending the dissolution time resulted in the re-folding of cytochrome c. In comparison, no unfolding was observed if cytochrome c was pre-dissolved in NH 4 Ac buffer and detected by nano-ESI. Furthermore, no unfolding was observed during the dissolution process of cytochrome c in water. Interactions between the residues of cytochrome c and the solute of NH 4 Ac might be the reason for the unfolding phenomenon. Similar unfolding phenomenon was observed on holo-myoglobin. However, the observed dissolution feature of insulin was different. No unfolding was observed on insulin during dissolution in NH 4 Ac buffers. Insulin underwent observable unfolding when water was used for dissolution. This might be due to the structural difference between different proteins. The obtained results in the present study furthered our insights into the interactions between proteins and the solvents during the phase transition of dissolution. Copyright © 2016 Elsevier B.V. All rights reserved.

Kinetics of Inorganic Calcite Dissolution in Seawater under Pressure

NASA Astrophysics Data System (ADS)

Dong, S.; Subhas, A.; Rollins, N.; Berelson, W.; Adkins, J. F.

2016-02-01

While understanding calcium carbonate dissolution is vital in constructing global carbon cycles and predicting the effect of seawater acidification as a result of increasing atmospheric CO2, there is still a major debate over the basic formulation of a dissolution rate law. The kinetics of calcium carbonate dissolution are typically described by the equation: Rate=k(1-Ω)n, while Ω=[Ca2+][CO32-]/Ksp. In this study, 13C-labeled calcite is dissolved in unlabeled seawater and the evolving d13C composition of the fluid is traced over time to establish dissolution rate. Instead of changing ion concentration to obtain varying Ω (as in our previous study; Subhas et al. 2015), we changed Ksp by conducting experiments under different pressures (described in theory as ∂lnKsp/∂P=-ΔV/RT, where ΔV is partial molal volume). This involved the construction of a pressure vessel that could hold our sample bag and provide aliquots while remaining pressurized. Pressure experiments were conducted between 0-2000PSI. Results support the conclusion in our previous study that near-equilibrium dissolution rates are highly nonlinear, but give a disparate relationship between undersaturation and dissolution rate if Ω is calculated assuming the specific ΔV embedded in CO2SYS. A revised ΔV from -37cm3 to -65cm3 would make the dissolution formulation equation agree, but clearly appears unreasonable. Our results are explained by a pressure effect on carbonate dissolution kinetics over and above the influence of pressure on Ω. If this is a phenomenon that occurs in nature, then we would predict that dissolution should be occurring shallower in the water column (as sometimes observed) than indicated by standard Ω calculations.

Kinetics of dissolution of UO2 in nitric acid solutions: A multiparametric study of the non-catalysed reaction

NASA Astrophysics Data System (ADS)

Cordara, T.; Szenknect, S.; Claparede, L.; Podor, R.; Mesbah, A.; Lavalette, C.; Dacheux, N.

2017-12-01

UO2 pellets were prepared by densification of oxides obtained from the conversion of the oxalate precursor. Then characterized in order to perform a multiparametric study of the dissolution in nitric acid medium. In this frame, for each sample, the densification rate, the grain size and the specific surface area of the prepared pellets were determined prior to the final dissolution experiments. By varying the concentration of the nitric acid solution and temperature, three different and successive steps were identified during the dissolution. Under the less aggressive conditions considered, a first transient step corresponding to the dissolution of the most reactive phases was observed at the solid/solution interface. Then, for all the tested conditions, a steady state step was established during which the normalised dissolution rate was found to be constant. It was followed by a third step characterized by a strong and continuous increase of the normalised dissolution rate. The duration of the steady state, also called "induction period", was found to vary drastically as a function of the HNO3 concentration and temperature. However, independently of the conditions, this steady state step stopped at almost similar dissolved material weight loss and dissolved uranium concentration. During the induction period, no important evolution of the topology of the solid/liquid interface was evidenced authorizing the use of the starting reactive specific surface area to evaluate the normalised dissolution rates thus the chemical durability of the sintered pellets. From the multiparametric study of UO2 dissolution proposed, oxidation of U(IV) to U(VI) by nitrate ions at the solid/liquid interface constitutes the limiting step in the overall dissolution mechanism associated to this induction period.

Real-time investigations of structural and optical changes in photochromic Ag/TiO2 nanocomposite thin films under laser irradiation

NASA Astrophysics Data System (ADS)

Babonneau, D.; Diop, D. K.; Simonot, L.; Lamongie, B.; Blanc, N.; Boudet, N.; Vocanson, F.; Destouches, N.

2018-03-01

Photochromic reaction dynamics in silver nanoparticles embedded in mesoporous titanium dioxide thin films is investigated by combining real-time grazing incidence small-angle x-ray scattering (GISAXS) and optical transmission measurements during UV-visible laser exposure cycles. While GISAXS probes changes in the particle size distribution, transmittance measurements are sensitive to spectral changes induced by photo-activated processes. Our results reveal a repeatable photochromic behavior with a good correlation in terms of kinetics between the morphological and optical fluctuations. Visible laser irradiation at 532 nm induces a preferential photo-dissolution of small silver particles, which in turn causes an increase in transmittance near the excitation wavelength. Furthermore, the photo-dissolution process can be significantly accelerated and amplified by associating visible laser with x-ray irradiation. Under UV laser irradiation at 360 nm, the bleaching process can be reverted by photocatalytic reduction with the mesopores in the TiO2 film acting as molds, which have the ability to confine the nanoparticle growth. However, in the irradiation conditions used in the present study, it appears that the photocatalytic growth of silver nanoparticles is slower than the photo-dissolution process, whereas its efficiency gradually degrades throughout the exposures to UV light.

Friction-induced structural transformations of the carbide phase in Hadfield steel

NASA Astrophysics Data System (ADS)

Korshunov, L. G.; Sagaradze, V. V.; Chernenko, N. L.; Shabashov, V. A.

2015-08-01

Structural transformations of the carbide phase in Hadfield steel (110G13) that occur upon plastic deformation by dry sliding friction have been studied by methods of optical metallography, X-ray diffraction, and transmission electron microscopy. Deformation is shown to lead to the refinement of the particles of the carbide phase (Fe, Mn)3C to a nanosized level. The effect of the deformation-induced dissolution of (Fe, Mn)3C carbides in austenite of 110G13 (Hadfield) steel has been revealed, which manifests in the appearance of new lines belonging to austenite with an unusually large lattice parameter ( a = 0.3660-0.3680 nm) in the X-ray diffraction patterns of steel tempered to obtain a fine-lamellar carbide phase after deformation. This austenite is the result of the deformation-induced dissolution of disperse (Fe, Mn)3C particles, which leads to the local enrichment of austenite with carbon and manganese. The tempering that leads to the formation of carbide particles in 110G13 steel exerts a negative influence on the strain hardening of the steel, despite the increase in the hardness of steel upon tempering and the development of the processes of the deformation-induced dissolution of the carbide phase, which leads to the strengthening of the γ solid solution.

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.

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.

Secondary calcification and dissolution respond differently to future ocean conditions

NASA Astrophysics Data System (ADS)

Silbiger, N. J.; Donahue, M. J.

2015-01-01

Climate change threatens both the accretion and erosion processes that sustain coral reefs. Secondary calcification, bioerosion, and reef dissolution are integral to the structural complexity and long-term persistence of coral reefs, yet these processes have received less research attention than reef accretion by corals. In this study, we use climate scenarios from RCP 8.5 to examine the combined effects of rising ocean acidity and sea surface temperature (SST) on both secondary calcification and dissolution rates of a natural coral rubble community using a flow-through aquarium system. We found that secondary reef calcification and dissolution responded differently to the combined effect of pCO2 and temperature. Calcification had a non-linear response to the combined effect of pCO2 and temperature: the highest calcification rate occurred slightly above ambient conditions and the lowest calcification rate was in the highest temperature-pCO2 condition. In contrast, dissolution increased linearly with temperature-pCO2 . The rubble community switched from net calcification to net dissolution at +271 μatm pCO2 and 0.75 °C above ambient conditions, suggesting that rubble reefs may shift from net calcification to net dissolution before the end of the century. Our results indicate that (i) dissolution may be more sensitive to climate change than calcification and (ii) that calcification and dissolution have different functional responses to climate stressors; this highlights the need to study the effects of climate stressors on both calcification and dissolution to predict future changes in coral reefs.

Secondary calcification and dissolution respond differently to future ocean conditions

NASA Astrophysics Data System (ADS)

Silbiger, N. J.; Donahue, M. J.

2014-09-01

Climate change threatens both the accretion and erosion processes that sustain coral reefs. Secondary calcification, bioerosion, and reef dissolution are integral to the structural complexity and long-term persistence of coral reefs, yet these processes have received less research attention than reef accretion by corals. In this study, we use climate scenarios from RCP8.5 to examine the combined effects of rising ocean acidity and SST on both secondary calcification and dissolution rates of a natural coral rubble community using a flow-through aquarium system. We found that secondary reef calcification and dissolution responded differently to the combined effect of pCO2 and temperature. Calcification had a non-linear response to the combined effect of pCO2-temperature: the highest calcification rate occurred slightly above ambient conditions and the lowest calcification rate was in the highest pCO2-temperature condition. In contrast, dissolution increased linearly with pCO2-temperature. The rubble community switched from net calcification to net dissolution at +272 μatm pCO2 and 0.84 °C above ambient conditions, suggesting that rubble reefs may shift from net calcification to net dissolution before the end of the century. Our results indicate that dissolution may be more sensitive to climate change than calcification, and that calcification and dissolution have different functional responses to climate stressors, highlighting the need to study the effects of climate stressors on both calcification and dissolution to predict future changes in coral reefs.

Impact of vibration and agitation speed on dissolution of USP prednisone tablets RS and various IR tablet formulations.

PubMed

Seeger, Nicole; Lange, Sigrid; Klein, Sandra

2015-08-01

Dissolution testing is an in vitro procedure which is widely used in quality control (QC) of solid oral dosage forms and, given that real biorelevant test conditions are applied, can also be used as a predictive tool for the in vivo performance of such formulations. However, if a dissolution method is intended to be used for such purposes, it has to deliver results that are only determined by the quality of the test product, but not by other variables. In the recent past, more and more questions were arising on how to address the effects of vibration on dissolution test results. The present study was performed to screen for the correlation of prednisone dissolution of USP Prednisone Tablets RS with vibration caused by a commercially available vibration source as well as to investigate how drug release from a range of immediate release formulations containing class 1-4 drugs of the biopharmaceutical classification scheme is affected by vibration when performing dissolution experiments at different agitation rates. Results of the present study show that the dissolution process of oral drug formulations can be affected by vibration. However, it also becomes clear that the degree of which a certain level of vibration impacts dissolution is strongly dependent on several factors such as drug properties, formulation parameters, and the design of the dissolution method. To ensure the establishment of robust and predictive dissolution test methods, the impact of variation should thus be considered in method design and validation.

Origin and diagenetic evolution of gypsum and microbialitic carbonates in the Late Sag of the Namibe Basin (SW Angola)

NASA Astrophysics Data System (ADS)

Laurent, Gindre-Chanu; Edoardo, Perri; Ian, Sharp R.; Peacock, D. C. P.; Roger, Swart; Ragnar, Poulsen; Hercinda, Ferreira; Vladimir, Machado

2016-08-01

Ephemeral evaporitic conditions developed within the uppermost part of the transgressive Late Sag sequence in the Namibe Basin (SW Angola), leading to the formation of extensive centimetre- to metre-thick sulphate-bearing deposits and correlative microbialitic carbonates rich in pseudomorphs after evaporite crystals. The onshore pre-salt beds examined in this study are located up to 25 m underneath the major mid-Aptian evaporitic succession, which is typified at the outcrop by gypsiferous Bambata Formation and in the subsurface by the halite-dominated Loeme Formation. Carbonate-evaporite cycles mostly occur at the top of metre-thick regressive parasequences, which progressively onlap and overstep landward the former faulted (rift) topography, or fill major pre-salt palaeo-valleys. The sulphate beds are made up of alabastrine gypsum associated with embedded botryoidal nodules, dissolution-related gypsum breccia, and are cross-cut by thin satin-spar gypsum veins. Nodular and fine-grained fabrics are interpreted as being diagenetic gypsum deposits resulting from the dissolution and recrystallisation of former depositional subaqueous sulphates, whereas gypsum veins and breccia result from telogenetic processes. The carbonates display a broader diversity of facies, characterised by rapid lateral variations along strike. Thin dolomitic and calcitic bacterial-mediated filamentous microbialitic boundstones enclose a broad variety of evaporite pseudomorphs and can pass laterally over a few metres into sulphate beds. Dissolution-related depositional breccias are also common and indicate early dissolution of former evaporite layers embedded within the microbialites. Sulphate and carbonate units are interpreted as being concomitantly deposited along a tide-dominated coastal supra- to intertidal- sabkha and constitute high-frequency hypersaline precursor events, prior to the accumulation of the giant saline mid-Aptian Bambata and Loeme Formations. Petrographic and geochemical analyses reveal successive dissolution, recrystallisation and cementation phases that occurred during burial, uplift and exhumation, implying a complex diagenetic evolution of both gypsum and carbonates, influenced by pore fluids of diverse composition which distinctly varied from meso- to telogenetic domains.

Kinetics of scheelite dissolution in groundwater: defining the release rate of tungsten contamination from a natural source

NASA Astrophysics Data System (ADS)

Montgomery, S. D.; Mckibben, M. A.

2011-12-01

Tungsten, an emerging contaminant, has no EPA standard for its permissible levels in drinking water. At sites in California, Nevada, and Arizona there may be a correlation between elevated levels of tungsten in drinking water and clusters of childhood acute lymphocytic leukemia (ALL). Developing a better understanding of how tungsten is released from rocks into surface and groundwaters is therefore of growing environmental interest. Knowledge of tungstate ore mineral weathering processes, particularly the rates of dissolution of scheelite (CaWO4) in groundwater, could improve models of how tungsten is released and transported in natural waters. Our research is focusing on experimental determination of the rates and products of tungstate mineral dissolution in synthetic groundwater, as a function of temperature, pH and mineral surface area. The initial rate method is being used to develop rate laws. Batch reactor experiments are conducted within constant temperature circulation baths over a pH range of 2-9. Cleaned scheelite powder with grain diameters of 106-150um is placed between two screens in a sample platform and then placed inside a two liter Teflon vessel filled with synthetic groundwater. Ports on the vessel allow sample extraction, temperature and pH measurement, gas inflow, and water circulation. Aliquots of solution are taken periodically for product analysis by ICP -MS. Changes in mineral surface characteristics are monitored using SEM and EDS methods. Results so far reveal that the dissolution of scheelite is incongruent at both neutral and low pH. Solid tungstic acid forms on scheelite mineral surfaces under acidic conditions, implying that this phase controls the dissolution rate in acidic environments. The influence of dissolved CO2 and resultant calcium carbonate precipitation on the dissolution of scheelite at higher pH is also being investigated. The rate law being developed for scheelite dissolution will be useful in reactive-transport computer codes designed to model tungsten contamination in a variety of surface and groundwater settings.

A Bioactive Hydrogel and 3D Printed Polycaprolactone System for Bone Tissue Engineering.

PubMed

Hernandez, Ivan; Kumar, Alok; Joddar, Binata

2017-09-01

In this study, a hybrid system consisting of 3D printed polycaprolactone (PCL) filled with hydrogel was developed as an application for reconstruction of long bone defects, which are innately difficult to repair due to large missing segments of bone. A 3D printed gyroid scaffold of PCL allowed a larger amount of hydrogel to be loaded within the scaffolds as compared to 3D printed mesh and honeycomb scaffolds of similar volumes and strut thicknesses. The hydrogel was a mixture of alginate, gelatin, and nano-hydroxyapatite, infiltrated with human mesenchymal stem cells (hMSC) to enhance the osteoconductivity and biocompatibility of the system. Adhesion and viability of hMSC in the PCL/hydrogel system confirmed its cytocompatibility. Biomineralization tests in simulated body fluid (SBF) showed the nucleation and growth of apatite crystals, which confirmed the bioactivity of the PCL/hydrogel system. Moreover, dissolution studies, in SBF revealed a sustained dissolution of the hydrogel with time. Overall, the present study provides a new approach in bone tissue engineering to repair bone defects with a bioactive hybrid system consisting of a polymeric scaffold, hydrogel, and hMSC.

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.

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.

Development and application of a biorelevant dissolution method using USP apparatus 4 in early phase formulation development.

PubMed

Fang, Jiang B; Robertson, Vivian K; Rawat, Archana; Flick, Tawnya; Tang, Zhe J; Cauchon, Nina S; McElvain, James S

2010-10-04

Dissolution testing is frequently used to determine the rate and extent at which a drug is released from a dosage form, and it plays many important roles throughout drug product development. However, the traditional dissolution approach often emphasizes its application in quality control testing and usually strives to obtain 100% drug release. As a result, dissolution methods are not necessarily biorelevant and meaningful application of traditional dissolution methods in the early phases of drug product development can be very limited. This article will describe the development of a biorelevant in vitro dissolution method using USP apparatus 4, biorelevant media, and real-time online UV analysis. Several case studies in the areas of formulation selection, lot-to-lot variability, and food effect will be presented to demonstrate the application of this method in early phase formulation development. This biorelevant dissolution method using USP apparatus 4 provides a valuable tool to predict certain aspects of the in vivo drug release. It can be used to facilitate the formulation development/selection for pharmacokinetic (PK) and clinical studies. It may also potentially be used to minimize the number of PK studies, and to aid in the design of more efficient PK and clinical studies.

[Preparation and in vitro dissolution of magnolol solid dispersion].

PubMed

Tang, Lan; Qiu, Shuai-Bo; Wu, Lan; Lv, Long-Fei; Lv, Hui-Xia; Shan, Wei-Guang

2016-02-01

In this study, solid dispersion system of magnolol in croscarmellose sodium was prepared by using the solvent evaporation method, in order to increase the drug dissolution. And its dissolution behavior, stability and physical characteristics were studied. The solid dispersion was prepared with magnolol and croscarmellose sodium, with the proportion of 1∶5, the in vitro dissolution of magnolol solid dispersion was up to 80.66% at 120 min, which was 6.9 times of magnolol. The results of DSC (differential scanning calorimetry), IR (infra-red) spectrum and SEM (scanning electron microscopy) showed that magnolol existed in solid dispersion in an amorphous form. After an accelerated stability test for six months, the drug dissolution and content in magnolol solid dispersion showed no significant change. So the solid dispersion prepared with croscarmellose sodium as the carrier can remarkably improve the stability and dissolution of magnolol. Copyright© by the Chinese Pharmaceutical Association.

Dissolution behaviour of 238U, 234U and 230Th deposited on filters from personal dosemeters.

PubMed

Becková, Vera; Malátová, Irena

2008-01-01

Kinetics of dissolution of (238)U, (234)U and (230)Th dust deposited on filters from personal alpha dosemeters was studied by means of a 26-d in vitro dissolution test with a serum ultrafiltrate simulant. Dosemeters had been used by miners at the uranium mine 'Dolní Rozínka' at Rozná, Czech Republic. The sampling flow-rate as declared by the producer is 4 l h(-1) and the sampling period is typically 1 month. Studied filters contained 125 +/- 6 mBq (238)U in equilibrium with (234)U and (230)Th; no (232)Th series nuclides were found. Half-time of rapid dissolution of 1.4 d for (238)U and (234)U and slow dissolution half-times of 173 and 116 d were found for (238)U and (234)U, respectively. No detectable dissolution of (230)Th was found.

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 of finasteride capsules-loaded drug nanoparticles: formulation, optimization, in vitro, and pharmacokinetic evaluation

PubMed Central

Ahmed, Tarek A

2016-01-01

In this study, optimized freeze-dried finasteride nanoparticles (NPs) were prepared from drug nanosuspension formulation that was developed using the bottom–up technique. The effects of four formulation and processing variables that affect the particle size and solubility enhancement of the NPs were explored using the response surface optimization design. The optimized formulation was morphologically characterized using transmission electron microscopy (TEM). Physicochemical interaction among the studied components was investigated. Crystalline change was investigated using X-ray powder diffraction (XRPD). Crystal growth of the freeze-dried NPs was compared to the corresponding aqueous drug nanosuspension. Freeze-dried NPs formulation was subsequently loaded into hard gelatin capsules that were examined for in vitro dissolution and pharmacokinetic behavior. Results revealed that in most of the studied variables, some of the quadratic and interaction effects had a significant effect on the studied responses. TEM image illustrated homogeneity and shape of the prepared NPs. No interaction among components was noticed. XRPD confirmed crystalline state change in the optimized NPs. An enhancement in the dissolution rate of more than 2.5 times from capsules filled with optimum drug NPs, when compared to capsules filled with pure drug, was obtained. Crystal growth, due to Ostwald ripening phenomenon and positive Gibbs free energy, was reduced following lyophilization of the nanosuspension formulation. Pharmacokinetic parameters from drug NPs were superior to that of pure drug and drug microparticles. In conclusion, freeze-dried NPs based on drug nanosuspension formulation is a successful technique in enhancing stability, solubility, and in vitro dissolution of poorly water-soluble drugs with possible impact on the drug bioavailability. PMID:26893559

Initial dissolution kinetics of cocrystal of carbamazepine with nicotinamide.

PubMed

Hattori, Yusuke; Sato, Maiko; Otsuka, Makoto

2015-11-01

Objectives of this study are investigating the initial dissolution kinetics of the cocrystal of carbamazepine (CBZ) with nicotinamide (NIC) and understanding its initial dissolution process. Cocrystal solids of CBZ with NIC were prepared by co-milling and solvent evaporation methods. The formation of cocrystal solid was verified via X-ray diffraction measurement. Dissolution tests of the solids were performed using an original flow cell and ultraviolet-visible spectroscopic detector. The spectra monitored in situ were analyzed to determine the dissolved compounds separately using the classical least squares regression method. The initial dissolution profiles were interpreted using simultaneous model of dissolution and phase changes. In the initial dissolution, CBZ in the cocrystal structure dissolved in water and it was suggested that CBZ reached a metastable intermediate state simultaneously with dissolution. The cocrystal solid prepared by solvent evaporation provided a higher rate constant of the phase change than that prepared by co-milling. Our results thus support the use of evaporation as the method of choice to produce ordered cocrystal structures. We suggest that CBZ forms dihydrate during the dissolution process; however, during the initial phase of dissolution, CBZ changes to a metastable intermediate phase. © 2015 Royal Pharmaceutical Society.

How does natural groundwater flow affect CO2 dissolution in saline aquifers?

NASA Astrophysics Data System (ADS)

Rosenzweig, R.; Michel-Meyer, I.; Tsinober, A.; Shavit, U.

2017-12-01

The dissolution of supercritical CO2 in aquifer brine is one of the most important trapping mechanisms in CO2 geological storage. Diffusion-limited dissolution is a very slow process. However, since the CO2-rich water is slightly denser than the CO2-free water, when CO2-free water is overlaid by heavier CO2-rich water, convective instability results in fingers of dense CO2-rich water that propagate downwards, causing CO2-unsaturated water to move upwards. This convection process significantly accelerates the dissolution rate of CO2 into the aquifer water.Most previous works have neglected the effect of natural groundwater flow and assumed it has no effect on the dissolution dynamics. However, it was found that in some of the saline aquifers groundwater flow rate, although small, is not zero. In this research, we study the effect of groundwater flow on dissolution by performing laboratory experiments in a bead pack cell using a mixture of methanol and ethylene-glycol as a CO2 analog while varying the water horizontal flow rate. We find that water horizontal flow decreases the number of fingers, their wavelength and their propagation velocity. When testing high water flow rates, no fingers were developed and the dissolution process was entirely diffusive. The effect of water flow on the dissolution rate did not show a clear picture. When increasing the horizontal flow rate the convective dissolution flux slightly decreased and then increased again. It seems that the combination of density-driven flow, water horizontal flow, mechanical dispersion and molecular diffusion affect the dissolution rate in a complex and non-monotonic manner. These intriguing dynamics should be further studied to understand their effect on dissolution trapping.

On the dissolution properties of GaAs in Ga

NASA Technical Reports Server (NTRS)

Davidson, M. C.; Moynahan, A. H.

1977-01-01

The dissolution of GaAs in Ga was studied to determine the nature and cause of faceting effects. Ga was allowed to dissolve single crystalline faces under isothermal conditions. Of the crystalline planes with low number indices, only the (100) surface showed a direct correlation of dissolution sites to dislocations. The type of dissolution experienced depended on temperature, and there were three distinct types of behavior.

On the effects of subsurface parameters on evaporite dissolution (Switzerland)

NASA Astrophysics Data System (ADS)

Zidane, Ali; Zechner, Eric; Huggenberger, Peter; Younes, Anis

2014-05-01

Uncontrolled subsurface evaporite dissolution could lead to hazards such as land subsidence. Observed subsidences in a study area of Northwestern Switzerland were mainly due to subsurface dissolution (subrosion) of evaporites such as halite and gypsum. A set of 2D density driven flow simulations were evaluated along 1000 m long and 150 m deep 2D cross sections within the study area that is characterized by tectonic horst and graben structures. The simulations were conducted to study the effect of the different subsurface parameters that could affect the dissolution process. The heterogeneity of normal faults and its impact on the dissolution of evaporites is studied by considering several permeable faults that include non-permeable areas. The mixed finite element method (MFE) is used to solve the flow equation, coupled with the multipoint flux approximation (MPFA) and the discontinuous Galerkin method (DG) to solve the diffusion and the advection parts of the transport equation.

Dissolution DNP-NMR spectroscopy using galvinoxyl as a polarizing agent

NASA Astrophysics Data System (ADS)

Lumata, Lloyd L.; Merritt, Matthew E.; Malloy, Craig R.; Sherry, A. Dean; van Tol, Johan; Song, Likai; Kovacs, Zoltan

2013-02-01

The goal of this work was to test feasibility of using galvinoxyl (2,6-di-tert-butyl-α-(3,5-di-tert-butyl-4-oxo-2,5-cyclohexadien-1-ylidene)-p-tolyloxy) as a polarizing agent for dissolution dynamic nuclear polarization (DNP) NMR spectroscopy. We have found that galvinoxyl is reasonably soluble in ethyl acetate, chloroform, or acetone and the solutions formed good glasses when mixed together or with other solvents such as dimethyl sulfoxide. W-band electron spin resonance (ESR) measurements revealed that galvinoxyl has an ESR linewidth D intermediate between that of carbon-centered free radical trityl OX063 and the nitroxide-based 4-oxo-TEMPO, thus the DNP with galvinoxyl for nuclei with low gyromagnetic ratio γ such as 13C and 15N is expected to proceed predominantly via the thermal mixing process. The optimum radical concentration that would afford the highest 13C nuclear polarization (approximately 6% for [1-13C]ethyl acetate) at 3.35 T and 1.4 K was found to be around 40 mM. After dissolution, large liquid-state NMR enhancements were achieved for a number of 13C and 15N compounds with long spin-lattice relaxation time T1. In addition, the hydrophobic galvinoxyl free radical can be easily filtered out from the dissolution liquid when water is used as the solvent. These results indicate that galvinoxyl can be considered as an easily available free radical polarizing agent for routine dissolution DNP-NMR spectroscopy.

Experiments and modeling of variably permeable carbonate reservoir samples in contact with CO₂-acidified brines

DOE PAGES

Smith, Megan M.; Hao, Yue; Mason, Harris E.; ...

2014-12-31

Reactive experiments were performed to expose sample cores from the Arbuckle carbonate reservoir to CO₂-acidified brine under reservoir temperature and pressure conditions. The samples consisted of dolomite with varying quantities of calcite and silica/chert. The timescales of monitored pressure decline across each sample in response to CO₂ exposure, as well as the amount of and nature of dissolution features, varied widely among these three experiments. For all samples cores, the experimentally measured initial permeability was at least one order of magnitude or more lower than the values estimated from downhole methods. Nondestructive X-ray computed tomography (XRCT) imaging revealed dissolution featuresmore » including “wormholes,” removal of fracture-filling crystals, and widening of pre-existing pore spaces. In the injection zone sample, multiple fractures may have contributed to the high initial permeability of this core and restricted the distribution of CO₂-induced mineral dissolution. In contrast, the pre-existing porosity of the baffle zone sample was much lower and less connected, leading to a lower initial permeability and contributing to the development of a single dissolution channel. While calcite may make up only a small percentage of the overall sample composition, its location and the effects of its dissolution have an outsized effect on permeability responses to CO₂ exposure. The XRCT data presented here are informative for building the model domain for numerical simulations of these experiments but require calibration by higher resolution means to confidently evaluate different porosity-permeability relationships.« less

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.

Development and Validation of New Discriminative Dissolution Method for Carvedilol Tablets

PubMed Central

Raju, V.; Murthy, K. V. R.

2011-01-01

The objective of the present study was to develop and validate a discriminative dissolution method for evaluation of carvedilol tablets. Different conditions such as type of dissolution medium, volume of dissolution medium and rotation speed of paddle were evaluated. The best in vitro dissolution profile was obtained using Apparatus II (paddle), 50 rpm, 900 ml of pH 6.8 phosphate buffer as dissolution medium. The drug release was evaluated by high-performance liquid chromatographic method. The dissolution method was validated according to current ICH and FDA guidelines using parameters such as the specificity, accuracy, precision and stability were evaluated and obtained results were within the acceptable range. The comparison of the obtained dissolution profiles of three different products were investigated using ANOVA-based, model-dependent and model-independent methods, results showed that there is significant difference between the products. The dissolution test developed and validated was adequate for its higher discriminative capacity in differentiating the release characteristics of the products tested and could be applied for development and quality control of carvedilol tablets. PMID:22923865

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.

What controls silicon isotope fractionation during dissolution of diatom opal?

NASA Astrophysics Data System (ADS)

Wetzel, F.; de Souza, G. F.; Reynolds, B. C.

2014-04-01

The silicon isotope composition of opal frustules from photosynthesising diatoms is a promising tool for studying past changes in the marine silicon cycle, and indirectly that of carbon. Dissolution of this opal may be accompanied by silicon isotope fractionation that could disturb the pristine silicon isotope composition of diatom opal acquired in the surface ocean. It has previously been shown that dissolution of fresh and sediment trap diatom opal in seawater does fractionate silicon isotopes. However, as the mechanism of silicon isotope fractionation remained elusive, it is uncertain whether opal dissolution in general is associated with silicon isotope fractionation considering that opal chemistry and surface properties are spatially and temporally (i.e. opal of different age) diverse. In this study we dissolved sediment core diatom opal in 5 mM NaOH and found that this process is not associated with significant silicon isotope fractionation. Since no variability of the isotope effect was observed over a wide range of dissolution rates, we can rule out the suggestion that back-reactions had a significant influence on the net isotope effect. Similarly, we did not observe an impact of temperature, specific surface area, or degree of undersaturation on silicon isotope partitioning during dissolution, such that these can most likely also be ruled out as controlling factors. We discuss the potential impacts of the chemical composition of the dissolution medium and age of diatom opal on silicon isotope fractionation during dissolution. It appears most likely that the controlling mechanism of silicon isotope fractionation during dissolution is related to the reactivity, or potentially, aluminium content of the opal. Such a dependency would imply that silicon isotope fractionation during dissolution of diatom opal is spatially and temporally variable. However, since the isotope effects during dissolution are small, the silicon isotope composition of diatom opal appears to be robust against dissolution in the deep sea sedimentary environment.

Dissolution mechanism of calcium apatites in acids: A review of literature

PubMed Central

Dorozhkin, Sergey V

2012-01-01

Eight dissolution models of calcium apatites (both fluorapatite and hydroxyapatite) in acids were drawn from the published literature, analyzed and discussed. Major limitations and drawbacks of the models were conversed in details. The models were shown to deal with different aspects of apatite dissolution phenomenon and none of them was able to describe the dissolution process in general. Therefore, an attempt to combine the findings obtained by different researchers was performed which resulted in creation of the general description of apatite dissolution in acids. For this purpose, eight dissolution models were assumed to complement each other and provide the correct description of the specific aspects of apatite dissolution. The general description considers all possible dissolution stages involved and points out to some missing and unclear phenomena to be experimentally studied and verified in future. This creates a new methodological approach to investigate reaction mechanisms based on sets of affine data, obtained by various research groups under dissimilar experimental conditions. PMID:25237611

[Evaluation of Dissolution Profiles of Famotidine from Over-the-counter Drugs].

PubMed

Saito, Yuji; Adachi, Naoki; Kato, Miki; Nadai, Masayuki

2018-03-27

  In recent years, self-medication has started to receive more attention in Japan owing to increasing medical costs and health awareness among people. One of the main roles of pharmacists in self-medication is to provide appropriate information regarding over-the-counter (OTC) drugs. However, pharmacists promoting the proper use of OTC drugs have little information on their formulation properties. In this study, we performed dissolution tests on both OTC drugs and ethical drug (ED) containing famotidine, and evaluated the differences in their dissolution profiles. Marked differences in dissolution profiles of OTC drugs were observed in test solutions at pH 1.2, 4.0, and 6.8 and in water. To evaluate the differences quantitatively, we calculated the lag time and dissolution rate constant from the dissolution profiles. Significant differences in lag times and dissolution rate constants between some OTC drugs and ED were observed. We also used similarity factor (f2), to quantify the similarity between dissolution profiles of OTC drugs and ED. f2 values less than 42 were observed in some OTC drugs, suggesting that these differences might influence absorption in vivo resulting in differences in their onset time and efficacy. The findings of this study will provide useful information for the promotion of proper use of OTC drugs.

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 of steel slags in aqueous media.

PubMed

Yadav, Shashikant; Mehra, Anurag

2017-07-01

Steel slag is a major industrial waste in steel industries, and its dissolution behavior in water needs to be characterized in the larger context of its potential use as an agent for sequestering CO 2 . For this purpose, a small closed system batch reactor was used to conduct the dissolution of steel slags in an aqueous medium under various dissolution conditions. In this study, two different types of steel slags were procured from steel plants in India, having diverse structural features, mineralogical compositions, and particle sizes. The experiment was performed at different temperatures for 240 h of dissolution at atmospheric pressure. The dissolution rates of major and minor slag elements were quantified through liquid-phase elemental analysis using an inductively coupled plasma atomic emission spectroscopy at different time intervals. Advanced analytical techniques such as field emission gun-scanning electron microscope, energy-dispersive X-ray, BET, and XRD were also used to analyze mineralogical and structural changes in the slag particles. High dissolution of slags was observed irrespective of the particle size distribution, which suggests high carbonation potential. Concentrations of toxic heavy metals in the leachate were far below maximum acceptable limits. Thus, the present study investigates the dissolution behavior of different mineral ions of steel slag in aqueous media in light of its potential application in CO 2 sequestration.

Extended defects and hydrogen interactions in ion implanted silicon

NASA Astrophysics Data System (ADS)

Rangan, Sanjay

The structural and electrical properties of extended defects generated because of ion implantation and the interaction of hydrogen with these defects have been studied in this work. Two distinct themes have been studied, the first where defects are a detrimental and the second where they are useful. In the first scenario, transient enhanced diffusion of boron has been studied and correlated with defect evolution studies due to silicon and argon ion implants. Spreading resistance profiles (SRP) correlated with deep level transient spectroscopy (DLTS) measurements, reveal that a low anneal temperatures (<650°C) defect dissolution and defect injection dominates, resulting in increased junction depths. At higher anneal temperatures, however, repair dominates over defect injection resulting in shallower junctions. Hydrogenation experiments shows that hydrogen enhances dopant activation and reduces TED at low anneal temperatures (<550°C). At anneal temperatures >550°C, the effect of hydrogen is lost, due to its out-diffusion. Moreover, due to catastrophic out-diffusion of hydrogen, additional damage is created resulting in deeper junctions in hydrogenated samples, compared to the non-hydrogenated ones. Comparing defect evolution due to Si and Ar ion implants at different anneal temperatures, while the type of defects is the same in the two cases, their (defect) dissolution occurs at lower anneal temperatures (˜850°C) for Si implants. Dissolution for Ar implants seems to occur at higher anneal temperatures. The difference has been attributed to the increased number of vacancies created by Ar to that of silicon implant. In second aspect, nano-cavity formation due to vacancy agglomeration has been studied by helium ion implantation and furnace anneal, where the effect of He dose, implant energy and anneal time have been processing parameters that have been varied. Cavities are formed only when the localized concentration of He is greater than 3 x 1020 cm-3. While at high implant doses, a continuous cavity layer is formed, at low implant doses a discontinuous layer is observed. The formation of cavities at low doses has been observed for the first time. Variation of anneal times reveal that cavities are initially facetted (for short anneal times) and tend to become spherical when annealed for along time (300min). Also presented is the recipe for formation of multiple cavity layers and the electrical and optical properties of these cavities. Electrically, these cavities are metastable, with two strong minority carrier peaks formed by multiple defect levels. Photoluminescence measurements reveal a strong 0.8eV photon peak.

