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.

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.

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.

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

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.

Accelerated dissolution testing for controlled release microspheres using the flow-through dissolution apparatus.

PubMed

Collier, Jarrod W; Thakare, Mohan; Garner, Solomon T; Israel, Bridg'ette; Ahmed, Hisham; Granade, Saundra; Strong, Deborah L; Price, James C; Capomacchia, A C

2009-01-01

Theophylline controlled release capsules (THEO-24 CR) were used as a model system to evaluate accelerated dissolution tests for process and quality control and formulation development of controlled release formulations. Dissolution test acceleration was provided by increasing temperature, pH, flow rate, or adding surfactant. Electron microscope studies on the theophylline microspheres subsequent to each experiment showed that at pH values of 6.6 and 7.6 the microspheres remained intact, but at pH 8.6 they showed deterioration. As temperature was increased from 37-57 degrees C, no change in microsphere integrity was noted. Increased flow rate also showed no detrimental effect on integrity. The effect of increased temperature was determined to be the statistically significant variable.

Enhancing the bioavailability of mebendazole by integrating the principles solid dispersion and nanocrystal techniques, for safe and effective management of human echinococcosis.

PubMed

Chaudhary, Sushant; Garg, Tarun; Rath, Goutam; Murthy, Rs Rayasa; Goyal, Amit K

2016-05-01

The method based on integrating the principles of solid dispersion and nanocrystal techniques was developed to prepare polymer crystals (PCs) of mebendazole (MBZ) and polyethylene glycol (PEG). Powder X-Ray diffraction (PXRD) of the PC crystals shows the required integrated crystalline and amorphous regions. The in vitro solubility studies showed a 32-fold increase in the solubility of the drug. Tests of dissolution of the PCs showed that the crystals have an enhanced dissolution rate in comparison to those in the MF. The results of the pharmacokinetic study showed a 2.12-fold increase in the bioavailability of the drug. Thus, the present study has proved the potential in enhancing solubility, dissolution, and bioavailability of the drug.

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

Preformulation studies and optimization of sodium alginate based floating drug delivery system for eradication of Helicobacter pylori.

PubMed

Diós, Péter; Nagy, Sándor; Pál, Szilárd; Pernecker, Tivadar; Kocsis, Béla; Budán, Ferenc; Horváth, Ildikó; Szigeti, Krisztián; Bölcskei, Kata; Máthé, Domokos; Dévay, Attila

2015-10-01

The aim of this study was to design a local, floating, mucoadhesive drug delivery system containing metronidazole for Helicobacter pylori eradication. Face-centered central composite design (with three factors, in three levels) was used for evaluation and optimization of in vitro floating and dissolution studies. Sodium alginate (X1), low substituted hydroxypropyl cellulose (L-HPC B1, X2) and sodium bicarbonate (X3) concentrations were the independent variables in the development of effervescent floating tablets. All tablets showed acceptable physicochemical properties. Statistical analysis revealed that tablets with 5.00% sodium alginate, 38.63% L-HPC B1 and 8.45% sodium bicarbonate content showed promising in vitro floating and dissolution properties for further examinations. Optimized floating tablets expressed remarkable floating force. Their in vitro dissolution studies were compared with two commercially available non-floating metronidazole products and then microbiologically detected dissolution, ex vivo detachment force, rheological mucoadhesion studies and compatibility studies were carried out. Remarkable similarity (f1, f2) between in vitro spectrophotometrically and microbiologically detected dissolutions was found. Studies revealed significant ex vivo mucoadhesion of optimized tablets, which was considerably increased by L-HPC. In vivo X-ray CT studies of optimized tablets showed 8h gastroretention in rats represented by an animation prepared by special CT technique. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

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.

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

PubMed

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

2014-10-01

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

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.

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.

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.

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.

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.

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.

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.

Effect drug loading process on dissolution mechanism of encapsulated amoxicillin trihydrate in hydrogel semi-IPN chitosan methyl cellulose with pore forming agent KHCO3 as a floating drug delivery system

NASA Astrophysics Data System (ADS)

Fithawati, Garnis; Budianto, Emil

2018-04-01

Common treatment for Helicobacter pylori by repeated oral consumption of amoxicillin trihydrate is not effective. Amoxicillin trihydrate has a very short residence time in stomach which leads into its ineffectiveness. Residence time of amoxicillin trihydrate can be improved by encapsulating amoxicillin trihydrate into a floating drug delivery system. In this study, amoxicillin trihydrate is encapsulated into hydrogel semi-IPN chitosan methyl cellulose matrix as a floating drug delivery system and then treated with 20% KHCO3 as pore forming agent. Drug loading process used are in-situ loading and post loading. In-situ loading process has higher efficiency percentage and dissolution percentage than post loading process. In-situ loading process resulted 100% efficiency with 92,70% dissolution percentage. Post loading process resulted 98,7% efficiency with 90,42% dissolution percentage. Mechanism of drug dissolution study by kinetics approach showed both in-situ loading process and post loading process are diffusion and degradation process (n=0,4913) and (n=0,4602) respectively. These results are supported by characterization data from optical microscope and scanning electron microscopy (SEM). Data from optical microscope showed both loading process resulted in coarser hydrogel surface. Characterization using SEM showed elongated pores in both loading process after dissolution test.

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.

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

Study on effect of L-arginine on solubility and dissolution of Zaltoprofen: Preparation and characterization of binary and ternary cyclodextrin inclusion complexes

NASA Astrophysics Data System (ADS)

Sherje, Atul P.; Patel, Forum; Murahari, Manikanta; Suvarna, Vasanti; Patel, Kavitkumar

2018-02-01

The present study demonstrated the binary and ternary complexes of Zaltoprofen (ZPF) with β-CD and HP-β-CD. The products were characterized using solubility, in vitro dissolution, and DSC studies. The mode of interaction of guest and host was revealed through 1H NMR and FT-IR studies. A significant increase was noticed in the stability constant (Kc) and complexation efficiency (CE) of β-CD and HP-β-CD due to addition of L-Arg in ternary complexes. The ternary complexes showed greater increase in solubility and dissolution of ZPF than binary complexes. Thus, ternary system of ZPF could be an innovative approach for its solubility and dissolution enhancement.

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.

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.

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.

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

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

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.

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.

Characterisation, solubility and intrinsic dissolution behaviour of benzamide: dibenzyl sulfoxide cocrystal.

PubMed

Grossjohann, Christine; Eccles, Kevin S; Maguire, Anita R; Lawrence, Simon E; Tajber, Lidia; Corrigan, Owen I; Healy, Anne Marie

2012-01-17

This study examined the 1:1 cocrystal benzamide:dibenzyl sulfoxide, comprising the poorly water soluble dibenzyl sulfoxide (DBSO) and the more soluble benzamide (BA), to establish if this cocrystal shows advantages in terms of solubility and dissolution in comparison to its pure components and to a physical mixture. Solubility studies were performed by measuring DBSO solubility as a function of BA concentration, and a ternary phase diagram was constructed. Dissolution was examined through intrinsic dissolution studies. Solid-state characterisation was carried out by powder X-ray diffraction (PXRD), energy-dispersive X-ray diffraction (EDX), infra-red spectroscopy (ATR-FTIR) and thermal analysis. DBSO solubility was increased by means of complexation with BA. For the cocrystal, the solubility of both components was decreased in comparison to pure components. The cocrystal was identified as metastable and incongruently saturating. Dissolution studies revealed that dissolution of DBSO from the cocrystal was not enhanced in comparison to the pure compound or a physical mix, while BA release was retarded and followed square root of time kinetics. At the disk surface a layer of DBSO was found. The extent of complexation in solution can change the stability of the complex substantially. Incongruent solubility and dissolution behaviour of a cocrystal can result in no enhancement in the dissolution of the less soluble component and retardation of release of the more soluble component. Copyright © 2011 Elsevier B.V. All rights reserved.

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

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

PubMed

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

2011-01-01

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

Dissolution and mechanical behaviors of recrystallized carbamazepine from alcohol solution in the presence of additives

NASA Astrophysics Data System (ADS)

Nokhodchi, A.; Bolourtchian, N.; Dinarvand, R.

2005-02-01

Carbamazepine (CBZ) crystals were grown from pure ethanol solutions containing various additives (PEG 4000, PVP K30 or Tween 80). Physical characteristics of the crystals were studied for the morphology of crystals using scanning electron microscope, for the identification of polymorphism by X-ray powder diffraction (XRPD) and FT-IR, and for thermodynamic properties using differential scanning calorimetery (DSC). The dissolution behaviour of various carbamazepine crystals was also studied by dissolution apparatus II at pH 7.4 containing 1% sodium lauryl sulphate (SLS). The scanning electron micrograph (SEM) studies showed that the presence of the additives in the solutions growth medium affected the morphology and size of carbamazepine crystals. SEMs of untreated and treated carbamazepine crystals obtained from alcohol containing PEG 4000, PVP K30 or Tween 80 showed that the crystal shape of untreated carbamazepine is flaky or thin plate-like, whereas the crystals obtained from alcohol containing no additive, PEG 4000, PVP K30 or Tween 80 are polyhedral prismatic, block-shaped, polyhedral or hexagonal, respectively. XRPD, FT-IR and DSC results showed that the untreated CBZ was form III and recrystallization of CBZ in the absence or presence of the additives did not cause any polymorphic changes. The results showed that the higher dissolution rate and compact strength were observed for the crystals obtained in the presence of PVP K30. The presence of the additives in crystallization medium alters crystal morphology of carbamazepine, but only the samples crystallized in the presence of PVP K30 showed an improvement in dissolution rate and tensile strength.

General solution for diffusion-controlled dissolution of spherical particles. 1. Theory.

PubMed

Wang, J; Flanagan, D R

1999-07-01

Three classical particle dissolution rate expressions are commonly used to interpret particle dissolution rate phenomena. Our analysis shows that an assumption used in the derivation of the traditional cube-root law may not be accurate under all conditions for diffusion-controlled particle dissolution. Mathematical analysis shows that the three classical particle dissolution rate expressions are approximate solutions to a general diffusion layer model. The cube-root law is most appropriate when particle size is much larger than the diffusion layer thickness, the two-thirds-root expression applies when the particle size is much smaller than the diffusion layer thickness. The square-root expression is intermediate between these two models. A general solution to the diffusion layer model for monodispersed spherical particles dissolution was derived for sink and nonsink conditions. Constant diffusion layer thickness was assumed in the derivation. Simulated dissolution data showed that the ratio between particle size and diffusion layer thickness (a0/h) is an important factor in controlling the shape of particle dissolution profiles. A new semiempirical general particle dissolution equation is also discussed which encompasses the three classical particle dissolution expressions. The success of the general equation in explaining limitations of traditional particle dissolution expressions demonstrates the usefulness of the general diffusion layer model.

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.

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

PubMed

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

2016-01-01

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

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.

Coherent anti-Stokes Raman Scattering (CARS) Microscopy Visualizes Pharmaceutical Tablets During Dissolution

PubMed Central

Fussell, Andrew L.; Kleinebudde, Peter; Herek, Jennifer; Strachan, Clare J.; Offerhaus, Herman L.

2014-01-01

Traditional pharmaceutical dissolution tests determine the amount of drug dissolved over time by measuring drug content in the dissolution medium. This method provides little direct information about what is happening on the surface of the dissolving tablet. As the tablet surface composition and structure can change during dissolution, it is essential to monitor it during dissolution testing. In this work coherent anti-Stokes Raman scattering microscopy is used to image the surface of tablets during dissolution while UV absorption spectroscopy is simultaneously providing inline analysis of dissolved drug concentration for tablets containing a 50% mixture of theophylline anhydrate and ethyl cellulose. The measurements showed that in situ CARS microscopy is capable of imaging selectively theophylline in the presence of ethyl cellulose. Additionally, the theophylline anhydrate converted to theophylline monohydrate during dissolution, with needle-shaped crystals growing on the tablet surface during dissolution. The conversion of theophylline anhydrate to monohydrate, combined with reduced exposure of the drug to the flowing dissolution medium resulted in decreased dissolution rates. Our results show that in situ CARS microscopy combined with inline UV absorption spectroscopy is capable of monitoring pharmaceutical tablet dissolution and correlating surface changes with changes in dissolution rate. PMID:25045833

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.

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.

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.

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.

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.

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.

Effect of Microenvironmental pH Modulation on the Dissolution Rate and Oral Absorption of the Salt of a Weak Acid - Case Study of GDC-0810.

PubMed

Hou, Hao Helen; Jia, Wei; Liu, Lichuan; Cheeti, Sravanthi; Li, Jane; Nauka, Ewa; Nagapudi, Karthik

2018-01-29

The purpose of this work is to investigate the effect of microenvironmental pH modulation on the in vitro dissolution rate and oral absorption of GDC-0810, an oral anti-cancer drug, in human. The pH-solubility profile of GDC-0810 free acid and pH max of its N-Methyl-D-glucamine (NMG) salt were determined. Precipitation studies were conducted for GDC-0810 NMG salt at different pH values. GDC-0810 200-mg dose NMG salt tablet formulations containing different levels of sodium bicarbonate as the pH modifier were tested for dissolution under the dual pH-dilution scheme. Three tablet formulations were evaluated in human as a part of a relative bioavailability study. A 200-mg dose of GDC-0810 was administered QD with low fat food. Intrinsic solubility of GDC-0810 free acid was found to be extremely low. The pH max of the NMG salt suggested a strong tendency for form conversion to the free acid under GI conditions. In vitro dissolution profiles showed that the dissolution rate and extent of GDC-0810 increased with increasing the level of sodium bicarbonate in the formulation. The human PK data showed a similar trend for the geometric mean of C max and AUC 0-t for formulations containing 5%, 10%, and 15% sodium bicarbonate, but the difference is not statistically significant. Incorporation of a basic pH modifier, sodium bicarbonate, in GDC-0810 NMG salt tablet formulations enhanced in vitro dissolution rate of GDC-0810 via microenvironmental pH modulation. The human PK data showed no statistically significant difference in drug exposure from tablets containing 5%, 10%, and 15% sodium bicarbonate.

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.

Comparative study on the in vitro performance of blister molded and conventional lornoxicam immediate release liquitablets: accelerated stability study and anti-inflammatory and ulcerogenic effects.

PubMed

El-Setouhy, Doaa Ahmed; Gamiel, Alaa Abdel-Rahman; Badawi, Alia Abd El-Latif; Osman, Afaf Sayed; Labib, Dina Ahmed

2017-03-01

Lornoxicam is a potent non-steroidal anti-inflammatory drug (NSAID). It shows limited solubility in the gastric pH, delayed bioavailability and pharmacodynamic effects with aggravated gastric side effects (due to longer residence in the stomach wall). To enhance dissolution of lornoxicam in the gastric fluid and expectedly absorption and pharmacological action, with less ulcerogenic effects. Formulation of immediate release (IR) lornoxicam liquitablets containing both liquid and solid release modulators (wetting agent, solubilizers and microenvironmental pH modifiers). Beside the traditional direct compression technique employed for the preparation of liquitablets a new technique, blister molding, was also used. The effect of the two different manufacturing methods on the fast release characteristics (rapid disintegration and dissolution) was studied. Stability and pharmacological activity of the optimum formula were also explored. Similarity factor pointed out the superiority of molding technique in enhancing dissolution of lornoxicam owing to significant crystallinity reduction (XRD). Optimum formula showed negligible change in drug content and dissolution profiles over 12 weeks, significantly improved anti-inflammatory activity and significantly reduced gastric ulcerative effect over pure lornoxicam and commercial formula. Blister molded lornoxicam liquitablet of improved dissolution and pharmacological activity and less gastric erosion was successfully prepared.

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

PubMed

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

2007-01-01

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

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.

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.

The dynamics of household dissolution and change in socio-economic position: A survival model in a rural South Africa

PubMed Central

Sartorius, Kurt; Sartorius, Benn KD; Collinson, Mark A; Tollman, Stephen M

2014-01-01

This paper investigates household dissolution and changes in asset wealth (socio-economic position) in a rural South African community containing settled refugees. Survival analysis applied to a longitudinal dataset indicated that the covariates increasing the risk of forced household dissolution were a reduction in socio-economic position (asset wealth), adult deaths and the permanent outmigration of more than 40% of the household. Conversely, the risk of dissolution was reduced by bigger households, state grants and older household heads. Significant spatial clusters of former refugee villages also showed a higher risk of dissolution after 20 years of permanent residence. A discussion of the dynamics of dissolution showed how an outflow/inflow of household assets (socio-economic position) was precipitated by each of the selected covariates. The paper shows how an understanding of the dynamics of forced household dissolution, combined with the use of geo-spatial mapping, can inform inter-disciplinary policy in a rural community. PMID:25937697

The dynamics of household dissolution and change in socio-economic position: A survival model in a rural South Africa.

PubMed

Sartorius, Kurt; Sartorius, Benn Kd; Collinson, Mark A; Tollman, Stephen M

2014-11-02

This paper investigates household dissolution and changes in asset wealth (socio-economic position) in a rural South African community containing settled refugees. Survival analysis applied to a longitudinal dataset indicated that the covariates increasing the risk of forced household dissolution were a reduction in socio-economic position (asset wealth), adult deaths and the permanent outmigration of more than 40% of the household. Conversely, the risk of dissolution was reduced by bigger households, state grants and older household heads. Significant spatial clusters of former refugee villages also showed a higher risk of dissolution after 20 years of permanent residence. A discussion of the dynamics of dissolution showed how an outflow/inflow of household assets (socio-economic position) was precipitated by each of the selected covariates. The paper shows how an understanding of the dynamics of forced household dissolution, combined with the use of geo-spatial mapping, can inform inter-disciplinary policy in a rural community.

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.

Theoretical study of the dissolution kinetics of galena and cerussite in an abandoned mining area (Zaida mine, Morocco)

NASA Astrophysics Data System (ADS)

El Alaoui, Lamiae; Dekayir, Abdelilah

2018-05-01

In the abandoned mine in Zaida, the pit lakes filled with water constitute significant water reserves. In these lakes, the waters are permanently in contact with ore deposit (cerussite and galena). The modelling of the interaction of waters with this mineralization shows that cerussite dissolves more rapidly than galena. This dissolution is controlled by the pH and dissolved oxygen concentration in solution. The lead concentrations recorded in these lakes come largely from the dissolution of cerussite.

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

Crystal faces of anhydrite (CaSO 4) and their preferential dissolution in aqueous solutions studied with AFM

NASA Astrophysics Data System (ADS)

Shindo, H.; Kaise, M.; Kondoh, H.; Nishihara, C.; Nozoye, H.

Structures of cleaved surfaces of anhydrite were studied with atomic force microscopy (AFM) before and after partial dissolution in aqueous solutions of NH 4Cl and NaHSO 4. Two crystal faces showed atom-resolved images just after cleavage, (100) and (010), of which the former was roughened by the dissolution, while step structures were developed on the latter. After dissolution, steplines ran along the a- and c-axes on the (010) face, while they ran in directions inclined to these axes before. It was revealed that the arrangement of dipoles is a key factor in determining stabilities of step structures on crystal faces. On the terraces, the arrangement of oxygen atoms of the sulfate groups and calcium ions were clearly observed.

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.

Formulation and Pharmacokinetic Evaluation of Polymeric Dispersions Containing Valsartan.

PubMed

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

2016-10-01

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

Preparation of novel porous starch microsphere foam for loading and release of poorly water soluble drug.

PubMed

Jiang, Tongying; Wu, Chao; Gao, Yikun; Zhu, Wenquan; Wan, Long; Wang, Zhanyou; Wang, Siling

2014-02-01

Organic porous material is a promising carrier for enhancing the dissolution of poorly water soluble drug. The aim of the present study was to enhance dissolution and oral bioavailability of lovastatin (LV) by preparing a porous starch microsphere foam (PSM) using a novel method, meanwhile, looking into the mechanism of improving dissolution of LV. PSM was prepared by the W/O emulsion-freeze thawing method. The porous structure of PSM was characterized by scanning electron microscopy (SEM) and nitrogen adsorption/desorption analysis. The adsorption role of nanopores on the drug dissolution and physical state of LV was systematically studied by instrumental analysis, and in vitro and in vivo drug dissolution studies. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate carrier cytotoxicity. The SEM images of PSM showed nanometer-sized pores. Physical state characterization indicated that porous structure effectively limited the degree of crystallinity of LV. The results of in vitro and in vivo tests testified that PSM accelerated the release of LV and enhanced its oral bioavailability in comparison with crude LV and commercial capsules. The loaded PSM powder indicated a good physical stability under storage for 12 months. MTT assay shows PSM has no toxicity for Caco-2 cell. The preparation was a promising method to produce small and uniform PSM with markedly enhanced dissolution rate and oral bioavailability due to the spatial confinement effect of porous structure. The present work demonstrates the significant potential for the use of PSM as a novel delivery system for poorly water soluble drugs.

Mechanism of Urea Crystal Dissolution in Water from Molecular Dynamics Simulation.

PubMed

Anand, Abhinav; Patey, G N

2018-01-25

Molecular dynamics simulations are used to determine the mechanism of urea crystal dissolution in water under sink conditions. Crystals of cubic and tablet shapes are considered, and results are reported for four commonly used water models. The dissolution rates for different water models can differ considerably, but the overall dissolution mechanism remains the same. Urea dissolution occurs in three stages: a relatively fast initial stage, a slower intermediate stage, and a final stage. We show that the long intermediate stage is well described by classical rate laws, which assume that the dissolution rate is proportional to the active surface area. By carrying out simulations at different temperatures, we show that urea dissolution is an activated process, with an activation energy of ∼32 kJ mol -1 . Our simulations give no indication of a significant diffusion layer, and we conclude that the detachment of molecules from the crystal is the rate-determining step for dissolution. The results we report for urea are consistent with earlier observations for the dissolution of NaCl crystals. This suggests that the three-stage mechanism and classical rate laws might apply to the dissolution of other ionic and molecular crystals.