Dissolution of Uranium(IV) Oxide in Solutions of Ammonium Carbonate and Hydrogen Peroxide

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

Smith, Steven C.; Peper, Shane M.; Douglas, Matthew

2009-09-12

Understanding the dissolution characteristics of uranium oxides is of fundamental scientific interest. Bench scale experiments were conducted to determine the optimal dissolution parameters of uranium(IV) oxide (UO2) powder in solutions of ammonium carbonate [(NH4)2CO3] and hydrogen peroxide (H2O2). Experimental parameters included variable peroxide and carbonate concentrations, and temperature. Results indicate the dissolution rate of UO2 in 1 M (NH4)2CO3 increases linearly with peroxide concentration ranging from 0.05 – 2 M (1:1 to 40:1 mol ratio H2O2:U), with no apparent maximum rate reached under the limited conditions used in our study. Temperature ranging studies show the dissolution rate of UO2 inmore » 1 M (NH4)2CO3 and 0.1 M H2O2 (2:1 mol ratio H2O2:U) increases linearly from 15 °C to 60 °C, again with no apparent maximum rate reached. Dissolution of UO2 in solutions with constant [H2O2] and [(NH4)2CO3] ranging from 0.5 to 2 M showed no difference in rate; however dissolution was significantly reduced in 0.05 M (NH4)2CO3 solution. The results of this study demonstrate the influence of [H2O2], [(NH4)2CO3], and temperature on the dissolution of UO2 in peroxide-containing (NH4)2CO3 solutions. Future studies are planned to elucidate the solution and solid state complexes in these systems.« less

Furosemide Loaded Silica-Lipid Hybrid Microparticles: Formulation Development, in vitro and ex vivo Evaluation.

PubMed

Sambaraj, Swapna; Ammula, Divya; Nagabandi, Vijaykumar

2015-09-01

The main objective of the current research work was to formulate and evaluate furosemide loaded silica lipid hybrid microparticles for improved oral delivery. A novel silica-lipid hybrid microparticulate system is used for enhancing the oral absorption of low solubility and low permeability of (BCS Class IV) drugs. Silica-lipid hybrid microparticles include the drug solubilising effect of dispersed lipids and stabilizing effect of hydrophilic silica particles to increase drug solubilisation, which leads to enhanced oral bioavailability. The slica lipid hybrid (SLH) microparticles were composed of poorly soluble drug (furosemide), dispersion of oil phase (Soya bean oil and miglyol) in lecithin (Phospholipoid 90H), non-ionic surfactant (Polysorbate 80) and adsorbent (Aerosol 380). Saturation solubility studies were performed in different oils and surfactants with increased concentration of drug revealed increased solubility of furosemide. In vitro dissolution studies conducted under simulated gastric medium revealed 2-4 fold increase in dissolution efficiencies for SLH microparticles compared to that of pure drug (furosemide) and marketed formulation Lasix®. Ex vivo studies showed enhanced lipid digestibility, which improved drug permeability. Solid-state characterization of SLH microparticles by X-ray powder diffraction and Fourier transform infrared spectroscopic analysis confirmed non-crystalline nature and more compatibility of furosemide in silica-lipid hybrid microparticles. It can be concluded that the role of lipids and hydrophilic silica based carrier highlighted in enhancing solubility and permeability, and hence the oral bioavailability of poorly soluble drugs.

Furosemide Loaded Silica-Lipid Hybrid Microparticles: Formulation Development, in vitro and ex vivo Evaluation

PubMed Central

Sambaraj, Swapna; Ammula, Divya; Nagabandi, Vijaykumar

2015-01-01

Purpose: The main objective of the current research work was to formulate and evaluate furosemide loaded silica lipid hybrid microparticles for improved oral delivery. A novel silica-lipid hybrid microparticulate system is used for enhancing the oral absorption of low solubility and low permeability of (BCS Class IV) drugs. Silica-lipid hybrid microparticles include the drug solubilising effect of dispersed lipids and stabilizing effect of hydrophilic silica particles to increase drug solubilisation, which leads to enhanced oral bioavailability. Methods: The slica lipid hybrid (SLH) microparticles were composed of poorly soluble drug (furosemide), dispersion of oil phase (Soya bean oil and miglyol) in lecithin (Phospholipoid 90H), non-ionic surfactant (Polysorbate 80) and adsorbent (Aerosol 380). Saturation solubility studies were performed in different oils and surfactants with increased concentration of drug revealed increased solubility of furosemide. Results: In vitro dissolution studies conducted under simulated gastric medium revealed 2-4 fold increase in dissolution efficiencies for SLH microparticles compared to that of pure drug (furosemide) and marketed formulation Lasix®. Ex vivo studies showed enhanced lipid digestibility, which improved drug permeability. Solid-state characterization of SLH microparticles by X-ray powder diffraction and Fourier transform infrared spectroscopic analysis confirmed non-crystalline nature and more compatibility of furosemide in silica-lipid hybrid microparticles. Conclusion: It can be concluded that the role of lipids and hydrophilic silica based carrier highlighted in enhancing solubility and permeability, and hence the oral bioavailability of poorly soluble drugs. PMID:26504763

Comparative studies of thin film growth on aluminium by AFM, TEM and GDOES characterization

NASA Astrophysics Data System (ADS)

Qi, Jiantao; Thompson, George E.

2016-07-01

In this present study, comparative studies of trivalent chromium conversion coating formation, associated with aluminium dissolution process, have been investigated using atomic force microscopy (AFM), transmission electron microscopy (TEM) and glow-discharge optical emission spectroscopy (GDOES). High-resolution electron micrographs revealed the evident and uniform coating initiation on the whole surface after conversion treatment for only 30 s, although a network of metal ridges was created by HF etching pre-treatment. In terms of conversion treatment process on electropolished aluminium, constant kinetics of coating growth, ∼0.30 ± 0.2 nm/s, were found after the prolonged conversion treatment for 600 s. The availability of electrolyte anions for coating deposition determined the growth process. Simultaneously, a proceeding process of aluminium dissolution during conversion treatment, of ∼0.11 ± 0.02 nm/s, was found for the first time, indicating constant kinetics of anodic reactions. The distinct process of aluminium consumption was assigned with loss of corrosion protection of the deposited coating material as evidenced in the electrochemical impedance spectroscopy. Based on the present data, a new mechanism of coating growth on aluminium was proposed, and it consisted of an activation period (0-30 s), a linear growth period (0.30 nm/s, up for 600 s) and limited growth period (0.17 nm/s, 600-1200 s). In addition, the air-drying post-treatment and a high-vacuum environment in the microscope revealed a coating shrinkage, especially in the coatings after conversion treatments for longer time.

Pinaverium Bromide: Development and Validation of Spectrophotometric Methods for Assay and Dissolution Studies.

PubMed

Martins, Danielly da Fonte Carvalho; Florindo, Lorena Coimbra; Machado, Anna Karolina Mouzer da Silva; Todeschini, Vítor; Sangoi, Maximiliano da Silva

2017-11-01

This study presents the development and validation of UV spectrophotometric methods for the determination of pinaverium bromide (PB) in tablet assay and dissolution studies. The methods were satisfactorily validated according to International Conference on Harmonization guidelines. The response was linear (r2 > 0.99) in the concentration ranges of 2-14 μg/mL at 213 nm and 10-70 μg/mL at 243 nm. The LOD and LOQ were 0.39 and 1.31 μg/mL, respectively, at 213 nm. For the 243 nm method, the LOD and LOQ were 2.93 and 9.77 μg/mL, respectively. Precision was evaluated by RSD, and the obtained results were lower than 2%. Adequate accuracy was also obtained. The methods proved to be robust using a full factorial design evaluation. For PB dissolution studies, the best conditions were achieved using a United States Pharmacopeia Dissolution Apparatus 2 (paddle) at 50 rpm and with 900 mL 0.1 M hydrochloric acid as the dissolution medium, presenting satisfactory results during the validation tests. In addition, the kinetic parameters of drug release were investigated using model-dependent methods, and the dissolution profiles were best described by the first-order model. Therefore, the proposed methods were successfully applied for the assay and dissolution analysis of PB in commercial tablets.

Distinct iron isotopic signatures and supply from marine sediment dissolution.

PubMed

Homoky, William B; John, Seth G; Conway, Tim M; Mills, Rachel A

2013-01-01

Oceanic iron inputs must be traced and quantified to learn how they affect primary productivity and climate. Chemical reduction of iron in continental margin sediments provides a substantial dissolved flux to the oceans, which is isotopically lighter than the crust, and so may be distinguished in seawater from other sources, such as wind-blown dust. However, heavy iron isotopes measured in seawater have recently led to the proposition of another source of dissolved iron from 'non-reductive' dissolution of continental margins. Here we present the first pore water iron isotope data from a passive-tectonic and semi-arid ocean margin (South Africa), which reveals a smaller and isotopically heavier flux of dissolved iron to seawater than active-tectonic and dysoxic continental margins. These data provide in situ evidence of non-reductive iron dissolution from a continental margin, and further show that geological and hydro-climatic factors may affect the amount and isotopic composition of iron entering the ocean.

APTES-modified mesoporous silicas as the carriers for poorly water-soluble drug. Modeling of diflunisal adsorption and release

NASA Astrophysics Data System (ADS)

Geszke-Moritz, Małgorzata; Moritz, Michał

2016-04-01

Four mesoporous siliceous materials such as SBA-16, SBA-15, PHTS and MCF functionalized with (3-aminopropyl)triethoxysilane were successfully prepared and applied as the carriers for poorly water-soluble drug diflunisal. Several techniques including nitrogen sorption analysis, XRD, TEM, FTIR and thermogravimetric analysis were employed to characterize mesoporous matrices. Adsorption isotherms were analyzed using Langmuir, Freundlich, Temkin and Dubinin-Radushkevich models. In order to find the best-fit isotherm for each model, both linear and nonlinear regressions were carried out. The equilibrium data were best fitted by the Langmuir isotherm model revealing maximum adsorption capacity of 217.4 mg/g for aminopropyl group-modified SBA-15. The negative values of Gibbs free energy change indicated that the adsorption of diflunisal is a spontaneous process. Weibull release model was employed to describe the dissolution profile of diflunisal. At pH 4.5 all prepared mesoporous matrices exhibited the improvement of drug dissolution kinetics as compared to the dissolution rate of pure diflunisal.

Distinct iron isotopic signatures and supply from marine sediment dissolution

PubMed Central

Homoky, William B.; John, Seth G.; Conway, Tim M.; Mills, Rachel A.

2013-01-01

Oceanic iron inputs must be traced and quantified to learn how they affect primary productivity and climate. Chemical reduction of iron in continental margin sediments provides a substantial dissolved flux to the oceans, which is isotopically lighter than the crust, and so may be distinguished in seawater from other sources, such as wind-blown dust. However, heavy iron isotopes measured in seawater have recently led to the proposition of another source of dissolved iron from ‘non-reductive’ dissolution of continental margins. Here we present the first pore water iron isotope data from a passive-tectonic and semi-arid ocean margin (South Africa), which reveals a smaller and isotopically heavier flux of dissolved iron to seawater than active-tectonic and dysoxic continental margins. These data provide in situ evidence of non-reductive iron dissolution from a continental margin, and further show that geological and hydro-climatic factors may affect the amount and isotopic composition of iron entering the ocean. PMID:23868399

Physicochemical and Pharmacokinetic Characterization of Amorphous Solid Dispersion of Meloxicam with Enhanced Dissolution Property and Storage Stability.

PubMed

Ochi, Masanori; Kimura, Keisuke; Kanda, Atsushi; Kawachi, Takaki; Matsuda, Akitoshi; Yuminoki, Kayo; Hashimoto, Naofumi

2016-08-01

The aim of the present study was to develop amorphous solid dispersion (ASD) of meloxicam (MEL) for providing rapid onset of action. ASDs of MEL with polyvinylpyrrolidone (PVP) K-30 (MEL/PVP), HPC-SSL (MEL/HPC), and Eudragit EPO (MEL/EPO) were prepared. The physicochemical properties were characterized by focusing on morphology, crystallinity, dissolution properties, stability, and the interaction of MEL with coexisting polymers. MEL/EPO was physicochemically stable after storage at 40°C/75% RH for 30 days. In contrast, recrystallization of MEL was observed in MEL/PVP and MEL/HPC at 40°C/50% RH for 30 days. Infrared spectroscopic studies and (1)H NMR analyses of MEL/EPO revealed that Eudragit EPO interacted with MEL and reduced intermolecular binding between MEL molecules. Intermolecular interaction of drug molecules is necessary for the formation of crystalline. Thus, the interaction of MEL with Eudragit EPO and interruption of the formation of supramolecular interaction between MEL molecules might lead to the inhibition of crystal growth of MEL. Of all the MEL solid dispersions prepared, MEL/EPO showed the largest improvement in dissolution behavior. Oral administration of MEL/EPO to rats showed rapid and enhanced MEL exposure with a 2.4-fold increase in bioavailability compared with crystalline MEL. Based on these findings, MEL/EPO was physicochemically stable and provided a rapid onset of action and enhanced bioavailability after oral administration.

pH-independent immediate release polymethacrylate formulations--an observational study.

PubMed

Claeys, Bart; Vandeputte, Reinout; De Geest, Bruno G; Remon, Jean Paul; Vervaet, Chris

2016-01-01

Using Eudragit® E PO (EudrE) as a polymethacrylate carrier, the aim of the study was to develop a pH-independent dosage form containing ibuprofen (IBP) as an active compound via chemical modification of the polymer (i.e. quaternization of amine function) or via the addition of dicarboxylic acids (succinic, glutaric and adipic acid) to create a pH micro-environment during dissolution. Biconvex tablets (diameter: 10 mm; height: 5 mm) were produced via hot melt extrusion and injection molding. In vitro dissolution experiments revealed that a minimum of 25% of quaternization was sufficient to partially (up to pH 5) eliminate the pH-dependent effect of the EudrE/IBP formulation. The addition of dicarboxylic acids did not alter IBP release in a pH 1 and 3 medium as the dimethyl amino groups of EudrE are already fully protonated, while in a pH 5 solvent IBP release was significantly improved (cf. from 0% to 92% release after 1 h dissolution experiments upon the addition of 20 wt.% succinic acid). Hence, both approaches resulted in a pH-independent (up to pH 5) immediate release formulation. However, the presence of a positively charged polymer induced stability issues (recrystallization of API) and the formulations containing dicarboxylic acids were classified as mechanically unstable. Hence, further research is needed to obtain a pH-independent immediate release formulation while using EudrE as a polmethacrylate carrier.

Effect of formulation variables on design, in vitro evaluation of valsartan SNEDDS and estimation of its antioxidant effect in adrenaline-induced acute myocardial infarction in rats.

PubMed

Amin, Maha M; El Gazayerly, Omaima N; Abd El-Gawad, Nabaweya A; Abd El-Halim, Shady M; El-Awdan, Sally A

2016-12-01

Valsartan is a specific angiotensin II antagonist used for the treatment of hypertension. It suffers from low aqueous solubility and high variability in its absorption after oral administration. The aim of this study was to improve the dissolution and thereby the bioavailability of Valsartan through the development of self nano-emulsifying drug delivery systems. Four ternary phase diagrams were constructed to identify the self-emulsification region of Capmul® MCM, Labrafil® M1944, Capryol™ 90 and Labrafac® PG together with Cremophore® RH 40 and Transcutol™ HP as oil, surfactant and co-surfactant, respectively. The effect of oil type, oil and surfactant concentration on droplet size and in vitro Valsartan dissolution were studied. The protective effect of the optimum formula F5 in adrenaline-induced oxidative stress in rats during myocardial infarction was determined. Formula F5 exhibited globule size of (13.95 nm) with 76.07% ± 1.10 of Valsartan dissolved after five minutes compared to Disartan 80 mg capsules (13.43%). Results revealed a significant reduction (p < 0.05) in serum aspartate transaminase, creatine kinase myocardial band and malondialdehyde levels, while a significant increase (p < 0.05) in serum glutathione in F5. Therefore, self nano-emulsifying drug delivery systems could be considered as a promising approach to improve the dissolution and thereby the bioavailability of Valsartan.

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.

Emotional and Cognitive Coping in Relationship Dissolution

ERIC Educational Resources Information Center

Wrape, Elizabeth R.; Jenkins, Sharon Rae; Callahan, Jennifer L.; Nowlin, Rachel B.

2016-01-01

Dissolution of a romantic relationship can adversely affect functioning among college students and represents one primary reason for seeking campus counseling. This study examined the associations among common coping strategies and distress following relationship dissolution. Avoidance and repetitive negative thinking (RNT) were significantly…

Dissolution-resistance of glass-added hydroxyapatite composites

NASA Astrophysics Data System (ADS)

Seo, Dong Seok; Lee, Jong Kook

2009-04-01

Hydroxyapatite (HA) has generated a great deal of interest as a promising implant material. However, its poor mechanical properties induced by severe dissolution in biological milieu limit medical applications and lead to clinical failure. In this study, HA ceramics with 30P2O5-30CaO-40Na2O glass (1.0 wt.% and 2.5 wt.%) were prepared to improve the resistance of monophase HA. The monophase HA sintered body showed microstructural degradation due to grain boundary dissolution in buffered water. However, the dissolution-resistance of HA/glass composites was significantly improved and showed no apparent evidence of dissolution. This suggests that a less soluble glass phase should be placed at grain boundaries to protect HA from dissolution.

Biomimetic Dissolution: A Tool to Predict Amorphous Solid Dispersion Performance.

PubMed

Puppolo, Michael M; Hughey, Justin R; Dillon, Traciann; Storey, David; Jansen-Varnum, Susan

2017-11-01

The presented study describes the development of a membrane permeation non-sink dissolution method that can provide analysis of complete drug speciation and emulate the in vivo performance of poorly water-soluble Biopharmaceutical Classification System class II compounds. The designed membrane permeation methodology permits evaluation of free/dissolved/unbound drug from amorphous solid dispersion formulations with the use of a two-cell apparatus, biorelevant dissolution media, and a biomimetic polymer membrane. It offers insight into oral drug dissolution, permeation, and absorption. Amorphous solid dispersions of felodipine were prepared by hot melt extrusion and spray drying techniques and evaluated for in vitro performance. Prior to ranking performance of extruded and spray-dried felodipine solid dispersions, optimization of the dissolution methodology was performed for parameters such as agitation rate, membrane type, and membrane pore size. The particle size and zeta potential were analyzed during dissolution experiments to understand drug/polymer speciation and supersaturation sustainment of felodipine solid dispersions. Bland-Altman analysis was performed to measure the agreement or equivalence between dissolution profiles acquired using polymer membranes and porcine intestines and to establish the biomimetic nature of the treated polymer membranes. The utility of the membrane permeation dissolution methodology is seen during the evaluation of felodipine solid dispersions produced by spray drying and hot melt extrusion. The membrane permeation dissolution methodology can suggest formulation performance and be employed as a screening tool for selection of candidates to move forward to pharmacokinetic studies. Furthermore, the presented model is a cost-effective technique.

Effects of Pump Pulsation on Hydrodynamic Properties and Dissolution Profiles in Flow-Through Dissolution Systems (USP 4).

PubMed

Yoshida, Hiroyuki; Kuwana, Akemi; Shibata, Hiroko; Izutsu, Ken-Ichi; Goda, Yukihiro

2016-06-01

To clarify the effects of pump pulsation and flow-through cell (FTC) dissolution system settings on the hydrodynamic properties and dissolution profiles of model formulations. Two FTC systems with different cell temperature control mechanisms were used. Particle image velocimetry (PIV) was used to analyze the hydrodynamic properties of test solutions in the flow-through dissolution test cell. Two pulsation pumps (semi-sine, full-sine) and a non-pulsatile pump were used to study the effects of varied flows on the dissolution profiles of United States Pharmacopeia standard tablets. PIV analysis showed periodic changes in the aligned upward fluid flow throughout the dissolution cell that was designed to reduce the temperature gradient during pump pulsation (0.5 s/pulse). The maximum instantaneous flow from the semi-sine pump was higher than that of the full-sine pump under all conditions. The flow from the semi-sine wave pump showed faster dissolution of salicylic acid and prednisone tablets than those from other pumps. The semi-sine wave pump flow showed similar dissolution profiles in the two FTC systems. Variations in instantaneous fluid flow caused by pump pulsation that meets the requirements of pharmacopoeias are a factor that affects the dissolution profiles of tablets in FTC systems.

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.

Investigation of the Dissolution-Reformation Cycle of the Passive Oxide Layer on NiTi Orthodontic Archwires

NASA Astrophysics Data System (ADS)

Uzer, B.; Birer, O.; Canadinc, D.

2017-09-01

Dissolution-reformation cycle of the passive oxide layer on the nickel-titanium (NiTi) orthodontic archwires was investigated, which has recently been recognized as one of the key parameters dictating the biocompatibility of archwires. Specifically, commercially available NiTi orthodontic archwires were immersed in artificial saliva solutions of different pH values (2.3, 3.3, and 4.3) for four different immersion periods: 1, 7, 14, and 30 days. Characterization of the virgin and tested samples revealed that the titanium oxide layer on the NiTi archwire surfaces exhibit a dissolution-reformation cycle within the first 14 days of the immersion period: the largest amount of Ni ion release occurred within the first week of immersion, while it significantly decreased during the reformation period from day 7 to day 14. Furthermore, the oxide layer reformation was catalyzed on the grooves within the peaks and valleys due to relatively larger surface energy of these regions, which eventually decreased the surface roughness significantly within the reformation period. Overall, the current results clearly demonstrate that the analyses of dissolution-reformation cycle of the oxide layer in orthodontic archwires, surface roughness, and ion release behavior constitute utmost importance in order to ensure both the highest degree of biocompatibility and an efficient medical treatment.

Influence of Calcium on Microbial Reduction of Solid Phase Uranium (VI)

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

Liu, Chongxuan; Jeon, Byong-Hun; Zachara, John M.

2007-06-27

The effect of calcium on microbial reduction of a solid phase U(VI), sodium boltwoodite (NaUO2SiO3OH ∙1.5H2O), was evaluated in a culture of a dissimilatory metal-reducing bacterium (DMRB), Shewanella oneidensis strain MR-1. Batch experiments were performed in a non-growth bicarbonate medium with lactate as electron donor at pH 7 buffered with PIPES. Calcium increased both the rate and extent of Na-boltwoodite dissolution by increasing its solubility through the formation of a ternary aqueous calcium-uranyl-carbonate species. The ternary species, however, decreased the rates of microbial reduction of aqueous U(VI). Laser-induced fluorescence spectroscopy (LIFS) and transmission electron microscopy (TEM) revealed that microbial reductionmore » of solid phase U(VI) is a sequentially coupled process of Na-boltwoodite dissolution, U(VI) aqueous speciation, and microbial reduction of dissolved U(VI) to U(IV) that accumulated on bacterial surfaces/periplasm. The overall rates of microbial reduction of solid phase U(VI) can be described by the coupled rates of dissolution and microbial reduction that were both influenced by calcium. The results demonstrated that dissolved U(VI) concentration during microbial reduction was a complex function of solid phase U(VI) dissolution kinetics, aqueous U(VI) speciation, and microbial activity.« less

Investigation of Ruthenium Dissolution in Advanced Membrane Electrode Assemblies for Direct Methanol Based Fuel Cell Stacks

NASA Technical Reports Server (NTRS)

Valdez, Thomas I.; Firdosy, S.; Koel, B. E.; Narayanan, S. R.

2005-01-01

Dissolution of ruthenium was observed in the 80-cell stack. Duration testing was performed in single cell MEAs to determine the pathway of cell degradation. EDAX analysis on each of the single cell MEAs has shown that the Johnson Matthey commercial catalyst is stable in DMFC operation for 250 hours, no ruthenium dissolution was observed. Changes in the hydrophobicity of the cathode backing papers was minimum. Electrode polarization analysis revealed that the MEA performance loss is attributed to changes in the cathode catalyst layer. Ruthenium migration does not seem to occur during cell operation but can occur when methanol is absent from the anode compartment, the cathode compartment has access to air, and the cells in the stack are electrically connected to a load (Shunt Currents). The open-to-air cathode stack design allowed for: a) The MEAs to have continual access to oxygen; and b) The stack to sustain shunt currents. Ruthenium dissolution in a DMFC stack can be prevented by: a) Developing an internally manifolded stacks that seal reactant compartments when not in operation; b) Bringing the cell voltages to zero quickly when not in operation; and c) Limiting the total number of cells to 25 in an effort to limit shunt currents.

Interface effects in the dissolution of silicon into thin gold films

NASA Technical Reports Server (NTRS)

Sankur, H.; Mccaldin, J. O.

1975-01-01

The dissolution of crystalline Si and amorphous Si substrates into thin films of evaporated Au was studied with an electron microprobe and scanning electron microscopy. The dissolution pattern was found to be nonuniform along the plane of the surface and dependent on the crystalline orientation of the Si substrate. The dissolution is greatly facilitated when a very thin layer of Pd is evaporated between the Si substrate and the Au film.

Phase Behavior of Ritonavir Amorphous Solid Dispersions during Hydration and Dissolution.

PubMed

Purohit, Hitesh S; Taylor, Lynne S

2017-12-01

The aim of this research was to study the interplay of solid and solution state phase transformations during the dissolution of ritonavir (RTV) amorphous solid dispersions (ASDs). RTV ASDs with polyvinylpyrrolidone (PVP), polyvinylpyrrolidone vinyl acetate (PVPVA) and hydroxypropyl methylcellulose acetate succinate (HPMCAS) were prepared at 10-50% drug loading by solvent evaporation. The miscibility of RTV ASDs was studied before and after exposure to 97% relative humidity (RH). Non-sink dissolution studies were performed on fresh and moisture-exposed ASDs. RTV and polymer release were monitored using ultraviolet-visible spectroscopy. Techniques including fluorescence spectroscopy, confocal imaging, scanning electron microscopy (SEM), atomic force microscopy (AFM), differential scanning calorimetry (DSC) and nanoparticle tracking analysis (NTA) were utilized to monitor solid and the solution state phase transformations. All RTV-PVP and RTV-PVPVA ASDs underwent moisture-induced amorphous-amorphous phase separation (AAPS) on high RH storage whereas RTV-HPMCAS ASDs remained miscible. Non-sink dissolution of PVP- and PVPVA-based ASDs at low drug loadings led to rapid RTV and polymer release resulting in concentrations in excess of amorphous solubility, liquid-liquid phase separation (LLPS) and amorphous nanodroplet formation. High drug loading PVP- and PVPVA-based ASDs did not exhibit LLPS upon dissolution as a consequence of extensive AAPS in the hydrated ASD matrix. All RTV-HPMCAS ASDs led to LLPS upon dissolution. RTV ASD dissolution is governed by a competition between the dissolution rate and the rate of phase separation in the hydrated ASD matrix. LLPS was observed for ASDs where the drug release was polymer controlled and only ASDs that remained miscible during the initial phase of dissolution led to LLPS. Techniques such as fluorescence spectroscopy, confocal imaging and SEM were useful in understanding the phase behavior of ASDs upon hydration and dissolution and were helpful in elucidating the mechanism of generation of amorphous nanodroplets.

Biocompatibility of “On-Command” Dissolvable Tympanostomy Tube in the Rat Model

PubMed Central

Mai, Johnny P.; Dumont, Matthieu; Rossi, Christopher; Cleary, Kevin; Wiedermann, Joshua; Reilly, Brian K.

2016-01-01

Objectives/Hypothesis A prototype tympanostomy tube, composed of (polybutyl/methyl methacrylate-co-dimethyl amino ethyl methacrylate (PBM)), was tested to (1) evaluate the effect of PBM tubes on rat dermis as a corollary for biocompatibility and (2) to observe the efficacy of dissolution with isopropyl alcohol (iPrOH) and ethanol (EtOH). Subjects and Methods A two-part study was conducted to assess biocompatible substance with inducible dissolvability as a critical characteristic for a newly engineered tympanostomy tube. First, tympanostomy tubes were inserted subcutaneously in 10 rats, which served as an animal model for biosafety and compared to traditional tubes with respect to histologic reaction. Tissue surrounding the PBM prototype tubes was submitted for histopathology and demonstrated no tissue reactivity or signs of major inflammation. In the second part, we evaluated the dissolvability of the tube with either isopropyl alcohol, ethanol, ofloxacin, ciprodex, water, and soapy water. PBM tubes were exposed to decreasing concentrations of iPrOH and EtOH with interval qualitative assessment of dissolution. Results (1) Histologic examination did not reveal pathology with PBM tubes; (2) Concentrations of at least 50% iPrOH and EtOH dissolve PBM tubes within 48 hours while concentrations of at least 75% iPrOH and EtOH were required for dissolution when exposure was limited to four 20-minute intervals. Conclusion PBM is biocompatible in the rat model. Additionally, PBM demonstrates rapid dissolution upon alcohol-based stimuli, validating the proof-of-concept of dissolvable “on-command” or biocommandible ear tubes. Further testing of PBM is needed with a less ototoxic dissolver and in a better simulated middle ear environment, before testing can be performed in humans. PMID:27796039

Tank 26F-2F Evaporator Study

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

Adu-Wusu, K.

2012-12-19

Tank 26F supernate sample was sent by Savannah River Remediation to Savannah River National Laboratory for evaporation test to help understand the underlying cause of the recent gravity drain line (GDL) pluggage during operation of the 2F Evaporator system. The supernate sample was characterized prior to the evaporation test. The evaporation test involved boiling the supernate in an open beaker until the density of the concentrate (evaporation product) was between 1.4 to 1.5 g/mL. It was followed by filtering and washing of the precipitated solids with deionized water. The concentrate supernate (or concentrate filtrate), the damp unwashed precipitated solids, andmore » the wash filtrates were characterized. All the precipitated solids dissolved during water washing. A semi-quantitative X-ray diffraction (XRD) analysis on the unwashed precipitated solids revealed their composition. All the compounds with the exception of silica (silicon oxide) are known to be readily soluble in water. Hence, their dissolution during water washing is not unexpected. Even though silica is a sparingly water-soluble compound, its dissolution is also not surprising. This stems from its small fraction in the solids as a whole and also its relative freshness. Assuming similar supernate characteristics, flushing the GDL with water (preferably warm) should facilitate dissolution and removal of future pluggage events as long as build up/aging of the sparingly soluble constituent (silica) is limited. On the other hand, since the amount of silica formed is relatively small, it is quite possible dissolution of the more soluble larger fraction will cause disintegration or fragmentation of the sparingly soluble smaller fraction (that may be embedded in the larger soluble solid mass) and allow its removal via suspension in the flushing water.« less

Formulation and characterization of an apigenin-phospholipid phytosome (APLC) for improved solubility, in vivo bioavailability, and antioxidant potential.

PubMed

Telange, Darshan R; Patil, Arun T; Pethe, Anil M; Fegade, Harshal; Anand, Sridhar; Dave, Vivek S

2017-10-15

The apigenin-phospholipid phytosome (APLC) was developed to improve the aqueous solubility, dissolution, in vivo bioavailability, and antioxidant activity of apigenin. The APLC synthesis was guided by a full factorial design strategy, incorporating specific formulation and process variables to deliver an optimized product. The design-optimized formulation was assayed for aqueous solubility, in vitro dissolution, pharmacokinetics, and antioxidant activity. The pharmacological evaluation was carried out by assessing its effects on carbon tetrachloride-induced elevation of liver function marker enzymes in a rat model. The antioxidant activity was assessed by studying its effects on the liver antioxidant marker enzymes. The developed model was validated using the design-optimized levels of formulation and process variables. The physical-chemical characterization confirmed the formation of phytosomes. The optimized formulation demonstrated over 36-fold higher aqueous solubility of apigenin, compared to that of pure apigenin. The formulation also exhibited a significantly higher rate and extent of apigenin release in dissolution studies. The pharmacokinetic analysis revealed a significant enhancement in the oral bioavailability of apigenin from the prepared formulation, compared to pure apigenin. The liver function tests indicated that the prepared phytosome showed a significantly improved restoration of all carbon tetrachloride-elevated rat liver function marker enzymes. The prepared formulation also exhibited antioxidant potential by significantly increasing the levels of glutathione, superoxide dismutase, catalase, and decreasing the levels of lipid peroxidase. The study shows that phospholipid-based phytosome is a promising and viable strategy for improving the delivery of apigenin and similar phytoconstituents with low aqueous solubility. Copyright © 2016 Elsevier B.V. All rights reserved.

Predictors of Marital Dissolution During a Period of Rapid Social Change: Evidence From South Asia.

PubMed

Jennings, Elyse A

2016-10-01

Few studies have examined the causes and consequences of marital dissolution in non-Western settings. This article explores the fundamental factors that may predict marital dissolution in a mainly agrarian setting in South Asia, where collectivism has historically been valued over individualism and where life is centered on the family. Using event history analyses with retrospective life history data from the Chitwan Valley Family Study conducted in rural Nepal, I explore the possible predictors of marital dissolution. Results suggest that couples in which wives married at older ages and chose their spouse in conjunction with their parents face lower risk of marital dissolution, while wives' work increases the risk. Moreover, couples married for longer durations and couples who have more children face lower risks of marital dissolution. The influences of many of these factors have changed over the last few decades, pointing toward the important role of changing social context on marital trajectories.

Integrating In Vitro, Modeling, and In Vivo Approaches to Investigate Warfarin Bioequivalence

PubMed Central

Wen, H; Fan, J; Vince, B; Li, T; Gao, W; Kinjo, M; Brown, J; Sun, W; Jiang, W; Lionberger, R

2017-01-01

We demonstrate the use of modeling and simulation to investigate bioequivalence (BE) concerns raised about generic warfarin products. To test the hypothesis that the loss of isopropyl alcohol and slow dissolution in acidic pH has significant impact on the pharmacokinetics of warfarin sodium tablets, we conducted physiologically based pharmacokinetic absorption modeling and simulation using formulation factors or in vitro dissolution profiles as input parameters. Sensitivity analyses indicated that warfarin pharmacokinetics was not sensitive to solubility, particle size, density, or dissolution rate in pH 4.5, but was affected by dissolution rate in pH 6.8 and potency. Virtual BE studies suggested that stressed warfarin sodium tablets with slow dissolution rate in pH 4.5 but having similar dissolution rate in pH 6.8 would be bioequivalent to the unstressed warfarin sodium tablets. A four‐way, crossover, single‐dose BE study in healthy subjects was conducted to test the same hypothesis and confirmed the simulation conclusion. PMID:28379643

Predictors of Marital Dissolution During a Period of Rapid Social Change: Evidence From South Asia

PubMed Central

Jennings, Elyse A.

2016-01-01

Few studies have examined the causes and consequences of marital dissolution in non-Western settings. This article explores the fundamental factors that may predict marital dissolution in a mainly agrarian setting in South Asia, where collectivism has historically been valued over individualism and where life is centered on the family. Using event history analyses with retrospective life history data from the Chitwan Valley Family Study, conducted in rural Nepal, I explore the possible predictors of marital dissolution. Results suggest that couples in which wives married at older ages and chose their spouse in conjunction with their parents face lower risk of marital dissolution, while wives’ work increases the risk. Moreover, couples married for longer durations and couples who have more children face lower risks of marital dissolution. The influences of many of these factors have changed over the last few decades, pointing toward the important role of changing social context on marital trajectories. PMID:27624319

Effect of sodium lauryl sulfate in dissolution media on dissolution of hard gelatin capsule shells.