Stability of surface nanobubbles

NASA Astrophysics Data System (ADS)

Maheshwari, Shantanu; van der Hoef, Martin; Zhang, Xuehua; Lohse, Detlef

2015-11-01

We have studied the stability and dissolution of surface nanobubbles on the chemical heterogenous surface by performing Molecular Dynamics (MD) simulations of binary mixture consists of Lennard-Jones (LJ) particles. Recently our group has derived the exact expression for equilibrium contact angle of surface nanobubbles as a function of oversaturation of the gas concentration in bulk liquid and the lateral length of bubble. It has been showed that the contact line pinning and the oversaturation of gas concentration in bulk liquid is crucial in the stability of surface nanobubbles. Our simulations showed that how pinning of the three-phase contact line on the chemical heterogenous surface lead to the stability of the nanobubble. We have calculated the equilibrium contact angle by varying the gas concentration in bulk liquid and the lateral length of the bubble. Our results showed that the equilibrium contact angle follows the expression derived analytically by our group. We have also studied the bubble dissolution dynamics and showed the ''stick-jump'' mechanism which was also observed experimentally in case of dissolution of nanodrops.

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

PubMed

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

2012-10-01

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

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.

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.

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

PubMed

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

2017-07-01

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

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

PubMed

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

2017-05-01

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

Calorimetric Studies of Precipitation and Dissolution Kinetics in Aluminum Alloys 2219 and 7075

NASA Astrophysics Data System (ADS)

Papazian, John M.

1982-05-01

Differential scanning calorimetry (DSC) was used to study the kinetics of precipitation and dissolution of metastable and stable phases in aluminum alloys 2219 and 7075. A comparison of DSC scans obtained at heating rates of 1, 5, 10, and 20 K per minute showed that, during a DSC scan, the rates of precipitation of θ' and θ in 2219 and η' and η in 7075 were limited by their reaction kinetics. Likewise, the rates of dissolution of GP zones, θ' and η', were found to be dominated by kinetics. In contrast, the dissolution of θ and η was dominated by the thermodynamic equilibrium between these phases and the matrix. Analysis of the kinetically dominated reaction peaks and their dependence on heating rate and particle size showed that the GP zone dissolution reaction could best be described by a three-dimensional volume diffusion limited rate expression with an activation energy equal to that for diffusion. The rate of formation of θ' was best described by an Avrami expression with n = 1.1, indicating that nucleation was not the rate controlling step. A pronounced dependence of the θ' formation rate on prior plastic deformation was observed and ascribed to the influence of the matrix dislocation density on diffusivity.

Formulation studies for mirtazapine orally disintegrating tablets.

PubMed

Yıldız, Simay; Aytekin, Eren; Yavuz, Burçin; Bozdağ Pehlivan, Sibel; Ünlü, Nurşen

2016-01-01

Orally disintegrating tablets (ODTs) recently have gained much attention to fulfill the needs for pediatric, geriatric, and psychiatric patients with dysphagia. Aim of this study was to develop new ODT formulations containing mirtazapine, an antidepressant drug molecule having bitter taste, by using simple and inexpensive preparation methods such as coacervation, direct compression and to compare their characteristics with those of reference product (Remereon SolTab). Coacervation method was chosen for taste masking of mirtazapine. In vitro characterization studies such as diameter and thickness, weight variation, tablet hardness, tablet friability and disintegration time were performed on tablet formulations. Wetting time and in vitro dissolution tests of developed ODTs also studied using 900 mL 0.1 N HCl medium, 900 mL pH 6.8 phosphate buffer or 900 mL pH 4.5 acetate buffer at 37 ± 0.2 °C as dissolution medium. Ratio of Eudragit® E-100 was chosen as 6% (w/w) since the dissolution profile of A1 (6% Eudragit® E-100) was found closer to the reference product than A2 (4% Eudragit® E-100) and A3 (8% Eudragit® E-100). Group D, E and F formulations were presented better results in terms of disintegration time. Dissolution results indicated that Group E and F formulations showed optimum properties in all three dissolution media. Formulations D1, D4, D5, E3, E4, F1 and F5 found suitable as ODT formulations due to their favorable disintegration times and dissolution profiles. Developed mirtazapine ODTs were found promising in terms of showing the similar characteristics to the original formulation.

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

PubMed

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

2013-10-01

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

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.

Short-time dissolution mechanisms of kaolinitic tropical soils

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

Malengreau, N.; Sposito, Garrison

1996-03-01

Previous research on the short-time dissolution behavior of kaolinitic Oxisols suggested pH-dependent kinetics involving ligand-promoted dissolution, metal readsorption, and colloidal dispersion, with soil organic matter conjectured to play a decisive role. A novel combination of spectroscopy, lightscattering, and batch dissolution experiments, conducted at controlled pH and ionic strength over five dissolution periods ranging from 1 to 12 h, was applied to evaluate this mechanism for samples of a representative kaolinitic Oxisol; collected at both forested and cultivated field sites (leading to significant differences in organic matter content and field soil pH). The overall characteristics of the pH-dependent net release kineticsmore » of Al, Fe, and Si by the soil samples, for any dissolution period in the range investigated, were determined by the pH value at which colloid dispersion commenced, which decreased significantly as the soil organic matter content increased. Plots of log(Si/Al released) (or Si/Fe released) vs. -log [H+] ([H+] is proton concentration) were superimposable for all dissolution periods studied, rising to a plateau value above the point of zero net charge of the soils (pH 3.2). Light-scattering and X-ray diffraction data showed conclusively that this plateau represented the release of siliceous colloids containing kaolinite and X-ray amorphous material. X-ray diffraction, UV-visible diffuse reflectance spectroscopy, and electron spin resonance spectroscopy, applied to the soil samples before and after dissolution, and after conventional chemical extractions to remove Al, C, Fe, and Si, showed that kaolinite and iron oxide phases (the latter being highly Al-substituted and present in both coatings and occlusions) were essentially unaltered by dissolution, even at -log [H+] = 2, whereas substantial dissolution loss of soil quartz occurred. Diffuse reflectance spectroscopy gave strong evidence that C in these soils occurs principally in discrete solid phases, not as a reactive coating on mineral surfaces.« less

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.

Influence of Structural Defects on Biomineralized ZnS Nanoparticle Dissolution: An in-Situ Electron Microscopy Study.

PubMed

Eskelsen, Jeremy R; Xu, Jie; Chiu, Michelle; Moon, Ji-Won; Wilkins, Branford; Graham, David E; Gu, Baohua; Pierce, Eric M

2018-02-06

The dissolution of metal sulfides, such as ZnS, is an important biogeochemical process affecting fate and transport of trace metals in the environment. However, current studies of in situ dissolution of metal sulfides and the effects of structural defects on dissolution are lacking. Here we have examined the dissolution behavior of ZnS nanoparticles synthesized via several abiotic and biological pathways. Specifically, we have examined biogenic ZnS nanoparticles produced by an anaerobic, metal-reducing bacterium Thermoanaerobacter sp. X513 in a Zn-amended, thiosulfate-containing growth medium in the presence or absence of silver (Ag), and abiogenic ZnS nanoparticles were produced by mixing an aqueous Zn solution with either H 2 S-rich gas or Na 2 S solution. The size distribution, crystal structure, aggregation behavior, and internal defects of the synthesized ZnS nanoparticles were examined using high-resolution transmission electron microscopy (TEM) coupled with X-ray energy dispersive spectroscopy. The characterization results show that both the biogenic and abiogenic samples were dominantly composed of sphalerite. In the absence of Ag, the biogenic ZnS nanoparticles were significantly larger (i.e., ∼10 nm) than the abiogenic ones (i.e., ∼3-5 nm) and contained structural defects (e.g., twins and stacking faults). The presence of trace Ag showed a restraining effect on the particle size of the biogenic ZnS, resulting in quantum-dot-sized nanoparticles (i.e., ∼3 nm). In situ dissolution experiments for the synthesized ZnS were conducted with a liquid-cell TEM (LCTEM), and the primary factors (i.e., the presence or absence structural defects) were evaluated for their effects on the dissolution behavior using the biogenic and abiogenic ZnS nanoparticle samples with the largest average particle size. Analysis of the dissolution results (i.e., change in particle radius with time) using the Kelvin equation shows that the defect-bearing biogenic ZnS nanoparticles (γ = 0.799 J/m 2 ) have a significantly higher surface energy than the abiogenic ZnS nanoparticles (γ = 0.277 J/m 2 ). Larger defect-bearing biogenic ZnS nanoparticles were thus more reactive than the smaller quantum-dot-sized ZnS nanoparticles. These findings provide new insight into the factors that affect the dissolution of metal sulfide nanoparticles in relevant natural and engineered scenarios, and have important implications for tracking the fate and transport of sulfide nanoparticles and associated metal ions in the environment. Moreover, our study exemplified the use of an in situ method (i.e., LCTEM) to investigate nanoparticle behavior (e.g., dissolution) in aqueous solutions.

Dissolution enhancement of a drug exhibiting thermal and acidic decomposition characteristics by fusion processing: a comparative study of hot melt extrusion and KinetiSol dispersing.

PubMed

Hughey, Justin R; DiNunzio, James C; Bennett, Ryan C; Brough, Chris; Miller, Dave A; Ma, Hua; Williams, Robert O; McGinity, James W

2010-06-01

In this study, hot melt extrusion (HME) and KinetiSol Dispersing (KSD) were utilized to prepare dissolution-enhanced solid dispersions of Roche Research Compound A (ROA), a BCS class II drug. Preformulation characterization studies showed that ROA was chemically unstable at elevated temperatures and acidic pH values. Eudragit L100-55 and AQOAT LF (HPMCAS) were evaluated as carrier polymers. Dispersions were characterized for ROA recovery, crystallinity, homogeneity, and non-sink dissolution. Eudragit L100-55 dispersions prepared by HME required the use of micronized ROA and reduced residence times in order to become substantially amorphous. Compositions containing HPMCAS were also prepared by HME, but an amorphous dispersion could not be obtained. All HME compositions contained ROA-related impurities. KSD was investigated as a method to reduce the decomposition of ROA while rendering compositions amorphous. Substantially amorphous, plasticizer free compositions were processed successfully by KSD with significantly higher ROA recovery values and amorphous character than those achieved by HME. A near-infrared chemical imaging analysis was conducted on the solid dispersions as a measure of homogeneity. A statistical analysis showed similar levels of homogeneity in compositions containing Eudragit L100-55, while differences were observed in those containing HMPCAS. Non-sink dissolution analysis of all compositions showed rapid supersaturation after pH adjustment to approximately two to three times the equilibrium solubility of ROA, which was maintained for at least 24 h. The results of the study demonstrated that KSD is an effective method of forming dissolution-enhanced amorphous solid solutions in cases where HME is not a feasible technique.

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.

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.

An electrochemical quartz crystal microbalance study of magnesium dissolution

NASA Astrophysics Data System (ADS)

Ralston, K. D.; Thomas, S.; Williams, G.; Birbilis, N.

2016-01-01

A quartz crystal microbalance (QCM) was used in conjunction with electrochemical measurements to study dissolution of pure magnesium (Mg) sensors in dilute NaCl electrolytes. Open circuit potential and potentiodynamic polarisation experiments were conducted in 0.01 M NaCl, having pH values 3 (buffered) and 6 (unbuffered). In the pH 3 solution, the Mg sensor showed a net mass-loss during the electrochemical tests, whereas, in the unbuffered pH 6 solution Mg showed a net mass-gain, corresponding to the growth of an Mg(OH)2 film on its surface. The loss in the electrochemical efficiency of Mg dissolution due to such direct parasitic Mg(OH)2 growth has been estimated to be around 17-34%. This loss relates to the low capacities and voltage fluctuations reported during discharge of primary Mg batteries.

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.