PubMed

Zhao, Fang; Malayev, Vyacheslav; Rao, Venkatramana; Hussain, Munir

2004-01-01

Sodium lauryl sulfate (SLS) is a commonly used surfactant in dissolution media for poorly water soluble drugs. However, it has occasionally been observed that SLS negatively impacts the dissolution of drug products formulated in gelatin capsules. This study investigated the effect of SLS on the dissolution of hard gelatin capsule shells. The USP paddle method was used with online UV monitoring at 214 nm (peptide bond). Empty size #0 capsule shells were held to the bottom of the dissolution vessel by magnetic three-prong sinkers. SLS significantly slowed down the dissolution of gelatin shells at pH < 5. Visually, the gelatin shells transformed into some less-soluble precipitate under these conditions. This precipitate was found to contain a higher sulfur content than the gelatin control sample by elemental analysis, indicating that SLS is part of the precipitate. Additionally, the slowdown of capsule shell dissolution was shown to be dependent on the SLS concentration and the ionic strength of the media. SLS interacts with gelatin to form a less-soluble precipitate at pH < 5. The use of SLS in dissolution media at acidic pH should be carefully evaluated for gelatin capsule products.

Regulatory Perspectives on Strength-Dependent Dissolution Profiles and Biowaiver Approaches for Immediate Release (IR) Oral Tablets in New Drug Applications.

PubMed

Suarez-Sharp, Sandra; Delvadia, Poonam R; Dorantes, Angelica; Duan, John; Externbrink, Anna; Gao, Zongming; Ghosh, Tapash; Miksinski, Sarah Pope; Seo, Paul

2016-05-01

Dissolution profile comparisons are used by the pharmaceutical industry to assess the similarity in the dissolution characteristics of two formulations to decide whether the implemented changes, usually minor/moderate in nature, will have an impact on the in vitro/in vivo performance of the drug product. When similarity testing is applied to support the approval of lower strengths of the same formulation, the traditional approach for dissolution profile comparison is not always applicable for drug products exhibiting strength-dependent dissolution and may lead to incorrect conclusions about product performance. The objective of this article is to describe reasonable biopharmaceutic approaches for developing a biowaiver strategy for low solubility, proportionally similar/non-proportionally similar in composition immediate release drug products that exhibit strength-dependent dissolution profiles. The paths highlighted in the article include (1) approaches to address biowaiver requests, such as the use of multi-unit dissolution testing to account for sink condition differences between the higher and lower strengths; (2) the use of a single- vs. strength-dependent dissolution method; and (3) the use of single- vs. strength-dependent dissolution acceptance criteria. These approaches are cost- and time-effective and can avoid unnecessary bioequivalence studies.

The effect of a new formaldehyde-free binder on the dissolution rate of glass wool fibre in physiological saline solution.

PubMed

Potter, Russell M; Olang, Nassreen

2013-04-12

The in-vitro dissolution rate of fibres is a good predictor of the in-vivo behavior and potential health effects of inhaled fibres. This study examines the effect of a new formaldehyde-free carbohydrate-polycarboxylic acid binder on the in-vitro dissolution rate of biosoluble glass fibres. Dissolution rate measurements in pH 7.4 physiological saline solution show that the presence of the binder on wool insulation glass fibres has no effect on their dissolution. There is no measurable difference between the dissolution rates of continuous draw fibres before and after binder was applied by dipping. Nor is there a measurable difference between the dissolution rates of a production glass wool sample with binder and that same sample after removal of the binder by low-temperature ashing. Morphological examination shows that swelling of the binder in the solution is at least partially responsible for the development of open channels around the glass-binder interface early in the dissolution. These channels allow fluid to reach the entire glass surface under the binder coating. There is no evidence of any delay in the dissolution rate as a result of the binder coating.

The effect of a new formaldehyde-free binder on the dissolution rate of glass wool fibre in physiological saline solution

PubMed Central

2013-01-01

The in-vitro dissolution rate of fibres is a good predictor of the in-vivo behavior and potential health effects of inhaled fibres. This study examines the effect of a new formaldehyde-free carbohydrate-polycarboxylic acid binder on the in-vitro dissolution rate of biosoluble glass fibres. Dissolution rate measurements in pH 7.4 physiological saline solution show that the presence of the binder on wool insulation glass fibres has no effect on their dissolution. There is no measurable difference between the dissolution rates of continuous draw fibres before and after binder was applied by dipping. Nor is there a measurable difference between the dissolution rates of a production glass wool sample with binder and that same sample after removal of the binder by low-temperature ashing. Morphological examination shows that swelling of the binder in the solution is at least partially responsible for the development of open channels around the glass-binder interface early in the dissolution. These channels allow fluid to reach the entire glass surface under the binder coating. There is no evidence of any delay in the dissolution rate as a result of the binder coating. PMID:23587247

The improved dissolution performance of a post processing treated spray-dried crystalline solid dispersion of poorly soluble drugs.

PubMed

Chan, Siok-Yee; Toh, Seok-Ming; Khan, Nasir Hayat; Chung, Yin-Ying; Cheah, Xin-Zi

2016-11-01

Solution-mediated transformation has been cited as one of the main problems that deteriorate dissolution performances of solid dispersion (SD). This is mainly attributed by the recrystallization tendency of poorly soluble drug. Eventually, it will lead to extensive agglomeration which is a key process in reducing the dissolution performance of SD and offsets the true benefit of SD system. Here, a post-processing treatment is suggested in order to reduce the recrystallization tendency and hence bring forth the dissolution advantage of SD system. The current study investigates the effect of a post processing treatment on dissolution performance of SD in comparison to their performances upon production. Two poorly soluble drugs were spray dried into SD using polyvinyl alcohol (PVA) as hydrophilic carrier. The obtained samples were post processing treated by exposure to high humidity, i.e. 75% RH at room temperature. The physical properties and release rate of the SD system were characterized upon production and after the post-processing treatment. XRPD, Infrared and DSC results showed partial crystallinity of the fresh SD systems. Crystallinity of these products was further increased after the post-processing treatment at 75% RH. This may be attributed to the high moisture absorption of the SD system that promotes recrystallization process of the drug. However, dissolution efficiencies of the post-treated systems were higher and more consistent than the fresh SD. The unexpected dissolution trend was further supported by the results intrinsic dissolution and solubility studies. An increase of crystallinity in a post humidity treated SD did not exert detrimental effect to their dissolution profiles. A more stabilized system with a preferable enhanced dissolution rate was obtained by exposing the SD to a post processing humidity treatment.

Formulation and evaluation of delayed-onset extended-release tablets of metoprolol tartrate using hydrophilic-swellable polymers.

PubMed

Dadarwal, Subhash Chand; Madan, Sarika; Agrawal, Shyam Sunder

2012-03-01

In view of the circadian rhythm of cardiovascular diseases, a delayed-onset extended-release (DOER) formulation of metoprolol tartrate (MT) was prepared. This was achieved through dissolution-guided optimization of the proportion of Methocel K4M and Methocel K15M. Core erosion ratio was greater than 50 %, thereby showing steady release of the drug after the lag time until complete dissolution. Optimized formulation produced a lag phase of 6 h followed by complete release of 98.7 ± 2.1 % in 24 h. Water uptake study revealed that Methocel K15M has lower water uptake (30 ± 1 %) than Methocel K4M (40 ± 2 %) after 24 h. Axial swelling of polymers was higher than swelling in the radial direction. Drug-polymer interaction study precludes any interaction between drug and polymer. Such a drug delivery system may provide a viable alternative for effective management of hypertension and other related disorders. This work also proposes an approach to attain DOER for a hydrophilic drug by using a hydrophilic swellable polymer in press coat.

Development of gastro intestinal sustained release tablet formulation containing acryl-EZE and pH-dependent swelling HPMC K 15 M.

PubMed

Lamoudi, Lynda; Chaumeil, Jean Claude; Daoud, Kamel

2012-05-01

The aim of this study was to evaluate physical properties and release from matrix tablets containing different ratios of HPMC 15 M and Acryl-EZE. A further aim is to assess their suitability for pH dependent controlled release. Matrix tablets containing HPMC 15 M and Acryl-EZE were manufactured using a fluidized bed. The release from this matrix using Sodium Diclofenac (SD) as model drug is studied in two dissolution media (0.1 N HCl or pH = 6.8 phosphate buffer solution); the release rate, mechanism, and pH dependence were characterized by fitting four kinetic models and by using a similarity factor analysis. The obtained results revealed that the presence of Acryl-EZE in the matrix tablets is effective in protecting the dosage forms from release in acid environments such as gastric fluid. In pH = 6.8 phosphate buffer, the drug release rate and mechanism of release from all matrices is mainly controlled by HPMC 15 M. The model of Korsmeyer-Peppas was found to fit experimental dissolution results.

Enhanced Bioavailability and Anticancer Effect of Curcumin-Loaded Electrospun Nanofiber: In Vitro and In Vivo Study

NASA Astrophysics Data System (ADS)

Wang, Chuan; Ma, Chao; Wu, Zhenkai; Liang, He; Yan, Peng; Song, Jia; Ma, Nan; Zhao, Qinghua

2015-11-01

Nanofibers have attracted increasing attention in drug delivery and other biomedical applications due to their some special properties. The present study aims to prepare a fiber-based nanosolid dispersion system to enhance the bioavailability of curcumin (CUR). CUR-loaded polyvinyl pyrrolidone (CUR@PVP) nanofibers were successfully prepared via electrospinning. Scanning electron microscopy (SEM) was employed to observe the morphology of the nanofibers, and the SEM image showed that the drug-loaded nanofibers were smooth, and no CUR clusters were found on the surface of the nanofibers. The results of X-ray diffraction (XRD) demonstrated that the CUR was evenly distributed in the nanofibers in an amorphous state. Fourier transform infrared (FTIR) spectroscopy analysis indicated that intermolecular hydrogen bonding occurred between the CUR and the polymer matrix. In vitro dissolution profiles showed that CUR@PVP nanofiber could be quickly dissolved in phosphate-buffered saline (PBS) solution, while negligible dissolution was observed in pure CUR sample. Importantly, in vitro cell viability assays and in vivo animal tests revealed that the nanosolid dispersion system dramatically enhanced the bioavailability and showed effective anticancer effect of the CUR.

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

Catalysis and chemical mechanisms of calcite dissolution in seawater.

PubMed

Subhas, Adam V; Adkins, Jess F; Rollins, Nick E; Naviaux, John; Erez, Jonathan; Berelson, William M

2017-07-18

Near-equilibrium calcite dissolution in seawater contributes significantly to the regulation of atmospheric [Formula: see text] on 1,000-y timescales. Despite many studies on far-from-equilibrium dissolution, little is known about the detailed mechanisms responsible for calcite dissolution in seawater. In this paper, we dissolve 13 C-labeled calcites in natural seawater. We show that the time-evolving enrichment of [Formula: see text] in solution is a direct measure of both dissolution and precipitation reactions across a large range of saturation states. Secondary Ion Mass Spectrometer profiles into the 13 C-labeled solids confirm the presence of precipitated material even in undersaturated conditions. The close balance of precipitation and dissolution near equilibrium can alter the chemical composition of calcite deeper than one monolayer into the crystal. This balance of dissolution-precipitation shifts significantly toward a dissolution-dominated mechanism below about [Formula: see text] Finally, we show that the enzyme carbonic anhydrase (CA) increases the dissolution rate across all saturation states, and the effect is most pronounced close to equilibrium. This finding suggests that the rate of hydration of [Formula: see text] is a rate-limiting step for calcite dissolution in seawater. We then interpret our dissolution data in a framework that incorporates both solution chemistry and geometric constraints on the calcite solid. Near equilibrium, this framework demonstrates a lowered free energy barrier at the solid-solution interface in the presence of CA. This framework also indicates a significant change in dissolution mechanism at [Formula: see text], which we interpret as the onset of homogeneous etch pit nucleation.

(W7860)Monte Carlo Simulations of the Dissolution of Borosilicate and Aluminoborosilicate

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

Kerisit, Sebastien; Pierce, Eric M

2011-01-01

The aim of this study was to provide atomic-level insights into the dissolution behavior of borosilicate and aluminoborosilicate glasses in dilute aqueous solutions. In the first part of this work, the effects of different structural features, such as the presence of non-bridging oxygens (NBO) or the formation of boroxol rings, on glass dissolution were evaluated separately and led to the following conclusions. (1) The dependence of the dissolution rate on the amount of NBO was found to be linear at all Si/B ratios and the accelerating effect of NBO was shown to increase with increasing Si/B ratio. (2) The formationmore » of boroxol rings and of clusters of boroxol rings resulted in an increase of the dissolution rate at all Si/B ratios and, again, the extent of the rate increase was strongly dependent on the Si/B ratio. (3) For aluminosilicate glasses, the implementation of the aluminum avoidance rule was found to increase the rate of dissolution relative to that obtained for a random distribution. In the second part of this work, the dissolution of the NeB glasses studied by Pierce et al. [Pierce E. M., Reed L. R., Shaw W. J., McGrail B. P., Icenhower J. P., Windisch C. F., Cordova E. A. and Broady J. (2010) Experimental determination of the effect of the ratio of B/Al on glass dissolution along the nepheline (NaAlSiO4) - Malinkoite (NaBSiO4) join. Geochim. Cosmochim. Acta 74, 2634-2654] was modeled in dilute aqueous solutions. Pierce et al. concluded from their study that either the rupture of the Al-O bonds or that of the Si O bonds was the rate-limiting step controlling the dissolution of the NeB glasses. The simulations refined this conclusion and showed that, at low B/Al ratios, the rupture of both Al O Si and Si O Si linkages contributed to the dissolution rate whereas, at high B/Al ratios, the dissolution rate was independent of the rupture of Al-O-Si linkages and was controlled by S1 sites (silicon sites at the glass-water interface with one connection to nearest-neighbor sites) and dissolution via detachment of clusters.« less

Influence of sodium lauryl sulfate and tween 80 on carbamazepine-nicotinamide cocrystal solubility and dissolution behaviour.

PubMed

Li, Mingzhong; Qiao, Ning; Wang, Ke

2013-10-11

The influence of the surfactants of sodium lauryl sulfate (SLS) and Tween 80 on carbamazepine-nicotinamide (CBZ-NIC) cocrystal solubility and dissolution behaviour has been studied in this work. The solubility of the CBZ-NIC cocrystal was determined by measuring the eutectic concentrations of the drug and the coformer. Evolution of the intrinsic dissolution rate (IDR) of the CBZ-NIC cocrystal was monitored by the UV imaging dissolution system during dissolution. Experimental results indicated that SLS and Tween 80 had little influence upon the solubility of the CBZ-NIC cocrystal but they had totally opposite effects on the IDR of the CBZ-NIC cocrystal during dissolution. SLS significantly increased the IDR of the CBZ-NIC cocrystal while Tween 80 decreased its IDR.

Influence of Sodium Lauryl Sulfate and Tween 80 on Carbamazepine–Nicotinamide Cocrystal Solubility and Dissolution Behaviour

PubMed Central

Li, Mingzhong; Qiao, Ning; Wang, Ke

2013-01-01

The influence of the surfactants of sodium lauryl sulfate (SLS) and Tween 80 on carbamazepine–nicotinamide (CBZ–NIC) cocrystal solubility and dissolution behaviour has been studied in this work. The solubility of the CBZ–NIC cocrystal was determined by measuring the eutectic concentrations of the drug and the coformer. Evolution of the intrinsic dissolution rate (IDR) of the CBZ–NIC cocrystal was monitored by the UV imaging dissolution system during dissolution. Experimental results indicated that SLS and Tween 80 had little influence upon the solubility of the CBZ–NIC cocrystal but they had totally opposite effects on the IDR of the CBZ–NIC cocrystal during dissolution. SLS significantly increased the IDR of the CBZ–NIC cocrystal while Tween 80 decreased its IDR. PMID:24300560

Development of In Vitro-In Vivo Correlation/Relationship Modeling Approaches for Immediate Release Formulations Using Compartmental Dynamic Dissolution Data from “Golem”: A Novel Apparatus

PubMed Central

Tuszyński, Paweł K.; Polak, Sebastian; Jachowicz, Renata; Mendyk, Aleksander; Dohnal, Jiří

2015-01-01

Different batches of atorvastatin, represented by two immediate release formulation designs, were studied using a novel dynamic dissolution apparatus, simulating stomach and small intestine. A universal dissolution method was employed which simulated the physiology of human gastrointestinal tract, including the precise chyme transit behavior and biorelevant conditions. The multicompartmental dissolution data allowed direct observation and qualitative discrimination of the differences resulting from highly pH dependent dissolution behavior of the tested batches. Further evaluation of results was performed using IVIVC/IVIVR development. While satisfactory correlation could not be achieved using a conventional deconvolution based-model, promising results were obtained through the use of a nonconventional approach exploiting the complex compartmental dissolution data. PMID:26120580

An inorganic CO2 diffusion and dissolution process explains negative CO2 fluxes in saline/alkaline soils.

PubMed

Ma, Jie; Wang, Zhong-Yuan; Stevenson, Bryan A; Zheng, Xin-Jun; Li, Yan

2013-01-01

An 'anomalous' negative flux, in which carbon dioxide (CO2) enters rather than is released from the ground, was studied in a saline/alkaline soil. Soil sterilization disclosed an inorganic process of CO2 dissolution into (during the night) and out of (during the day) the soil solution, driven by variation in soil temperature. Experimental and modeling analysis revealed that pH and soil moisture were the most important determinants of the magnitude of this inorganic CO2 flux. In the extreme cases of air-dried saline/alkaline soils, this inorganic process was predominant. While the diurnal flux measured was zero sum, leaching of the dissolved inorganic carbon in the soil solution could potentially effect net carbon ecosystem exchange. This finding implies that an inorganic module should be incorporated when dealing with the CO2 flux of saline/alkaline land. Neglecting this inorganic flux may induce erroneous or misleading conclusions in interpreting CO2 fluxes of these ecosystems.

An inorganic CO2 diffusion and dissolution process explains negative CO2 fluxes in saline/alkaline soils

PubMed Central

Ma, Jie; Wang, Zhong-Yuan; Stevenson, Bryan A.; Zheng, Xin-Jun; Li, Yan

2013-01-01

An ‘anomalous' negative flux, in which carbon dioxide (CO2) enters rather than is released from the ground, was studied in a saline/alkaline soil. Soil sterilization disclosed an inorganic process of CO2 dissolution into (during the night) and out of (during the day) the soil solution, driven by variation in soil temperature. Experimental and modeling analysis revealed that pH and soil moisture were the most important determinants of the magnitude of this inorganic CO2 flux. In the extreme cases of air-dried saline/alkaline soils, this inorganic process was predominant. While the diurnal flux measured was zero sum, leaching of the dissolved inorganic carbon in the soil solution could potentially effect net carbon ecosystem exchange. This finding implies that an inorganic module should be incorporated when dealing with the CO2 flux of saline/alkaline land. Neglecting this inorganic flux may induce erroneous or misleading conclusions in interpreting CO2 fluxes of these ecosystems. PMID:23778238

Factors Affecting the Dissolution of Indomethacin Solid Dispersions.

PubMed

Zhang, Wei; Zhang, Chen-Ning; He, Yue; Duan, Ban-Yan; Yang, Guang-Yi; Ma, Wei-Dong; Zhang, Yong-Hong

2017-11-01

The aim of this study was to investigate the influence of factors such as carrier type, drug/carrier ratio, binary carriers, and preparation method on the dissolution of an insoluble drug, indomethacin (IM), under supersaturation conditions. Using a solvent evaporation (SE) method, poloxamer 188 and PVP K30 showed better dissolution among the selected carriers. Furthermore, as the ratio of carriers increased (drug/carrier ratio from 1:0.5 to 1:2), the dissolution rate increased especially in almost two times poloxamer 188 solid dispersions (SDs), while the reverse results were observed for PVP K30 SDs. For the binary carrier SD, a lower dissolution was found. Under hot melt extrusion (HME), the dissolution of poloxamer 188 SD and PVP K30 SD was 0.83- and 0.94-folds lower than that using SE, respectively, while the binary carrier SD showed the best dissolution. For poloxamer 188 SDs, the drug's crystal form changed when using SE, while no crystal form change was observed using HME. IM was amorphous in PVP K30 SDs prepared by both methods. For binary carrier systems, amorphous and crystalline drugs coexisted in SD using SE, and negligible amorphous IM was in SD using HME. This study indicated that a higher amorphous proportion in SD did not correlate with higher dissolution rate, and other factors, such as carrier type, particle size, and density, were also critical.

Dissolution of explosive compounds TNT, RDX, and HMX under continuous flow conditions.

PubMed

Wang, Chao; Fuller, Mark E; Schaefer, Charles; Caplan, Jeffrey L; Jin, Yan

2012-05-30

2,4,6-trinitrotoluene (TNT), hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) are common contaminants around active military firing ranges. Dissolution of these compounds is usually the first step prior to their spreading in subsurface environments. Nevertheless, dissolution of individual TNT, RDX, and HMX under continuous flow conditions has not been well investigated. This study applied spectral confocal microscopy to observe and quantify the dissolution of TNT, RDX, and HMX (<100 μm crystals) in micromodel channels. Dissolution models were developed to describe the changes of their radii, surface areas, volumes, and specific surface areas as a function of time. Results indicated that a model incorporating a resistance term that accounts for the surface area in direct contact with the channel surfaces (and hence, was not exposed to the flowing water) described the dissolution processes well. The model without the resistance term, however, could not capture the observed data at the late stage of TNT dissolution. The model-fitted mass transfer coefficients were in agreement with the previous reports. The study highlights the importance of including the resistance term in the dissolution model and illustrates the utility of the newly developed spectral imaging method for quantification of mass transfer of TNT, RDX, and HMX. Copyright © 2012 Elsevier B.V. All rights reserved.

[A Case of Intestinal Obstruction Caused by a Bezoar after Pylous-Preserving Gastrectomy].

PubMed

Yamazato, Yuzo; Kosuga, Toshiyuki; Ichikawa, Daisuke; Kubota, Takeshi; Okamoto, Kazuma; Konishi, Hirotaka; Shiozaki, Atsushi; Fujiwara, Hitoshi; Arita, Tomohiro; Morimura, Ryo; Murayama, Yasutoshi; Kuriu, Yoshiaki; Ikoma, Hisashi; Nakanishi, Masayoshi; Otsuji, Eigo

2017-11-01

A 65-year-old woman with a history of pylorus-preserving gastrectomy(PPG)for early gastric cancer visited our hospital because of vomiting. Gastrointestinal endoscopy revealed a large bezoar in the anastomotic site of the stomach. Because the bezoar was too large to be collected orally, the dissolution therapy with taking Coca-Cola®was continued. On the 3rd day after hospitalization, she felt acute abdominal pain with vomiting. Computed tomography revealed intestinal obstruction by a mass with air bubbles inside in the ileum. Emergency operation was performed under a diagnosis of intestinal obstruction due to the bezoar. The black brown bezoar sized 80×35×30mm was extracted through an ileotomy. The delayed gastric empty is considered to involve in the bezoar formation. Therefore, the appropriate education of diet and periodic endoscopic screening are necessary for patients with large amounts of gastric residues especially after PPG. In the dissolution therapy, physicians need to be careful of intestinal obstruction by a bezoar.

Assessment of Efficacy and Quality of Two Albendazole Brands Commonly Used against Soil-Transmitted Helminth Infections in School Children in Jimma Town, Ethiopia

PubMed Central

Suleman, Sultan; Mohammed, Tesfaye; Deti, Habetewold; D'Hondt, Matthias; Wynendaele, Evelien; Mekonnen, Zeleke; Vercruysse, Jozef; Duchateau, Luc; De Spiegeleer, Bart; Levecke, Bruno

2015-01-01

Background There is a worldwide upscale in mass drug administration (MDA) programs to control the morbidity caused by soil-transmitted helminths (STHs): Ascaris lumbricoides, Trichuris trichiura and hookworm. Although anthelminthic drugs which are used for MDA are supplied by two pharmaceutical companies through donation, there is a wide range of brands available on local markets for which the efficacy against STHs and quality remain poorly explored. In the present study, we evaluated the drug efficacy and quality of two albendazole brands (Bendex and Ovis) available on the local market in Ethiopia. Methodology/Principal Findings A randomized clinical trial was conducted according to the World Health Organization (WHO) guidelines to assess drug efficacy, by means of egg reduction rate (ERR), of Bendex and Ovis against STH infections in school children in Jimma, Ethiopia. In addition, the chemical and physicochemical quality of the drugs was assessed according to the United States and European Pharmacopoeia, encompassing mass uniformity of the tablets, amount of active compound and dissolution profile. Both drugs were highly efficacious against A. lumbricoides (>97%), but showed poor efficacy against T. trichiura (~20%). For hookworms, Ovis was significantly (p < 0.05) more efficacious compared to Bendex (98.1% vs. 88.7%). Assessment of the physicochemical quality of the drugs revealed a significant difference in dissolution profile, with Bendex having a slower dissolution than Ovis. Conclusion/Significance The study revealed that differences in efficacy between the two brands of albendazole (ABZ) tablets against hookworm are linked to the differences in the in-vitro drug release profile. Differences in uptake and metabolism of this benzimidazole drug among different helminth species may explain that this efficacy difference was only observed in hookworms and not in the two other species. The results of the present study underscore the importance of assessing the chemical and physicochemical quality of drugs before conducting efficacy assessment in any clinical trials to ensure appropriate therapeutic efficacy and to exclude poor drug quality as a factor of reduced drug efficacy other than anthelminthic resistance. Overall, this paper demonstrates that “all medicines are not created equal”. PMID:26406600

Assessment of Efficacy and Quality of Two Albendazole Brands Commonly Used against Soil-Transmitted Helminth Infections in School Children in Jimma Town, Ethiopia.

PubMed

Belew, Sileshi; Getachew, Mestawet; Suleman, Sultan; Mohammed, Tesfaye; Deti, Habetewold; D'Hondt, Matthias; Wynendaele, Evelien; Mekonnen, Zeleke; Vercruysse, Jozef; Duchateau, Luc; De Spiegeleer, Bart; Levecke, Bruno

2015-09-01

There is a worldwide upscale in mass drug administration (MDA) programs to control the morbidity caused by soil-transmitted helminths (STHs): Ascaris lumbricoides, Trichuris trichiura and hookworm. Although anthelminthic drugs which are used for MDA are supplied by two pharmaceutical companies through donation, there is a wide range of brands available on local markets for which the efficacy against STHs and quality remain poorly explored. In the present study, we evaluated the drug efficacy and quality of two albendazole brands (Bendex and Ovis) available on the local market in Ethiopia. A randomized clinical trial was conducted according to the World Health Organization (WHO) guidelines to assess drug efficacy, by means of egg reduction rate (ERR), of Bendex and Ovis against STH infections in school children in Jimma, Ethiopia. In addition, the chemical and physicochemical quality of the drugs was assessed according to the United States and European Pharmacopoeia, encompassing mass uniformity of the tablets, amount of active compound and dissolution profile. Both drugs were highly efficacious against A. lumbricoides (>97%), but showed poor efficacy against T. trichiura (~20%). For hookworms, Ovis was significantly (p < 0.05) more efficacious compared to Bendex (98.1% vs. 88.7%). Assessment of the physicochemical quality of the drugs revealed a significant difference in dissolution profile, with Bendex having a slower dissolution than Ovis. The study revealed that differences in efficacy between the two brands of albendazole (ABZ) tablets against hookworm are linked to the differences in the in-vitro drug release profile. Differences in uptake and metabolism of this benzimidazole drug among different helminth species may explain that this efficacy difference was only observed in hookworms and not in the two other species. The results of the present study underscore the importance of assessing the chemical and physicochemical quality of drugs before conducting efficacy assessment in any clinical trials to ensure appropriate therapeutic efficacy and to exclude poor drug quality as a factor of reduced drug efficacy other than anthelminthic resistance. Overall, this paper demonstrates that "all medicines are not created equal".

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

Mechanism-based selection of stabilization strategy for amorphous formulations: Insights into crystallization pathways.

PubMed

Edueng, Khadijah; Mahlin, Denny; Larsson, Per; Bergström, Christel A S

2017-06-28

We developed a step-by-step experimental protocol using differential scanning calorimetry (DSC), dynamic vapour sorption (DVS), polarized light microscopy (PLM) and a small-scale dissolution apparatus (μDISS Profiler) to investigate the mechanism (solid-to-solid or solution-mediated) by which crystallization of amorphous drugs occurs upon dissolution. This protocol then guided how to stabilize the amorphous formulation. Indapamide, metolazone, glibenclamide and glipizide were selected as model drugs and HPMC (Pharmacoat 606) and PVP (K30) as stabilizing polymers. Spray-dried amorphous indapamide, metolazone and glibenclamide crystallized via solution-mediated nucleation while glipizide suffered from solid-to-solid crystallization. The addition of 0.001%-0.01% (w/v) HPMC into the dissolution medium successfully prevented the crystallization of supersaturated solutions of indapamide and metolazone whereas it only reduced the crystallization rate for glibenclamide. Amorphous solid dispersion (ASD) formulation of glipizide and PVP K30, at a ratio of 50:50% (w/w) reduced but did not completely eliminate the solid-to-solid crystallization of glipizide even though the overall dissolution rate was enhanced both in the absence and presence of HPMC. Raman spectroscopy indicated the formation of a glipizide polymorph in the dissolution medium with higher solubility than the stable polymorph. As a complementary technique, molecular dynamics (MD) simulations of indapamide and glibenclamide with HPMC was performed. It was revealed that hydrogen bonding patterns of the two drugs with HPMC differed significantly, suggesting that hydrogen bonding may play a role in the greater stabilizing effect on supersaturation of indapamide, compared to glibenclamide. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Assessment of pharmaceutical quality of furosemide tablets from multinational markets.

PubMed

Qureshi, S A; McGilveray, I J

1998-11-01

This report describes results of a collaborative study in which samples of the 40-mg strength of furosemide tablets were evaluated following a common protocol based on British (BP), European (Ph. Eur.), and US Pharmacopoeial (USP) specifications. Several tests, including identification, uniformity of mass, and dissolution, were performed. In total, excluding Lasix lots, results for 162 lots obtained from 115 manufacturers or suppliers were submitted. Also, 23 laboratories identified and submitted data for 34 lots of Lasix products available in their countries. There were no reported abnormalities in the physical test requirements of the products analyzed. The summaries (n, mean, and 95% CI) of the assay results for the "standard sample" (a common sample), Lasix lots from participating countries, and for all other furosemide products, respectively, are as follows: 30, 99.8%, 96-104; 33, 100.0%, 94-106; and 162, 99.6, 94-105. About half (approximately 62%) of the reported uniformity of mass results based on tablet weights were in the range 150-175 mg/tablet. However, there appears to be notable variability in tablet weights that would result in significant differences in the ratios (0.14 to 0.40) of active ingredient to excipient. The reported disintegration times ranged from 0 (instantaneous) to 18 min, with most less than 1 min. The drug dissolution testing was conducted with phosphate buffer at pH 5.8 (USP recommended). Another test was conducted with acetate buffer at pH 4.6 (noncompendial). There appears to be remarkable similarity in overall percentage of drug release from the three types of products (standard sample, Lasix lots, and other products). Although apparently there is a very wide spread in dissolution characteristics of the products tested, the analyses of variance did not detect differences among the products tested and, to this extent, would not indicate differences in bioavailability characteristics for most of these products. It is observed that about 20-38% of the variability in dissolution testing is not product related (i.e., it is from the dissolution testing itself), while the remaining 62-80% variability is product related (manufacturing, formulation, etc). The results of this multinational collaborative study showed that most of the furosemide products available in different countries met the required pharmaceutical quality standards, including drug-release characteristics. Based on an extensive statistical analysis, the main concern from the study was that the high variability in drug dissolution testing would require wide tolerance standards (e.g., pharmacopoeial standards). This may result in lack of needed discriminating ability of the test in revealing the impacts of formulation and manufacturing changes on in vitro, and perhaps in vivo, drug-release characteristics.

Biological Redox Cycling Of Iron In Nontronite And Its Potential Application In Nitrate Removal

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

Zhao, Linduo; Dong, Hailiang; Kukkadapu, Ravi K.

2015-05-05

Redox cycling of structural Fe in phyllosilicates provides a potential method to remediate nitrate contamination in natural environment. Past research has only studied chemical redox cycles or a single biologically mediated redox cycle of Fe in phyllosilicates. The objective of this research was to study three microbially driven redox cycles of Fe in one phyllosilicate, nontronite (NAu-2). During the reduction phase structural Fe(III) in NAu-2 served as electron acceptor, lactate as electron donor, AQDS as electron shuttle, and dissimilatory Fe(III)-reducing bacteria Shewanella putrefaciens CN32 as mediator in bicarbonate-buffered and PIPES-buffered media. During the oxidation phase, biogenic Fe(II) served an electronmore » donor, nitrate as electron acceptor, and nitrate-dependent Fe(II)-oxidizing bacteria Pseudogulbenkiania sp. strain 2002 as mediator in the same media. For all three cycles, structural Fe in NAu-2 was able to reversibly undergo 3 redox cycles without significant reductive or oxidative dissolution. X-ray diffraction and scanning and transmission electron microscopy revealed that NAu-2 was the dominant residual mineral throughout the 3 redox cycles with some dissolution textures but no significant secondary mineralization. Mössbauer spectroscopy revealed that Fe(II) in bio-reduced samples likely occurred in two distinct environments, at edges and the interior of the NAu-2 structure. Nitrate was completely reduced to nitrogen gas under both buffer conditions and this extent and rate did not change with Fe redox cycles. Mössbauer spectroscopy further revealed that nitrate reduction was coupled to predominant/preferred oxidation of edge Fe(II). These results suggest that structural Fe in phyllosilicates may represent a renewable source to continuously remove nitrate in natural environments.« less

Improved oral absorption of tacrolimus by a solid dispersion with hypromellose and sodium lauryl sulfate.

PubMed

Jung, Hyuck Jun; Ahn, Hye In; Park, Ji Yeon; Ho, Myoung Jin; Lee, Dae Ro; Cho, Ha Ra; Park, Jun Seo; Choi, Yong Seok; Kang, Myung Joo

2016-02-01

A novel surfactant-incorporated hydroxypropyl methylcellulose (HPMC) solid dispersion (SD) system was constructed in order to facilitate the release rate and oral absorption of tacrolimus (FK506), a poorly water-soluble immunosuppressant. Several emulsifiers including sodium lauryl sulfate (SLS), as drug release promotors, were employed with HPMC to fabricate SD using the solvent wetting method. The solid state characteristics using differential scanning calorimetry and X-ray powder diffraction, revealed that FK506 was molecularly distributed within all dispersions in amorphous form. The dissolution rates of FK506 in SLS-incorporated SDs were much higher than those in SDs prepared with HPMC alone, and even with stearoyl polyoxyl-32 glycerides or tocopheryl polyethylene glycol 1000 succinate. In particular, the greatest dissolution enhancement was obtained from the SD consisting of the drug, HPMC, and SLS in a weight ratio of 1:1:3, providing a 50-fold higher drug concentration within 15 min, compared with HPMC SD. In vivo absorption study in rats demonstrates that the optimized formula remarkably increased the oral absorption of FK506, providing about 4.0-fold greater bioavailability (p<0.05) compared with the marketed product (Prograf®, Astellas Pharma). These data suggest that a novel SLS/HPMC SD may be an advantageous dosage form of FK506, boosting the dissolution and absorption in gastrointestinal tract. Copyright © 2015 Elsevier B.V. All rights reserved.

Polymer coated CaAl-layered double hydroxide nanomaterials for potential calcium supplement.

PubMed

Kim, Tae-Hyun; Lee, Jeong-A; Choi, Soo-Jin; Oh, Jae-Min

2014-12-05

We have successfully prepared layered double hydroxide (LDH) nanomaterials containing calcium and aluminum ions in the framework (CaAl-LDH). The surface of CaAl-LDH was coated with enteric polymer, Eudragit®L 100 in order to protect nanomaterials from fast dissolution under gastric condition of pH 1.2. The X-ray diffraction patterns, Fourier transform infrared spectroscopy, scanning electron and transmission electron microscopy revealed that the pristine LDH was well prepared having hydrocalumite structure, and that the polymer effectively coated the surface of LDH without disturbing structure. From thermal analysis, it was determined that only a small amount (less than 1%) of polymer was coated on the LDH surface. Metal dissolution from LDH nanomaterials was significantly reduced upon Eudragit®L 100 coating at pH 1.2, 6.8 and 7.4, which simulates gastric, enteric and plasma conditions, respectively, and the dissolution effect was the most suppressed at pH 1.2. The LDH nanomaterials did not exhibit any significant cytotoxicity up to 1000 μg/mL and intracellular calcium concentration significantly increased in LDH-treated human intestinal cells. Pharmacokinetic study demonstrated absorption efficiency of Eudragit®L 100 coated LDH following oral administration to rats. Moreover, the LDH nanomaterials did not cause acute toxic effect in vivo. All the results suggest the great potential of CaAl-LDH nanomaterials as a calcium supplement.