INFLUENCE OF TYPE AND NEUTRALISATION CAPACITY OF ANTACIDS ON DISSOLUTION RATE OF CIPROFLOXACIN AND MOXIFLOXACIN FROM TABLETS

PubMed Central

Uzunović, Alija; Vranić, Edina

2009-01-01

Dissolution rate of two fluoroquinolone antibiotics (ciprofloxacin and moxifloxacin) was analysed in presence/absence of three antacid formulations. Disintegration time and neutralisation capacity of antacid tablets were also checked. Variation in disintegration time indicated the importance of this parameter, and allowed evaluation of the influence of postponed antacid-fluoroquinolone contact. The results obtained in this study showed decreased dissolution rate of fluoroquinolone antibiotics from tablets in simultaneous presence of antacids, regardless of their type and neutralisation capacity. PMID:19284403

Novel biorelevant dissolution medium as a prognostic tool for polysaccharide-based colon-targeted drug delivery system.

PubMed

Yadav, Ankit Kumar; Sadora, Manik; Singh, Sachin Kumar; Gulati, Monica; Maharshi, Peddi; Sharma, Abhinav; Kumar, Bimlesh; Rathee, Harish; Ghai, Deepak; Malik, Adil Hussain; Garg, Varun; Gowthamrajan, K

2017-01-01

To overcome the limitations of the conventionally used methods for evaluation of orally administered colon-targeted delivery systems, a novel dissolution method using probiotics has been recently reported. In the present study, universal suitability of this medium composed of five different probiotics is established. Different delivery systems - mini tablets, liquisolid compacts, and microspheres coated with different polysaccharides - were prepared and subjected to sequential dissolution testing in medium with and without microbiota. The results obtained from fluid thioglycollate medium (FTM)-based probiotic medium for all the polysaccharide-based formulations showed statistically similar dissolution profile to that in the rat and goat cecal content media. Hence, it can be concluded that the developed FTM-based probiotic medium, once established, may eliminate the need for further animal sacrifice in the dissolution testing of polysaccharide-based colon-targeted delivery system.

Modeling solid-state transformations occurring in dissolution testing.

PubMed

Laaksonen, Timo; Aaltonen, Jaakko

2013-04-15

Changes in the solid-state form can occur during dissolution testing of drugs. This can often complicate interpretation of results. Additionally, there can be several mechanisms through which such a change proceeds, e.g. solvent-mediated transformation or crystal growth within the drug material itself. Here, a mathematical model was constructed to study the dissolution testing of a material, which undergoes such changes. The model consisted of two processes: the recrystallization of the drug from a supersaturated liquid state caused by the dissolution of the more soluble solid form and the crystal growth of the stable solid form at the surface of the drug formulation. Comparison to experimental data on theophylline dissolution showed that the results obtained with the model matched real solid-state changes and that it was able to distinguish between cases where the transformation was controlled either by solvent-mediated crystallization or solid-state crystal growth. Copyright © 2013 Elsevier B.V. All rights reserved.

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

PubMed

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

1999-09-01

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

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.

Antisolvent precipitation technique: A very promising approach to crystallize curcumin in presence of polyvinyl pyrrolidon for solubility and dissolution enhancement.

PubMed

Sadeghi, Fatemeh; Ashofteh, Mohammad; Homayouni, Alireza; Abbaspour, Mohammadreza; Nokhodchi, Ali; Garekani, Hadi Afrasiabi

2016-11-01

Curcumin with a vast number of pharmacological activities is a poorly water soluble drug which its oral bioavailability is profoundly limited by its dissolution or solubility in GI tract. Curcumin could be a good anticancer drug if its solubility could be increased. Therefore, the aim of the present study was to increase the dissolution rate of curcumin by employing antisolvent crystallization technique and to investigate the effect of polyvinyl pyrrolidone K30 (PVP) as colloidal particles in crystallization medium on resultant particles. Curcumin was crystalized in the presence of different amounts of PVP by antisolvent crystallization method and their physical mixtures were prepared for comparison purposes. The samples were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and Fourier transform infrared spectroscopy (FT-IR). The solubility and dissolution of the treated and untreated curcumin were also determined. Antisolvent crystallization of curcumin led to the formation of particles with no definite geometric shape. It was interesting to note that the DSC and XRPD studies indicated the formation of a new polymorph and less crystallinity for particles crystallized in the absence of PVP. However, the crystallized curcumin in the presence of PVP was completely amorphous. All crystalized curcumin samples showed much higher dissolution rate compared to untreated curcumin. The amount of curcumin dissolved within 10 for treated curcumin in the presence of PVP (1:1 curcumin:PVP) was 7 times higher than untreated curcumin and this enhancement in the dissolution for curcumin samples crystallized in the absence of PVP was around 5 times. Overall' the results of this study showed that antisolvent crystallization method in the absence or presence of small amounts of PVP is very efficient in increasing the dissolution rate of curcumin to achieve better efficiency for curcumin. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

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

PubMed

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

2017-01-01

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

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

PubMed

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

2003-03-26

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

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.

Chemometrics-assisted spectrophotometric green method for correcting interferences in biowaiver studies: Application to assay and dissolution profiling study of donepezil hydrochloride tablets

NASA Astrophysics Data System (ADS)

Korany, Mohamed A.; Mahgoub, Hoda; Haggag, Rim S.; Ragab, Marwa A. A.; Elmallah, Osama A.

2018-06-01

A green, simple and cost effective chemometric UV-Vis spectrophotometric method has been developed and validated for correcting interferences that arise during conducting biowaiver studies. Chemometric manipulation has been done for enhancing the results of direct absorbance, resulting from very low concentrations (high incidence of background noise interference) of earlier points in the dissolution timing in case of dissolution profile using first and second derivative (D1 & D2) methods and their corresponding Fourier function convoluted methods (D1/FF& D2/FF). The method applied for biowaiver study of Donepezil Hydrochloride (DH) as a representative model was done by comparing two different dosage forms containing 5 mg DH per tablet as an application of a developed chemometric method for correcting interferences as well as for the assay and dissolution testing in its tablet dosage form. The results showed that first derivative technique can be used for enhancement of the data in case of low concentration range of DH (1-8 μg mL-1) in the three different pH dissolution media which were used to estimate the low drug concentrations dissolved at the early points in the biowaiver study. Furthermore, the results showed similarity in phosphate buffer pH 6.8 and dissimilarity in the other 2 pH media. The method was validated according to ICH guidelines and USP monograph for both assays (HCl of pH 1.2) and dissolution study in 3 pH media (HCl of pH 1.2, acetate buffer of pH 4.5 and phosphate buffer of pH 6.8). Finally, the assessment of the method greenness was done using two different assessment techniques: National Environmental Method Index label and Eco scale methods. Both techniques ascertained the greenness of the proposed method.

Chemometrics-assisted spectrophotometric green method for correcting interferences in biowaiver studies: Application to assay and dissolution profiling study of donepezil hydrochloride tablets.

PubMed

Korany, Mohamed A; Mahgoub, Hoda; Haggag, Rim S; Ragab, Marwa A A; Elmallah, Osama A

2018-06-15

A green, simple and cost effective chemometric UV-Vis spectrophotometric method has been developed and validated for correcting interferences that arise during conducting biowaiver studies. Chemometric manipulation has been done for enhancing the results of direct absorbance, resulting from very low concentrations (high incidence of background noise interference) of earlier points in the dissolution timing in case of dissolution profile using first and second derivative (D1 & D2) methods and their corresponding Fourier function convoluted methods (D1/FF& D2/FF). The method applied for biowaiver study of Donepezil Hydrochloride (DH) as a representative model was done by comparing two different dosage forms containing 5mg DH per tablet as an application of a developed chemometric method for correcting interferences as well as for the assay and dissolution testing in its tablet dosage form. The results showed that first derivative technique can be used for enhancement of the data in case of low concentration range of DH (1-8μgmL -1 ) in the three different pH dissolution media which were used to estimate the low drug concentrations dissolved at the early points in the biowaiver study. Furthermore, the results showed similarity in phosphate buffer pH6.8 and dissimilarity in the other 2pH media. The method was validated according to ICH guidelines and USP monograph for both assays (HCl of pH1.2) and dissolution study in 3pH media (HCl of pH1.2, acetate buffer of pH4.5 and phosphate buffer of pH6.8). Finally, the assessment of the method greenness was done using two different assessment techniques: National Environmental Method Index label and Eco scale methods. Both techniques ascertained the greenness of the proposed method. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

Influence of oxygen, albumin and pH on copper dissolution in a simulated uterine fluid.

PubMed

Bastidas, D M; Cano, E; Mora, E M

2005-06-01

The aim of this paper is to study the influence of albumin content, from 5 to 45 g/L, on copper dissolution and compounds composition in a simulated uterine solution. Experiments were performed in atmospheric pressure conditions and with an additional oxygen pressure of 0.2 atmospheres, at 6.3 and 8.0 pH values, and at a temperature of 37 +/- 0.1 degrees C for 1, 3, 7, and 30 days experimentation time. The copper dissolution rate has been determined using absorbance measurements, finding the highest value for pH 8.0, 35 g/L albumin, and with an additional oxygen pressure of 0.2 atmospheres: 674 microg/day for 1 day, and 301 microg/day for 30 days. X-ray photoelectron spectroscopy (XPS) results show copper(II) as the main copper oxidation state at pH 8.0; and copper(I) and metallic copper at pH 6.3. The presence of albumin up to 35 g/L, accelerates copper dissolution. For high albumin content a stabilisation on the copper dissolution takes place. Corrosion product layer morphology is poorly protective, showing paths through which copper ions can release.

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.

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

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

Improvement of the stability of hydroxyapatite through glass ceramic reinforcement.

PubMed

Ha, Na Ra; Yang, Zheng Xun; Hwang, Kyu Hong; Kim, Tae Suk; Lee, Jong Kook

2010-05-01

Hydroxyapatite has achieved significant application in orthopedic and dental implants due to its excellent biocompatibility. Sintered hydroxyapatites showed significant dissolution, however, after their immersion in water or simulated body fluid (SBF). This grain boundary dissolution, even in pure hydroxyapatites, resulted in grain separation at the surfaces, and finally, in fracture. In this study, hydroxyapatite ceramics containing apatite-wollastonite (AW) or calcium silicate (SG) glass ceramics as additives were prepared to prevent the dissolution. AW and SG glass ceramics were added at 0-7 wt% and powder-compacted uniaxially followed by firing at moisture conditions. The glass phase was incorporated into the hydroxyapatite to act as a sintering aid, followed by crystallization, to improve the mechanical properties without reducing the biocompatibility. As seen in the results of the dissolution test, a significant amount of damage was reduced even after more than 14 days. TEM and SEM showed no decomposition of HA to the secondary phase, and the fracture toughness increased, becoming even higher than that of the commercial hydroxyapatite.

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

PubMed

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

2014-06-01

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

Dissolution Mechanisms of LiNi1/3Mn1/3Co1/3O2 Positive Electrode Material from Lithium-Ion Batteries in Acid Solution.