Influence of oxidation state on water solubility of Si nanoparticles prepared by laser ablation in water

NASA Astrophysics Data System (ADS)

Ryabchikov, Yu. V.; Al-Kattan, A.; Chirvony, V.; Sanchez-Royo, J. F.; Sentis, M.; Timoshenko, V. Yu.; Kabashin, A. V.

2017-02-01

Femtosecond laser fragmentation from preliminarily prepared water-dispersed Si microcolloids was used to synthesize bare (ligand-free) spherical silicon nanoparticles (Si-NPs) with low size dispersion and controllable mean size from a few nm to several tens of nm. In order to control the oxidation state of Si-NPs, the fragmentation was performed in normal oxygen-saturated water (oxygen-rich conditions) or in water disoxygenated by pumping with noble gases (Ag, He) before and during the experiment (oxygen-free conditions). XPS and TEM studies revealed that Si-NPs were composed of Si nanocrystals with inclusions of silicon oxide species, covered by SiOx (1 < x < 2) shell, while the total oxide content depended whether Si-NPs were prepared in oxygen-rich or oxygen-free conditions. When placed into a dialysis box, waterdispersed Si-NPs rapidly dissolved, which was evidenced by TEM data. In this case, NPs prepared under oxygen-rich conditions demonstrated much faster dissolution kinetics and their complete disappearance after 7-10 days, while the dissolution process of less oxidized counterparts could last much longer (25-30 days). Much fast dissolution kinetics of more oxidized Si-NPs was attributed to more friable structure of nanoparticle core due to the presence of numerous oxidation-induced defects. Laser-synthesized Si-NPs are of paramount importance for biomedical applications.

Dynamics and mass transport of solutal convection in a closed porous media system

NASA Astrophysics Data System (ADS)

Wen, Baole; Akhbari, Daria; Hesse, Marc

2016-11-01

Most of the recent studies of CO2 sequestration are performed in open systems where the constant partial pressure of CO2 in the vapor phase results in a time-invariant saturated concentration of CO2 in the brine (Cs). However, in some closed natural CO2 reservoirs, e.g., Bravo Dome in New Mexico, the continuous dissolution of CO2 leads to a pressure drop in the gas that is accompanied by a reduction of Cs and thereby affects the dynamics and mass transport of convection in the brine. In this talk, I discuss the characteristics of convective CO2 dissolution in a closed system. The gas is assumed to be ideal and its solubility given by Henry's law. An analytical solution shows that the diffusive base state is no longer self-similar and that diffusive mass transfer declines rapidly. Scaling analysis reveals that the volume ratio of brine and gas η determines the behavior of the system. DNS show that no constant flux regime exists for η > 0 nevertheless, the quantity F /Cs2 remains constant, where F is the dissolution flux. The onset time is only affected by η when the Rayleigh number Ra is small. In this case, the drop in Cs during the initial diffusive regime significantly reduces the effective Ra and therefore delays the onset.

Improvement of solubility, dissolution and stability profile of artemether solid dispersions and self emulsified solid dispersions by solvent evaporation method.

PubMed

Tayyab Ansari, Muhammad; Arshad, Muhammad Sohail; Hussain, Altaf; Ahmad, Zeeshan

2016-12-08

The purpose of this study was to investigate changes in the water solubility of artemether; a poorly soluble drug used for the treatment of malaria. Different solid dispersions (SDs) of artemether were prepared using artemether and polyethylene glycol 6000 at ratio 12:88 (Group 1), self-emulsified solid dispersions (SESDs) containing artemether, polyethylene glycol 6000, cremophor-A-25, olive oil, hydroxypropylmethylcellulose and transcutol in the ratio 12:75:5:4:2:2, respectively (Group 2). SESDs were also prepared by substituting cremophor-A-25 in Group 2 with poloxamer 188 (noted as Group 3). Each of these preparations was formulated using physical mixing and the solvent evaporation method. Aqueous solubility of artemether improved 11-, 95- and 102-fold, while dissolution (in simulated gastric fluid) increased 3-, 13- and 14-fold, for formulation groups 1, 2 and 3, respectively. X-ray diffraction patterns of SDs indicated a decrease in peak intensities at 10° implying reduced artemether crystallinity. Scanning electron micrographs invariably revealed embedment of artemether by various excipients and a glassy appearance for solvent evaporated mixtures for all three formulation Groups. Our findings indicate improved hydrophilic interactions for drug particles yield greater solubility and dissolution in the following order for artemether formulating methods: solvent evaporation mixtures > physical mixtures > pure artemether.

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.

Synergistic effect of reductive and ligand-promoted dissolution of goethite.

PubMed

Wang, Zimeng; Schenkeveld, Walter D C; Kraemer, Stephan M; Giammar, Daniel E

2015-06-16

Ligand-promoted dissolution and reductive dissolution of iron (hydr)oxide minerals control the bioavailability of iron in many environmental systems and have been recognized as biological iron acquisition strategies. This study investigated the potential synergism between ligands (desferrioxamine B (DFOB) or N,N'-Di(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (HBED)) and a reductant (ascorbate) in goethite dissolution. Batch experiments were performed at pH 6 with ligand or reductant alone and in combination, and under both oxic and anoxic conditions. Goethite dissolution in the presence of reductant or ligand alone followed classic surface-controlled dissolution kinetics. Ascorbate alone does not promote goethite dissolution under oxic conditions due to rapid reoxidation of Fe(II). The rate coefficients for goethite dissolution by ligands are closely correlated with the stability constants of the aqueous Fe(III)-ligand complexes. A synergistic effect of DFOB and ascorbate on the rate of goethite dissolution was observed (total rates greater than the sum of the individual rates), and this effect was most pronounced under oxic conditions. For HBED, macroscopically the synergistic effect was hidden due to the inhibitory effect of ascorbate on HBED adsorption. After accounting for the concentrations of adsorbed ascorbate and HBED, a synergistic effect could still be identified. The potential synergism between ligand and reductant for iron (hydr)oxide dissolution may have important implications for iron bioavailability in soil environments.

Understanding the structural drivers governing glass-water interactions in borosilicate based model bioactive glasses.

PubMed

Stone-Weiss, Nicholas; Pierce, Eric M; Youngman, Randall E; Gulbiten, Ozgur; Smith, Nicholas J; Du, Jincheng; Goel, Ashutosh

2018-01-01

The past decade has witnessed a significant upsurge in the development of borate and borosilicate based resorbable bioactive glasses owing to their faster degradation rate in comparison to their silicate counterparts. However, due to our lack of understanding about the fundamental science governing the aqueous corrosion of these glasses, most of the borate/borosilicate based bioactive glasses reported in the literature have been designed by "trial-and-error" approach. With an ever-increasing demand for their application in treating a broad spectrum of non-skeletal health problems, it is becoming increasingly difficult to design advanced glass formulations using the same conventional approach. Therefore, a paradigm shift from the "trial-and-error" approach to "materials-by-design" approach is required to develop new-generations of bioactive glasses with controlled release of functional ions tailored for specific patients and disease states, whereby material functions and properties can be predicted from first principles. Realizing this goal, however, requires a thorough understanding of the complex sequence of reactions that control the dissolution kinetics of bioactive glasses and the structural drivers that govern them. While there is a considerable amount of literature published on chemical dissolution behavior and apatite-forming ability of potentially bioactive glasses, the majority of this literature has been produced on silicate glass chemistries using different experimental and measurement protocols. It follows that inter-comparison of different datasets reveals inconsistencies between experimental groups. There are also some major experimental challenges or choices that need to be carefully navigated to unearth the mechanisms governing the chemical degradation behavior and kinetics of boron-containing bioactive glasses, and to accurately determine the composition-structure-property relationships. In order to address these challenges, a simplified borosilicate based model melt-quenched bioactive glass system has been studied to depict the impact of thermal history on its molecular structure and dissolution behavior in water. It has been shown that the methodology of quenching of the glass melt impacts the dissolution rate of the studied glasses by 1.5×-3× depending on the changes induced in their molecular structure due to variation in thermal history. Further, a recommendation has been made to study dissolution behavior of bioactive glasses using surface area of the sample - to - volume of solution (SA/V) approach instead of the currently followed mass of sample - to - volume of solution approach. The structural and chemical dissolution data obtained from bioactive glasses following the approach presented in this paper can be used to develop the structural descriptors and potential energy functions over a broad range of bioactive glass compositions. Realizing the goal of designing third generation bioactive glasses requires a thorough understanding of the complex sequence of reactions that control their rate of degradation (in physiological fluids) and the structural drivers that control them. In this article, we have highlighted some major experimental challenges and choices that need to be carefully navigated in order to unearth the mechanisms governing the chemical dissolution behavior of borosilicate based bioactive glasses. The proposed experimental approach allows us to gain a new level of conceptual understanding about the composition-structure-property relationships in these glass systems, which can be applied to attain a significant leap in designing borosilicate based bioactive glasses with controlled dissolution rates tailored for specific patient and disease states. Copyright © 2017 Acta Materialia Inc. All rights reserved.

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.

The effect of pH, buffer capacity and ionic strength on quetiapine fumarate release from matrix tablets prepared using two different polymeric blends.

PubMed

Hamed, Rania; AlJanabi, Reem; Sunoqrot, Suhair; Abbas, Aiman

2017-08-01

The objective of this study was to investigate the effect of the different physiological parameters of the gastrointestinal (GI) fluid (pH, buffer capacity, and ionic strength) on the in vitro release of the weakly basic BCS class II drug quetiapine fumarate (QF) from two once-a-day matrix tablet formulations (F1 and F2) developed as potential generic equivalents to Seroquel ® XR. F1 tablets were prepared using blends of high and low viscosity grades of hydroxypropyl methylcellulose (HPMC K4M and K100LV, respectively), while F2 tablets were prepared from HPMC K4M and PEGylated glyceryl behenate (Compritol ® HD5 ATO). The two formulations attained release profiles of QF over 24 h similar to that of Seroquel ® XR using the dissolution medium published by the Food and Drug Administration (FDA). A series of solubility and in vitro dissolution studies was then carried out using media that simulate the gastric and intestinal fluids and cover the physiological pH, buffer capacity and ionic strength range of the GIT. Solubility studies revealed that QF exhibits a typical weak base pH-dependent solubility profile and that the solubility of QF increases with increasing the buffer capacity and ionic strength of the media. The release profiles of QF from F1, F2 and Seroquel ® XR tablets were found to be influenced by the pH, buffer capacity and ionic strength of the dissolution media to varying degrees. Results highlight the importance of studying the physiological variables along the GIT in designing controlled release formulations for more predictive in vitro-in vivo correlations.

[Effect of plant extracts on the in vitro dissolution of cystine stones: a study at the mesoscopic scale].

PubMed

Hannache, B; Bazin, D; Boutefnouchet, A; Daudon, M

2012-09-01

Assessing the efficacy to dissolve cystine stones in vitro of plant extracts used in traditional medicine to treat or prevent urolithiasis. Pure cystine stones were incubated during 8 weeks under magnetic stirring in the presence of four plant extracts or of NaCl 9 g/l solution used as control. Plants under examination were Arenaria ammophila (leaves and stems), Parietaria officinalis (leaves and flowers studied separately), Paronychia argentea (flowers). Each experiment was performed in triplicate. The mass loss of the stones and the pH of the solution were measured after each two weeks period. Possible changes in the cystine crystals at the stone surface were assessed at the mesoscopic scale using a scanning electron microscope. None of the plant extracts has revealed a significant effect to dissolve cystine stones by comparison to the control during the time of the experiment. The best result was a mass loss of 99 mg at the end of experiment in the presence of A. ammophila vs. 43.7 mg for the NaCl solution (P=0.051). Considering the slopes of the dissolution, only that extract could have an actual efficacy on a more prolonged period. Our study failed to demonstrate a significant effect of the tested plant extracts to dissolve cystine stones in vitro. However, the examination of the dissolution curves suggests that a more prolonged test period could allow an efficacy of some extracts, especially A. ammophila. Further studies are needed to verify such hypothesis. However, we cannot recommend the use of the tested plants to treat cystine stones in vivo. Copyright © 2012 Elsevier Masson SAS. 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.

Development and validation of dissolution study of sustained release dextromethorphan hydrobromide tablets.

PubMed

Rajan, Sekar; Colaco, Socorrina; Ramesh, N; Meyyanathan, Subramania Nainar; Elango, K

2014-02-01

This study describes the development and validation of dissolution tests for sustained release Dextromethorphan hydrobromide tablets using an HPLC method. Chromatographic separation was achieved on a C18 column utilizing 0.5% triethylamine (pH 7.5) and acetonitrile in the ratio of 50:50. The detection wavelength was 280 nm. The method was validated and response was found to be linear in the drug concentration range of 10-80 microg mL(-1). The suitable conditions were clearly decided after testing sink conditions, dissolution medium and agitation intensity. The most excellent dissolution conditions tested, for the Dextromethorphan hydrobromide was applied to appraise the dissolution profiles. The method was validated and response was found to be linear in the drug concentration range of 10-80 microg mL(-1). The method was established to have sufficient intermediate precision as similar separation was achieved on another instrument handled by different operators. Mean Recovery was 101.82%. Intra precisions for three different concentrations were 1.23, 1.10 0.72 and 1.57, 1.69, 0.95 and inter run precisions were % RSD 0.83, 1.36 and 1.57%, respectively. The method was successfully applied for dissolution study of the developed Dextromethorphan hydrobromide tablets.

Dissolution of solid lipid extrudates in biorelevant media.

PubMed

Witzleb, R; Müllertz, A; Kanikanti, V-R; Hamann, H-J; Kleinebudde, P

2012-01-17

Solid lipid extrudates with the model drug praziquantel were produced with chemically diverse lipids and investigated regarding their dissolution behaviour in different media. The lipids used in this study were glyceryl tripalmitate, glyceryl dibehenate, glyceryl monostearate, cetyl palmitate and solid paraffin. Thermoanalytical and dissolution behaviour was investigated directly after extrusion and after 3 and 6 months open storage at 40°C/75% RH. Dissolution studies were conducted in hydrochloric acid (HCl) pH 1.2 with different levels of polysorbate 20 and with a biorelevant medium containing pancreatic lipase, bile salts and phospholipids. Furthermore, the impact of lipid digestion on drug release was studied using in vitro lipolysis. The release of praziquantel from cetyl palmitate and glyceryl monostearate in the biorelevant medium was much faster than in HCl, whereas there was hardly any difference for the other lipids. It was shown that drug release from glyceryl monostearate matrices is driven by both solubilisation and enzymatic degradation of the lipid, whereas dissolution from cetyl palmitate extrudates is dependent only on solubilisation by surfactants in the medium. Moreover, storage influenced the appearance of the extrudate surface and the dissolution rate for all lipids except solid paraffin. Copyright © 2011 Elsevier B.V. All rights reserved.

Dilatometry Analysis of Dissolution of Cr-Rich Carbides in Martensitic Stainless Steels

NASA Astrophysics Data System (ADS)

Huang, Qiuliang; Volkova, Olena; Biermann, Horst; Mola, Javad

2017-12-01

The dissolution of Cr-rich carbides formed in the martensitic constituent of a 13 pct Cr stainless steel was studied by dilatometry and correlative electron channeling contrast examinations. The dissolution of carbides subsequent to the martensite reversion to austenite was associated with a net volume expansion which in turn increased the dilatometry-based apparent coefficient of thermal expansion (CTEa) during continuous heating. The effects of carbides fraction and size on the CTEa variations during carbides dissolution are discussed.

Kinetics of carbonate mineral dissolution in CO2-acidified brines at storage reservoir conditions.

PubMed

Peng, Cheng; Anabaraonye, Benaiah U; Crawshaw, John P; Maitland, Geoffrey C; Trusler, J P Martin

2016-10-20

We report experimental measurements of the dissolution rate of several carbonate minerals in CO 2 -saturated water or brine at temperatures between 323 K and 373 K and at pressures up to 15 MPa. The dissolution kinetics of pure calcite were studied in CO 2 -saturated NaCl brines with molalities of up to 5 mol kg -1 . The results of these experiments were found to depend only weakly on the brine molality and to conform reasonably well with a kinetic model involving two parallel first-order reactions: one involving reactions with protons and the other involving reaction with carbonic acid. The dissolution rates of dolomite and magnesite were studied in both aqueous HCl solution and in CO 2 -saturated water. For these minerals, the dissolution rates could be explained by a simpler kinetic model involving only direct reaction between protons and the mineral surface. Finally, the rates of dissolution of two carbonate-reservoir analogue minerals (Ketton limestone and North-Sea chalk) in CO 2 -saturated water were found to follow the same kinetics as found for pure calcite. Vertical scanning interferometry was used to study the surface morphology of unreacted and reacted samples. The results of the present study may find application in reactive-flow simulations of CO 2 -injection into carbonate-mineral saline aquifers.

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.

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.

The use of ordered mixtures for improving the dissolution rate of low solubility compounds.

PubMed

Nyström, C; Westerberg, M

1986-03-01

The dissolution rate of micronized griseofulvin has been investigated, both for the agglomerated raw material and the material formulated as an ordered mixture, by means of the USP XX paddle method. During the experiments, which were performed at sink condition and constant temperature, the effects of adding a surfactant and of agitation were tested. The ordered mixture with sodium chloride gave a fast dissolution rate, practically independent of the test parameters. Micronized griseofulvin alone gave dissolution profiles that were improved by adding polysorbate 80 and by increased agitation, but the dissolution rates obtained were much lower than those for the ordered mixture. It was concluded that the rate limiting step in the dissolution of griseofulvin as the raw material is the penetration of the dissolution medium into the agglomerates. With an ordered mixture, these agglomerates were deaggregated during the mixing process, producing a system in which the entire external surface area of the primary particles was exposed to the dissolution medium. This conclusion was supported by calculation of the contact surface areas taking part in the dissolution process for the systems tested. The procedure developed in this study could be applied to preformulation work where a cohesive, low solubility drug of hydrophobic nature is to be formulated.

Calcite Dissolution Kinetics

NASA Astrophysics Data System (ADS)

Berelson, W.; Subhas, A.; Dong, S.; Naviaux, J.; Adkins, J. F.

2016-12-01

A geological buffer for high atmospheric CO2 concentrations is neutralization via reaction with CaCO3. We have been studying the dissolution kinetics of carbonate minerals using labeled 13C calcite and Picarro-based measurements of 13C enrichments in solution DIC. This methodology has greatly facilitated our investigation of dissolution kinetics as a function of water carbonate chemistry, temperature and pressure. One can adjust the saturation state Omega by changing the ion activity product (e.g. adjusting carbonate ion concentration), or by changing the solubility product (e.g. adjusting temperature or pressure). The canonical formulation of dissolution rate vs. omega has been refined (Subhas et al. 2015) and shows distinct non-linear behavior near equilibrium and rates in sea water of 1-3 e-6 g/cm2day at omega = 0.8. Carbonic anhydrase (CA), an enzyme that catalyzes the hydration of dissolved CO2 to carbonic acid, was shown (in concentrations <=0.04 g/L) to enhance the dissolution rate at low degrees of undersaturation by >500x. This result points to the importance of carbonic acid in enhancing dissolution at low degrees of undersaturation. CA activity and abundance in nature must be considered regarding the role it plays in catalyzing dissolution. We also have been investigating the role of temperature on dissolution kinetics. An increase of 16C yields an order of magnitude increase in dissolution rate. Temperature (and P) also change Omega critical, the saturation state where dissolution rates change substantially. Increasing pressure (achieved in a pressure reaction chamber we built) also shifts Omega critical closer to equilibrium and small pressure increases have large impact on dissolution kinetics. Dissolution rates are enhanced by an order of magnitude for a change in pressure of 1500 psi relative to the dissolution rate achieved by water chemistry effects alone for an omega of 0.8. We've shown that the thermodynamic determination of saturation state does not adequately describe the kinetics of dissolution. The interplay of mineral composition and surface area, solution carbonate chemistry, temperature and pressure are factors the impact carbonate dissolution rates in natural settings. We suggest that these parameters be considered in CO2 mitigation strategies.

A novel lipid nanoemulsion system for improved permeation of granisetron.

PubMed

Doh, Hea-Jeong; Jung, Yunjin; Balakrishnan, Prabagar; Cho, Hyun-Jong; Kim, Dae-Duk

2013-01-01

A new lipid nanoemulsion (LNE) system containing granisetron (GRN) was developed and its in vitro permeation-enhancing effect was evaluated using Caco-2 cell monolayers. Particle size, polydispersity index (PI) and stability of the prepared GRN-loaded LNE systems were also characterized. The mean diameters of prepared LNEs were around 50 nm with PI<0.2. Developed LNEs were stable at 4°C in the dark place over a period of 12 weeks. In vitro drug dissolution and cytotoxicity studies of GRN-loaded LNEs were performed. GRN-loaded LNEs exhibited significantly higher drug dissolution than GRN suspension at pH 6.8 for 2h (P<0.05). In vitro permeation study in Caco-2 cell monolayers showed that the LNEs significantly enhanced the drug permeation compared to GRN powder. The in vivo toxicity study in the rat jejunum revealed that the prepared GRN-loaded LNE was as safe as the commercial formulation (Kytril). These results suggest that LNE could be used as a potential oral liquid formulation of GRN for anti-emetic treatment on the post-operative and chemotherapeutic patients. Copyright © 2012 Elsevier B.V. All rights reserved.

Delamination mechanism study of large size waste printed circuit boards by using dimethylacetamide.

PubMed

Verma, Himanshu Ranjan; Singh, Kamalesh K; Mankhand, Tilak Raj

2017-07-01

Present work investigates the recycling of waste printed circuit boards (PCBs) by cracking of its multi-layered structure by using dimethylacetamide (DMA). The study shows that cracking and separation of layers of PCBs increases as the temperature increases; and decreases as the surface area of PCBs increases. After separation of layers, the used solvent was analyzed by proton and carbon nuclear magnetic resonance spectroscopy (NMR) to understand the dissolution phenomenon of resin. Further, NMR and Fourier transform infrared spectroscopy analysis of DMA sample after 1h, 2h, 3h, 4h and 8h of reaction with PCBs at 433K and PCB:DMA ratio (wt/vol) of 3:10 has been carried out to investigate the mechanism of dissolution of resin. These studies revealed that hydroxyl group of PCBs polymeric chain participates in hydrogen bonding with parent carbonyl group of DMA molecule that results in the solvation of resin. Possible chemical reaction based on the above finding has been discussed. Using this technique, separation of the metallic fraction without application of any energy intensive mechanical pre-processing is possible. Copyright © 2017 Elsevier Ltd. All rights reserved.

Catalysis and chemical mechanisms of calcite dissolution in seawater

PubMed Central

Adkins, Jess F.; Rollins, Nick E.; Naviaux, John; Erez, Jonathan; Berelson, William M.

2017-01-01

Near-equilibrium calcite dissolution in seawater contributes significantly to the regulation of atmospheric CO2 on 1,000-y timescales. Despite many studies on far-from-equilibrium dissolution, little is known about the detailed mechanisms responsible for calcite dissolution in seawater. In this paper, we dissolve 13C-labeled calcites in natural seawater. We show that the time-evolving enrichment of 𝜹13C in solution is a direct measure of both dissolution and precipitation reactions across a large range of saturation states. Secondary Ion Mass Spectrometer profiles into the 13C-labeled solids confirm the presence of precipitated material even in undersaturated conditions. The close balance of precipitation and dissolution near equilibrium can alter the chemical composition of calcite deeper than one monolayer into the crystal. This balance of dissolution–precipitation shifts significantly toward a dissolution-dominated mechanism below about Ω= 0.7. Finally, we show that the enzyme carbonic anhydrase (CA) increases the dissolution rate across all saturation states, and the effect is most pronounced close to equilibrium. This finding suggests that the rate of hydration of CO2 is a rate-limiting step for calcite dissolution in seawater. We then interpret our dissolution data in a framework that incorporates both solution chemistry and geometric constraints on the calcite solid. Near equilibrium, this framework demonstrates a lowered free energy barrier at the solid–solution interface in the presence of CA. This framework also indicates a significant change in dissolution mechanism at Ω= 0.7, which we interpret as the onset of homogeneous etch pit nucleation. PMID:28720698

Marital and Cohabitation Dissolution and Parental Depressive Symptoms in Fragile Families

ERIC Educational Resources Information Center

Kamp Dush, Claire M.

2013-01-01

The consequences of divorce are pronounced for parents of young children, and cohabitation dissolution is increasing in this population and has important implications. The mental health consequences of union dissolution were examined, by union type and parental gender, using the Fragile Families and Child Wellbeing Study ("n" = 1,998 for mothers…

Educational Differences in Marital Dissolution: Comparison of White and African American Women

ERIC Educational Resources Information Center

Kim, Jeounghee

2012-01-01

Although the trend of marital dissolution has diverged by education in recent decades, literature was not clear about whether African Americans experienced a significant educational difference in marital dissolution. This study hypothesized that educational differences within the African American community have emerged and that the growth in this…

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.

In vitro dissolution method fitted to in vivo absorption profile of rivaroxaban immediate-release tablets applying in silico data.

PubMed

Wingert, Nathalie R; Dos Santos, Natália O; Campanharo, Sarah C; Simon, Elisa S; Volpato, Nadia M; Steppe, Martin

2018-05-01

This study aimed to develop and validate an in vitro dissolution method based on in silico-in vivo data to determine whether an in vitro-in vivo relationship could be established for rivaroxaban in immediate-release tablets. Oral drugs with high permeability but poorly soluble in aqueous media, such as the anticoagulant rivaroxaban, have a major potential to reach a high level of in vitro-in vivo relationship. Currently, there is no study on scientific literature approaching the development of RIV dissolution profile based on its in vivo performance. Drug plasma concentration values were modeled using computer simulation with adjustment of pharmacokinetic properties. Those values were converted into drug fractions absorbed by the Wagner-Nelson deconvolution approach. Gradual and continuous dissolution of RIV tablets was obtained with a 30 rpm basket on 50 mM sodium acetate +0.2% SDS, pH 6.5 medium. Dissolution was conducted for up to 180 min. The fraction absorbed was plotted against the drug fraction dissolved, and a linear point-to-point regression (R 2  = 0.9961) obtained. The in vitro dissolution method designed promoted a more convenient dissolution profile of RIV tablets, whereas it suggests a better relationship with in vivo performance.

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.

Modeling Paragenesis: Erosion Opposite to Gravity in Cave Channels

NASA Astrophysics Data System (ADS)

Cooper, M. P.; Covington, M. D.

2017-12-01

Sediment plays an important role in bedrock channels, providing both tools and cover that influence patterns of bed erosion. It has also been shown that sediment load influences bedrock channel width, with increased sediment leading to wider channels. A variety of models have been developed to explore these effects. In caves, it is hypothesized that sediments covering the floors of fully flooded channels that are forming beneath the water table (phreatic zone) can force dissolution upwards towards the water table, leading to upward erosion balanced by gradual deposition of sediment within the channel bottom. This strange process is termed paragenesis, and while there are conceptual and experimental models of the process, no prior mathematical models of cave passage evolution has captured these effects. Consequently, there is little quantitative understanding of the processes that drive paragenesis and how they link to the morphology of the cave channels that develop. We adapt a previously developed algorithm for estimating boundary shear stress within channels with free-surface flows to enable calculation of boundary shear stress in pipe-full conditions. This model successfully duplicates scaling relationships in surface channels, and geometries of caves formed in the phreatic zone such as phreatic tubes. Once sediment flux is incorporated the model successfully duplicates the hypothesized processes of paragenetic gallery formation: the cover effect prevents dissolution in the direction of gravity; passages are enlarged upwards reducing the sediment transport capacity; sediment is deposited and the process drives a continuing feedback loop. Simulations reveal that equilibrium paragenetic channel widths scale with both sediment flux and discharge. Unlike in open channel settings, increased sediment load actually narrows paragenetic channels. The cross section evolution model also reveals that the existence of equilibrium widths in such galleries requires erosion to scale with shear stress, suggesting a role of either mechanical erosion or transport limited dissolution. These types of erosion contrast with current numerical models of speleogenesis, where chemically limited dissolution, a process independent of shear stress, is predicted to occur in most turbulent flow settings.

Glass-water interactions: Effect of high-valence cations on glass structure and chemical durability

DOE PAGES

Pierce, Eric M.; Kerisit, Sebastien N.; Charpentier, Thibault; ...

2016-02-27

Spectroscopic measurements, dissolution experiments, and Monte Carlo simulations were performed to investigate the effect of high valence cations (HVC) on the mechanisms of glass dissolution under dilute and near-saturated conditions. Raman and NMR spectroscopy were used to determine the structural changes that occur in glass, specifically network formers (e.g., Al, Si, and B), with the addition of the HVC element hafnium in the Na 2O Al 2O 3 B 2O 3 HfO 2 SiO 2 system (e.g., Na/(Al+B) = 1.0 and HfO 2/SiO 2 from 0.0 to 0.42). Spectroscopic measurements revealed that increasing hafnium content decreases N 4 and increasesmore » the amount of Si–O–Hf moieties in the glass. Results from flow through experiments conducted under dilute and near saturated conditions show a decrease of approximately 100 or more in the dissolution rate over the series from 0 to 20 mol% HfO 2. Comparing the average steady-state rates obtained under dilute conditions to the rates obtained for near-saturated conditions reveal a divergence in the magnitude between the average steady state rates measured in these different conditions. The reason for this divergence was investigated more thoroughly using Monte Carlo simulations. Simulations indicate that the divergence in glass dissolution behavior under dilute and near-saturated conditions result from the formation of a low coordination Si sites when Si from the saturated solution adsorbs to Hf on the glass surface. The residence time of the newly formed low coordination Si sites is longer at the glass surface and increases the density of anchor sites from which altered layers with higher Si densities can form than in the absence of Hf. These results illustrate the importance of understanding solid water/solid-fluid interactions by linking macroscopic reaction kinetics to nanometer scale interfacial processes.« less

Dewetting kinetics of metallic liquid films: Competition between unbalanced Young's force and dissolutive reaction

NASA Astrophysics Data System (ADS)

Lu, Gui; Lin, Lin; Hui, Sheng; Wang, Shuo-Lin; Wang, Xiao-Dong; Lee, Duu-Jong

2017-11-01

Dewetting kinetics of Al and NiAl metallic liquid films on NiAl (1 0 0) substrates was studied using molecular dynamics simulations. A new dewetting-spreading transitional behavior was observed for high temperature dewetting. The dewetting-spreading transition comes from the competition between unbalanced Young's force and dissolutive reaction. Without dissolutive reaction, liquid films keep dewetting, but immediately turn into spreading when the dissolutive reaction involved. The dissolutive reaction depends on the initial Ni atom contents rather than the contact areas of dewetting films. The far-away-from saturated Ni content is the main mechanism which accelerates the wetting and reverses the dewetting process at high temperatures.

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.

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.

On the influence of carbonate in mineral dissolution: I. The thermodynamics and kinetics of hematite dissolution in bicarbonate solutions at T = 25° C

NASA Astrophysics Data System (ADS)

Bruno, Jordi; Stumm, Werner; Wersin, Paul; Brandberg, Frederick

1992-03-01

We have studied the thermodynamics and kinetics of hematite dissolution in bicarbonate solutions under constant pCO 2. The solubility of hematite is increased in the presence of bicarbonate. We have established that the complexes responsible for this increase are FeOHCO 3 (aq) and Fe(CO 3) 2-. The stability constants of these complexes at the infinite dilution standard state are log β 11 = -3.83 ± 0.21 and log β 2 = 7.40 ± 0.11 , respectively (all errors are given at 2σ confidence level through this work). The rate of dissolution of hematite is enhanced in bicarbonate solutions. This rate of dissolution can be expressed as R diss = k 1[HCO 3-] 0.23 (mol m -2h -1), with k 1 = 1.42 10 -7h -1. The combination of the study of the surface complexation and kinetics of dissolution of hematite in bicarbonate solutions indicate that the dissolution of hematite is surface controlled and bicarbonate promoted. The rate of dissolution follows the expression R diss = k HCO 3-FeOH - HCO 3-}, where k HCO 3- = 1.1 10 -3 h -1. The implications of these findings in the oxic cycle of iron in natural waters are discussed, most importantly in order to explain the high-Fe(III) concentrations measured in groundwaters from the Poços de Caldas complex in Brazil.

Effect of drug loading method against drug dissolution mechanism of encapsulated amoxicillin trihydrate in matrix of semi-IPN chitosan-poly(N-vinylpyrrolidone) hydrogel with KHCO3 as pore forming agent in floating drug delivery system

NASA Astrophysics Data System (ADS)

Fimantari, Khansa; Budianto, Emil

2018-04-01

Helicobacterpylori infection can be treated using trihydrate amoxicillin. However, this treatment is not effective enough, as the conventional dosage treatment has a relatively short retention time in the human stomach. In the present study, the amoxicillin trihydrate drug will be encapsulated into a semi-IPN K-PNVP hydrogel matrix with 7,5% KHCO3 as a pore-forming agent. The encapsulated drug is tested with in vitro method to see the efficiency of its encapsulation and dissolution. The hydrogel in situ loading produces an encapsulation efficiency value. The values of the encapsulation efficiency are 95% and 98%, while post loading hydrogel yields an encapsulation efficiency value is 77% and the dissolution is 84%. The study of drug dissolution mechanism was done by using mathematical equation model to know its kinetics and its mechanism of dissolution. The post loading hydrogel was done by using thefirst-order model, while hydrogel in situ loading used Higuchi model. The Korsmeyer-Peppas model shows that post loading hydrogel dissolution mechanism is a mixture of diffusion and erosion, and in situ loading hydrogel in the form of diffusion. It is supported by the results of hydrogel characterization, before and after dissolution test with an optical microscope. The results of the optical microscope show that the hydrogel surface before and after the dissolution tested for both methods shows the change becomes rougher.

Controlled evaluation of silver nanoparticle dissolution using atomic force microscopy.

PubMed

Kent, Ronald D; Vikesland, Peter J

2012-07-03

Incorporation of silver nanoparticles (AgNPs) into an increasing number of consumer products has led to concern over the potential ecological impacts of their unintended release to the environment. Dissolution is an important environmental transformation that affects the form and concentration of AgNPs in natural waters; however, studies on AgNP dissolution kinetics are complicated by nanoparticle aggregation. Herein, nanosphere lithography (NSL) was used to fabricate uniform arrays of AgNPs immobilized on glass substrates. Nanoparticle immobilization enabled controlled evaluation of AgNP dissolution in an air-saturated phosphate buffer (pH 7.0, 25 °C) under variable NaCl concentrations in the absence of aggregation. Atomic force microscopy (AFM) was used to monitor changes in particle morphology and dissolution. Over the first day of exposure to ≥10 mM NaCl, the in-plane AgNP shape changed from triangular to circular, the sidewalls steepened, the in-plane radius decreased by 5-11 nm, and the height increased by 6-12 nm. Subsequently, particle height and in-plane radius decreased at a constant rate over a 2-week period. Dissolution rates varied linearly from 0.4 to 2.2 nm/d over the 10-550 mM NaCl concentration range tested. NaCl-catalyzed dissolution of AgNPs may play an important role in AgNP fate in saline waters and biological media. This study demonstrates the utility of NSL and AFM for the direct investigation of unaggregated AgNP dissolution.

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

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.

Olivine dissolution from Indian dunite in saline water.

PubMed

Agrawal, Amit Kumar; Mehra, Anurag

2016-11-01

The rate and mechanism of olivine dissolution was studied using naturally weathered dunite FO 98.21 (Mg 1.884 Fe 0.391 SiO 4 ) from an Indian source, that also contains serpentine mineral lizardite. A series of batch dissolution experiments were carried out to check the influence of temperature (30-75 ∘ C), initial dunite concentration (0.5 and 20 g/L), and salinity (0-35 g/L NaCl) under fixed head space CO 2 pressure (P[Formula: see text] = 1 barg) on dunite dissolution. Dissolved Mg, Si, and Fe concentrations were determined by inductive coupled plasma atomic emission spectroscopy. End-product solids were characterized by scanning electron microscopy and X-ray diffraction. Initially, rates of dissolution of Si and Mg were observed to be in stoichiometric proportion. After 8 h, the dissolution rate was observed to decline. At the end of the experiment (504 h), an amorphous silica-rich layer was observed over the dunite surface. This results in decay of the dissolution rate. The operating conditions (i.e., salinity, temperature, and mineral loading) affect the dissolution kinetics in a very complex manner because of which the observed experimental trends do not exhibit a direct trend.

The impact of posttraumatic stress symptoms, posttraumatic stress cognitions and interpersonal dependency on psychological co-morbidities following relationship dissolution among college students.

PubMed

Fang, Siqi; Chung, Man Cheung; Watson, Clare

2018-02-13

Relationship dissolution is a distressing experience which can result in the emergence of posttraumatic stress (i.e. post-dissolution PTSS) and other psychological symptoms among college students. Little is known, however, whether posttraumatic stress cognitions and interpersonal dependency may influence the severity of these distress outcomes. This study examined the interrelationship between posttraumatic stress symptoms (PTSS), posttraumatic stress cognitions, interpersonal dependency and psychological co-morbidities following relationship dissolution. One hundred and eighty college students (M = 69, F = 111) who had experienced relationship dissolution completed the Posttraumatic Stress Diagnostic Scale, Posttraumatic Stress Cognition Inventory, Interpersonal Dependency Inventory and General Health Questionnaire-28. Posttraumatic stress symptoms following relationship dissolution (post-dissolution PTSS) were associated with increased psychological co-morbidities. Negative view of oneself and self-blame mediated between PTSS and psychological co-morbidities. Assertion of autonomy moderated the mediational effects of negative cognitions on psychological co-morbidities. People can develop PTSSs and other psychological symptoms following the dissolution of a romantic relationship. Their concept of self and tendency to seek independence and control played a key role in determining the severity of distress symptoms.

Health behaviors and union dissolution among parents of young children: Differences by marital status

PubMed Central

Meyer, Jess M.

2017-01-01

Previous research finds that marriage is associated with better health and lower mortality, and one of the mechanisms underlying this association is health-related selection out of marriage. Using longitudinal survey data from 2,348 couples from the Fragile Families and Child Wellbeing Study, we examine whether certain health behaviors—smoking and binge drinking—are associated with risk of union dissolution among couples with young children. We use discrete time hazard models to test whether associations between health behaviors and union dissolution differ between married and cohabiting parents. We find no statistically significant association between binge drinking and union dissolution for either cohabiting or married couples. Parental smoking, however, is associated with union dissolution. On average, married and cohabiting couples in which both parents smoke have a higher risk of union dissolution than couples in which neither parent smokes. Additionally, father’s smoking (in couples in which the mother does not smoke) is associated with union dissolution, but only for married couples. These findings illustrate the importance of considering the health behaviors of both partners and provide further evidence of differences in union dissolution dynamics between married and cohabiting couples. PMID:28796826

Health behaviors and union dissolution among parents of young children: Differences by marital status.

PubMed

Meyer, Jess M; Percheski, Christine

2017-01-01

Previous research finds that marriage is associated with better health and lower mortality, and one of the mechanisms underlying this association is health-related selection out of marriage. Using longitudinal survey data from 2,348 couples from the Fragile Families and Child Wellbeing Study, we examine whether certain health behaviors-smoking and binge drinking-are associated with risk of union dissolution among couples with young children. We use discrete time hazard models to test whether associations between health behaviors and union dissolution differ between married and cohabiting parents. We find no statistically significant association between binge drinking and union dissolution for either cohabiting or married couples. Parental smoking, however, is associated with union dissolution. On average, married and cohabiting couples in which both parents smoke have a higher risk of union dissolution than couples in which neither parent smokes. Additionally, father's smoking (in couples in which the mother does not smoke) is associated with union dissolution, but only for married couples. These findings illustrate the importance of considering the health behaviors of both partners and provide further evidence of differences in union dissolution dynamics between married and cohabiting couples.

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.

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

Level A in vitro-in vivo correlation: Application to establish a dissolution test for artemether and lumefantrine tablets.

PubMed

Rivelli, Graziella Gomes; Ricoy, Letícia Brandão Magalhães; César, Isabela Costa; Fernandes, Christian; Pianetti, Gérson Antônio

2018-06-05

Malaria is the most incident parasite infection worldwide. Artemisinin based combination therapy (ACT) has been proposed as a promising treatment for malaria, and artemether + lumefantrine (20 + 120 mg) is the recommended association in endemic areas. Despite its widespread use, there is still scarce information about dissolution of artemether and lumefantrine, reflecting in the absence of a specific method in pharmacopoeias and international compendia. Because the of their low solubility, both artemether and lumefantrine are candidates for in vitro-in vivo correlation (IVIVC) studies. Previous equilibrium solubility studies have been carried out for both drugs using the shake-flask method and dissolution profiles. Experiments were conducted with a range of parameters such as medium composition, pH and surfactants. In vivo data obtained in a previous pharmacokinetic study was used to select the optimum conditions for dissolution test, based on IVIVC. For drug quantitation, a selective method by high performance liquid chromatography was optimized and validated. For this dosage form, the best dissolution conditions found for artemether were: paddles, 900 mL of dissolution medium containing phosphate buffer pH 6.8 with 1.0% sodium lauryl sulfate and rotation speed of 100 rpm. The same was obtained for lumefantrine, except the dissolution medium, which was pH 1.2 with 1.0% polysorbate 80. After obtaining the curve of in vitro dissolved fraction versus in vivo absorbed fraction, the calculated coefficient of determination (R squared) was close to 1.00 for both drugs, indicating a level A correlation. Therefore, a novel method for assessing dissolution of arthemeter and lumefantrine tablets was established and validated. Copyright © 2018 Elsevier B.V. All rights reserved.

Quality-by-design case study: investigation of the role of poloxamer in immediate-release tablets by experimental design and multivariate data analysis.

PubMed

Kaul, Goldi; Huang, Jun; Chatlapalli, Ramarao; Ghosh, Krishnendu; Nagi, Arwinder

2011-12-01

The role of poloxamer 188, water and binder addition rate, on retarding dissolution in immediate-release tablets of a model drug from BCS class II was investigated by means of multivariate data analysis (MVDA) combined with design of experiments (DOE). While the DOE analysis yielded important clues into the cause-and-effect relationship between the responses and design factors, multivariate data analysis of the 40+ variables provided additional information on slowdown in tablet dissolution. A steep dependence of both tablet dissolution and disintegration on the poloxamer and less so on other design variables was observed. Poloxamer was found to increase dissolution rates in granules as expected of surfactants in general but retard dissolution in tablets. The unexpected effect of poloxamer in tablets was accompanied by an increase in tablet-disintegration-time-mediated slowdown of tablet dissolution and by a surrogate binding effect of poloxamer at higher concentrations. It was additionally realized through MVDA that poloxamer in tablets either acts as a binder by itself or promotes binder action of the binder povidone resulting in increased intragranular cohesion. Additionally, poloxamer was found to mediate tablet dissolution on stability as well. In contrast to tablet dissolution at release (time zero), poloxamer appeared to increase tablet dissolution in a concentration-dependent manner on accelerated open-dish stability. Substituting polysorbate 80 as an alternate surfactant in place of poloxamer in the formulation was found to stabilize tablet dissolution.

Combinatorial localized dissolution analysis: Application to acid-induced dissolution of dental enamel and the effect of surface treatments.

PubMed

Parker, Alexander S; Al Botros, Rehab; Kinnear, Sophie L; Snowden, Michael E; McKelvey, Kim; Ashcroft, Alexander T; Carvell, Mel; Joiner, Andrew; Peruffo, Massimo; Philpotts, Carol; Unwin, Patrick R

2016-08-15

A combination of scanning electrochemical cell microscopy (SECCM) and atomic force microscopy (AFM) is used to quantitatively study the acid-induced dissolution of dental enamel. A micron-scale liquid meniscus formed at the end of a dual barrelled pipette, which constitutes the SECCM probe, is brought into contact with the enamel surface for a defined period. Dissolution occurs at the interface of the meniscus and the enamel surface, under conditions of well-defined mass transport, creating etch pits that are then analysed via AFM. This technique is applied to bovine dental enamel, and the effect of various treatments of the enamel surface on acid dissolution (1mM HNO3) is studied. The treatments investigated are zinc ions, fluoride ions and the two combined. A finite element method (FEM) simulation of SECCM mass transport and interfacial reactivity, allows the intrinsic rate constant for acid-induced dissolution to be quantitatively determined. The dissolution of enamel, in terms of Ca(2+) flux ( [Formula: see text] ), is first order with respect to the interfacial proton concentration and given by the following rate law: [Formula: see text] , with k0=0.099±0.008cms(-1). Treating the enamel with either fluoride or zinc ions slows the dissolution rate, although in this model system the partly protective barrier only extends around 10-20nm into the enamel surface, so that after a period of a few seconds dissolution of modified surfaces tends towards that of native enamel. A combination of both treatments exhibits the greatest protection to the enamel surface, but the effect is again transient. Copyright © 2016 Elsevier Inc. All rights reserved.

Hydrogen production from the dissolution of nano zero valent iron and its effect on anaerobic digestion.

PubMed

Huang, Yu-Xi; Guo, Jialiang; Zhang, Chunyang; Hu, Zhiqiang

2016-01-01

Nano zero valent iron (NZVI) has shown inhibition on methanogenesis in anaerobic digestion due to its reductive decomposition of cell membrane. The inhibition was accompanied by the accumulation of hydrogen gas due to rapid NZVI dissolution. It is not clear whether and how rapid hydrogen release from NZVI dissolution directly affects anaerobic digestion. In this study, the hydrogen release kinetics from NZVI (average size = 55 ± 11 nm) dissolution in deionized water under anaerobic conditions was first evaluated. The first-order NZVI dissolution rate constant was 2.62 ± 0.26 h(-1) with its half-life of 0.26 ± 0.03 h. Two sets of anaerobic digestion experiments (i.e., in the presence of glucose or without any substrate but at different anaerobic sludge concentrations) were performed to study the impact of H2 release from rapid NZVI dissolution, in which H2 was generated in a separate water bottle containing NZVI (i.e., ex situ H2 or externally supplied from NZVI dissolution) before hydrogen gas was introduced to anaerobic digestion. The results showed that the H2 partial pressure in the headspace of the digestion bottle reached as high as 0.27 atm due to rapid NZVI dissolution, resulting in temporary inhibition of methane production. Nevertheless, the 5-d cumulative methane volume in the group with ex situ H2 production due to NZVI dissolution was actually higher than that of control, suggesting NZVI inhibition on methanogenesis is solely due to the reductive decomposition of cell membrane after direct contact with NZVI. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dissolution enhancement of gliclazide using pH change approach in presence of twelve stabilizers with various physico-chemical properties.

PubMed

Talari, Roya; Varshosaz, Jaleh; Mostafavi, Seyed Abolfazl; Nokhodchi, Ali

2009-01-01

The micronization using milling process to enhance dissolution rate is extremely inefficient due to a high energy input, and disruptions in the crystal lattice which can cause physical or chemical instability. Therefore, the aim of the present study is to use in situ micronization process through pH change method to produce micron-size gliclazide particles for fast dissolution hence better bioavailability. Gliclazide was recrystallized in presence of 12 different stabilizers and the effects of each stabilizer on micromeritic behaviors, morphology of microcrystals, dissolution rate and solid state of recrystallized drug particles were investigated. The results showed that recrystallized samples showed faster dissolution rate than untreated gliclazide particles and the fastest dissolution rate was observed for the samples recrystallized in presence of PEG 1500. Some of the recrystallized drug samples in presence of stabilizers dissolved 100% within the first 5 min showing at least 10 times greater dissolution rate than the dissolution rate of untreated gliclazide powders. Micromeritic studies showed that in situ micronization technique via pH change method is able to produce smaller particle size with a high surface area. The results also showed that the type of stabilizer had significant impact on morphology of recrystallized drug particles. The untreated gliclazide is rod or rectangular shape, whereas the crystals produced in presence of stabilizers, depending on the type of stabilizer, were very fine particles with irregular, cubic, rectangular, granular and spherical/modular shape. The results showed that crystallization of gliclazide in presence of stabilizers reduced the crystallinity of the samples as confirmed by XRPD and DSC results. In situ micronization of gliclazide through pH change method can successfully be used to produce micron-sized drug particles to enhance dissolution rate.

Limited Carbonate Dissolution by Boring Microflora at Two Volcanically Acidified Temperate Sites: Ischia (Italy, Mediterranean Sea) and Faial (Azores, NE Atlantic Ocean)

NASA Astrophysics Data System (ADS)

Tribollet, A.; Grange, J. S.; Parra, H.; Rodolfo-Metalpa, R.; Carreiro-Silva, M.

2018-01-01

In situ effects of ocean acidification on carbonate dissolution by microboring flora, also called biogenic dissolution, have only been studied once in tropical environments. Naturally acidified seawaters due to CO2 vents offer a perfect setting to study these effects in temperate systems. Three sites were selected at Ischia (Italy, Mediterranean Sea) with one experiencing ambient pH and the two others a mean pHT of 7.2 and 7.5. At Faial (Azores, NE Atlantic), one site with ambient pH and one acidified site with a mean pHT of 7.4 were selected. Experiments were carried out during 1.5 months and 6 months in Azores and Ischia, respectively, to determine the effects of OA on microboring communities in various carbonate substrates. Low pH influenced negatively boring microflora development by limiting their depth of penetration and abundance in substrates. Biogenic dissolution was thus reduced by a factor 3 to 7 depending on sites and substrate types. At sites with ambient pH in Faial, biogenic dissolution contributed up to 23% to the total weight loss, while it contributed less than 1% to the total weight loss of substrates at the acidified sites. Most of the dissolution at these sites was due to chemical dissolution (often Ω ≤ 1). Such conditions maintained microboring communities at a pioneer stage with a limited depth of penetration in substrates. Our results, together with previous findings that showed an increase of biogenic dissolution at pH > 7.7, suggest that there is a pH tipping point below which microborer development and thus carbonate biogenic dissolution is strongly limited.

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.

Microfluidics experiments of dissolution in a fracture. Influence of Damköhler and Péclet numbers, and of the geometry on the dissolution pattern

NASA Astrophysics Data System (ADS)

Osselin, Florian; Budek, Agnieszka; Cybulski, Olgierd; Szymczak, Piotr

2015-04-01

Dissolution of natural rocks is an ever present phenomenon in nature. The shaping of natural landscapes by the dissolution of limestone gives for example birth to exceptional features like karsts. Currently dissolution is also at the heart of key research topics as Carbon Capture and Storage or Enhanced Oil Recovery. The basics principles of dissolution are well-known, however, the sheer amount of different patterns arising from these mechanisms and the strong dependency on parameters such as pore network, chemical composition and flow rate, make it particularly difficult to study theoretically and experimentally. In this study we present a microfluidic experiment simulating the behavior of a dissolving fluid in a fracture. The experiments consist of a chip of gyspum inserted between two polycarbonate plates and subjected to a constant flow rate of pure water. The point in using microfluidics is that it allows a complete control on the experimental parameters such as geometry and chemical composition of the porous medium, flow rate, fracture aperture, roughness of the fracture walls, and an in situ observation of the geometry evolution which is impossible with 3D natural rocks. Thanks to our experiments we have been able to cover the whole range of dissolution patterns, from wormholing or DLA fingering to homogeneous dissolution, by changing Péclet and Damköhler numbers. Moreover, we have been able to tweak the geometry of our artificial fracture, inserting finger seeds or non-dissolvable obstacles. The comparison of the experimental patterns with the numerical dissolution code dissol (Szymczak and Ladd 2011) has then shown a very good correlation of the patterns, giving confidence in both experiments and modeling.

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

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.

An integrated system for dissolution studies and magnetic resonance imaging of controlled release, polymer-based dosage forms-a tool for quantitative assessment of hydrogel formation processes.

PubMed

Kulinowski, Piotr; Dorozyński, Przemysław; Jachowicz, Renata; Weglarz, Władysław P

2008-11-04

Controlled release (CR) dosage forms are often based on polymeric matrices, e.g., sustained-release tablets and capsules. It is crucial to visualise and quantify processes of the hydrogel formation during the standard dissolution study. A method for imaging of CR, polymer-based dosage forms during dissolution study in vitro is presented. Imaging was performed in a non-invasive way by means of the magnetic resonance imaging (MRI). This study was designed to simulate in vivo conditions regarding temperature, volume, state and composition of dissolution media. Two formulations of hydrodynamically balanced systems (HBS) were chosen as model CR dosage forms. HBS release active substance in stomach while floating on the surface of the gastric content. Time evolutions of the diffusion region, hydrogel formation region and "dry core" region were obtained during a dissolution study of L-dopa as a model drug in two simulated gastric fluids (i.e. in fed and fasted state). This method seems to be a very promising tool for examining properties of new formulations of CR, polymer-based dosage forms or for comparison of generic and originator dosage forms before carrying out bioequivalence studies.

Spatially Resolved Acid Dissolution of IDPs: The State of Carbon and the Abundance of Diamonds in the Dust

NASA Technical Reports Server (NTRS)

Brownlee, D. E.; Joswiak, D. J.; Bradley, J. P.; Gezo, J. C.; Hill, H. G. M.

2000-01-01

Ultramicrotome sections of IDPs have been successfully etched with HF to isolate and reveal the microdistribution of carbonaceous material. The sections are evaluated for nanodiamonds, 3.4 micron feature, GEMS and the origin of low albedo in small interplanetary particles.

Effect of amphiphilic graft co-polymer-carrier on physical stability of bosentan nanocomposite: Assessment of solubility, dissolution and bioavailability.

PubMed

Kendre, Prakash N; Chaudhari, Pravin D

2018-05-01

Bosentan is a dual endothelin receptor antagonist used in the treatment of pulmonary arterial hypertension (PAH). But the solubility and bioavailability of this drug are poor, which has restricted the design and development of dosage forms for efficient and successful therapy. The present study was carried out to develop nanocomposites using an amphiphilic graft co-polymer (Soluplus®) as a carrier to enhance the solubility and bioavailability of bosentan. The graft co-polymer-based nanocomposite formulation was prepared using the single-emulsion technique. The nanocomposite was characterised in terms of particle size analysis, solubility, percentage entrapment efficiency, drug-loading capacity, surface morphology, drug content, in vitro dissolution, stability and bioavailability. FT-IR study revealed that there was no interaction between the drug and Soluplus®. DSC analysis of the nanocomposite formulation confirmed that the bosentan was completely encapsulated within a Soluplus®. XRD analysis showed that the drug was converted to an amorphous form irreversibly. SEM images showed that the particles were of size 96-129μm and had slightly smooth to rough textured surface. TEM analysis indicated that the diameters of the prepared bosentan nanocomposite after dispersion in distilled water were 13.69-96.78nm. Statistically significant increases in the solubility, dissolution and bioavailability of the drug were observed. It was confirmed that the use of a graft co-polymer carrier-based nanocomposite formulation is a good approach for efficient delivery of bosentan, the solubility and bioavailability being increased manifold. Copyright © 2017 Elsevier B.V. All rights reserved.

In Situ Salt Formation during Melt Extrusion for Improved Chemical Stability and Dissolution Performance of a Meloxicam-Copovidone Amorphous Solid Dispersion.

PubMed

Haser, Abbe; Cao, Tu; Lubach, Joseph W; Zhang, Feng

2018-03-05

As the pipeline for poorly soluble compounds continues to grow, drug degradation during melt extrusion must be addressed. We present a novel method for stabilizing a thermally labile drug substance while preserving its physical stability and even improving its dissolution performance. In a previous study, we found that incorporating meglumine during extrusion of meloxicam results in chemical stabilization that cannot be achieved using process optimization alone. The purpose of this study is to understand the mechanism behind this stabilization and its impact on the performance of a meloxicam-Kollidon VA64 amorphous solid dispersion. The meloxicam concentration was maintained at 10% (w/w) for blends with and without meglumine. The optimal meglumine blend contained an equimolar amount of meloxicam to meglumine with the remainder consisting of Kollidon VA64. Both formulations were processed with optimized extrusion conditions and analyzed by HPLC for purity. Meglumine at a 1:1 molar ratio with meloxicam results in 100% purity of meloxicam after melt extrusion. Solid-state NMR revealed a proton transfer between the meloxicam and meglumine indicating an in situ salt formation. During non-sink dissolution, the meglumine ASD enables meloxicam to maintain supersaturatation (≅50 times more than meloxicam free acid) for >7.25 h. The ASD without meglumine began precipitating 2.25 h following the pH shift. The ASDs were placed at 40 °C/75% RH for 6 months, and their stability was assessed. No significant chemical degradation, recrystallization, or significant moisture uptake was observed after six months' storage at 40 °C/75% RH.

Crystal-liquid Fugacity Ratio as a Surrogate Parameter for Intestinal Permeability.

PubMed

Zakeri-Milani, Parvin; Fasihi, Zohreh; Akbari, Jafar; Jannatabadi, Ensieh; Barzegar-Jalali, Mohammad; Loebenberg, Raimar; Valizadeh, Hadi

We assessed the feasibility of using crystal-liquid fugacity ratio (CLFR) as an alternative parameter for intestinal permeability in the biopharmaceutical classification (BCS) of passively absorbed drugs. Dose number, fraction of dose absorbed, intestinal permeability, and intrinsic dissolution rate were used as the input parameters. CLFR was determined using thermodynamic parameters i.e., melting point, molar fusion enthalpy, and entropy of drug molecules obtained using differential scanning calorimetry. The CLFR values were in the range of 0.06-41.76 mole percent. There was a close relationship between CLFR and in vivo intestinal permeability (r > 0.8). CLFR values of greater than 2 mole percent corresponded to complete intestinal absorption. Applying CLFR versus dose number or intrinsic dissolution rate, more than 92% of tested drugs were correctly classified with respect to the reported classification system on the basis of human intestinal permeability and solubility. This investigation revealed that the CLFR might be an appropriate parameter for quantitative biopharmaceutical classification. This could be attributed to the fact that CLFR could be a measure of solubility of compounds in lipid bilayer which was found in this study to be directly proportional to the intestinal permeability of compounds. This classification enables researchers to define characteristics for intestinal absorption of all four BCS drug classes using suitable cutoff points for both intrinsic dissolution rate and crystal-liquid fugacity ratio. Therefore, it may be used as a surrogate for permeability studies. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Use of glancing angle X-ray powder diffractometry to depth-profile phase transformations during dissolution of indomethacin and theophylline tablets.

PubMed

Debnath, Smita; Predecki, Paul; Suryanarayanan, Raj

2004-01-01

The purpose of this study was (i) to develop glancing angle x-ray powder diffractometry (XRD) as a method for profiling phase transformations as a function of tablet depth; and (ii) to apply this technique to (a) study indomethacin crystallization during dissolution of partially amorphous indomethacin tablets and to (b) profile anhydrate --> hydrate transformations during dissolution of theophylline tablets. The intrinsic dissolution rates of indomethacin and theophylline were determined after different pharmaceutical processing steps. Phase transformations during dissolution were evaluated by various techniques. Transformation in the bulk and on the tablet surface was characterized by conventional XRD and scanning electron microscopy, respectively. Glancing angle XRD enabled us to profile these transformations as a function of depth from the tablet surface. Pharmaceutical processing resulted in a decrease in crystallinity of both indomethacin and theophylline. When placed in contact with the dissolution medium, while indomethacin recrystallized, theophylline anhydrate rapidly converted to theophylline monohydrate. Due to intimate contact with the dissolution medium, drug transformation occurred to a greater extent at or near the tablet surface. Glancing angle XRD enabled us to depth profile the extent of phase transformations as a function of the distance from the tablet surface. The processed sample (both indomethacin and theophylline) transformed more rapidly than did the corresponding unprocessed drug. Several challenges associated with the glancing angle technique, that is, the effects of sorbed water, phase transformations during the experimental timescale, and the influence of phase transformation on penetration depth, were addressed. Increased solubility, and consequently dissolution rate, is one of the potential advantages of metastable phases. This advantage is negated if, during dissolution, the metastable to stable transformation rate > dissolution rate. Glancing angle XRD enabled us to quantify and thereby profile phase transformations as a function of compact depth. The technique has potential utility in monitoring surface reactions, both chemical decomposition and physical transformations, in pharmaceutical systems.

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

The Use of Artificial Neural Network for Prediction of Dissolution Kinetics

PubMed Central

Elçiçek, H.; Akdoğan, E.; Karagöz, S.

2014-01-01

Colemanite is a preferred boron mineral in industry, such as boric acid production, fabrication of heat resistant glass, and cleaning agents. Dissolution of the mineral is one of the most important processes for these industries. In this study, dissolution of colemanite was examined in water saturated with carbon dioxide solutions. Also, prediction of dissolution rate was determined using artificial neural networks (ANNs) which are based on the multilayered perceptron. Reaction temperature, total pressure, stirring speed, solid/liquid ratio, particle size, and reaction time were selected as input parameters to predict the dissolution rate. Experimental dataset was used to train multilayer perceptron (MLP) networks to allow for prediction of dissolution kinetics. Developing ANNs has provided highly accurate predictions in comparison with an obtained mathematical model used through regression method. We conclude that ANNs may be a preferred alternative approach instead of conventional statistical methods for prediction of boron minerals. PMID:25028674

Radiocarbon dating of planktonic foraminifer shells: A cautionary tale

NASA Astrophysics Data System (ADS)

Mekik, Figen

2014-01-01

rate, bioturbation, winnowing, and calcite dissolution produce significant radiocarbon age offsets among multiple species of coexisting planktonic foraminifers and pteropod fragments. We compare the radiocarbon age of foraminifer species and pteropod fragments with estimates of percent calcite dissolved made with a sedimentary proxy (Globorotalia menardii fragmentation index—MFI) to delineate the effect of dissolution on radiocarbon age of foraminifers. Data from two core top transects on the Rio Grande Rise (RIO) and Ontong Java Plateau (OJP) and from down core sediments of varying sedimentation rates in the tropical Pacific (ME-27, MD98 2177, and MW91-9 56GGC) reveal that sediments with the greatest accumulation rates produce the least age offsets among coexisting species. Age offsets among coexisting foraminifers are about 3500 years on RIO, and 1000 years on OJP. Two core tops from RIO yield an age of the Last Glacial Maximum possibly due to mass displacement of younger sediments downslope. Foraminifer age increases with increasing dissolution and there is a consistent pattern of older foraminifer fragments coexisting with younger whole shells of the same species. The only exception is sediments which have experienced high dissolution where fragments are younger than whole shells. The age offset between fragments of G. menardii and its coexisting whole shells does not exceed the age offset among other coexisting foraminifer species in the same core tops.

Solid-state characterization of nevirapine.

PubMed

Sarkar, Mahua; Perumal, O P; Panchagnula, R

2008-09-01

The purpose of this investigation is to characterize nevirapine from commercial samples and samples crystallized from different solvents under various conditions. The solid-state behavior of nevirapine samples was investigated using a variety of complementary techniques such as microscopy (optical, polarized, hot stage microscopy), differential scanning calorimeter, thermogravimetric analysis, Fourier transform infrared spectroscopy and powder X-ray diffractometry. The commercial samples of nevirapine had the same polymorphic crystalline form with an anhedral crystal habit. Intrinsic dissolution of nevirapine was similar for both the commercial batches. Powder dissolution showed pH dependency, with maximum dissolution in acidic pH and there was no significant effect of particle size. The samples recrystallized from different solvent systems with varying polarity yielded different crystal habits. Stirring and degrees of supersaturation influenced the size and shape of the crystals. The recrystallized samples did not produce any new polymorphic form, but weak solvates with varying crystal habit were produced. Recrystallized samples showed differences in the x-ray diffractograms. However, all the samples had the same internal crystal lattice as revealed from their similar melting points and heat of fusion. The intrinsic dissolution rate of recrystallized samples was lower than the commercial sample. It was found that the compression pressure resulted in desolvation and partial conversion of the crystal form. After compression, the recrystallized samples showed similar x-ray diffractograms to the commercial sample. Amorphous form showed slightly higher aqueous solubility than the commercial crystalline form.

Dissolution enhancement and mathematical modeling of removal of residual trichloroethene in sands by ozonation during flushing with micro-nano-bubble solution

NASA Astrophysics Data System (ADS)

Sung, Menghau; Teng, Chun-Hao; Yang, Tsung-Hsien

2017-07-01

Soil flushing using micro-nano-sized bubbles (MNB) in water as the flushing solution was tested in laboratory sand columns for the cleanup of residual trichloroethene (TCE) non-aqueous-phase-liquid (NAPL). Experiments considering flushing with MNB as well as ozone MNB (OZMNB) in water to treat soils contaminated with residual TCE liquid were conducted to examine effects of ozone on dissolution enhancement. The degrees of residual TCE saturation in soils, ranging from 0.44% to 7.6%, were tested. During flushings, aqueous TCE concentrations at the column exit were monitored and TCE masses remained in the columns after flushing were determined. Experimental results between runs with MNB and OZMNB in water revealed that dissolution enhancement was dependent on residual saturation conditions, and the maximum enhancement was around 9%. Governing equations consisting of three coupled partial differential equations (PDEs) were developed to model the system, and high-order finite difference (HOFD) method was employed to solve these PDEs. From mathematical modeling of reactive mass transfer under low residual saturation conditions (0.44% and 1.9%), experimental data were simulated and important controlling mechanisms were identified. It was concluded that a specific parameter pertinent to NAPL-water interfacial area in the Sherwood number had to be modified to satisfactorily describe the dissolution of TCE in the presence of MNB in water.

Tadalafil inclusion in microporous silica as effective dissolution enhancer: optimization of loading procedure and molecular state characterization.

PubMed

Mehanna, Mohammed M; Motawaa, Adel M; Samaha, Magda W

2011-05-01

Tadalafil is an efficient drug used to treat erectile dysfunction characterized by poor water solubility, which has a negative influence on its bioavailability. Utilization of microporous silica represents an effective and facile technology to increase the dissolution rate of poorly soluble drugs. Our strategy involved directly introducing tadalafil as guest molecule into microporous silica as host material by incipient wetness impregnation method. To optimize tadalafil inclusion, response surface methodology (RSM) using 3(3) factorial design was utilized. Furthermore, to investigate the molecular state of tadalafil, Fourier-transform infrared spectroscopy, differential scanning calorimetery, thermal gravimetrical analysis, nitrogen adsorption, and powder X-ray diffraction (PXRD) were carried out. The results obtained pointed out that the quantity of microporous silica was the predominant factor that increased the loading efficiency. For the optimized formula, the loading efficiency was 42.50 wt %. Adsorption-desorption experiments indicated that tadalafil has been introduced into the micropores. Powder XRD and differential scanning calorimetry analyses revealed that tadalafil is arranged in amorphous form. In addition, the dissolution rate of tadalafil from the microporous silica was faster than that of free drug. Amorphous tadalafil occluded in microporous silica did not crystallize over 3 months. These findings contributed in opening a new strategy concerning the utilization of porous silica for the dissolution rate enhancement. Copyright © 2010 Wiley-Liss, Inc.

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.

"We Decided to Call It Quits": An Exercise in Applying Duck's Dissolution Model to Students' Breakup Stories

ERIC Educational Resources Information Center

Barton, Matthew H.; Turman, Paul D.

2008-01-01

Steve Duck's scholarship has made a noticeable impact on the study of interpersonal communication. Of his works, one of the most noteworthy is the explanatory model of relationship disengagement and dissolution. Duck's Dissolution Model (DDM) explains the stages that relationships pass through when they encounter stress resulting in two…

Relationship-Specific Investments, Family Chaos, and Cohabitation Dissolution Following a Nonmarital Birth

ERIC Educational Resources Information Center

Kamp Dush, Claire M.

2011-01-01

Predictors of two types of cohabitation dissolution, dissolution with a continued romantic relationship and without (i.e., breakup), were examined using data from mothers cohabiting at the time of a nonmarital birth in the Fragile Families and Child Wellbeing Study (N = 1,624). Life tables indicated 64% of unions dissolved within 5 years; of…

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

Preparation of goreisan suppository and pharmacokinetics of trans-cinnamic acid after administration to rabbits.

PubMed

Katagiri, Yukiko; Miyazaki, Yasunori; Uchino, Tomonobu; Kagawa, Yoshiyuki

2014-01-01

Goreisan suppository is prepared as a hospital preparation, and successfully used for the treatment of diarrhea and vomiting in young children with common cold. While clinical efficacy of the suppository has been reported, few studies have been carried out to clarify the preparation procedure and pharmacokinetics of the suppository. In this study, trans-cinnamic acid (CA) was used as a representative substance of goreisan constituents, and assayed by HPLC-UV. We investigated the properties of goreisan suppositories prepared using various sizes of pulverized goreisan extract granules, in vitro dissolution profiles using the reciprocating dialysis tube method, and pharmacokinetics in rabbits compared with those for goreisan enema. Mass and content uniformity tests on the suppositories of three size fractions, 0-75, 75-150, and 150-300 µm, showed good acceptance for all kinds of suppository. Storage stability at 4°C was maintained until 4 months. In vitro dissolution of CA from the suppository was proportional to time until 45 min, and slower than that from the enema. Finally, 80% of CA had dissolved at 60 min. Pharmacokinetic study in rabbits revealed that the area under the plasma concentration-time curve from 0 to 120 min (AUC0-120 min) of the suppository was twice that of the enema. Moreover, from a study in rabbits using CA injection and CA suppository, we revealed that CA was rapidly and well absorbed from the rectum, showing 84% absolute bioavailability. Thus, we illustrated the defined preparation procedure of the suppository and the superiority of the suppository over the enema. This study will support evidence that the suppository is fast-acting and efficacious in clinical use.

Using SEM Analysis on Ion-Milled Shale Surface to Determine Shale-Fracturing Fluid Interaction

NASA Astrophysics Data System (ADS)

Lu, J.; Mickler, P. J.; Nicot, J. P.

2014-12-01

It is important to document and assess shale-fluid interaction during hydraulic fracturing (HF) in order to understand its impact on flowback water chemistry and rock property. A series of autoclave experiments were conducted to react shale samples from major oil and gas shales with synthetic HF containing various additives. To better determine mineral dissolution and precipitation at the rock-fluid interface, ion-milling technique was applied to create extremely flat rock surfaces that were examined before and after the autoclave experiments using a scanning electron microscope (SEM) coupled with energy dispersive spectroscopy (EDS) detectors. This method is able to reveal a level of detail not observable on broken surface or mechanically polished surface. It allows direct comparison of the same mineral and organic matter particles before and after the reaction experiments. Minerals undergone dissolution and newly precipitated materials are readily determined by comparing to the exact locations before reaction. The dissolution porosity and the thickness of precipitates can be quantified by tracing and measuring the geometry of the pores and precipitates. Changes in porosity and permeability were confirmed by mercury intrusion capillary tests.

Dissolution and oral bioavailability enhancement of praziquantel by solid dispersions.

PubMed

Liu, Yanyan; Wang, Tianzi; Ding, Wenya; Dong, Chunliu; Wang, Xiaoting; Chen, Jianqing; Li, Yanhua

2018-06-01

The aim of the present investigation was to enhance the solubility, dissolution, and oral bioavailability of praziquantel (PZQ), a poorly water-soluble BCS II drug (Biopharmaceutical Classification System), using a solid dispersion (SD) technique involving hydrophilic copolymers. The SD formulations were prepared by a solvent evaporation method with PZQ and PEG 4000 (polyethylene glycol 4000), PEG 6000, or P 188 polymers at various weight ratios or a combination of PEG 4000/P 188. The optimized SD formulation, which had the highest solubility in distilled water, was further characterized by its surface morphology, crystallinity, and dissolution in 0.1 M HCl with 0.2% w/v of sodium dodecyl sulfate (SDS). X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) revealed the amorphous form of PZQ in the SDs. Moreover, at an oral dosage of 5 mg/kg PZQ, the SDs had higher C max values and areas under the curve (AUCs) compared to those of commercial PZQ tablets. Preparation of PZQ-loaded SDs using PEG 4000/P 188 is a promising strategy to improve the oral bioavailability of PZQ.