PubMed

Billy, Emmanuel; Joulié, Marion; Laucournet, Richard; Boulineau, Adrien; De Vito, Eric; Meyer, Daniel

2018-05-04

The sustainability through the energy and environmental costs involve the development of new cathode materials, considering the material abundance, the toxicity, and the end of life. Currently, some synthesis methods of new cathode materials and a large majority of recycling processes are based on the use of acidic solutions. This study addresses the mechanistic and limiting aspects on the dissolution of the layered LiNi 1/3 Mn 1/3 Co 1/3 O 2 oxide in acidic solution. The results show a dissolution of the active cathode material in two steps, which leads to the formation of a well-defined core-shell structure inducing an enrichment in manganese on the particle surface. The crucial role of lithium extraction is discussed and considered as the source of a "self-regulating" dissolution process. The delithiation involves a cumulative charge compensation by the cationic and anionic redox reactions. The electrons generated from the compensation of charge conduct to the dissolution by the protons. The delithiation and its implications on the side reactions, by the modification of the potential, explain the structural and compositional evolutions observed toward a composite material MnO 2 ·Li x MO 2 (M = Ni, Mn, and Co). The study shows a clear way to produce new cathode materials and recover transition metals from Li-ion batteries by hydrometallurgical processes.

Kinetics of dissolution of sapphire in melts in the CaO-Al2O3-SiO2 system

NASA Astrophysics Data System (ADS)

Shaw, Cliff S. J.; Klausen, Kim B.; Mao, Huahai

2018-05-01

The dissolution rate of sapphire in melts in the CAS system of varying silica activity, viscosity and degree of alumina saturation has been determined at 1600 °C and 1.5 GPa. After an initiation period of up to 1800 s, dissolution is controlled by diffusion of cations through the boundary layer adjacent to the dissolving sapphire. The dissolution rate decreases with increasing silica activity, viscosity and molar Al2O3/CaO. The calculated diffusion matrix for each solvent melt shows that CAS 1 and 9 which have molar Al2O3/CaO of 0.33 and 0.6 and dissolution rate constants of 0.65 × 10-6 and 0.59 × 10-6 m/s0.5 have similar directions and magnitudes of diffusive coupling: DCaO-Al2O3 and DAl2O3-CaO are both negative are approximately equal. The solvent with the fastest dissolution rate: CAS 4, which has a rate constant of 1.5 × 10-6 m/s0.5 and Al2O3/CaO of 0.31 has positive DCaO-Al2O3 and negative DAl2O3-CaO and the absolute values vary by a factor of 4. Although many studies show that aluminium is added to the melts via the reaction: Si4+ =Al3+ + 0.5Ca2+ the compositional profiles show that this reaction is not the only one involved in accommodating the aluminium added during sapphire dissolution. Rather, aluminium is incorporated as both tetrahedrally coordinated Al charge balanced by Ca and as aluminium not charge balanced by Ca (termed Alxs). This reaction: AlIV -Ca =Alxs +CaNBO where CaNBO is a non-bridging oxygen associated with calcium, may involve the formation of aluminium triclusters. The shape of the compositional profiles and oxide-oxide composition paths is controlled by the aluminium addition reaction. When Alxs exceeds 2%, CaO diffusion becomes increasingly anomalous and since the bond strength of Alxs correlates with CaO/CaO + Al2O3, the presence of more than 2% Alxs leads to significantly slower dissolution than when Alxs is absent or at low concentration. Thus, dissolution is controlled by diffusion of cations through the boundary layer, but this diffusion is itself controlled by the structural modifications required by the addition of new components to the melt. Comparison of quartz dissolution rates in similar melts shows that dissolution is much faster for quartz than for sapphire and that dissolution rates show the same correlation with silica activity and viscosity. We suggest that diffusive fluxes are related to changes in melt structure and the nature of the reaction that incorporates the added component. For the slow eigendirection, SiO2 addition occurs by a single reaction whereas Al2O3 addition requires a more complex two part reaction in which Al is accommodated by charge balance with Ca until Al is in excess of that which can be charge balanced. The Alxs incorporation reaction, is slower than the Si incorporation reaction which inhibits sapphire dissolution relative to quartz in melts of the same composition.

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.

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.

Contact Angle Measurements: an Alternative Approach Towards Understanding the Mechanism of Increased Drug Dissolution from Ethylcellulose Tablets Containing Surfactant and Exploring the Relationship Between Their Contact Angles and Dissolution Behaviors.

PubMed

Liu, Tiaotiao; Hao, Jingqiang; Yang, Baixue; Hu, Beibei; Cui, Zhixiang; Li, Sanming

2018-05-01

The addition of surfactant in tablet was a well-defined approach to improve drug dissolution rate. While the selected surfactant played a vital role in improving the wettability of tablet by medium, it was equally important to improve the dissolution rate by permeation effect due to production of pores or the reduced inter-particle adhesion. Furthermore, understanding the mechanism of dissolution rate increased was significant. In this work, contact angle measurement was taken up as an alternative approach for understanding the dissolution rate enhancement for tablet containing surfactant. Ethylcellulose, as a substrate, was used to prepare tablet. Four surfactants, sodium dodecyl sulfate (SDS), sodium dodecylbenzenesulfonate (SDBS), dodecyltrimethylammonium bromide (DTAB), and sodium lauryl sulfonate (SLS), were used. Berberine hydrochloride, metformin hydrochloride, and rutin were selected as model drugs. The contact angle of tablet in the absence and presence of surfactant was measured to explore the mechanism. The dissolution test was investigated to verify the mechanism and to establish a correlation with the contact angle. The result showed that the mechanism was the penetration effect rather than the wetting effect. The dissolution increased with a reduction in the contact angle. DTAB was found to obtain the highest level of dissolution enhancement and the lowest contact angle, while SDS, SDBS, and SLS were found to be the less effective in both dissolution enhancement and contact angle decrease. Therefore, contact angle was a good indicator for dissolution behavior besides exploring the mechanism of increased dissolution, which shows great potential in formula screening.

In situ dissolution analysis of pharmaceutical dosage forms using coherent anti-Stokes Raman scattering (CARS) microscopy

NASA Astrophysics Data System (ADS)

Fussell, A. L.; Garbacik, E. T.; Löbmann, K.; Offerhaus, H. L.; Kleinebudde, P.; Strachan, C. J.

2014-02-01

A custom-built intrinsic flow-through dissolution setup was developed and incorporated into a home-built CARS microscope consisting of a synchronously pumped optical parametric oscillator (OPO) and an inverted microscope with a 20X/0.5NA objective. CARS dissolution images (512×512 pixels) were collected every 1.12s for the duration of the dissolution experiment. Hyperspectral CARS images were obtained pre- and postdissolution by rapidly imaging while sweeping the wavelength of the OPO in discrete steps so that each frame in the data stack corresponds to a vibrational frequency. An image-processing routine projects this hyperspectral data into a single image wherein each compound appears with a unique color. Dissolution was conducted using theophylline and cimetidine-naproxen co-amorphous mixture. After 15 minutes of theophylline dissolution, hyperspectral imaging showed a conversion of theophylline anhydrate to the monohydrate, confirmed by a peak shift in the CARS spectra. CARS dissolution images showed that monohydrate crystal growth began immediately and reached a maximum with complete surface coverage at about 300s. This result correlated with the UV dissolution data where surface crystal growth on theophylline compacts resulted in a rapidly reducing dissolution rate during the first 300s. Co-amorphous cimetidinenaproxen didn't appear to crystallize during dissolution. We observed solid-state conversions on the compact's surface in situ during dissolution. Hyperspectral CARS imaging allowed visual discrimination between the solid-state forms on the compact's surface. In the case of theophylline we were able to correlate the solid-state change with a change in dissolution rate.

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

NASA Astrophysics Data System (ADS)

Dewantara, Fauzi; Budianto, Emil

2018-04-01

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

Downstream processing of a ternary amorphous solid dispersion: The impacts of spray drying and hot melt extrusion on powder flow, compression and dissolution.

PubMed

Davis, Mark T; Potter, Catherine B; Walker, Gavin M

2018-06-10

Downstream processing aspects of a stable form of amorphous itraconazole exhibiting enhanced dissolution properties were studied. Preparation of this ternary amorphous solid dispersion by either spray drying or hot melt extrusion led to significantly different powder processing properties. Particle size and morphology was analysed using scanning electron microscopy. Flow, compression, blending and dissolution were studied using rheometry, compaction simulation and a dissolution kit. The spray dried material exhibited poorer flow and reduced sensitivity to aeration relative to the milled extrudate. Good agreement was observed between differing forms of flow measurement, such as Flow Function, Relative flow function, Flow rate index, Aeration rate, the Hausner ratio and the Carr index. The stability index indicated that both powders were stable with respect to agglomeration, de-agglomeration and attrition. Tablet ability and compressibility studies showed that spray dried material could be compressed into stronger compacts than extruded material. Blending of the powders with low moisture, freely-flowing excipients was shown to influence both flow and compression. Porosity studies revealed that blending could influence the mechanism of densification in extrudate and blended extrudate formulations. Following blending, the powders were compressed into four 500 mg tablets, each containing a 100 mg dose of amorphous itraconazole. Dissolution studies revealed that the spray dried material released drug faster and more completely and that blending excipients could further influence the dissolution rate. Copyright © 2018 Elsevier B.V. All rights reserved.

In Vitro and In Vivo Evaluation of Casein as a Drug Carrier for Enzymatically Triggered Dissolution Enhancement from Solid Dispersions.

PubMed

Bani-Jaber, Ahmad; Alshawabkeh, Iyad; Abdullah, Samaa; Hamdan, Imad; Ardakani, Adel; Habash, Maha

2017-07-01

Due to its unique properties, such as biodegradability, biocompatibility, high amphiphilic property, and micelle formation, casein (CS) has been increasingly studied for drug delivery. We used CS as a drug carrier in solid dispersions (SDs) and evaluated the effect of its degradation by trypsin on drug dissolution from the dispersions. SDs of CS and mefenamic acid (MA) were prepared by physical mixing, kneading, and coprecipitation methods. In comparison to pure MA, the dispersions were evaluated for drug-protein interaction, loss of drug crystalinity, and drug morphology by differential scanning calorimetry, X-ray diffractometry, Fourier transform infrared spectroscopy, and scanning electron microscopy. Drug dissolution from the dispersions was evaluated in simulated intestinal fluid as enzyme free and trypsin-enriched media. Furthermore, in vivo drug absorption of MA from CS-MA coprecipitate was evaluated in rats, in comparison with a reference SD of polyethylene glycol and MA (PEG-MA SD). Relative to other CS preparations, CS-MA coprecipitate showed the highest loss of drug crystallinity, drug micronization, and CS-MA interaction. CS remarkably enhanced the dissolution rate and extent of MA from the physical and kneaded mixtures. However, the highest dissolution enhancement was obtained when MA was coprecipitated with CS. Trypsin that can hydrolyze CS during dissolution resulted in further enhancement of MA dissolution from the physical and kneaded mixtures. However, a corresponding retardation effect was obtained for the coprecipitate. In correlation with in vitro drug release, CS-MA coprecipitate also showed significantly higher MA bioavailability in rats than PEG-MA SD.

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 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

Convective dissolution of carbon dioxide in saline aquifers

NASA Astrophysics Data System (ADS)

Neufeld, Jerome A.; Hesse, Marc A.; Riaz, Amir; Hallworth, Mark A.; Tchelepi, Hamdi A.; Huppert, Herbert E.