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.

Impact and oxidation of single silver nanoparticles at electrode surfaces: one shot versus multiple events† †Electronic supplementary information (ESI) available: Summary of previous studies; Ag NP characterization: TEM and DLS; event duration histogram; maximum current histogram. See DOI: 10.1039/c6sc04483b Click here for additional data file.

PubMed Central

Kang, Minkyung; Bullions, Erin

2017-01-01

Single nanoparticle (NP) electrochemical impacts is a rapidly expanding field of fundamental electrochemistry, with applications from electrocatalysis to electroanalysis. These studies, which involve monitoring the electrochemical (usually current–time, I–t) response when a NP from solution impacts with a collector electrode, have the scope to provide considerable information on the properties of individual NPs. Taking the widely studied oxidative dissolution of individual silver nanoparticles (Ag NPs) as an important example, we present measurements with unprecedented noise (< 5 pA) and time resolution (time constant 100 μs) that are highly revealing of Ag NP dissolution dynamics. Whereas Ag NPs of diameter, d = 10 nm are mostly dissolved in a single event (on the timescale of the measurements), a wide variety of complex processes operate for NPs of larger diameter (d ≥ 20 nm). Detailed quantitative analysis of the I–t features, consumed charge, event duration and impact frequency leads to a major conclusion: Ag NPs undergo sequential partial stripping (oxidative dissolution) events, where a fraction of a NP is electrochemically oxidized, followed by the NP drifting away and back to the tunnelling region before the next partial stripping event. As a consequence, analysis of the charge consumed by single events (so-called “impact coulometry”) cannot be used as a general method to determine the size of colloidal NPs. However, a proper analysis of the I–t responses provides highly valuable information on the transient physicochemical interactions between NPs and polarized surfaces. PMID:28553474

Growth and dissolution of apatite precipitates formed in vivo on the surface of a bioactive glass coating film and its relevance to bioactivity

NASA Astrophysics Data System (ADS)

Jallot, E.; Benhayoune, H.; Kilian, L.; Irigaray, J. L.; Balossier, G.; Bonhomme, P.

2000-11-01

Development of bioactive glasses for use as a coating on Ti6Al4V prostheses requires a better understanding of reactions at the bone/bioactive glass interface. Indeed, the bioactive glasses bond to bone through physico-chemical reactions. In vivo, an apatite rich layer is built up on top of a pure silica rich layer at the bioactive glass periphery. In this paper, we have studied Ti6Al4V cylinders coated with a bioactive glass and implanted in sheep femora for two, three and six months. At each time period, the samples were analysed with scanning transmission electron microscopy coupled with energy dispersive x-ray spectroscopy. In vivo, the bioactive glass dissolution led to the formation on its surface of spherical particles with different sizes. The distributions of Si, Al, Ca, P and Mg concentrations across the particles reveal precipitation of apatite with the incorporation of magnesium. Apatite precipitation is governed by diffusion through an Si layer and occurs under specific supersaturation conditions. Measurements of supersaturation for Ca and P demonstrate that the largest precipitates grow and the smallest dissolve. These results allow us to study the growth and dissolution rate of the apatite precipitates and their relevance to bioactivity. Particles with a radius twice the average radius () grow the fastest and, if the radius increases, the rate of growth decreases. Before three months, the growth of apatite precipitates (≈1 µm) leads to the growth of a Ca-P interfacial layer. After three months, is of the order of 0.5 µm, and the majority of the apatite layer dissolves. The effects of aluminium and magnesium on apatite generation are also studied.

Successful topical dissolution of cholesterol gallbladder stones using ethyl propionate.

PubMed

Hofmann, A F; Amelsberg, A; Esch, O; Schteingart, C D; Lyche, K; Jinich, H; Vansonnenberg, E; D'Agostino, H B

1997-06-01

Topical dissolution of cholesterol gallbladder stones using methyl tert-butyl ether (MTBE) is useful in symptomatic patients judged too ill for surgery. Previous studies showed that ethyl propionate (EP), a C5 ester, dissolves cholesterol gallstones rapidly in vitro, but differs from MTBE in being eliminated so rapidly by the liver that blood levels remain undetectable. Our aim was to test EP as a topical dissolution agent for cholesterol gallbladder stones. Five high-risk patients underwent topical dissolution of gallbladder stones by EP. In three patients, the solvent was instilled via a cholecystostomy tube placed previously to treat acute cholecystitis; in two patients, a percutaneous transhepatic catheter was placed in the gallbladder electively. Gallstone dissolution was assessed by chromatography, by gravimetry, and by catheter cholecystography. Total dissolution of gallstones was obtained in four patients after 6-10 hr of lavage; in the fifth patient, partial gallstone dissolution facilitated basketing of the stones. In two patients, cholesterol dissolution was measured and averaged 30 mg/min. Side effects were limited to one episode of transient hypotension and pain at the infusion site; no patient developed somnolence or nausea. Gallstone elimination was associated with relief of symptoms. EP is an acceptable alternative to MTBE for topical dissolution of cholesterol gallbladder stones in high-risk patients. The lower volatility and rapid hepatic extraction of EP suggest that it may be preferable to MTBE in this investigational procedure.

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.

Mineral dissolution and secondary precipitation on quartz sand in simulated Hanford tank solutions affecting subsurface porosity

NASA Astrophysics Data System (ADS)

Wang, Guohui; Um, Wooyong

2012-11-01

Highly alkaline nuclear waste solutions have been released from underground nuclear waste storage tanks and pipelines into the vadose zone at the US Department of Energy's Hanford Site in Washington, causing mineral dissolution and re-precipitation upon contact with subsurface sediments. High pH caustic NaNO3 solutions with and without dissolved Al were reacted with quartz sand through flow-through columns stepwise at 45, 51, and 89 °C to simulate possible reactions between leaked nuclear waste solution and primary subsurface mineral. Upon reaction, Si was released from the dissolution of quartz sand, and nitrate-cancrinite [Na8Si6Al6O24(NO3)2] precipitated on the quartz surface as a secondary mineral phase. Both steady-state dissolution and precipitation kinetics were quantified, and quartz dissolution apparent activation energy was determined. Mineral alteration through dissolution and precipitation processes results in pore volume and structure changes in the subsurface porous media. In this study, the column porosity increased up to 40.3% in the pure dissolution column when no dissolved Al was present in the leachate, whereas up to a 26.5% porosity decrease was found in columns where both dissolution and precipitation were observed because of the presence of Al in the input solution. The porosity change was also confirmed by calculation using the dissolution and precipitation rates and mineral volume changes.

Role of fiber dissolution in biological activity in rats.

PubMed

Eastes, W; Hadley, J G

1994-12-01

This report deals with the role of dissolution in removing long fibers from the lung and with a mathematical model that predicts chronic effects in rats following inhalation or intraperitoneal (i.p.) injection of fibers. Results of intratracheal instillation studies and inhalation studies in rats demonstrate clearly that long vitreous fibers dissolve in vivo at about the same rate measured in vitro in fluid designed to stimulate the extracellular lung fluid. For the glass, rock, and slag wool fibers tested, dissolution removed most of the fibers longer than 20 microns inhaled into the rats' lungs within 6 months after both short-term (5 days) and long-term (1 to 2 years) exposures. A mathematical model was developed that is based on fiber dissolution and allows one to predict the development of chronic lung diseases in rats. The model predicted the incidence of fibrosis and lung tumors in a series of recent inhalation studies and tumors following ip injection to within about the error of the experiments. The model suggests that all fibers, regardless of their dissolution rate in lung fluid, can produce tumors after ip injection because the dose can be unlimited by this route. After inhalation, in contrast, dissolution of many types of long vitreous fibers occurs rapidly, and disease does not ensue for these fibers.

Investigating the Impact of Drug Crystallinity in Amorphous Tacrolimus Capsules on Pharmacokinetics and Bioequivalence Using Discriminatory In Vitro Dissolution Testing and Physiologically Based Pharmacokinetic Modeling and Simulation.

PubMed

Purohit, Hitesh S; Trasi, Niraj S; Sun, Dajun D; Chow, Edwin C Y; Wen, Hong; Zhang, Xinyuan; Gao, Yi; Taylor, Lynne S

2018-05-01

Delivering a drug in amorphous form in a formulated product is a strategy used to enhance the apparent solubility of a drug substance and its oral bioavailability. Drug crystallization in such products may occur during the manufacturing process or on storage, reducing the solubility advantage of the amorphous drug. However, the impact of partial drug crystallization in the drug product on the resulting bioavailability and pharmacokinetics is unknown. In this study, dissolution testing of commercial tacrolimus capsules (which are formulated to contain amorphous drug), both fresh and those containing different amounts of crystalline drug, was conducted using both United States Pharmacopeia and noncompendial dissolution tests with different dissolution media and volumes. A physiologically based pharmacokinetic (PBPK) absorption model was developed to predict the impact of crystallinity extent on the oral absorption of the products and to evaluate the discriminatory ability of the different dissolution methods. Virtual bioequivalence simulations between partially crystallized tacrolimus capsules versus fresh Prograf or generic tacrolimus capsules were performed using the PBPK model and in vitro dissolution data of the various fresh and partially crystallized capsules under United States Pharmacopeia and noncompendial dissolution conditions. The results suggest that compendial dissolution tests may not be sufficiently discriminatory with respect to the presence of crystallinity in an amorphous formulation. Nonsink dissolution tests using lower dissolution volumes generate more discriminatory profiles that predict different pharmacokinetics of tacrolimus capsules containing different extents of drug crystallinity. In conclusion, the PBPK modeling approach can be used to assess the impact of partial drug crystallinity in the formulated product and to guide the development of appropriate dissolution methods. Copyright © 2018 American Pharmacists Association®. All rights reserved.

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.

Computational fluid dynamics (CFD) studies of a miniaturized dissolution system.

PubMed

Frenning, G; Ahnfelt, E; Sjögren, E; Lennernäs, H

2017-04-15

Dissolution testing is an important tool that has applications ranging from fundamental studies of drug-release mechanisms to quality control of the final product. The rate of release of the drug from the delivery system is known to be affected by hydrodynamics. In this study we used computational fluid dynamics to simulate and investigate the hydrodynamics in a novel miniaturized dissolution method for parenteral formulations. The dissolution method is based on a rotating disc system and uses a rotating sample reservoir which is separated from the remaining dissolution medium by a nylon screen. Sample reservoirs of two sizes were investigated (SR6 and SR8) and the hydrodynamic studies were performed at rotation rates of 100, 200 and 400rpm. The overall fluid flow was similar for all investigated cases, with a lateral upward spiraling motion and central downward motion in the form of a vortex to and through the screen. The simulations indicated that the exchange of dissolution medium between the sample reservoir and the remaining release medium was rapid for typical screens, for which almost complete mixing would be expected to occur within less than one minute at 400rpm. The local hydrodynamic conditions in the sample reservoirs depended on their size; SR8 appeared to be relatively more affected than SR6 by the resistance to liquid flow resulting from the screen. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Yin, Lan; Harburg, Daniel V.; Rogers, John A., E-mail: jrogers@illinois.edu

Tungsten interconnects in silicon integrated circuits built at the 90 nm node with releasable configurations on silicon on insulator wafers serve as the basis for advanced forms of water-soluble electronics. These physically transient systems have potential uses in applications that range from temporary biomedical implants to zero-waste environmental sensors. Systematic experimental studies and modeling efforts reveal essential aspects of electrical performance in field effect transistors and complementary ring oscillators with as many as 499 stages. Accelerated tests reveal timescales for dissolution of the various constituent materials, including tungsten, silicon, and silicon dioxide. The results demonstrate that silicon complementary metal-oxide-semiconductor circuits formedmore » with tungsten interconnects in foundry-compatible fabrication processes can serve as a path to high performance, mass-produced transient electronic systems.« less

Effect of iron oxide reductive dissolution on the transformation and immobilization of arsenic in soils: New insights from X-ray photoelectron and X-ray absorption spectroscopy.

PubMed

Fan, Jian-Xin; Wang, Yu-Jun; Liu, Cun; Wang, Li-Hua; Yang, Ke; Zhou, Dong-Mei; Li, Wei; Sparks, Donald L

2014-08-30

The geochemical behavior and speciation of arsenic (As) in paddy soils is strongly controlled by soil redox conditions and the sequestration by soil iron oxyhydroxides. Hence, the effects of iron oxide reductive dissolution on the adsorption, transformation and precipitation of As(III) and As(V) in soils were investigated using batch experiments and synchrotron based techniques to gain a deeper understanding at both macroscopic and microscopic scales. The results of batch sorption experiments revealed that the sorption capacity of As(V) on anoxic soil was much higher than that on control soil. Synchrotron based X-ray fluorescence (μ-XRF) mapping studies indicated that As was heterogeneously distributed and was mainly associated with iron in the soil. X-ray absorption near edge structure (XANES), micro-X-ray absorption near edge structure (μ-XANES) and X-ray photoelectron spectroscopy (XPS) analyses revealed that the primary speciation of As in the soil is As(V). These results further suggested that, when As(V) was introduced into the anoxic soil, the rapid coprecipitation of As(V) with ferric/ferrous ion prevented its reduction to As(III), and was the main mechanism controlling the immobilization of As. This research could improve the current understanding of soil As chemistry in paddy and wetland soils. Copyright © 2014 Elsevier B.V. All rights reserved.

Nanostructured TiO2 and ZnO prepared by using pressurized hot water and their eco-toxicological evaluation

NASA Astrophysics Data System (ADS)

Troppová, Ivana; Matějová, Lenka; Sezimová, Hana; Matěj, Zdeněk; Peikertová, Pavlína; Lang, Jaroslav

2017-06-01

The eco-toxicological effects of unconventionally prepared nanostructured TiO2 and ZnO were evaluated in this study, since both oxides are keenly investigated semiconductor photocatalysts in the last three decades. Unconventional processing by pressurized hot water was applied in order to crystallize oxide materials as an alternative to standard calcination. Acute biological toxicity of the synthesized oxides was evaluated using germination of Sinapis alba seed (ISO 11269-1) and growth of Lemna minor fronds (ISO 20079) and was compared to commercially available TiO2 Degussa P25. Toxicity results revealed that synthesized ZnO as well as TiO2 is toxic contrary to commercial TiO2 Degussa P25 which showled stimulation effect to L. minor and no toxicity to S. alba. ZnO was significantly more toxic than TiO2. The effect of crystallite size was considered, and it was revealed that small crystallite size and large surface area are not the toxicity-determining factors. Factors such as the rate of nanosized crystallites aggregation and concentration, shape and surface properties of TiO2 nanoparticles affect TiO2 toxicity to both plant species. Seriously, the dissolution of Ti4+ ions from TiO2 was also observed which may contribute to its toxicity. In case of ZnO, the dissolution of Zn2+ ions stays the main cause of its toxicity.

A Comprehensive Study on the Electronic State of Hydrogen in α-Phase PdH(D)x-Does a Chemical Bond Between Pd and H(D) Exist?

PubMed

Dekura, Shun; Kobayashi, Hirokazu; Ikeda, Ryuichi; Maesato, Mitsuhiko; Yoshino, Haruka; Ohba, Masaaki; Ishimoto, Takayoshi; Kawaguchi, Shogo; Kubota, Yoshiki; Yoshioka, Satoru; Matsumura, Syo; Sugiyama, Takeharu; Kitagawa, Hiroshi

2018-06-12

The palladium(Pd)-hydrogen(H) system is one of the most famous hydrogen storage systems. Although there has been much research on β-phase PdH(D)x, we comprehensively investigated the nature of the interaction between Pd and H(D) in α-phase PdH(D)x (x < 0.03 at 303 K), and revealed the existence of Pd-H(D) chemical bond for the first time, by various in situ experimental techniques and first-principles theoretical calculations. The lattice expansion by H(D) dissolution in the α-phase lattice suggests the existence of interaction between Pd and H(D). The decrease of magnetic susceptibility and the increase of electrical resistivity indicate that the electronic states are changed by the H(D) dissolution in the α phase. In situ solid-state 1H and 2H NMR results and first-principles theoretical calculations revealed that a Pd-H(D) chemical bond exists in the α phase, but the bonding character of the Pd-H(D) chemical bond in the α phase is quite different from that in the β phase; the nature of the Pd-H(D) chemical bond in the α phase is a localized covalent bond whereas that in the β phase is a metallic bond. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

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.

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.

Effect of bacteria and dissolved organics on mineral dissolution kinetics:

NASA Astrophysics Data System (ADS)

Pokrovsky, Oleg; Shirokova, Liudmila; Benezeth, Pascale; Zabelina, Svetlana

2010-05-01

Quantification of the effect of microorganisms and associated organic ligands on mineral dissolution rate is one among the last remaining challenges in modeling of water-rock interactions under earth surface and subsurface environments. This is especially true for deep underground settings within the context of CO2 capture, sequestration and storage. First, elevated CO2 pressures create numerous experimental difficulties for performing robust flow-through experiments at a given saturation state. Second, reactivity of main rock-forming minerals in abiotic systems at pCO2 >> 1 atm and circumneutral pH is still poorly constrained. And third, most of microbial habitats of the subsurface biosphere are not suitable for routine culturing in the laboratory, many of them are anaerobic and even strictly anaerobic, and many bacteria and archae cultures can live only in the consortium of microorganisms which is very hard to maintain at a controlled and stable biomass concentration. For experimental modeling of bio-mineral interactions in the laboratory, two other main conceptual challenges exist. Typical concentration of dissolved organic carbon that serves as a main nutrient for heterotrophic bacteria in underground waters rarely exceeds 3-5 mg/L. Typical concentration of DOC in nutrient media used for bacteria culturing is between 100 and 10,000 mg/L. Therefore, performing mineral-bacteria interactions in the laboratory under environmentally-sound conditions requires significant dilution of the nutrient media or the use of flow-through reactors. Concerning the effect of organic ligands and bacterial excudates on rock-forming mineral dissolution, at the present time, mostly empirical (phenomenological) approach can be used. Indeed, the pioneering studies of Stumm and co-workers have established a firm basis for modeling the catalyzing and inhibiting effects of ligands on metal oxide dissolution rate. This approach, very efficient for studying the interaction of organic and inorganic ligands with trivalent metal oxides, is based on applying multiple spectroscopic techniques allowing to reveal the chemical structure of adsorbed complexes. However, due to i) low surface area of most rock-forming minerals (carbonates, non-clay silicates), ii) difficulties of applying surface spectroscopic techniques at elevated pressures, and iii) very complex nature of bacterial exometabolites, it is not possible at the present time, to use rigorous surface complexation approach for rationalizing ligand- and bacteria-affected mineral dissolution under sub-surface CO2 storage environment. In this work, we present examples of overcoming these difficulties via concerted study of olivine, wollastonite and calcite interaction with heterotrophic bacteria and methanogenic archaes.

Dissolution of minerals with rough surfaces

NASA Astrophysics Data System (ADS)

de Assis, Thiago A.; Aarão Reis, Fábio D. A.

2018-05-01

We study dissolution of minerals with initial rough surfaces using kinetic Monte Carlo simulations and a scaling approach. We consider a simple cubic lattice structure, a thermally activated rate of detachment of a molecule (site), and rough surface configurations produced by fractional Brownian motion algorithm. First we revisit the problem of dissolution of initial flat surfaces, in which the dissolution rate rF reaches an approximately constant value at short times and is controlled by detachment of step edge sites. For initial rough surfaces, the dissolution rate r at short times is much larger than rF ; after dissolution of some hundreds of molecular layers, r decreases by some orders of magnitude across several time decades. Meanwhile, the surface evolves through configurations of decreasing energy, beginning with dissolution of isolated sites, then formation of terraces with disordered boundaries, their growth, and final smoothing. A crossover time to a smooth configuration is defined when r = 1.5rF ; the surface retreat at the crossover is approximately 3 times the initial roughness and is temperature-independent, while the crossover time is proportional to the initial roughness and is controlled by step-edge site detachment. The initial dissolution process is described by the so-called rough rates, which are measured for fixed ratios between the surface retreat and the initial roughness. The temperature dependence of the rough rates indicates control by kink site detachment; in general, it suggests that rough rates are controlled by the weakest microscopic bonds during the nucleation and formation of the lowest energy configurations of the crystalline surface. Our results are related to recent laboratory studies which show enhanced dissolution in polished calcite surfaces. In the application to calcite dissolution in alkaline environment, the minimal values of recently measured dissolution rate spectra give rF ∼10-9 mol/(m2 s), and the calculated rate laws of our model give rough rates in the range 10-6 -10-5 mol/(m2 s). This estimate is consistent with the range of calcite dissolution rates obtained in a recent work after treatment of literature data, which suggests the universal control of kink site dissolution in short term laboratory works. The weak effects of lattice size on our results also suggest that smoothing of mineral grain surfaces across geological times may be a microscopic explanation for the difference of chemical weathering rate of silicate minerals in laboratory and in the environment.

[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.

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

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.

Feed additive production by fermentation of herb Polygonum hydropiper L. and cassava pulp with simultaneous flavonoid dissolution.

PubMed

Song, Zhen-Tao; Zhu, Ming-Jun

2017-03-01

Fermentation of herb Polygonum hydropiper L. (PHL) and cassava pulp (CP) for feed additive production with simultaneous flavonoid dissolution was investigated, and a two-stage response surface methodology (RSM) based on Plackett-Burman factorial design (PB design) was used to optimize the flavonoid dissolution and protein content. Using the screening function of PB design, four different significant factors for the two response variables were acquired: factors A (CP) and B (PHL) for the flavonoid dissolution versus factors G (inoculum size) and H (fermentation time) for protein content. Then, two RSMs were used sequentially to improve the values of the two response variables separately. The mutual corroboration of the experimental results in the present study confirmed the validity of the associated experimental design. The validation experiment showed a flavonoid dissolution rate of 94.00%, and a protein content of 18.20%, gaining an increase in 21.20% and 199.10% over the control, respectively. The present study confirms the feasibility of feed additive production by Saccharomyces cerevisiae with CP and PHL and simultaneous optimization of flavonoid dissolution and protein content using a two-stage RSM. © 2016 International Union of Biochemistry and Molecular Biology, Inc.

Modeling spray/puddle dissolution processes for deep-ultraviolet acid-hardened resists

NASA Astrophysics Data System (ADS)

Hutchinson, John M.; Das, Siddhartha; Qian, Qi-De; Gaw, Henry T.

1993-10-01

A study of the dissolution behavior of acid-hardened resists (AHR) was undertaken for spray and spray/puddle development processes. The Site Services DSM-100 end-point detection system is used to measure both spray and puddle dissolution data for a commercially available deep-ultraviolet AHR resist, Shipley SNR-248. The DSM allows in situ measurement of dissolution rate on the wafer chuck and hence allows parameter extraction for modeling spray and puddle processes. The dissolution data for spray and puddle processes was collected across a range of exposure dose and postexposure bake temperature. The development recipe was varied to decouple the contribution of the spray and puddle modes to the overall dissolution characteristics. The mechanisms involved in spray versus puddle dissolution and the impact of spray versus puddle dissolution on process performance metrics has been investigated. We used the effective-dose-modeling approach and the measurement capability of the DSM-100 and developed a lumped parameter model for acid-hardened resists that incorporates the effects of exposure, postexposure bake temperature and time, and development condition. The PARMEX photoresist-modeling program is used to determine parameters for the spray and for the puddle process. The lumped parameter AHR model developed showed good agreement with experimental data.

Use of bicarbonate buffer systems for dissolution characterization of enteric-coated proton pump inhibitor tablets.

PubMed

Shibata, Hiroko; Yoshida, Hiroyuki; Izutsu, Ken-Ichi; Goda, Yukihiro

2016-04-01

The aim of this study was to assess the effects of buffer systems (bicarbonate or phosphate at different concentrations) on the in vitro dissolution profiles of commercially available enteric-coated tablets. In vitro dissolution tests were conducted using an USP apparatus II on 12 enteric-coated omeprazole and rabeprazole tablets, including innovator and generic formulations in phosphate buffers, bicarbonate buffers and a media modified Hanks (mHanks) buffer. Both omeprazole and rabeprazole tablets showed similar dissolution profiles among products in the compendial phosphate buffer system. However, there were large differences between products in dissolution lag time in mHanks buffer and bicarbonate buffers. All formulations showed longer dissolution lag times at lower concentrations of bicarbonate or phosphate buffers. The dissolution rank order of each formulation differed between mHanks buffer and bicarbonate buffers. A rabeprazole formulation coated with a methacrylic acid copolymer showed the shortest lag time in the high concentration bicarbonate buffer, suggesting varied responses depending on the coating layer and buffer components. Use of multiple dissolution media during in vitro testing, including high concentration bicarbonate buffer, would contribute to the efficient design of enteric-coated drug formulations. © 2016 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology.

Miniaturized INtrinsic DISsolution Screening (MINDISS) assay for preformulation.

PubMed

Alsenz, Jochem; Haenel, Elisabeth; Anedda, Aline; Du Castel, Pauline; Cirelli, Giorgio

2016-05-25

This study describes a novel Miniaturized INtrinsic DISsolution Screening (MINDISS) assay for measuring disk intrinsic dissolution rates (DIDR). In MINDISS, compacted mini disks of drugs (2-5mg/disk) are prepared in custom made holders with a surface area of 3mm(2). Disks are immersed, pellet side down, into 0.35ml of appropriate dissolution media per well in 96-well microtiter plates, media are stirred and disk-holders are transferred to new wells after defined periods of time. After filtration, drug concentration in dissolution media is quantified by Ultra Performance Liquid Chromatography (UPLC) and solid state property of the disk is characterized by Raman spectroscopy. MINDISS was identified as an easy-to-use tool for rapid, parallel determination of DIDR of compounds that requires only small amounts of compound and of dissolution medium. Results obtained with marketed drugs in MINDISS correlate well with large scale DIDR methods and indicate that MINDISS can be used for (1) rank-ordering of compounds by intrinsic dissolution in late phase discovery and early development, (2) comparison of polymorphic forms and salts, (3) screening and selection of appropriate dissolution media, and (4) characterization of the intestinal release behavior of compounds along the gastro intestinal tract by changing biorelevant media during experiments. Copyright © 2015 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.

[Key physical parameters of hawthorn leaf granules by stepwise regression analysis method].

PubMed

Jiang, Qie-Ying; Zeng, Rong-Gui; Li, Zhe; Luo, Juan; Zhao, Guo-Wei; Lv, Dan; Liao, Zheng-Gen

2017-05-01

The purpose of this study was to investigate the effect of key physical properties of hawthorn leaf granule on its dissolution behavior. Hawthorn leaves extract was utilized as a model drug. The extract was mixed with microcrystalline cellulose or starch with the same ratio by using different methods. Appropriate amount of lubricant and disintegrating agent was added into part of the mixed powder, and then the granules were prepared by using extrusion granulation and high shear granulation. The granules dissolution behavior was evaluated by using equilibrium dissolution quantity and dissolution rate constant of the hypericin as the indicators. Then the effect of physical properties on dissolution behavior was analyzed through the stepwise regression analysis method. The equilibrium dissolution quantity of hypericin and adsorption heat constant in hawthorn leaves were positively correlated with the monolayer adsorption capacity and negatively correlated with the moisture absorption rate constant. The dissolution rate constants were decreased with the increase of Hausner rate, monolayer adsorption capacity and adsorption heat constant, and were increased with the increase of Carr index and specific surface area. Adsorption heat constant, monolayer adsorption capacity, moisture absorption rate constant, Carr index and specific surface area were the key physical properties of hawthorn leaf granule to affect its dissolution behavior. Copyright© by the Chinese Pharmaceutical Association.

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.

Development of PVA based micro-porous polymer electrolyte by a novel preferential polymer dissolution process

NASA Astrophysics Data System (ADS)

Subramania, A.; Kalyana Sundaram, N. T.; Sukumar, N.

A micro-porous polymer electrolyte based on PVA was obtained from PVA-PVC based polymer blend film by a novel preferential polymer dissolution technique. The ionic conductivity of micro-porous polymer electrolyte increases with increase in the removal of PVC content. Finally, the effect of variation of lithium salt concentration is studied for micro-porous polymer electrolyte of high ionic conductivity composition. The ionic conductivity of the micro-porous polymer electrolyte is measured in the temperature range of 301-351 K. It is observed that a 2 M LiClO 4 solution of micro-porous polymer electrolyte has high ionic conductivity of 1.5055 × 10 -3 S cm -1 at ambient temperature. Complexation and surface morphology of the micro-porous polymer electrolytes are studied by X-ray diffraction and SEM analysis. TG/DTA analysis informs that the micro-porous polymer electrolyte is thermally stable upto 277.9 °C. Chronoamperommetry and linear sweep voltammetry studies were made to find out lithium transference number and stability of micro-porous polymer electrolyte membrane, respectively. Cyclic voltammetry study was performed for carbon/micro-porous polymer electrolyte/LiMn 2O 4 cell to reveal the compatibility and electrochemical stability between electrode materials.

Bioweathering of nontronite colloids in hybrid silica gel: implications for iron mobilization.

PubMed

Oulkadi, D; Balland-Bolou-Bi, C; Michot, L J; Grybos, M; Billard, P; Mustin, C; Banon, S

2014-02-01

This study aimed to study biotic iron dissolution using a new hybrid material constituted of well-dispersed mineral colloids in a silica gel matrix. This permitted to prevent adsorption of colloidal mineral particles on bacteria. Hybrid silica gel (HSG) permitted to study bioweathering mechanisms by diffusing molecules. Hybrid silica gel was synthesized through a classical sol-gel procedure in which mineral colloidal particles (NAu-2) were embedded in a porous silica matrix. Rahnella aquatilis RA1, isolated from a wheat rhizosphere was chosen for its ability to dissolve minerals by producing various organic acids and siderophores. Pyruvic, acetic and lactic acids were the major organic acids produced by R. aquatilis RA1 followed by oxalic and citric acids at the end of incubation. Comparison of abiotic and biotic experiments revealed a high efficiency of R. aquatilis RA1 for iron dissolution suggesting an optimized action of different ligands that solubilized or mobilized iron. Hybrid silica gel allowed focusing on the colloidal mineral weathering by metabolites diffusion without mineral adsorption on bacteria. Hybrid silica gels are new and efficient tools to study colloidal mineral bioweathering. Adjusting HSG porosity and hydrophobicity should permit to precise the influence of limiting diffusion of siderophores or aliphatic organic acids on mineral weathering. © 2013 The Society for Applied Microbiology.

Microbial- and thiosulfate-mediated dissolution of mercury sulfide minerals and transformation to gaseous mercury

DOE PAGES

Vázquez-Rodríguez, Adiari I.; Hansel, Colleen M.; Zhang, Tong; ...

2015-06-23

Mercury (Hg) is a toxic heavy metal that poses significant environmental and human health risks. Soils and sediments, where Hg can exist as the Hg sulfide mineral metacinnabar (β-HgS), represent major Hg reservoirs in aquatic environments. Metacinnabar has historically been considered a sink for Hg in all but severely acidic environments, and thus disregarded as a potential source of Hg back to aqueous or gaseous pools. In this study, we conducted a combination of field and laboratory incubations to identify the potential for metacinnabar as a source of dissolved Hg within near neutral pH environments and the underpinning (a)biotic mechanismsmore » at play. We show that the abundant and widespread sulfur-oxidizing bacteria of the genus Thiobacillus extensively colonized metacinnabar chips incubated within aerobic, near neutral pH creek sediments. Laboratory incubations of axenic Thiobacillus thioparus cultures led to the release of metacinnabar-hosted Hg(II) and subsequent volatilization to Hg(0). This dissolution and volatilization was greatly enhanced in the presence of thiosulfate, which served a dual role by enhancing HgS dissolution through Hg complexation and providing an additional metabolic substrate for Thiobacillus. These findings reveal a new coupled abiotic-biotic pathway for the transformation of metacinnabar-bound Hg(II) to Hg(0), while expanding the sulfide substrates available for neutrophilic chemosynthetic bacteria to Hg-laden sulfides. Lastly, they also point to mineral-hosted Hg as an underappreciated source of gaseous elemental Hg to the environment.« less

[Effects of post-harvest processing and extraction methods on polysaccharides content of Dendrobium officinale].

PubMed

Li, Cong; Ning, Li-Dan; Si, Jin-Ping; Wu, Ling-Shang; Liu, Jing-Jing; Song, Xian-Shui; Yu, Qiao-Xian

2013-02-01

To reveal the quality variation of polysaccharide in Dendrobium officinale by post-harvest processing and extraction methods, and provide a basis for post-harvest processing and clinical and hygienical applications of Tiepifengdou (Dendrobii Officinalis Caulis). The content of polysaccharides were studied by 4 post-harvest processing methods, i. e. drying by drying closet, drying after scalding by boiling water, drying while twisting, and drying while twisting after scalding by boiling water. And a series of temperatures were set in each processing procedure. An orthogonal test L9 (3(4)) with crushed degrees, solid-liquid ratio, extraction time and extraction times as factors were designed to analyze the dissolution rate of polysaccharides in Tiepifengdou processed by drying while twisting at 80 degrees C. The content of polysaccharides was ranged from 26.59% to 32.70% in different samples processed by different processing methods, among which drying while twisting at 80 degrees C and 100 degrees C respectively were the best. Crushed degree was the most important influence on the dissolution rate of polysaccharides. The dissolution rate of polysaccharides was extremely low when the sample was boiled directly without crushing and sieving. Drying while twisting at 80 degrees C was the best post-harvest processing method, which can help to dry the fresh herbs and improve the accumulation of polysaccharides. Boiling the uncrushed Tiepifengdou for a long time as traditional method could not fully extract polysaccharides, while boiling the crushed Tiepifengdou can efficiently extract polysaccharides.

Physical solid-state properties and dissolution of sustained-release matrices of polyvinylacetate.

PubMed

Gonzalez Novoa, Gelsys Ananay; Heinämäki, Jyrki; Mirza, Sabir; Antikainen, Osmo; Colarte, Antonio Iraizoz; Paz, Alberto Suzarte; Yliruusi, Jouko

2005-02-01

Solid-state compatibility and in vitro dissolution of direct-compressed sustained-release matrices of polyvinylacetate (PVAc) and polyvinylpyrrolidone (PVP) containing ibuprofen as a model drug were studied. Polyvinylalcohol (PVA) was used as an alternative water-soluble polymer to PVP. Differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) were used for characterizing solid-state polymer-polymer and drug-polymer interactions. The mechanical treatment for preparing physical mixtures of polyvinyl polymers and the drug (i.e. simple blending or stressed cogrinding) was shown not to affect the physical state of the drug and the polymers. With the drug-polymer mixtures the endothermic effect due to drug melting was always evident, but a considerable modification of the melting point of the drug in physical binary mixtures (drug:PVP) was observed, suggesting some interaction between the two. On the other hand, the lack of a significant shift of the melting endothermic peak of the drug in physical tertiary drug-polymer mixtures revealed no evidence of solid-state interaction between the drug and the present polymers. Sustained-release dissolution profiles were achieved from the direct-compressed matrices made from powder mixtures of the drug and PVAc combined with PVP, and the proportion of PVAc in the mixture clearly altered the drug release profiles in vitro. The drug release from the present matrix systems is controlled by both diffusion of the drug through the hydrate matrix and the erosion of the matrix itself.

In Sickness and in Health? Physical Illness as a Risk Factor for Marital Dissolution in Later Life

PubMed Central

Karraker, Amelia; Latham, Kenzie

2016-01-01

The health consequences of marital dissolution are well-known, but little work has examined the impact of health on the risk of marital dissolution. In this study we use a sample of 2,701 marriages from the Health and Retirement Study (HRS; 1992–2010) to examine the role of serious physical illness onset (i.e., cancer, heart problems, lung disease, and/or stroke) in subsequent marital dissolution due to either divorce or widowhood. We use a series of discrete-time event history models with competing risks to estimate the impact of husband’s and wife’s physical illness onset on risk of divorce and widowhood. We find that only wife’s illness onset is associated with elevated risk of divorce, while either husband’s or wife’s illness onset is associated with elevated risk of widowhood. These findings suggest the importance of health as a determinant of marital dissolution in later life via both biological and gendered social pathways. PMID:26315504

Monte Carlo Simulations of the Dissolution of Borosilicate and Aluminoborosilicate Glasses in Dilute Aqueous Solutions

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

Kerisit, Sebastien N.; Pierce, Eric M.

The aim of this study was to provide atomic-level insights into the dissolution behavior of borosilicate and aluminoborosilicate glasses to complement and help interpret previous experimental work on the NeB glass series studied by Pierce et al. [Pierce E. M., Reed L. R., Shaw W. J., McGrail B. P., Icenhower J. P., Windisch C. F., Cordova E. A. and Broady J. (2010) Experimental determination of the effect of the ratio of B/Al on glass dissolution along the nepheline (NaAlSiO4) - Malinkoite (NaBSiO4) join. Geochim. Cosmochim. Acta 74, 2634-2654]. The composition of these glasses was 50 mol% SiO2 - 25 mol%more » Na2O - (25-x) mol% Al2O3 - x mol% B2O3, with x varying from 0 to 20 mol%. In the first part of this work, the different structural features of these glasses (e.g., presence of non-bridging oxygens, partition of boron between trigonal and tetrahedral bonding environments, and formation of boroxol rings), identified in the study of Pierce et al., were implemented in the Monte Carlo program. Their effects on the dissolution of borosilicate and aluminosilicate glasses were then evaluated individually and led to the following conclusions. (1) The dependence of the dissolution rate on the amount of non-bridging oxygens was found to be linear at all Si/B ratios and the accelerating effect of non-bridging oxygens was shown to increase with increasing Si/B ratio. (2) The formation of boroxol rings and of clusters of boroxol rings resulted in an increase of the dissolution rate at all Si/B ratios and, again, the extent of the rate increase was strongly dependent on the Si/B ratio. (3) For aluminosilicate glasses, the implementation of the aluminum avoidance rule was found to increase the rate of dissolution relative to that obtained for a random distribution. In the second part of this work, Monte Carlo simulations were performed to model the dissolution of the NeB glasses in dilute conditions. One of the conclusions that emerged from the study of Pierce et al. was that either the rupture of the Al-O bonds or that of the Si-O bonds was the rate-limiting step controlling the dissolution of the NeB glasses. The Monte Carlo simulations carried out in this work enabled us to refine this conclusion. Indeed, the simulations showed that, at low B/Al ratios, the rupture of both Al-O-Si and Si-O-Si linkages contributed to the dissolution rate whereas, at high B/Al ratios, the dissolution rate was independent of the rupture of Al-O-Si linkages and was controlled by S1 sites (silicon sites at the glass-water interface with one bond to nearest-neighbor sites) and dissolution via detachment of clusters.« less

Effect of clayey groundwater on the dissolution rate of SON68 simulated nuclear waste glass at 70 °C

NASA Astrophysics Data System (ADS)

De Echave, T.; Tribet, M.; Jollivet, P.; Marques, C.; Gin, S.; Jégou, C.

2018-05-01

To predict the long-term behavior of high-level radioactive waste glass, it is necessary to study aqueous dissolution of the glass matrix under geological repository conditions. The present article focuses on SON68 (an inactive surrogate of the R7T7 glass) glass alteration in synthetic clayey groundwater at 70 °C. Experiments in deionized water as reference were also performed in the same conditions. Results are in agreement with those of previous studies showing that magnesium present in the solution is responsible for higher glass alteration. This effect is transient and pH-dependent: Once all the magnesium is consumed, the glass alteration rate diminishes. Precipitation of magnesium silicate of the smectite group seems to be the main factor for the increased glass alteration. A pH threshold of 7.5-7.8 was found, above which precipitation of these magnesium silicates at 70 °C is possible. TEM observations reveal that magnesium silicates grow at the expense of the passivating gel, which partly dissolves, forming large pores which increase mass transfer between the reacting glass surface and the bulk solution.

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 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.

THE MINERALOGY OF PB SCALES IN DRINKING WATER DISTRIBUTION SYSTEMS AS REVEALED BY COMBINED XRD AND MICRO-RAMAN SPECTROSCOPY

EPA Science Inventory

Dissolving Pb from lead service lines and Pb-containing brasses and solders has become a major health issue for many water distribution systems. Knowledge of the mineralogy of scales in these pipes is key to modeling this dissolution. The traditional method of determining their ...

Mineral Dissolution and Secondary Precipitation on Quartz Sand in Simulated Hanford Tank Solutions Affecting Subsurface Porosity

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

Wang, Guohui; Um, Wooyong

2012-11-23

Highly alkaline nuclear waste solutions have been released from underground nuclear waste storage tanks and pipelines into the vadose zone at the U.S. Department of Energy’s Hanford Site in Washington, causing mineral dissolution and re-precipitation upon contact with subsurface sediments. High pH caustic NaNO3 solutions with and without dissolved Al were reacted with quartz sand through flow-through columns stepwise at 45, 51, and 89°C to simulate possible reactions between leaked nuclear waste solution and primary subsurface mineral. Upon reaction, Si was released from the dissolution of quartz sand, and nitrate-cancrinite [Na8Si6Al6O24(NO3)2] precipitated on the quartz surface as a secondary mineralmore » phase. Both steady-state dissolution and precipitation kinetics were quantified, and quartz dissolution apparent activation energy was determined. Mineral alteration through dissolution and precipitation processes results in pore volume and structure changes in the subsurface porous media. In this study, the column porosity increased up to 40.3% in the pure dissolution column when no dissolved Al was present in the leachate, whereas up to a 26.5% porosity decrease was found in columns where both dissolution and precipitation were observed because of the presence of Al in the input solution. The porosity change was also confirmed by calculation using the dissolution and precipitation rates and mineral volume changes.« less

Variation in Supersaturation and Phase Behavior of Ezetimibe Amorphous Solid Dispersions upon Dissolution in Different Biorelevant Media.

PubMed

Elkhabaz, Ahmed; Sarkar, Sreya; Dinh, Janny K; Simpson, Garth J; Taylor, Lynne S

2018-01-02

The delivery of poorly water-soluble drugs using amorphous solid dispersions (ASDs) has been widely acknowledged as a promising strategy for enhancing oral bioavailability. Upon dissolution, ASDs have accelerated dissolution rates and yield supersaturated solutions leading to higher apparent solubilities. Understanding the complex phase behavior of ASDs during dissolution is crucial for developing an effective formulation. Since the absorption of a lipophilic, high permeability drug is determined primarily by the intraluminal dissolution process and the final concentration achieved, there is a need for evaluation in biorelevant dissolution media that simulate both fasting and fed gastrointestinal states. In this study, using ezetimibe as a model drug, three different ASDs were prepared using poly(acrylic acid) (PAA), polyvinylpyrrolidone (PVP), and hydroxypropyl methylcellulose acetyl succinate (HPMC-AS). Dissolution of ASDs was carried out in sodium phosphate buffer, fed-state simulated intestinal fluid (FeSSIF), and Ensure Plus to evaluate the impact of different dissolution media on release profile, supersaturation, and phase behavior. The supersaturation level and crystallization kinetics varied among the dispersions and were found to be highly dependent on the medium employed. The presence of solubilizing additives in biorelevant media greatly affected the generation and stabilization of supersaturated solutions. Second harmonic generation microscopy was found to enable the detection of crystals in all media including the highly turbid Ensure Plus system. In conclusion, it is important to evaluate the impact of complex biorelevant media on the dissolution performance of ASDs to better design supersaturating formulations for oral delivery.

Feasibility of Using Gluconolactone, Trehalose and Hydroxy-Propyl Gamma Cyclodextrin to Enhance Bendroflumethiazide Dissolution Using Lyophilisation and Physical Mixing Techniques.

PubMed

Saleh, Ashraf; McGarry, Kenneth; Chaw, Cheng Shu; Elkordy, Amal Ali

2018-02-01

Hydrophobic drugs are facing a major challenge in dissolution rate enhancement and solubility in aqueous solutions; therefore, a variety of methods have been used to improve dissolution rate and/or solubility of bendroflumethiazide as a model hydrophobic drug. In this study, two main methods (physical mixing and lyophilisation) were used with gluconolactone, hydroxyl propyl γ-ccyclodextrin, and trehalose to explore this challenge. Bendroflumethiazide, practically insoluble in water, was mixed with one of the three excipients gluconolactone, hydroxyl propyl γ-cyclodextrin, and trehalose in three different ratios 1:1, 1:2, 1:5. To the best of our knowledge, the dissolution of the drug has not been previously enhanced by using either these methods or any of the used excipients. Samples containing drug and each of the excipients were characterized via dissolution testing, Fourier Transform infra-red spectroscopy, differential scanning calorimetry, and scanning electron microscopy. The used methods showed a significant enhancement in dug dissolution rate; physical mixing significantly, p < 0.05, increased the percentage of the drug released with time; for example, bendroflumethiazide dissolution in distilled water was improved from less than 20% to 99.79% within 90 min for physically mixed drug-cyclodextrin 1:5. The lyophilisation process was enhanced and the drug dissolution rate and the highest drug dissolution was achieved for (drug-gluconolactone 1:1) with 98.98% drug release within 90 min. the physical mixing and freeze drying processes significantly increased the percentage of drug release with time.

Revisiting the electrochemical impedance spectroscopy of magnesium with online inductively coupled plasma atomic emission spectroscopy.

PubMed

Shkirskiy, Viacheslav; King, Andrew D; Gharbi, Oumaïma; Volovitch, Polina; Scully, John R; Ogle, Kevin; Birbilis, Nick

2015-02-23

The electrochemical impedance of reactive metals such as magnesium is often complicated by an obvious inductive loop with decreasing frequency of the AC polarising signal. The characterisation and ensuing explanation of this phenomenon has been lacking in the literature to date, being either ignored or speculated. Herein, we couple electrochemical impedance spectroscopy (EIS) with online atomic emission spectroelectrochemistry (AESEC) to simultaneously measure Mg-ion concentration and electrochemical impedance spectra during Mg corrosion, in real time. It is revealed that Mg dissolution occurs via Mg(2+) , and that corrosion is activated, as measured by AC frequencies less than approximately 1 Hz approaching DC conditions. The result of this is a higher rate of Mg(2+) dissolution, as the voltage excitation becomes slow enough to enable all Mg(2+) -enabling processes to adjust in real time. The manifestation of this in EIS data is an inductive loop. The rationalisation of such EIS behaviour, as it relates to Mg, is revealed for the first time by using concurrent AESEC. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mechanistic Analysis of Cocrystal Dissolution as a Function of pH and Micellar Solubilization

PubMed Central

2016-01-01

The purpose of this work is to provide a mechanistic understanding of the dissolution behavior of cocrystals under the influence of ionization and micellar solubilization. Mass transport models were developed by applying Fick’s law of diffusion to dissolution with simultaneous chemical reactions in the hydrodynamic boundary layer adjacent to the dissolving cocrystal surface to predict the pH at the dissolving solid–liquid interface (i.e., interfacial pH) and the flux of cocrystals. To evaluate the predictive power of these models, dissolution studies of carbamazepine–saccharin (CBZ-SAC) and carbamazepine–salicylic acid (CBZ-SLC) cocrystals were performed at varied pH and surfactant concentrations above the critical stabilization concentration (CSC), where the cocrystals were thermodynamically stable. The findings in this work demonstrate that the pH dependent dissolution behavior of cocrystals with ionizable components is dependent on interfacial pH. This mass transport analysis demonstrates the importance of pH, cocrystal solubility, diffusivity, and micellar solubilization on the dissolution rates of cocrystals. PMID:26877267

Mechanistic Analysis of Cocrystal Dissolution as a Function of pH and Micellar Solubilization.

PubMed

Cao, Fengjuan; Amidon, Gordon L; Rodriguez-Hornedo, Nair; Amidon, Gregory E

2016-03-07

The purpose of this work is to provide a mechanistic understanding of the dissolution behavior of cocrystals under the influence of ionization and micellar solubilization. Mass transport models were developed by applying Fick's law of diffusion to dissolution with simultaneous chemical reactions in the hydrodynamic boundary layer adjacent to the dissolving cocrystal surface to predict the pH at the dissolving solid-liquid interface (i.e., interfacial pH) and the flux of cocrystals. To evaluate the predictive power of these models, dissolution studies of carbamazepine-saccharin (CBZ-SAC) and carbamazepine-salicylic acid (CBZ-SLC) cocrystals were performed at varied pH and surfactant concentrations above the critical stabilization concentration (CSC), where the cocrystals were thermodynamically stable. The findings in this work demonstrate that the pH dependent dissolution behavior of cocrystals with ionizable components is dependent on interfacial pH. This mass transport analysis demonstrates the importance of pH, cocrystal solubility, diffusivity, and micellar solubilization on the dissolution rates of cocrystals.

Developing dissolution testing methodologies for extended-release oral dosage forms with supersaturating properties. Case example: Solid dispersion matrix of indomethacin.

PubMed

Tajiri, Tomokazu; Morita, Shigeaki; Sakamoto, Ryosaku; Mimura, Hisahi; Ozaki, Yukihiro; Reppas, Christos; Kitamura, Satoshi

2015-07-25

The objective of this study was to develop an in vitro dissolution test method with discrimination ability for an extended-release solid dispersion matrix of a lipophilic drug using the United States Pharmacopeia (USP) Apparatus 4, flow-through cell apparatus. In the open-loop configuration, the sink condition was maintained by manipulating the flow rate of the dissolution medium. To evaluate the testing conditions, the drug release mechanism from an extended-release solid dispersion matrix containing hydrophobic and hydrophilic polymers was investigated. As the hydroxypropyl methylcellulose (HPMC) maintained concentrations of indomethacin higher than the solubility in a dissolution medium, the release of HPMC into the dissolution medium was also quantified using size-exclusion chromatography. We concluded that the USP Apparatus 4 is suitable for application to an in vitro dissolution method for orally administered extended-release solid dispersion matrix formulations containing poorly water-soluble drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Preparation of olanzapine and methyl-β-cyclodextrin complexes using a single-step, organic solvent-free supercritical fluid process: An approach to enhance the solubility and dissolution properties.

PubMed

Rudrangi, Shashi Ravi Suman; Trivedi, Vivek; Mitchell, John C; Wicks, Stephen Richard; Alexander, Bruce David

2015-10-15

The purpose of this study was to evaluate a single-step, organic solvent-free supercritical fluid process for the preparation of olanzapine-methyl-β-cyclodextrin complexes with an express goal to enhance the dissolution properties of olanzapine. The complexes were prepared by supercritical carbon dioxide processing, co-evaporation, freeze drying and physical mixing. The prepared complexes were then analysed by differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy, solubility and dissolution studies. Computational molecular docking studies were performed to study the formation of molecular inclusion complexation of olanzapine with methyl-β-cyclodextrin. All the binary mixtures of olanzapine with methyl-β-cyclodextrin, except physical mixture, exhibited a faster and greater extent of drug dissolution than the drug alone. Products obtained by the supercritical carbon dioxide processing method exhibited the highest apparent drug dissolution. The characterisation by different analytical techniques suggests complete complexation or amorphisation of olanzapine and methyl-β-cyclodextrin complexes prepared by supercritical carbon dioxide processing method. Therefore, organic solvent-free supercritical carbon dioxide processing method proved to be novel and efficient for the preparation of solid inclusion complexes of olanzapine with methyl-β-cyclodextrin. The preliminary data also suggests that the complexes of olanzapine with methyl-β-cyclodextrin will lead to better therapeutic efficacy due to better solubility and dissolution properties. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

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.

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.

Determination of the dissolution slowness surface by study of etched shapes I. Morphology of the dissolution slowness surface and theoretical etched shapes

NASA Astrophysics Data System (ADS)

Leblois, T.; Tellier, C. R.

1992-07-01

We propose a theoretical model for the anisotropic etching of crystals, in order to be applied in the micromachining. The originality of the model is due to the introduction of dissolution tensors to express the representative surface of the dissolution slowness. The knowledge of the equation of the slowness surface allows us to determine the trajectories of all the elements which compose the starting surface. It is then possible to construct the final etched shape by numerical simulation. Several examples are given in this paper which show that the final etched shapes are correlated to the extrema of the dissolution slowness. Since the slowness surface must be determined from experiments, emphasis is placed on difficulties encountered when we correlate theory to experiments. Nous avons modélisé le processus de dissolution anisotrope des cristaux en vue d'une application à la simulation des formes obtenues par photolithogravure chimique. La principale originalité de ce modèle tient à l'introduction de tenseurs de dissolution pour exprimer la surface représentative de la lenteur de dissolution. La connaissance de l'équation de la lenteur de dissolution permet de calculer les trajectoires des différents éléments constituant la surface de départ puis de reconstituer par simulation la forme dissoute. Les simulations démontrent que les formes limites des cristaux dissous sont corrélées aux extrema de la lenteur de dissolution. La détermination de la surface de la lenteur se faisant à partir de mesures expérimetales, nous nous sommes efforcés de montrer toutes les difficultés attachées à cette analyse.

Triticonazole enantiomers: Separation by supercritical fluid chromatography and the effect of the chromatographic conditions.

PubMed

He, Jianfeng; Fan, Jun; Yan, Yilun; Chen, Xiaodong; Wang, Tai; Zhang, Yaomou; Zhang, Weiguang

2016-11-01

Enantiomeric pairs of triticonazole have been successfully separated by supercritical fluid chromatography coupled with a tris(3,5-dimethylphenylcarbamoyl) cellulose-coated chiral stationary phase in this work. The effects of co-solvent, dissolution solvent, flow rate, backpressure, and column temperature have been studied in detail with respect to retention, selectivity, and resolution of triticonazole. As indicated, the co-solvents mostly affected the retention factors and resolution, due to the different molecular structure and polarity. In addition, the dissolution solvents, namely, chloromethanes and alcohols, have been also important for enantioseparation because of the different interaction with stationary phase. Higher flow rate and backpressure led to faster elution of the triticonazole molecules, and the change of column temperature showed slight effect on the resolution of triticonazole racemate. Moreover, a comparative separation experiment between supercritical fluid chromatography and high performance liquid chromatography revealed that chiral supercritical fluid chromatography gave the 3.5 times value of R s /t R2 than high performance liquid chromatography, which demonstrated that supercritical fluid chromatography had much higher separation efficiency. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A study of X100 pipeline steel passivation in mildly alkaline bicarbonate solutions using electrochemical impedance spectroscopy under potentiodynamic conditions and Mott-Schottky

NASA Astrophysics Data System (ADS)

Gadala, Ibrahim M.; Alfantazi, Akram

2015-12-01

The key steps involved in X100 pipeline steel passivation in bicarbonate-based simulated soil solutions from the pre-passive to transpassive potential regions have been analyzed here using a step-wise anodizing-electrochemical impedance spectroscopy (EIS) routine. Pre-passive steps involve parallel dissolution-adsorption in early stages followed by clear diffusion-adsorption control shortly before iron hydroxide formation. Aggressive NS4 chlorides/sulfate promote steel dissolution whilst inhibiting diffusion in pre-passive steps. Diffusive and adsorptive effects remain during iron hydroxide formation, but withdraw shortly thereafter during its removal and the development of the stable iron carbonate passive layer. Passive layer protectiveness is evaluated using EIS fitting, current density analysis, and correlations with semiconductive parameters, consistently revealing improved robustness in colder, bicarbonate-rich, chloride/sulfate-free conditions. Ferrous oxide formation at higher potentials results in markedly lower impedances with disordered behavior, and the involvement of the iron(III) valence state is observed in Mott-Schottky tests exclusively for 75 °C conditions.

Mechanistic modelling of drug release from a polymer matrix using magnetic resonance microimaging.

PubMed

Kaunisto, Erik; Tajarobi, Farhad; Abrahmsen-Alami, Susanna; Larsson, Anette; Nilsson, Bernt; Axelsson, Anders

2013-03-12

In this paper a new model describing drug release from a polymer matrix tablet is presented. The utilization of the model is described as a two step process where, initially, polymer parameters are obtained from a previously published pure polymer dissolution model. The results are then combined with drug parameters obtained from literature data in the new model to predict solvent and drug concentration profiles and polymer and drug release profiles. The modelling approach was applied to the case of a HPMC matrix highly loaded with mannitol (model drug). The results showed that the drug release rate can be successfully predicted, using the suggested modelling approach. However, the model was not able to accurately predict the polymer release profile, possibly due to the sparse amount of usable pure polymer dissolution data. In addition to the case study, a sensitivity analysis of model parameters relevant to drug release was performed. The analysis revealed important information that can be useful in the drug formulation process. Copyright © 2013 Elsevier B.V. All rights reserved.

Preparation of Spray-Dried Soy Isoflavone-Loaded Gelatin Microspheres for Enhancement of Dissolution: Formulation, Characterization and in Vitro Evaluation

PubMed Central

Panizzon, Gean Pier; Bueno, Fernanda Giacomini; Ueda-Nakamura, Tânia; Nakamura, Celso Vataru; Dias Filho, Benedito Prado

2014-01-01

The most bioactive soy isoflavones (SI), daidzein (DAI) and genistein (GEN) have poor water solubility, which reduces their bioavailability and health benefits and limits their use in industry. The goal of this study was to develop and characterize a new gelatin matrix to microencapsulate DAI and GEN from soy extract (SE) by spray drying, in order to obtain solid dispersions to overcome solubility problems and to allow controlled release. The influences of 1:2 (MP2) and 1:3 (MP3) SE/polymer ratios on the solid state, yield, morphology, encapsulation efficiency, particle size distribution, release kinetics and cumulative release were evaluated. Analyses showed integral microparticles and high drug content. MP3 and MP2 yield were 43.6% and 55.9%, respectively, with similar mean size (p > 0.05), respectively. X-ray diffraction revealed the amorphous solid state of SE. In vitro release tests showed that dissolution was drastically increased. The results indicated that SE microencapsulation might offer a good system to control SI release, as an alternative to improve bioavailability and industrial applications. PMID:25494200

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.

Biorelevant Dissolution Models for a Weak Base To Facilitate Formulation Development and Overcome Reduced Bioavailability Caused by Hypochlordyria or Achlorhydria.

PubMed

Kou, Dawen; Dwaraknath, Sudharsan; Fischer, Yannick; Nguyen, Daniel; Kim, Myeonghui; Yiu, Hiuwing; Patel, Preeti; Ng, Tania; Mao, Chen; Durk, Matthew; Chinn, Leslie; Winter, Helen; Wigman, Larry; Yehl, Peter

2017-10-02

In this study, two dissolution models were developed to achieve in vitro-in vivo relationship for immediate release formulations of Compound-A, a poorly soluble weak base with pH-dependent solubility and low bioavailability in hypochlorhydric and achlorhydric patients. The dissolution models were designed to approximate the hypo-/achlorhydric and normal fasted stomach conditions after a glass of water was ingested with the drug. The dissolution data from the two models were predictive of the relative in vivo bioavailability of various formulations under the same gastric condition, hypo-/achlorhydric or normal. Furthermore, the dissolution data were able to estimate the relative performance under hypo-/achlorhydric and normal fasted conditions for the same formulation. Together, these biorelevant dissolution models facilitated formulation development for Compound-A by identifying the right type and amount of key excipient to enhance bioavailability and mitigate the negative effect of hypo-/achlorhydria due to drug-drug interaction with acid-reducing agents. The dissolution models use readily available USP apparatus 2, and their broader utility can be evaluated on other BCS 2B compounds with reduced bioavailability caused by hypo-/achlorhydria.

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.

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

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.

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

[Efficient Pharmaceutical Formulation Designs and Their Development Using Mathematical and Statistical Analysis].

PubMed

Iwao, Yasunori

2015-01-01

With the aim of directly predicting the functionality and mechanism of pharmaceutical excipients, we investigated an analysis method based on available surface area (S(t)), which is the surface area of a drug in direct contact with the external solvent during dissolution. First, to study the effect of lubricant concentration on the dissolution rate of acetaminophen (APAP), the dissolution behaviors as well as the change over time in S(t) of APAP tablets were examined. In the dissolution tests, a retarded dissolution of APAP was not observed with new lubricant triglycerin full behenate (TR-FB), whereas magnesium stearate (Mg-St) retarded the dissolution. The S(t) profiles for APAP with Mg-St at>0.5% showed downward curvature indicating a gradual decrease in surface area over time. Conversely, with TR-FB, even when its concentration was increased, the S(t) profile for APAP had a maximum value. The differences between Mg-St and TR-FB could be explained by the differences in extensibility deriving from their morphology. Next, we evaluated the effect of disintegtant concentration using five disintegrants. When disintegrant was added to ethenzamide tablet formulation, an increase in the dissolution rate and S(t) dependent on disintegrant concentration was observed, according to the type of disintegrant. It was found that the water absorption ability of disintegrants had strong correlations with the parameters of S(t). Taken together, this study demonstrates that analysis of S(t) can directly provide useful information, especially about the functionality of pharmaceutical excipients.

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.

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

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.

Structure-solubility relationships in fluoride-containing phosphate based bioactive glasses

NASA Astrophysics Data System (ADS)

Shaharyar, Yaqoot

The dissolution of fluoride-containing bioactive glasses critically affects their biomedical applications. Most commercial fluoride-releasing bioactive glasses have been designed in the soda-lime-silica system. However, their relatively slow chemical dissolution and the adverse effect of fluoride on their bioactivity are stimulating the study of novel biodegradable materials with higher bioactivity, such as biodegradable phosphate-based bioactive glasses, which can be a viable alternative for applications where a fast release of active ions is sought. In order to design new biomaterials with controlled degradability and high bioactivity, it is essential to understand the connection between chemical composition, molecular structure, and solubility in physiological fluids.Accordingly, in this work we have combined the strengths of various experimental techniques with Molecular Dynamics (MD) simulations, to elucidate the impact of fluoride ions on the structure and chemical dissolution of bioactive phosphate glasses in the system: 10Na2O - (45-x) CaO - 45P2O5 - xCaF2, where x varies between 0 -- 10 mol.%. NMR and MD data reveal that the medium-range atomic-scale structure of thse glasses is dominated by Q2 phosphate units followed by Q1 units, and the MD simulations further show that fluoride tends to associate with network modifier cations to form alkali/alkaline-earth rich ionic aggregates. On a macroscopic scale, we find that incorporating fluoride in phosphate glasses does not affect the rate of apatite formation on the glass surface in simulated body fluid (SBF). However, fluoride has a marked favorable impact on the glass dissolution in deionized water. Similarly, fluoride incorporation in the glasses results in significant weight gain due to adsorption of water (in the form of OH ions). These macroscopic trends are discussed on the basis of the F effect on the atomistic structure of the glasses, such as the F-induced phosphate network re-polymerization, in a first attempt to establish composition-structure-property relationships for these biomaterials.

Controlling the Optical and Magnetic Properties of Nanostructured Cuprous Oxide Synthesized from Waste Electric Cables

NASA Astrophysics Data System (ADS)

Abdelbasir, S. M.; El-Sheikh, S. M.; Rashad, M. M.; Rayan, D. A.

2018-03-01

Cuprous oxide Cu2O nanopowders were purposefully synthesised from waste electric cables (WECs) via a simple precipitation route at room temperature using lactose as a reducing agent. In this regard, dimethyl sulfoxide (DMSO) was first applied as an organic solvent for the dissolution of the cable insulating materials. Several parameters were investigated during dissolution of WECs such as dissolution temperature, time and solid/liquid ratio to determine the dissolution percentage of the insulating materials in DMSO. The morphology and the optical properties of the formed Cu2O particles were investigated using X-ray diffraction (XRD), field emission-scanning electron microscopy (FE-SEM), Fourier-transform infrared spectroscopy and UV-visible-near IR spectrophotometer. XRD data confirmed the presence of single crystalline phase of Cu2O nanoparticles. FE-SEM and TEM images revealed spherical, cubic and octahedral shapes with the various particle sizes ranged from 16 to 57 nm depending on the synthesis conditions. A possible mechanism explaining the Cu2O nanostructures formation was proposed. The band gap energies of the Cu2O nanostructures were estimated and the values were located between 1.5 and 2.08 eV. Photoluminescence spectroscopy analysis clearly showed a noticeably blue-shifted emission for the synthesized samples compared to spectrum of the bulk. Eventually, magnetic properties of the synthesized nanoparticles have been measured by vibrating sample magnetometer and the attained results implied that the synthesized particles are weakly ferromagnetic in nature at normal temperature.

Role of Water Sorption in Tablet Crushing Strength, Disintegration, and Dissolution.

PubMed

Sacchetti, M; Teerakapibal, R; Kim, K; Elder, E J

2017-08-01

Drugs formulated as tablets are subjected to accelerated stability conditions with the goal of identifying a stable formulation that will exhibit a sufficiently long shelf life. Water sorption at a condition such as 40°C/75% RH can result in significant changes in tablet properties such as a decrease in dissolution rate, the cause of which may be difficult to interpret, given the complex nature of ingredients and their interactions in a tablet. In this research, three drugs, displaying a wide range of physicochemical properties, were formulated with commonly used diluents, disintegrants, and binders, using a design of experiments approach. The tablets were stored at accelerated conditions and assessed for content, dissolution, disintegration, and crushing strength, as well as other properties. The research demonstrated many water-induced effects in tablet properties. Due to the experimental design approach that revealed many interactions, it was possible to interpret all of the changes observed in tablet crushing strength, disintegration, and dissolution for the drugs using a common set of physical principles. Specifically, the relevant factors considered were (1) mechanical properties of materials, (2) water sorption surface effects in surface diffusion and capillary condensation, (3) water sorption bulk effects for amorphous materials such as viscous flow/spreading, and (4) water-induced stress on interparticle bonding arising from volume expansion. These physical principles enable a comprehensive interpretation of the complex changes observed in tablet properties, which should be valuable in the design of tablet formulations that will be stable to accelerated storage conditions.

Natural versus human control on subsurface salt dissolution and development of thousands of sinkholes along the Dead Sea coast

NASA Astrophysics Data System (ADS)

Abelson, Meir; Yechieli, Yoseph; Baer, Gidon; Lapid, Gil; Behar, Nicole; Calvo, Ran; Rosensaft, Marcelo

2017-06-01

One of the most hazardous results of the human-induced Dead Sea (DS) shrinkage is the formation of more than 6000 sinkholes over the last 25 years. The DS shrinkage caused eastward retreat of underground brine replaced by fresh groundwater, which in turn dissolved a subsurface salt layer, to generate cavities and collapse sinkholes. The areal growth rate of sinkhole clusters is considered the most pertinent proxy for sinkholes development. Analysis of light detection and ranging, digital elevation models, and interferometric synthetic aperture radar allows translation of the areal growth rate to a salt dissolution rate of the salt layer, revealing two peaks in the history of the salt dissolution rate. These peaks cannot be attributed to the decline of the DS level. Instead, we show that they are related to long-term variations of precipitation in the groundwater source region, the Judea Mountains, and the delayed response of the aquifer system between the mountains and the DS rift. This response is documented by groundwater levels and salinity variations. We thus conclude that while the DS level decline is the major trigger for sinkholes formation, the rainfall variations more than 30 km to the west dominate their evolution rate. The influence of increasing rainfall in the Judea Mountains reaches the DS at a typical time lag of 4 years, and the resulting increase in the salt dissolution rate lags by a total time of 5-6 years.

Evolution of a mini-scale biphasic dissolution model: Impact of model parameters on partitioning of dissolved API and modelling of in vivo-relevant kinetics.

PubMed

Locher, Kathrin; Borghardt, Jens M; Frank, Kerstin J; Kloft, Charlotte; Wagner, Karl G

2016-08-01

Biphasic dissolution models are proposed to have good predictive power for the in vivo absorption. The aim of this study was to improve our previously introduced mini-scale dissolution model to mimic in vivo situations more realistically and to increase the robustness of the experimental model. Six dissolved APIs (BCS II) were tested applying the improved mini-scale biphasic dissolution model (miBIdi-pH-II). The influence of experimental model parameters including various excipients, API concentrations, dual paddle and its rotation speed was investigated. The kinetics in the biphasic model was described applying a one- and four-compartment pharmacokinetic (PK) model. The improved biphasic dissolution model was robust related to differing APIs and excipient concentrations. The dual paddle guaranteed homogenous mixing in both phases; the optimal rotation speed was 25 and 75rpm for the aqueous and the octanol phase, respectively. A one-compartment PK model adequately characterised the data of fully dissolved APIs. A four-compartment PK model best quantified dissolution, precipitation, and partitioning also of undissolved amounts due to realistic pH profiles. The improved dissolution model is a powerful tool for investigating the interplay between dissolution, precipitation and partitioning of various poorly soluble APIs (BCS II). In vivo-relevant PK parameters could be estimated applying respective PK models. Copyright © 2016 Elsevier B.V. All rights reserved.

Solid-state characterization and dissolution properties of meloxicam-moringa coagulant-PVP ternary solid dispersions.

PubMed

Noolkar, Suhail B; Jadhav, Namdeo R; Bhende, Santosh A; Killedar, Suresh G

2013-06-01

The effect of ternary solid dispersions of poor water-soluble NSAID meloxicam with moringa coagulant (obtained by salt extraction of moringa seeds) and polyvinylpyrrolidone on the in vitro dissolution properties has been investigated. Binary (meloxicam-moringa and meloxicam-polyvinylpyrrolidone (PVP)) and ternary (meloxicam-moringa-PVP) systems were prepared by physical kneading and ball milling and characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffractometry. The in vitro dissolution behavior of meloxicam from the different products was evaluated by means of United States Pharmacopeia type II dissolution apparatus. The results of solid-state studies indicated the presence of strong interactions between meloxicam, moringa, and PVP which were of totally amorphous nature. All ternary combinations were significantly more effective than the corresponding binary systems in improving the dissolution rate of meloxicam. The best performance in this respect was given by the ternary combination employing meloxicam-moringa-PVP ratio of [1:(3:1)] prepared by ball milling, with about six times increase in percent dissolution rate, whereas meloxicam-moringa (1:3) and meloxicam-PVP (1:4) prepared by ball milling improved dissolution of meloxicam by almost 3- and 2.5-folds, respectively. The achieved excellent dissolution enhancement of meloxicam in the ternary systems was attributed to the combined effects of impartation of hydrophilic characteristic by PVP, as well as to the synergistic interaction between moringa and PVP.

Effect of particle size on solubility, dissolution rate, and oral bioavailability: evaluation using coenzyme Q10 as naked nanocrystals

PubMed Central

Sun, Jiao; Wang, Fan; Sui, Yue; She, Zhennan; Zhai, Wenjun; Wang, Chunling; Deng, Yihui

2012-01-01

In this paper work, four naked nanocrystals (size range 80–700 nm) were prepared without any surfactant or polymer using the solvent/nonsolvent method. The effects of particle size on their solubility, dissolution, and oral bioavailability were investigated. Solubility and dissolution testing were performed in three types of dissolution medium, and the studies demonstrated that the equilibrium solubilities of coenzyme Q10 nanocrystals and bulk drugs were not affected by the dissolution media but the kinetic solubilities were. Kinetic solubility curves and changes in particle size distribution were determined and well explained by the proposed solubilization model for the nanocrystals and bulk drugs. The particle size effect on dissolution was clearly influenced by the diffusion coefficients of the various dissolution media, and the dissolution velocity of coenzyme Q10 increased as particle size decreased. The bioavailability of coenzyme Q10 after oral administration in beagle dogs was improved by reducing the particle size. For 700 nm nanocrystals, the AUC0–48 was 4.4-fold greater than that for the coarse suspensions, but a further decrease in particle size from 700 nm to 120 nm did not contribute to improvement in bioavailability until the particle size was reduced to 80 nm, when bioavailability was increased by 7.3-fold. PMID:23166438

Atomic-scale imaging of the dissolution of NaCl islands by water at low temperature

NASA Astrophysics Data System (ADS)

Peng, Jinbo; Guo, Jing; Ma, Runze; Meng, Xiangzhi; Jiang, Ying

2017-03-01

The dissolution of sodium chloride (NaCl) in water is a frequently encountered process in our daily lives. While the NaCl dissolution process in liquid water has been extensively studied, whether and how the dissolution occurs below the freezing point is still not clear. Using a low-temperature scanning tunneling microscope (STM), here we were able to directly visualize the dissolution of Au-supported NaCl (0 0 1) bilayer islands by water at atomic level. We found that the single water molecule on the STM tip can assist the extraction of single Na+ from the NaCl surface even at 5 K, while leaving the Cl- intact. When covered with a full water monolayer, the NaCl islands started to dissolve from the step edges and also showed evidence of dissolution inside the terraces as the temperature was raised up to 145 K. At 155 K, the water molecules completely desorbed from the surface, which was accompanied with the decomposition and restructuring of the bilayer NaCl islands. Those results suggest that the dissolution of NaCl may occur well below the freezing point at the ice/NaCl interfaces and is mainly driven by the interaction between the water molecules and the Na+, which is in clear contrast with the NaCl dissolution in liquid water.