2010-11-01

Geological carbon dioxide (CO2) storage is a means of reducing anthropogenic emissions. Dissolution of CO2 into the brine, resulting in stable stratification, increases storage security. The dissolution rate is determined by convection in the brine driven by the increase of brine density with CO2 saturation. We present a new analogue fluid system that reproduces the convective behaviour of CO2-enriched brine. Laboratory experiments and high-resolution numerical simulations show that the convective flux scales with the Rayleigh number to the 4/5 power, in contrast with a classical linear relationship. A scaling argument for the convective flux incorporating lateral diffusion from downwelling plumes explains this nonlinear relationship for the convective flux, provides a physical picture of high Rayleigh number convection in a porous medium, and predicts the CO2 dissolution rates in CO2 accumulations. These estimates of the dissolution rate show that convective dissolution can play an important role in enhancing storage security.

Studies on dissolution enhancement and mathematical modeling of drug release of a poorly water-soluble drug using water-soluble carriers.

PubMed

Ahuja, Naveen; Katare, Om Prakash; Singh, Bhupinder

2007-01-01

Role of various water-soluble carriers was studied for dissolution enhancement of a poorly soluble model drug, rofecoxib, using solid dispersion approach. Diverse carriers viz. polyethylene glycols (PEG 4000 and 6000), polyglycolized fatty acid ester (Gelucire 44/14), polyvinylpyrollidone K25 (PVP), poloxamers (Lutrol F127 and F68), polyols (mannitol, sorbitol), organic acid (citric acid) and hydrotropes (urea, nicotinamide) were investigated for the purpose. Phase-solubility studies revealed AL type of curves for each carrier, indicating linear increase in drug solubility with carrier concentration. The sign and magnitude of the thermodynamic parameter, Gibbs free energy of transfer, indicated spontaneity of solubilization process. All the solid dispersions showed dissolution improvement vis-à-vis pure drug to varying degrees, with citric acid, PVP and poloxamers as the most promising carriers. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer-Peppas model and the drug release kinetics primarily as Fickian diffusion. Solid state characterization of the drug-poloxamer binary system using XRD, FTIR, DSC and SEM techniques revealed distinct loss of drug crystallinity in the formulation, ostensibly accounting for enhancement in dissolution rate.

Modeling growth and dissolution of inclusions during fusion welding of steels

NASA Astrophysics Data System (ADS)

Hong, Tao

The characteristics of inclusions in the weld metals are critical factors to determine the structure, properties and performance of weldments. The research in the present thesis applied computational modeling to study inclusion behavior considering thermodynamics and kinetics of nucleation, growth and dissolution of inclusion along its trajectory calculated from the heat transfer and fluid flow model in the weld pool. The objective of this research is to predict the characteristics of inclusions, such as composition, size distribution, and number density in the weld metal from different welding parameters and steel compositions. To synthesize the knowledge of thermodynamics and kinetics of nucleation, growth and dissolution of inclusion in the liquid metal, a set of time-temperature-transformation (TTT) diagrams are constructed to represent the effects of time and temperature on the isothermal growth and dissolution behavior of fourteen types of individual inclusions. The non-isothermal behavior of growth and dissolution of inclusions is predicted from their isothermal behavior by constructing continuous-cooling-transformation (CCT) diagrams using Scheil additive rule. A well verified fluid flow and heat transfer model developed at Penn State is used to calculate the temperature and velocity fields in the weld pool for different welding processes. A turbulent model considering enhanced viscosity and thermal conductivity (k-ε model) is applied. The calculations show that there is vigorous circulation of metal in the weld pool. The heat transfer and fluid flow model helps to understand not only the fundamentals of the physical phenomena (luring welding, but also the basis to study the growth and dissolution of inclusions. The calculations of particle tracking of thousands of inclusions show that most inclusions undergo complex gyrations and thermal cycles in the weld pool. The inclusions experience both growth and dissolution during their lifetime. Thermal cycles of thousand of inclusions nucleated in the liquid region are tracked and their growth and dissolution are calculated to estimate the final size distribution and number density of inclusions statistically. The calculations show that welding conditions and weld metal compositions affect the inclusion characteristics significantly. Good agreement between the computed and the experimentally observed inclusion size distribution indicates that the inclusion behavior in the weld pool can be understood from the fundamentals of transport phenomena and transformation kinetics.

Silver Nanoparticles: A study of dissolution, kinetics, and factors affecting pulmonary inflammation

NASA Astrophysics Data System (ADS)

Saunders, Eric L.

The growing use of silver (Ag) nanoparticles (NP) in consumer and industrial goods has led to an increase in interest in the health effects associated with exposure, both occupationally and environmentally. The aim of this research is to examine the contribution of size, shape, and dissolution of AgNP, with its corresponding effect on pulmonary inflammation and clearance. In addition this study looks at metallothionein (MT) and the role it plays as an inflammatory modulator. A nose only exposure method was used to expose three strains of mouse (two inbred, one knockout) to two different sizes of AgNP (˜25 nm and ˜100 nm). This research demonstrates that size, chemistry, and dissolution play key roles in NP deposition and inflammatory response, while no conclusions could be drawn about shape. Additionally, this study found that the main factors affecting the deposition of NP in mice both acutely and sub-chronically are particle size and mouse strain. The results of this study also indicate a relationship between MT2 and inflammation. It was found that the mRNA levels of MT2 were greatly up-regulated in the livers and lungs of mice exposed to AgNP, while MT protein levels were not significantly altered to correlate with the altered regulation of mRNA. Finally, this study showed that, for AgNP, the mechanisms of pulmonary clearance and dissolution happened rapidly and that they, combined, likely represent a major pathway of AgNP transport out of the lung. Taken as a whole, the data in this study show that dissolution, coupled with protein interaction, is a significant mediator of pulmonary inflammation and translocation of AgNP.

Dissolution of spent nuclear fuel in carbonate-peroxide solution

NASA Astrophysics Data System (ADS)

Soderquist, Chuck; Hanson, Brady

2010-01-01

This study shows that spent UO2 fuel can be completely dissolved in a room temperature carbonate-peroxide solution apparently without attacking the metallic Mo-Tc-Ru-Rh-Pd fission product phase. In parallel tests, identical samples of spent nuclear fuel were dissolved in nitric acid and in an ammonium carbonate, hydrogen peroxide solution. The resulting solutions were analyzed for strontium-90, technetium-99, cesium-137, europium-154, plutonium, and americium-241. The results were identical for all analytes except technetium, where the carbonate-peroxide dissolution had only about 25% of the technetium that the nitric acid dissolution had.

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

PubMed

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

2015-01-01

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

(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

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 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.

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.

Dissolution kinetics of volatile organic compound vapors in water: An integrated experimental and computational study

NASA Astrophysics Data System (ADS)

Mahmoodlu, Mojtaba G.; Pontedeiro, Elizabeth M.; Pérez Guerrero, Jesús S.; Raoof, Amir; Majid Hassanizadeh, S.; van Genuchten, Martinus Th.

2017-01-01

In this study we performed batch experiments to investigate the dissolution kinetics of trichloroethylene (TCE) and toluene vapors in water at room temperature and atmospheric pressure. The batch systems consisted of a water reservoir and a connected headspace, the latter containing a small glass cylinder filled with pure volatile organic compound (VOC). Results showed that air phase concentrations of both TCE and toluene increased relatively quickly to their maximum values and then became constant. We considered subsequent dissolution into both stirred and unstirred water reservoirs. Results of the stirred experiments showed a quick increase in the VOC concentrations with time up to their solubility limit in water. VOC vapor dissolution was found to be independent of pH. In contrast, salinity had a significant effect on the solubility of TCE and toluene vapors. VOC evaporation and vapor dissolution in the stirred water reservoirs followed first-order rate processes. Observed data could be described well using both simplified analytical solutions, which decoupled the VOC dynamics in the air and water phases, as well as using more complete coupled solutions. However, the estimated evaporation (ke) and dissolution (kd) rate constants differed by up to 70% between the coupled and uncoupled formulations. We also numerically investigated the effects of fluid withdrawal from the small water reservoir due to sampling. While decoupling the VOC air and water phase mass transfer processes produced unreliable estimates of kd, the effects of fluid withdrawal on the estimated rate constants were found to be less important. The unstirred experiments showed a much slower increase in the dissolved VOC concentrations versus time. Molecular diffusion of the VOCs within the aqueous phase became then the limiting factor for mass transfer from air to water. Fluid withdrawal during sampling likely caused some minor convection within the reservoir, which was simulated by increasing the apparent liquid diffusion coefficient.

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.

Biomolecular imaging of 13C-butyrate with dissolution-DNP: Polarization enhancement and formulation for in vivo studies

NASA Astrophysics Data System (ADS)

Flori, Alessandra; Giovannetti, Giulio; Santarelli, Maria Filomena; Aquaro, Giovanni Donato; De Marchi, Daniele; Burchielli, Silvia; Frijia, Francesca; Positano, Vincenzo; Landini, Luigi; Menichetti, Luca

2018-06-01

Magnetic Resonance Spectroscopy of hyperpolarized isotopically enriched molecules facilitates the non-invasive real-time investigation of in vivo tissue metabolism in the time-frame of a few minutes; this opens up a new avenue in the development of biomolecular probes. Dissolution Dynamic Nuclear Polarization is a hyperpolarization technique yielding a more than four orders of magnitude increase in the 13C polarization for in vivo Magnetic Resonance Spectroscopy studies. As reported in several studies, the dissolution Dynamic Nuclear Polarization polarization performance relies on the chemico-physical properties of the sample. In this study, we describe and quantify the effects of the different sample components on the dissolution Dynamic Nuclear Polarization performance of [1-13C]butyrate. In particular, we focus on the polarization enhancement provided by the incremental addition of the glassy agent dimethyl sulfoxide and gadolinium chelate to the formulation. Finally, preliminary results obtained after injection in healthy rats are also reported, showing the feasibility of an in vivo Magnetic Resonance Spectroscopy study with hyperpolarized [1-13C]butyrate using a 3T clinical set-up.

Study on dissolution behavior of polymer-bound and polymer-blended photo-acid generator (PAG) resists

NASA Astrophysics Data System (ADS)

Yamamoto, Hiroki; Kozawa, Takahiro; Tagawa, Seiichi

2013-03-01

The requirements for the next generation resist materials are so challenging that it is indispensable for feasibility of EUV lithography to grasp basic chemistry of resist matrices in all stage of resist processes. Under such circumstances, it is very important to know dissolution characteristics of the resist film into alkaline developer though the dissolution of exposed area of resist films in alkaline developer to form a pattern is a complex reactive process. In this study, the influence of EUV and KrF exposure on the dissolution behavior of polymer bound PAG and polymer blended PAG was studied in detail using quartz crystal microbalance (QCM) methods. The difference in swelling formation between KrF and EUV exposure was observed. It is likely that difference of reaction mechanism induces the difference of these swelling. Also, it is observed that the swelling of polymer-bound PAG is less than that of polymer blended PAG in both KrF and EUV exposure. This result indicates that polymer-bound PAG suppresses swelling very well and showed an excellent performance. Actually, the developed polymer bound-PAG resist showed an excellent performance (half pitch 50 nm line and space pattern). Thus, polymer bound PAG is one of the promising candidate for 16 nm EUV resist.

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.

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.

[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.

Development of megestrol acetate solid dispersion nanoparticles for enhanced oral delivery by using a supercritical antisolvent process.