From Nm-Scale Measurements Of Mineral Dissolution Rate To Overall Dissolution Rate Laws: A Case Study Based On Diopside

NASA Astrophysics Data System (ADS)

Daval, D.; Saldi, G.; Hellmann, R.; Knauss, K.

2011-12-01

While we expect conventional reactive transport simulations to provide reliable estimations of the evolution of fluid-rock interactions over time scales of centuries and even more, recent experimental studies showed that they could hardly be satisfactorily used on simplified systems (e.g. batch carbonation experiments on single minerals), on time scales of weeks [1]. Among the reasons for such inconsistencies is the nature of the rate laws used in the geochemical codes, which heavily relies on our description of the fundamental mechanisms involved during water(-CO2)-mineral reactions. Silicate dissolution constitutes a key step of GCS processes. Whereas the dissolution rate of silicate minerals has been extensively studied at far-from-equilibrium conditions, extrapolating such rates over a broad range of solution composition relevant for GCS has proven challenging. Regarding diopside, recent studies [2, 3] suggested that below 125 °C, an unexpected drop of the rate occurred for Gibbs free energies of reaction (ΔGr) as low as -76 kJ.mol-1, with severe consequences on our ability to predict the rate of complex processes such as carbonation reactions [3]. The mechanism responsible for such a drop remains unclear and therefore needs to be deciphered. An examination of our previous data [3] led us to envisage that two different, non-exclusive aspects were worth investigating: (i) the possible passivating ability of interfacial, nm-thick Si-rich layers developed on weathered silicate surface, and (ii) the stop of etch pits formation on crystal surface, each mechanism being found to be responsible for drops of olivine [1] and albite [4] dissolution rates, respectively. Our ongoing experiments aim at better constraining these two mechanisms, and determining in turn whether one of them could explain the above-mentioned drop of diopside dissolution rate. Classical flow-through experiments with controlled SiO2(aq) concentrations are combined with both ex situ AFM and VSI measurements and in situ monitoring of the topography of the dissolving surface of diopside in a hydrothermal AFM flow-cell (e.g. [5]). By investigating the dissolution of several cleavages, we will show how these latter techniques represent a powerful tool for studying the anisotropy of diopside dissolution, and determining which face ultimately controls its dissolution rate. An attempt to link these observations to macroscopic determination of diopside dissolution rates as a function of fluid composition will be discussed. [1] Daval et al. (2011) Chem. Geol., 284, 193-209. [2] Dixit & Carroll (2007) Geochem. T, 8, 1-14. [3] Daval et al. (2010) Geochim. Cosmochim. Ac., 74, 2615-2633. [4] Arvidson & Luttge (2010) Chem. Geol., 269, 79-88. [5] Saldi et al. (2009) Geochim. Cosmochim. Ac., 73, 5646-5657.

Solution-processing of chalcogenide materials for device applications

NASA Astrophysics Data System (ADS)

Zha, Yunlai

Chalcogenide glasses are well-known for their desirable optical properties, which have enabled many infrared applications in the fields of photonics, medicine, environmental sensing and security. Conventional deposition methods such as thermal evaporation, chemical vapor deposition, sputtering or pulse laser deposition are efficient for fabricating structures on flat surfaces. However, they have limitations in deposition on curved surfaces, deposition of thick layers and component integration. In these cases, solution-based methods, which involve the dissolution of chalcogenide glasses and processing as a liquid, become a better choice for their flexibility. After proper treatment, the associated structures can have similar optical, chemical and physical properties to the bulk. This thesis presents an in-depth study of solution-processing chalcogenide glasses, starting from the "solution state" to the "film state" and the "structure state". Firstly, chalcogenide dissolution is studied to reveal the mechanisms at molecular level and build a foundation for material processing. Dissolution processes for various chalcogenide solvent pairs are reviewed and compared. Secondly, thermal processing, in the context of high temperature annealing, is explained along with the chemical and physical properties of the annealed films. Another focus is on nanopore formation in propylamine-processed arsenic sulfide films. Pore density changes with respect to annealing temperatures and durations are characterized. Base on a proposed vacancy coalescence theory, we have identified new dissolution strategies and achieved the breakthrough of pore-free film deposition. Thirdly, several solution methods developed along with the associated photonic structures are demonstrated. The first example is "spin-coating and lamination", which produces thick (over 10 mum) chalcogenide structures. Both homogeneous thick chalcogenide structures and heterogeneous layers of different chalcogenide glasses or metals can be fabricated. Second, "micro-molding in capillaries" (MIMIC) and "micro-transfer molding" (muTM) methods are introduced for fabricating waveguides on flat and curved surfaces. The flexibility of the solution process allows waveguides to be patterned, for the first time, on a curved surface. Third, "micro channel filling" is demonstrated to produce the lowest loss among solution-processed chalcogenide waveguides. These results contribute to the advancement of chalcogenide processing technologies and help move closer towards the ultimate goal of fabricating reliable IR sensors.

The Influence of Alumina Properties on its Dissolution in Smelting Electrolyte

NASA Astrophysics Data System (ADS)

Bagshaw, A. N.; Welch, B. J.

The dissolution of a wide range of commercially produced aluminas in modified cryolite bath was studied on a laboratory scale. Most of the aluminas were products of conventional refineries and smelter dry scrubbing systems; a few were produced in laboratory and pilot calciners, enabling greater flexibility in the calcination process and the final properties. The mode of alumina feeding and the size of addition approximated to the point feeder situation. Alpha-alumina content, B.E.T. surface area and median particle size had little impact on dissolution behaviour. The volatiles content, expressed as L.O.I., the morphology of the original hydrate and the mode of calcination had the most influence. Discrete intermediate oxide phases were identified in all samples; delta-alumina content impacted most on dissolution. The flow properties of an alumina affected its overall dissolution.

Breaking up Isn't Hard to Do: Exploring the Dissolution of Teachers' and School Leaders' Work-Related Ties

ERIC Educational Resources Information Center

Spillane, James P.; Shirrell, Matthew

2017-01-01

Purpose: School leaders are central to the development of work-related ties among school staff. Although prior work has examined the predictors of the presence of work-related ties, little is known about the breakup or dissolution of ties among school staff. This study examines the extent of tie dissolution among school staff, as well as both the…

X-ray reflectivity study of formation of multilayer porous anodic oxides of silicon.

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

Chu, Y.; Fenollosa, R.; Parkhutik, V.

1999-07-21

The paper reports data on the kinetics of anodic oxide films growth on silicon in aqueous solutions of phosphoric acids as well as a study of the morphology of the oxides grown in a special regime of the oscillating anodic potential. X-ray reflectivity measurements were performed on the samples of anodic oxides using an intense synchrotron radiation source. They have a multilayer structure as revealed by theoretical fitting of the reflectivity data. The oscillations of the anodic potential are explained in terms of synchronized oxidation/dissolution reactions at the silicon surface and accumulation of mechanic stress in the oxide film.

Dissolution of cholesterol gall stones using methyltertbutyl ether: a safe effective treatment.

PubMed Central

McNulty, J; Chua, A; Keating, J; Ah-Kion, S; Weir, D G; Keeling, P W

1991-01-01

Methyltertbutyl ether (MTBE) administered by percutaneous transhepatic catheter rapidly dissolves radiolucent cholesterol gall bladder stones. However, complete dissolution and clearance of non-cholesterol debris is essential to prevent recurrence. In this study we analysed 25 consecutive patients with reference to efficacy and recurrence based on the presence or absence of non-cholesterol stone fragments after dissolution. Placement of the catheter was successful in 24 patients, one patient requiring cholecystectomy for bile peritonitis. MTBE was infused and aspirated continuously, four to six cycles per minute, resulting in rapid stone dissolution (median six hours; range 4-23 hours for solitary stones and median seven hours, range 4-30 hours for multiple stones). In 18 patients who had complete dissolution, four (22%) had recurrent stones within six to 18 months. Five patients had residual debris which failed to clear completely despite bile acid treatment. One patient with an incomplete rim of calcium in a large stone did not respond to MTBE treatment. A further patient required cholecystectomy for symptomatic recurrence. There were no serious side effects observed. MTBE treatment is a rapid, safe, and effective treatment for patients who refuse surgery or who for medical reasons cannot undergo cholecystectomy. The results of this study confirm that complete dissolution of all fragments is essential and may prevent recurrence. Images Figure 2 PMID:1773965

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.

Dissolution of salt on the east flank of the Permian Basin in the southwestern U.S.A.

USGS Publications Warehouse

Johnson, K.S.

1981-01-01

Hydrogeologic studies prove that natural dissolution of bedded salt occurs at shallow depths in many parts of the Permian Basin of the southwestern U.S.A. This is especially well-documented on the east side of the basin in study areas on the Cimarron River and Elm Fork in western Oklahoma, and on the Red River in the southeastern part of the Texas Panhandle. Four requirements for salt dissolution are: (1) a deposit of salt; (2) a supply of water unsaturated with respect to NaCl; (3) an outlet for removal of brine; and (4) energy to cause water to flow through the system. The supply of fresh groundwater in the region is recharged through permeable rocks, alluvium, terrace deposits, karstic features and fractures. Groundwater dissolves salt at depths of 10-250 m, and the resulting brine moves laterally and upward under hydrostatic pressure through caverns, fractures in disrupted rock, and clastic or carbonate aquifers until it reaches the land surface, where it forms salt plains and salt springs. In many areas, salt dissolution produces a self-perpetuating cycle: dissolution causes cavern development, followed by collapse and subsidence of overlying rock; then the resulting disrupted rock has a greater vertical permeability that allows increased water percolation and additional salt dissolution. ?? 1981.

A method for phenomenological and chemical kinetics study of autocatalytic reactive dissolution by optical microscopy. The case of uranium dioxide dissolution in nitric acid media

NASA Astrophysics Data System (ADS)

Marc, Philippe; Magnaldo, Alastair; Godard, Jérémy; Schaer, Éric

2018-03-01

Dissolution is a milestone of the head-end of hydrometallurgical processes, as the stabilization rates of the chemical elements determine the process performance and hold-up. This study aims at better understanding the chemical and physico-chemical phenomena of uranium dioxide dissolution reactions in nitric acid media in the Purex process, which separates the reusable materials and the final wastes of the spent nuclear fuels. It has been documented that the attack of sintering-manufactured uranium dioxide solids occurs through preferential attack sites, which leads to the development of cracks in the solids. Optical microscopy observations show that in some cases, the development of these cracks leads to the solid cleavage. It is shown here that the dissolution of the detached fragments is much slower than the process of the complete cleavage of the solid, and occurs with no disturbing phenomena, like gas bubbling. This fact has motivated the measurement of dissolution kinetics using optical microscopy and image processing. By further discriminating between external resistance and chemical reaction, the "true" chemical kinetics of the reaction have been measured, and the highly autocatalytic nature of the reaction confirmed. Based on these results, the constants of the chemical reactions kinetic laws have also been evaluated.

Dissolution and Precipitation Behaviour during Continuous Heating of Al–Mg–Si Alloys in a Wide Range of Heating Rates

PubMed Central

Osten, Julia; Milkereit, Benjamin; Schick, Christoph; Kessler, Olaf

2015-01-01

In the present study, the dissolution and precipitation behaviour of four different aluminium alloys (EN AW-6005A, EN AW-6082, EN AW-6016, and EN AW-6181) in four different initial heat treatment conditions (T4, T6, overaged, and soft annealed) was investigated during heating in a wide dynamic range. Differential scanning calorimetry (DSC) was used to record heating curves between 20 and 600 °C. Heating rates were studied from 0.01 K/s to 5 K/s. We paid particular attention to control baseline stability, generating flat baselines and allowing accurate quantitative evaluation of the resulting DSC curves. As the heating rate increases, the individual dissolution and precipitation reactions shift to higher temperatures. The reactions during heating are significantly superimposed and partially run simultaneously. In addition, precipitation and dissolution reactions are increasingly suppressed as the heating rate increases, whereby exothermic precipitation reactions are suppressed earlier than endothermic dissolution reactions. Integrating the heating curves allowed the enthalpy levels of the different initial microstructural conditions to be quantified. Referring to time–temperature–austenitisation diagrams for steels, continuous heating dissolution diagrams for aluminium alloys were constructed to summarise the results in graphical form. These diagrams may support process optimisation in heat treatment shops.

Non-destructive prediction of enteric coating layer thickness and drug dissolution rate by near-infrared spectroscopy and X-ray computed tomography.

PubMed

Ariyasu, Aoi; Hattori, Yusuke; Otsuka, Makoto

2017-06-15

The coating layer thickness of enteric-coated tablets is a key factor that determines the drug dissolution rate from the tablet. Near-infrared spectroscopy (NIRS) enables non-destructive and quick measurement of the coating layer thickness, and thus allows the investigation of the relation between enteric coating layer thickness and drug dissolution rate. Two marketed products of aspirin enteric-coated tablets were used in this study, and the correlation between the predicted coating layer thickness and the obtained drug dissolution rate was investigated. Our results showed correlation for one product; the drug dissolution rate decreased with the increase in enteric coating layer thickness, whereas, there was no correlation for the other product. Additional examination of the distribution of coating layer thickness by X-ray computed tomography (CT) showed homogenous distribution of coating layer thickness for the former product, whereas the latter product exhibited heterogeneous distribution within the tablet, as well as inconsistent trend in the thickness distribution between the tablets. It was suggested that this heterogeneity and inconsistent trend in layer thickness distribution contributed to the absence of correlation between the layer thickness of the face and side regions of the tablets, which resulted in the loss of correlation between the coating layer thickness and drug dissolution rate. Therefore, the predictability of drug dissolution rate from enteric-coated tablets depended on the homogeneity of the coating layer thickness. In addition, the importance of micro analysis, X-ray CT in this study, was suggested even if the macro analysis, NIRS in this study, are finally applied for the measurement. Copyright © 2017 Elsevier B.V. All rights reserved.

[The in vitro dissolution of total composition of the tablet of rhizomes of Ligusticum chuanxiong components and in vitro-in vivo correlation by the method of area under the absorbance-wavelength curve].

PubMed

Lai, Hong-qiang; Hu, Yue; Li, Xiao-dong

2015-06-01

To discuss the availability of evaluation on the dissolution studies of the multicomponents in traditional Chinese medicine, the in vitro dissolution of total composition of the tablet of rhizomes of Ligusticum chuanxiong components and its correlation with the in vivo were studied by the method of area under the absorbance-wavelength curve (AUAWC). Taken the tablet of rhizomes of Ligusticum chuanxiong components which is composed of sodium ferulate and ligustrazine hydrochloride as subject model, the dissolution tests were carried out with basket method. The plasma concentrations of tablets in different rats were determined by AUAWC at different interval times. The in vivo absorption percentage was calculated by Wagner-Nelson equation to evaluate the in vitro and in vivo correlation. According to the results, the cumulative dissolution in vitro of total composition of tablets of rhizomes of Ligusticum chuanxiong components at 60 min was 90.65% in water by AUAWC. The in vivo pharmacokinetics is fitted with an one-compartment model. The linear equation based on the cumulative dissolution rate (fr) and absorption percentage (fa) at 5, 10, 20, 30 and 60 min was fa = 0.819 7 fr+0.183 and the correlation coefficient was 0.959 5, which showed a good correlation between the in vitro dissolution and the in vivo absorption percentage. The method of AUAWC can be used accurately, feasibly and conveniently to evaluate the in vitro and in vivo correlation of total composition of tablets of rhizomes of Ligusticum chuanxiong components, which will provide better guidance to study the in vitro and in vivo correlation of sustained release preparation etc under complex system of traditional Chinese medicine in the future.

Dissolution and dissolution/permeation experiments for predicting systemic exposure following oral administration of the BCS class II drug clarithromycin.

PubMed

Kristin, Forner; René, Holm; Boontida, Morakul; Buraphacheep, Junyaprasert Varaporn; Maximilian, Ackermann; Johanna, Mazur; Peter, Langguth

2017-04-01

In order to save time and resources in early drug development, in vitro methods that correctly predict the formulation effect on oral drug absorption are necessary. The aim of this study was to 1) evaluate various BCS class II drug formulations with in vitro methods and in vivo in order to 2) determine which in vitro method best correlates with the in vivo results. Clarithromycin served as model compound in formulations with different particle sizes and content of excipients. The performed in vitro experiments were dissolution and dissolution/permeation experiments across two types of membrane, Caco-2 cells and excised rat intestinal sheets. The in vivo study was performed in rats. The oral absorption was enhanced by downsizing drug particles and by increasing the excipient concentration. This correlated strongly with the flux across Caco-2 cells but not with the other in vitro experiments. The insufficient correlation with the dissolution experiments can be partly explained by excipient caused problems during the filtration step. The very poor correlation of the in vivo data with the flux across excised rat intestinal sheets might be due to an artificially enlarged mucus layer ex vivo. In conclusion, downsizing BCS class II drug particles and the addition of surfactants enhanced the in vivo absorption, which was best depicted by dissolution/permeation experiments across Caco-2 cells. This setup is proposed as best model to predict the in vivo formulation effect. Also, this is the first study to evaluate the impact of the nature of the permeation membrane in dissolution/permeation experiments. Copyright © 2017 Elsevier B.V. All rights reserved.

Enhancement of dissolution and oral bioavailability of lacidipine via pluronic P123/F127 mixed polymeric micelles: formulation, optimization using central composite design and in vivo bioavailability study.

PubMed

Fares, Ahmed R; ElMeshad, Aliaa N; Kassem, Mohamed A A

2018-11-01

This study aims at preparing and optimizing lacidipine (LCDP) polymeric micelles using thin film hydration technique in order to overcome LCDP solubility-limited oral bioavailability. A two-factor three-level central composite face-centered design (CCFD) was employed to optimize the formulation variables to obtain LCDP polymeric micelles of high entrapment efficiency and small and uniform particle size (PS). Formulation variables were: Pluronic to drug ratio (A) and Pluronic P123 percentage (B). LCDP polymeric micelles were assessed for entrapment efficiency (EE%), PS and polydispersity index (PDI). The formula with the highest desirability (0.959) was chosen as the optimized formula. The values of the formulation variables (A and B) in the optimized polymeric micelles formula were 45% and 80%, respectively. Optimum LCDP polymeric micelles had entrapment efficiency of 99.23%, PS of 21.08 nm and PDI of 0.11. Optimum LCDP polymeric micelles formula was physically characterized using transmission electron microscopy. LCDP polymeric micelles showed saturation solubility approximately 450 times that of raw LCDP in addition to significantly enhanced dissolution rate. Bioavailability study of optimum LCDP polymeric micelles formula in rabbits revealed a 6.85-fold increase in LCDP bioavailability compared to LCDP oral suspension.

Product Development Studies on Sonocrystallized Curcumin for the Treatment of Gastric Cancer

PubMed Central

Ashif Khan, Mohammad; Akhtar, Nida; Sharma, Vijay; Pathak, Kamla

2015-01-01

Curcumin suffers from the limitation of poor solubility and low dissolution that can lead to limited applications. The investigation was aimed to substantiate the potentiality of melt sonocrystallized gastroretentive tablets of curcumin. Melt sonocrystallized curcumin (MSC CMN) was developed and its therapeutic potential was validated by in vitro cytotoxicity studies against Human oral cancer cell line KB. MSC curcumin was then formulated as floating tablet and evaluated. MSC form of CMN exhibited 2.36-fold and 2.40-fold solubility enhancement in distilled water and phosphate buffer, pH 4.5, respectively, better flow properties and intrinsic dissolution rate (0.242 ± 1.42 and 0.195 ± 1.26 mg/cm2/min) in comparison to its original form. The GI50 value of MSC CMN was found to be less than 10, specifying inhibition of growth more effectively at its least concentration by 50%. The gastroretentive-floating tablet (Formulation F4) displayed controlled drug release (96.22% ± 1.43%) for over 12 h. The present study revealed melt sonocrystallization can be used to produce particles with superior biopharmaceutical properties without the use of organic solvents or the addition of other excipients, and amenable to formulation in to a pharmaceutical dosage form. PMID:25923809

Product development studies on sonocrystallized curcumin for the treatment of gastric cancer.

PubMed

Khan, Mohammad Ashif; Akhtar, Nida; Sharma, Vijay; Pathak, Kamla

2015-04-27

Curcumin suffers from the limitation of poor solubility and low dissolution that can lead to limited applications. The investigation was aimed to substantiate the potentiality of melt sonocrystallized gastroretentive tablets of curcumin. Melt sonocrystallized curcumin (MSC CMN) was developed and its therapeutic potential was validated by in vitro cytotoxicity studies against Human oral cancer cell line KB. MSC curcumin was then formulated as floating tablet and evaluated. MSC form of CMN exhibited 2.36-fold and 2.40-fold solubility enhancement in distilled water and phosphate buffer, pH 4.5, respectively, better flow properties and intrinsic dissolution rate (0.242 ± 1.42 and 0.195 ± 1.26 mg/cm2/min) in comparison to its original form. The GI50 value of MSC CMN was found to be less than 10, specifying inhibition of growth more effectively at its least concentration by 50%. The gastroretentive-floating tablet (Formulation F4) displayed controlled drug release (96.22% ± 1.43%) for over 12 h. The present study revealed melt sonocrystallization can be used to produce particles with superior biopharmaceutical properties without the use of organic solvents or the addition of other excipients, and amenable to formulation in to a pharmaceutical dosage form.

Host-guest complexes of 2-hydroxypropyl-β-cyclodextrin/β-cyclodextrin and nifedipine: 1H NMR, molecular modeling, and dissolution studies

NASA Astrophysics Data System (ADS)

de Araújo, Márcia Valéria Gaspar; Vieira, João Victor Francisco; da Silva, Caroline W. P.; Barison, Andersson; Andrade, George Ricardo Santana; da Costa, Nivan Bezerra; Barboza, Fernanda Malaquias; Nadal, Jessica Mendes; Novatski, Andressa; Farago, Paulo Vitor; Zawadzki, Sônia Faria

2017-12-01

Nifedipine (NIF) is a hydrophobic drug widely used for treating cardiovascular diseases. This calcium channel blocker can present a higher apparent solubility by its inclusion into different cyclodextrins (CDs) as host-guest complexes. This paper focused on the structural investigation and dissolution behavior of inclusion complexes prepared with 2-hydroxypropyl-β-cyclodextrin (HPβCD) or β-cyclodextrin (βCD) and NIF. Drug amorphization was observed for HPβCD/NIF and βCD/NIF inclusion complexes by X-ray diffractometry (XRD). The sharp endothermic peak of NIF was not observed for these both host-guest complexes by differential scanning calorimetry (DSC). These results of XRD and DSC provide evidences of complexation between drug and the investigated CDs. 1H and saturation transfer difference nuclear magnetic resonance studies revealed the enhancement in the signal at 2.27 ppm for HPβCD/NIF and βCD/NIF inclusion complexes that corresponded to the methyl groups of NIF from the non-aromatic ring. This result suggested that non-aromatic ring of NIF was inserted into HPβCD and βCD cavities. Considering the mathematical simulations, it was observed that the inclusion process can occur in the both NH-in or NH-out forms. However, since it was used aqueous medium, it is possible to indicate that the obtained host-guest complexes HPβCD/NIF and βCD/NIF are in NH-in form which corresponded to the previous results obtained by 1H NMR experiments. Dissolution assays demonstrated that NIF inclusion complexes improved the drug release nevertheless without changing its biexponential release behavior. These host-guest complexes can be further used as feasible NIF carriers in solid dosage forms.

Dissolution mechanism of aluminum hydroxides in acid media

NASA Astrophysics Data System (ADS)

Lainer, Yu. A.; Gorichev, I. G.; Tuzhilin, A. S.; Gololobova, E. G.

2008-08-01

The effects of the concentration, temperature, and potential at the hydroxide/electrolyte interface on the aluminum hydroxide dissolution in sulfuric, hydrochloric, and perchloric acids are studied. The limiting stage of the aluminum hydroxide dissolution in the acids is found to be the transition of the complexes that form on the aluminum hydroxide surface from the solid phase into the solution. The results of the calculation of the acid-base equilibrium constants at the oxide (hydroxide)/solution interface using the experimental data on the potentiometric titration of Al2O3 and AlOOH suspensions are analyzed. A mechanism is proposed for the dissolution of aluminum hydroxides in acid media.

Difference in the Dissolution Behaviors of Tablets Containing Polyvinylpolypyrrolidone (PVPP) Depending on Pharmaceutical Formulation After Storage Under High Temperature and Humid Conditions.

PubMed

Takekuma, Yoh; Ishizaka, Haruka; Sumi, Masato; Sato, Yuki; Sugawara, Mitsuru

Storage under high temperature and humid conditions has been reported to decrease the dissolution rate for some kinds of tablets containing polyvinylpolypyrrolidone (PVPP) as a disintegrant. The aim of this study was to elucidate the properties of pharmaceutical formulations with PVPP that cause a decrease in the dissolution rate after storage under high temperature and humid conditions by using model tablets with a simple composition. Model tablets, which consisted of rosuvastatin calcium or 5 simple structure compounds, salicylic acid, 2-aminodiphenylmethane, 2-aminobiphenyl, 2-(p-tolyl)benzoic acid or 4.4'-biphenol as principal agents, cellulose, lactose hydrate, PVPP and magnesium stearate as additives, were made by direct compression. The model tables were wrapped in paraffin papers and stored for 2 weeks at 40°C/75% relative humidity (RH). Dissolution tests were carried out by the paddle method in the Japanese Pharmacopoeia 16th edition. Model tablets with a simple composition were able to reproduce a decreased dissolution rate after storage at 40°C/75% RH. These tablets showed significantly decreased water absorption activities after storage. In the case of tablets without lactose hydrate by replacing with cellulose, a decreased dissolution rate was not observed. Carboxyl and amino groups in the structure of the principal agent were not directly involved in the decreased dissolution. 2-Benzylaniline tablets showed a remarkably decreased dissolution rate and 2-aminobiphenyl and 2-(p-tolyl)benzoic acid tablets showed slightly decreased dissolution rates, though 4,4'-biphenol tablets did not show a decrease dissolution rate. We demonstrated that additives and structure of the principal agent were involved in the decreased in dissolution rate for tablets with PVPP. The results suggested that one of the reasons for a decreased dissolution rate was the inclusion of lactose hydrate in tablets. The results also indicated that compounds as principal agents with low affinity for PVPP may be easily affected by airborne water under high temperature and humid conditions. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

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

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.

Materials and fabrication sequences for water soluble silicon integrated circuits at the 90 nm node

NASA Astrophysics Data System (ADS)

Yin, Lan; Bozler, Carl; Harburg, Daniel V.; Omenetto, Fiorenzo; Rogers, John A.

2015-01-01

Tungsten interconnects in silicon integrated circuits built at the 90 nm node with releasable configurations on silicon on insulator wafers serve as the basis for advanced forms of water-soluble electronics. These physically transient systems have potential uses in applications that range from temporary biomedical implants to zero-waste environmental sensors. Systematic experimental studies and modeling efforts reveal essential aspects of electrical performance in field effect transistors and complementary ring oscillators with as many as 499 stages. Accelerated tests reveal timescales for dissolution of the various constituent materials, including tungsten, silicon, and silicon dioxide. The results demonstrate that silicon complementary metal-oxide-semiconductor circuits formed with tungsten interconnects in foundry-compatible fabrication processes can serve as a path to high performance, mass-produced transient electronic systems.

MRI studies of the hydrodynamics in a USP 4 dissolution testing cell.

PubMed

Shiko, G; Gladden, L F; Sederman, A J; Connolly, P C; Butler, J M

2011-03-01

We present a detailed study of hydrodynamics inside the flow-through dissolution apparatus when operated according to USP recommendations. The pulsatile flow inside the flow-through cell was measured quantitatively using magnetic resonance imaging (MRI) at a spatial resolution of 234 × 234 μm(2) and slice thickness of 1 mm. We report the experimental protocols developed for in situ MRI studies and the effect that the operating conditions and tablet orientation have on the hydrodynamics inside commercial flow cells. It was found that the flow field inside the dissolution cells was, at most operating conditions, heterogeneous, rather than fully developed laminar flow, and characterised by re-circulation and backward flow. A model tablet was shown to be contacted by a wide distribution of local velocities as a function of position and orientation in the flow cell. The use of 1 mm beads acted as a distributor of the flow but did not suffice to ensure a fully developed laminar flow profile. These results emphasise the necessity to understand the influence of test conditions on dissolution behaviour in defining robust flow-through dissolution methods. Copyright © 2010 Wiley-Liss, Inc.

Development and validation of a discriminative dissolution test for nimesulide suspensions.

PubMed

da Fonseca, Laís Bastos; Labastie, Márcio; de Sousa, Valéria Pereira; Volpato, Nadia Maria

2009-01-01

The dissolution test for oral dosage forms has recently widened to a variety of special dosage forms such as suspensions. For class II drugs, such as nimesulide (NMS), this study is very important because formulation problems may compromise drug bioavailability. In the present work, tests with four brands of commercially available NMS (RA, TS, TB, and TC) have been performed in order to study their dissolution at different conditions. The suspensions have been characterized relatively to particle size, pH, and density besides NMS assay and the amount of drug in solution in the suspension vehicles. The dissolution study was conducted using the following media: simulated intestinal fluid, pH 6.8, containing polysorbate 80 (P80) or sodium lauryl sulfate (SLS); phosphate buffer, pH 7.4, with P80 and aqueous solution of SLS. Concerning the quantitative analysis, the UV-VIS spectrophotometry could have been used in substitution to high-performance liquid chromatography since the methodology had been adequately validated. The influence of the drug particle size distribution was significant on the dissolution profiles of NMS formulations, confirming to be a factor that should be strictly controlled in the development of oral suspensions.

Effects of ranitidine (antacid), food, and formulation on the pharmacokinetics of fostamatinib: results from five phase I clinical studies.

PubMed

Flanagan, Talia; Martin, Paul; Gillen, Michael; Mathews, David; Lisbon, Eleanor; Kruusmägi, Martin

2017-02-01

Fostamatinib is an orally dosed phosphate prodrug that is cleaved by intestinal alkaline phosphatase to the active metabolite R406. Clinical studies were performed to assess the effect of food and ranitidine on exposure, to support in vitro-in vivo relationships (IVIVR) understanding and formulation transitions and to investigate absolute oral bioavailability. A series of in vitro dissolution and clinical pharmacokinetic studies were performed to support the design and introduction of a new formulation, understand the impact of changes in in vitro dissolution on in vivo performance for two fostamatinib formulations, to characterize the effects of food and ranitidine on exposure, and determine the absolute oral bioavailability. The in vivo performance of fostamatinib was generally insensitive to changes in in vitro dissolution performance, although marked slowing of the dissolution rate did impact exposures. Food and ranitidine had minor effects on R406 exposure that were not considered clinically relevant. The absolute oral bioavailability of fostamatinib was 54.6 %. The absolute oral bioavailability of fostamatinib was ~55 %. Food and ranitidine had minor effects on R406 exposure. An in vitro dissolution versus clinical performance relationship was determined that supported formulation transitions.

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.

Coupled dissolution-precipitation in natural monazite: effect of irradiation damage or fluid mediation?

NASA Astrophysics Data System (ADS)

Seydoux-Guillaume, Anne-Magali; Montel, Jean-Marc; de Parseval, Philippe; Bingen, Bernard; Janots, Emilie

2010-05-01

The LREE orthophosphate monazite is a common accessory mineral, important as a U-Th-Pb geochronometer in both metamorphic and magmatic rocks. In order to correctly interpret measured ages, it is essential to properly understand mechanisms that control them. Few studies have shown that coupled dissolution-crystallisation in the presence of a fluid phase is a mechanism incomparably more efficient that solid state diffusion to reset isotopic signature within monazite grains. It is known that dissolution-precipitation is efficiency enhanced by the presence of defects within crystals. Because of its high actinide contents (U and Th), monazite receives intense self-irradiation doses. In contrast to zircon (a silicate), monazite (a phosphate) is less sensitive to irradiation. Natural amorphous monazite has never been reported and the only proof that monazite lattice was destroyed by irradiation is shown by the presence of lattice distortion (strained lattice); this is because defect healing is more efficient than amorphization. The present study focuses on large (cm) single monazite crystals from five distinct localities in Norway, Madagascar, Srilanka, Zwaziland and Morefield. They have different chemical compositions, especially with regard to U, Th and Pb contents, and have ages ranging from ca. 500 to 1000 Ma. Nevertheless, all of them share the same petrographic features. Optical microscope and SEM images reveal variably intense fracturation. BSE imaging in the SEM indicates that monazite is composed of multiple phases: an unaltered monazite (Mnz1) + an altered monazite (Mnz2) associated with Th-rich phase (Thorium silicate or Thorium oxide) +/- Xenotime, depending on the initial composition of Mnz1. Analogous textures were already described by Seydoux-Guillaume et al. (2007) and Hetherington and Harlov (2008;). The alteration textures are always associated with radial cracks emanating from the high radioactive phase (Th-rich phase). The question addressed in the discussion is the role and the chronology of each process, i.e. irradiation vs coupled dissolution-precipitation. U-Th-Pb ages obtained by chemical dating on electron microprobe from altered and unaltered monazites show no significant differences. Therefore U-Pb dating using SIMS and LA-ICP-MS are in progress to determine precise isotopic age that would refine the alteration chronology. Finally, these results will be compared with experimental work, which are currently investigating the role of structural defects on coupled dissolution-precipitation in monazite. Hetherington and Harlov (2008). Am. Mineral., 93, 806-820. Seydoux-Guillaume et al. (2007). Eur. J. Mineral., 19, 7-14.

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.

Enhancing Pre-Service Elementary Teachers' Conceptual Understanding of Solution Chemistry with Conceptual Change Text

ERIC Educational Resources Information Center

Calik, Muammer; Ayas, Alipasa; Coll, Richard Kevin

2007-01-01

This paper reports on the use of a constructivist-based pedagogy to enhance understanding of some features of solution chemistry. Pre-service science teacher trainees' prior knowledge about the dissolution of salts and sugar in water were elicited by the use of a simple diagnostic tool. The test revealed widespread alternative conceptions. These…

Validating empirical force fields for molecular-level simulation of cellulose dissolution

USDA-ARS?s Scientific Manuscript database

The calculations presented here, which include dynamics simulations using analytical force fields and first principles studies, indicate that the COMPASS force field is preferred over the Dreiding and Universal force fields for studying dissolution of large cellulose structures. The validity of thes...

Effect of radiation-induced amorphization on smectite dissolution.

PubMed

Fourdrin, C; Allard, T; Monnet, I; Menguy, N; Benedetti, M; Calas, G

2010-04-01

Effects of radiation-induced amorphization of smectite were investigated using artificial irradiation. Beams of 925 MeV Xenon ions with radiation dose reaching 73 MGy were used to simulate the effects generated by alpha recoil nuclei or fission products in the context of high level nuclear waste repository. Amorphization was controlled by X-ray diffraction, transmission electron microscopy, and Fourier transform infrared spectroscopy. An important coalescence of the smectite sheets was observed which lead to a loss of interparticle porosity. The amorphization is revealed by a loss of long-range structure and accompanied by dehydroxylation. The dissolution rate far-from-equilibrium shows that the amount of silica in solution is two times larger in the amorphous sample than in the reference clay, a value which may be enhanced by orders of magnitude when considering the relative surface area of the samples. Irradiation-induced amorphization thus facilitates dissolution of the clay-derived material. This has to be taken into account for the safety assessment of high level nuclear waste repository, particularly in a scenario of leakage of the waste package which would deliver alpha emitters able to amorphize smectite after a limited period of time.

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

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 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.

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.

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.