PubMed

Ha, Eun-Sol; Kim, Jeong-Soo; Baek, In-Hwan; Yoo, Jin-Wook; Jung, Yunjin; Moon, Hyung Ryong; Kim, Min-Soo

2015-01-01

In the present study, solid dispersion nanoparticles with a hydrophilic polymer and surfactant were developed using the supercritical antisolvent (SAS) process to improve the dissolution and oral absorption of megestrol acetate. The physicochemical properties of the megestrol acetate solid dispersion nanoparticles were characterized using scanning electron microscopy, differential scanning calorimetry, powder X-ray diffraction, and a particle-size analyzer. The dissolution and oral bioavailability of the nanoparticles were also evaluated in rats. The mean particle size of all solid dispersion nanoparticles that were prepared was <500 nm. Powder X-ray diffraction and differential scanning calorimetry measurements showed that megestrol acetate was present in an amorphous or molecular dispersion state within the solid dispersion nanoparticles. Hydroxypropylmethyl cellulose (HPMC) solid dispersion nanoparticles significantly increased the maximum dissolution when compared with polyvinylpyrrolidone K30 solid dispersion nanoparticles. The extent and rate of dissolution of megestrol acetate increased after the addition of a surfactant into the HPMC solid dispersion nanoparticles. The most effective surfactant was Ryoto sugar ester L1695, followed by D-α-tocopheryl polyethylene glycol 1000 succinate. In this study, the solid dispersion nanoparticles with a drug:HPMC:Ryoto sugar ester L1695 ratio of 1:2:1 showed >95% rapid dissolution within 30 minutes, in addition to good oral bioavailability, with approximately 4.0- and 5.5-fold higher area under the curve (0-24 hours) and maximum concentration, respectively, than raw megestrol acetate powder. These results suggest that the preparation of megestrol acetate solid dispersion nanoparticles using the supercritical antisolvent process is a promising approach to improve the dissolution and absorption properties of megestrol acetate.

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

PubMed

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

2018-03-01

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

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

PubMed Central

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

2015-01-01

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

Atypical effects of incorporated surfactants on stability and dissolution properties of amorphous polymeric dispersions.

PubMed

Al-Obaidi, Hisham; Lawrence, M Jayne; Buckton, Graham

2016-11-01

To understand the impact of ionic and non-ionic surfactants on the dissolution and stability properties of amorphous polymeric dispersions using griseofulvin (GF) as a model for poorly soluble drugs. Solid dispersions of the poorly water-soluble drug, griseofulvin (GF) and the polymers, poly(vinylpyrrolidone) (PVP) and poly(2-hydroxypropyl methacrylate) (PHPMA), have been prepared by spray drying and bead milling and the effect of the ionic and non-ionic surfactants, namely sodium dodecyl sulphate (SDS) and Tween-80, on the physico-chemical properties of the solid dispersions studied. The X-ray powder diffraction data and hot-stage microscopy showed a fast re-crystallisation of GF. While dynamic vapour sorption (DVS) measurements indicated an increased water uptake, slow dissolution rates were observed for the solid dispersions incorporating surfactants. The order by which surfactants free dispersions were prepared seemed critical as indicated by DVS and thermal analysis. Dispersions prepared by milling with SDS showed significantly better stability than spray-dried dispersions (drug remained amorphous for more than 6 months) as well as improved dissolution profile. We suggest that surfactants can hinder the dissolution by promoting aggregation of polymeric chains, however that effect depends mainly on how the particles were prepared. © 2016 Royal Pharmaceutical Society.

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

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

Improvement of physicomechanical properties of carbamazepine by recrystallization at different pH values.

PubMed

Javadzadeh, Yousef; Mohammadi, Ameneh; Khoei, Nazaninossadat Seyed; Nokhodchi, Ali

2009-06-01

The morphology of crystals has an appreciable impact role on the physicochemical properties of drugs. Drug properties such as flowability, dissolution, hardness and bioavailability may be affected by crystallinity behaviours of drugs. The objective of this study was to achieve an improved physicomechanical property of carbamazepine powder through recrystallization from aqueous solutions at different pH values. For this purpose, carbamazapine was recrystallized from aqueous solutions at different pH values (1, 7, 11). The morphology of crystals was investigated using scanning electron microscopy; X-ray powder diffraction (XRPD) was used to identify polymorphism; thermodynamic properties were analyzed using differential scanning calorimetery (DSC). Dissolution rate was determined using USP dissolution apparatus. Mechanical behavior of recrystallized carbamazepine powders was investigated by making tablets under different compaction pressure and measuring their hardness. SEM studies showed that the carbamazepine crystallization in different media affected the morphology and size of carbamazepine crystals. The shape of carbamazepine crystals changed from flaky or thin plate-like to needle shape. XRPD and DSC results ruled out any crystallinity changes occurring due to the temperature during recrystallization procedure or pH of crystallization media. The crushing strength of tablets indicated that all of the recrystallized carbamazepine samples had better compactiblity than the original carbamazepine powder. In vitro dissolution studies of carbamazepine samples showed a higher dissolution rate for carbamazepine crystals obtained from media with pH 11 and 1. Carbamazepine particles recrystallized from aqueous solutions of different pH values (all media) appeared to have superior mechanical properties to those of the original carbamazepine sample.

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

Autotrophic denitrification supported by biotite dissolution in crystalline aquifers (1): New insights from short-term batch experiments.

PubMed

Aquilina, Luc; Roques, Clément; Boisson, Alexandre; Vergnaud-Ayraud, Virginie; Labasque, Thierry; Pauwels, Hélène; Pételet-Giraud, Emmanuelle; Pettenati, Marie; Dufresne, Alexis; Bethencourt, Lorine; Bour, Olivier

2018-04-01

We investigate denitrification mechanisms through batch experiments using crushed rock and groundwater from a granitic aquifer subject to long term pumping (Ploemeur, France). Except for sterilized experiments, extensive denitrification reaction induces NO 3 decreases ranging from 0.3 to 0.6mmol/L. Carbon concentrations, either organic or inorganic, remain relatively stable and do not document potential heterotrophic denitrification. Batch experiments show a clear effect of mineral dissolution which is documented through cation (K, Na, Ca) and Fluoride production. These productions are tightly related to denitrification progress during the experiment. Conversely, limited amounts of SO 4 , systematically lower than autotrophic denitrification coupled to sulfur oxidation stoichiometry, are produced during the experiments which indicates that sulfur oxidation is not likely even when pyrite is added to the experiments. Analysis of cation ratios, both in isolated minerals of the granite and within water of the batch, allow the mineral dissolution during the experiments to be quantified. Using cation ratios, we show that batch experiments are characterized mainly by biotite dissolution. As biotite contains 21 to 30% of Fe and 0.3 to 1.7% of F, it constitutes a potential source for these two elements. Denitrification could be attributed to the oxidation of Fe(II) contained in biotite. We computed the amount of K and F produced through biotite dissolution when entirely attributing denitrification to biotite dissolution. Computed amounts show that this process may account for the observed K and F produced. We interpret these results as the development of microbial activity which induces mineral dissolution in order to uptake Fe(II) which is used for denitrification. Although pyrite is probably available, SO 4 and cation measurements favor a large biotite dissolution reaction which could account for all the observed Fe production. Chemical composition of groundwater produced from the Ploemeur site indicates similar denitrification processes although original composition shows mainly plagioclase dissolution. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Comparison and analysis of theoretical models for diffusion-controlled dissolution.

PubMed

Wang, Yanxing; Abrahamsson, Bertil; Lindfors, Lennart; Brasseur, James G

2012-05-07

Dissolution models require, at their core, an accurate diffusion model. The accuracy of the model for diffusion-dominated dissolution is particularly important with the trend toward micro- and nanoscale drug particles. Often such models are based on the concept of a "diffusion layer." Here a framework is developed for diffusion-dominated dissolution models, and we discuss the inadequacy of classical models that are based on an unphysical constant diffusion layer thickness assumption, or do not correctly modify dissolution rate due to "confinement effects": (1) the increase in bulk concentration from confinement of the dissolution process, (2) the modification of the flux model (the Sherwood number) by confinement. We derive the exact mathematical solution for a spherical particle in a confined fluid with impermeable boundaries. Using this solution, we analyze the accuracy of a time-dependent "infinite domain model" (IDM) and "quasi steady-state model" (QSM), both formally derived for infinite domains but which can be applied in approximate fashion to confined dissolution with proper adjustment of a concentration parameter. We show that dissolution rate is sensitive to the degree of confinement or, equivalently, to the total concentration C(tot). The most practical model, the QSM, is shown to be very accurate for most applications and, consequently, can be used with confidence in design-level dissolution models so long as confinement is accurately treated. The QSM predicts the ratio of diffusion layer thickness to particle radius (the Sherwood number) as a constant plus a correction that depends on the degree of confinement. The QSM also predicts that the time required for complete saturation or dissolution in diffusion-controlled dissolution experiments is singular (i.e., infinite) when total concentration equals the solubility. Using the QSM, we show that measured differences in dissolution rate in a diffusion-controlled dissolution experiment are a result of differences in the degree of confinement on the increase in bulk concentration independent of container geometry and polydisperse vs single particle dissolution. We conclude that the constant diffusion-layer thickness assumption is incorrect in principle and should be replaced by the QSM with accurate treatment of confinement in models of diffusion-controlled dissolution.

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.

Solid dispersion tablets of breviscapine with polyvinylpyrrolidone K30 for improved dissolution and bioavailability to commercial breviscapine tablets in beagle dogs.

PubMed

Cong, Wenjuan; Shen, Lan; Xu, Desheng; Zhao, Lijie; Ruan, Kefeng; Feng, Yi

2014-09-01

Breviscapine, one of cardiovascular drugs extracted from a Chinese herb Erigeron breviscapinus, has been frequently used to treat cardiovascular diseases such as hypertension, angina pectoris, coronary heart disease and stroke. However, its poor water solubility and low bioavailability in vivo severely restrict the clinical application. To overcome these drawbacks, breviscapine solid dispersion tablets consisting of breviscapine, polyvinylpyrrolidone K30 (PVP K30), microcrystalline cellulose and crospovidone were appropriately prepared. In vitro dissolution profiles showed that breviscapine released percentage of solid dispersion tablets reached 90 %, whereas it was only 40 % for commercial breviscapine tablets. Comparative pharmacokinetic study between solid dispersion tablets and commercial products was investigated on the normal beagle dogs after oral administration. Results showed that the bioavailability of breviscapine was greatly increased by 3.45-fold for solid dispersion tablets. The greatly improved dissolution rate and bioavailability might be attributed to intermolecular hydrogen bonding reactions between PVP K30 and scutellarin. These findings suggest that our solid dispersion tablets can greatly improve the bioavailability as well as the dissolution rate of breviscapine.

Scaling of Convective Mixing in Porous Media

NASA Astrophysics Data System (ADS)

Hidalgo, Juan J.; Fe, Jaime; Cueto-Felgueroso, Luis; Juanes, Ruben

2012-12-01

Convective mixing in porous media is triggered by a Rayleigh-Bénard-type hydrodynamic instability as a result of an unstable density stratification of fluids. While convective mixing has been studied extensively, the fundamental behavior of the dissolution flux and its dependence on the system parameters are not yet well understood. Here, we show that the dissolution flux and the rate of fluid mixing are determined by the mean scalar dissipation rate. We use this theoretical result to provide computational evidence that the classical model of convective mixing in porous media exhibits, in the regime of high Rayleigh number, a dissolution flux that is constant and independent of the Rayleigh number. Our findings support the universal character of convective mixing and point to the need for alternative explanations for nonlinear scalings of the dissolution flux with the Rayleigh number, recently observed experimentally.

High temperature dissolution of oxides in complexing media

NASA Astrophysics Data System (ADS)

Sathyaseelan, Valil S.; Rufus, Appadurai L.; Subramanian, Hariharan; Bhaskarapillai, Anupkumar; Wilson, Shiny; Narasimhan, Sevilimedu V.; Velmurugan, Sankaralingam

2011-12-01

Dissolution of transition metal oxides such as magnetite (Fe 3O 4), mixed ferrites (NiFe 2O 4, ZnFe 2O 4, MgFe 2O 4), bonaccordite (Ni 2FeBO 5) and chromium oxide (Cr 2O 3) in organic complexing media was attempted at higher temperatures (80-180 °C). On increasing the temperature from 80 to 180 °C, the dissolution rate of magnetite in nitrilo triacetic acid (NTA) medium increased six folds. The trend obtained for the dissolution of other oxides was ZnFe 2O 4 > NiFe 2O 4 > MgFe 2O 4 > Cr 2O 3, which followed the same trend as the lability of their metal-oxo bonds. Other complexing agents such as ethylene diamine tetra acetic acid (EDTA), pyridine dicarboxylic acid (PDCA), citric acid and reducing agents viz., oxalic acid and ascorbic acid were also evaluated for their oxide dissolution efficiency at 160 °C. EDTA showed maximum dissolution rate of 21.4 μm/h for magnetite. Addition of oxalic acid/ascorbic acid to complexing media (NTA/EDTA) showed identical effect on the dissolution of magnetite. Addition of hydrazine, another reducing agent, to NTA decreased the rate of dissolution of magnetite by 50%.

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

The development and in vitro evaluation of herbal pellets coated with Eudragit FS 30.

PubMed

Kaledaite, Rasa; Bernatoniene, Jurga; Dvořáčková, Kateřina; Gajdziok, Jan; Muselík, Jan; Pečiūra, Rimantas; Masteikova, Ruta

2014-05-20

Abstract The objective of this study was to prepare pellets of thyme (Thymus vulgaris L.), stinging nettle (Urtica dioica L.) and sage (Salvia officinalis L.) dry extracts by extrusion-spheronization technique to improve technological properties and investigate dissolution profiles of pellets covered different levels of pH-sensitive polymer Eudragit® FS. Optimal sample of pellets were prepared using microcrystalline cellulose and lactose as excipients and demonstrated excellent technological quality properties such as Hausner ratio (1.07 ± 0.11) and compressibility index (6.73 ± 0.94%) value, spericity (0.87 ± 0.001) and friability (0.22 ± 0.08 N). Pellets were coated by 10-35% (w/w) of Eudragit® FS. Dissolution studies showed that less than 20% of coating could not prevent dissolution of phenols in pH 1.2, 20% Eudragit® FS coating is enough to prevent herbal extract against dissolution in the stomach. There were observed no statistical significant differences between 20% and 25% or higher amount of coating polymer to a dissolution of phenols in low pH.

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.

[Aluminum dissolution and changes of pH in soil solution during sorption of copper by aggregates of paddy soil].

PubMed

Xu, Hai-Bo; Zhao, Dao-Yuan; Qin, Chao; Li, Yu-Jiao; Dong, Chang-Xun

2014-01-01

Size fractions of soil aggregates in Lake Tai region were collected by the low-energy ultrasonic dispersion and the freeze-desiccation methods. The dissolution of aluminum and changes of pH in soil solution during sorption of Cu2+ and changes of the dissolution of aluminum at different pH in the solution of Cu2+ by aggregates were studied by the equilibrium sorption method. The results showed that in the process of Cu2+ sorption by aggregates, the aluminum was dissoluted and the pH decreased. The elution amount of aluminum and the decrease of pH changed with the sorption of Cu2+, both increasing with the increase of Cu2+ sorption. Under the same conditions, the dissolution of aluminum and the decrease of pH were in the order of coarse silt fraction > silt fraction > sand fraction > clay fraction, which was negatively correlated with the amount of iron oxide, aluminum and organic matter. It suggested that iron oxide, aluminum and organic matters had inhibitory and buffering effect on the aluminum dissolution and the decrease of pH during the sorption of Cu2+.

Dissolution without disappearing: multicomponent gas exchange for CO2 bubbles in a microfluidic channel.

PubMed

Shim, Suin; Wan, Jiandi; Hilgenfeldt, Sascha; Panchal, Prathamesh D; Stone, Howard A

2014-07-21

We studied the dissolution dynamics of CO2 gas bubbles in a microfluidic channel, both experimentally and theoretically. In the experiments, spherical CO2 bubbles in a flow of a solution of sodium dodecyl sulfate (SDS) first shrink rapidly before attaining an equilibrium size. In the rapid dissolution regime, the time to obtain a new equilibrium is 30 ms regardless of SDS concentration, and the equilibrium radius achieved varies with the SDS concentration. To explain the lack of complete dissolution, we interpret the results by considering the effects of other gases (O2, N2) that are already dissolved in the aqueous phase, and we develop a multicomponent dissolution model that includes the effect of surface tension and the liquid pressure drop along the channel. Solutions of the model for a stationary gas bubble show good agreement with the experimental results, which lead to our conclusion that the equilibrium regime is obtained by gas exchange between the bubbles and liquid phase. Also, our observations from experiments and model calculations suggest that SDS molecules on the gas-liquid interface form a diffusion barrier, which controls the dissolution behaviour and the eventual equilibrium radius of the bubble.

Formulation and Solid State Characterization of Nicotinamide-based Co-crystals of Fenofibrate

PubMed Central

Shewale, Sheetal; Shete, A. S.; Doijad, R. C.; Kadam, S. S.; Patil, V. A.; Yadav, A. V.

2015-01-01

The present investigation deals with formulation of nicotinamide-based co-crystals of fenofibrate by different methods and solid-state characterization of the prepared co-crystals. Fenofibrate and nicotinamide as a coformer in 1:1 molar ratio were used to formulate molecular complexes by kneading, solution crystallization, antisolvent addition and solvent drop grinding methods. The prepared molecular complexes were characterized by powder X-ray diffractometry, differential scanning calorimetry, Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy and in vitro dissolution study. Considerable improvement in the dissolution rate of fenofibrate from optimized co-crystal formulation was due to an increased solubility that is attributed to the super saturation from the fine co-crystals is faster because of large specific surface area of small particles and prevention of phase transformation to pure fenofibrate. In vitro dissolution study showed that the formation of co-crystals improves the dissolution rate of fenofibrate. Nicotinamide forms the co-crystals with fenofibrate, theoretically and practically. PMID:26180279

[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.

EFFECT OF MAGNESIUM STEARATE CONCENTRATION ON DISSOLUTION PROPERTIES OF RANITIDINE HYDROCHLORIDE COATED TABLETS

PubMed Central

Uzunović, Alija; Vranić, Edina

2007-01-01

Most pharmaceutical formulations also include a certain amount of lubricant to improve their flowability and prevent their adhesion to the surfaces of processing equipment. Magnesium stearate is an additive that is most frequently used as a lubricant. Magnesium stearate is capable of forming films on other tablet excipients during prolonged mixing, leading to a prolonged drug liberation time, a decrease in hardness, and an increase in disintegration time. It is hydrophobic, and there are many reports in the literature concerning its adverse effect on dissolution rates. The objective of this study was to evaluate the effects of two different concentrations of magnesium stearate on dissolution properties of ranitidine hydrochloride coated tablet formulations labeled to contain 150 mg. The uniformity content was also checked. During the drug formulation development, several samples were designed for choice of the formulation. For this study, two formulations containing 0,77 and 1,1% of magnesium stearate added in the manufacture of cores were chosen. Fraction of ranitidine hydrochloride released in dissolution medium was calculated from calibration curves. The data were analyzed using pharmaco-peial test for similarity of dissolution profiles (f2 equation), previously proposed by Moore and Flanner. Application of f2 equation showed differences in time-course of ranitidine hydrochloride dissolution properties. The obtained values indicate differences in drug release from analyzed ranitidine hydrochloride formulations and could cause differences in therapeutic response. PMID:17848158

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

PubMed

Ghorab, M K; Adeyeye, M C

2001-08-01

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

[Study on solid dispersion of precipitated calcium carbonate-based oleanolic acid].

PubMed

Yan, Hong-mei; Zhang, Zhen-hai; Jia, Xiao-bin; Jiang, Yan-rong; Sun, E

2015-05-01

Oleanolic acid-precipitated calcium carbonate solid dispersion was prepared by using solvent evaporation method. The microscopic structure and physicochemical properties of solid dispersion were analyzed using differential scanning calorimetry and scanning electron microscopy (SEM). And its in vitro release also was investigated. The properties of the precipitated calcium carbonate was studied which was as a carrier of oleanolic acid solid dispersion. Differential scanning calorimetry analysis suggested that oleanolic acid may be present in solid dispersion as amorphous substance. The in vitro release determination results of oleanolic acid-precipitated calcium carbonate (1: 5) solid dispersion showed accumulated dissolution rate of.oleanolic acid was up to 90% at 45 min. Accelerating experiment showed that content and in vitro dissolution of oleanolic acid solid dispersion did not change after storing over 6 months. The results indicated that in vitro dissolution of oleanolic acid was improved greatly by the solid dispersion with precipitated calcium carbonate as a carrier. The solid dispersion is a stabilizing system which has actual applied value.

Influence of Structural Defects on Biomineralized ZnS Nanoparticle Dissolution: An In-Situ Electron Microscopy Study

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

Eskelsen, Jeremy R.; Xu, Jie; Chiu, Michelle Y.

The dissolution of metal sulfides, such as ZnS, plays an important role in the fate of metal contaminants in the environment. Here we have examined the dissolution behavior of ZnS nanoparticles synthesized via several abiotic and biological pathways. Specifically, the biogenic ZnS nanoparticles were produced by an anaerobic, metal-reducing bacterium Thermoanaerobacter sp. X513 in a Zn-amended, thiosulfate-containing growth medium, whereas the abiogenic ZnS nanoparticles were produced by mixing an aqueous Zn solution with either H 2S-rich gas or Na 2S solution. For biogenic synthesis, we prepared two types of samples, in the presence or absence of trace silver (Ag). Themore » size distribution, crystal structure, aggregation behavior, and internal defects of the synthesized ZnS nanoparticles were primarily examined using high-resolution transmission electron microscopy coupled with X-ray energy dispersive spectroscopy. The characterization results show that both the biogenic and abiogenic samples were dominantly composed of sphalerite. In the absence of Ag, the biogenic ZnS nanoparticles were significantly larger (i.e., ~10 nm) than the abiogenic ones (i.e., ~3–5 nm) and contained structural defects (e.g., twins and stacking faults). The presence of trace Ag showed a restraining effect on the particle size of the biogenic ZnS, resulting in quantum-dot-sized nanoparticles (i.e., ~3 nm). In situ dissolution experiments for the synthesized ZnS were conducted with a liquid-cell coupled to a transmission electron microscope (LCTEM), and the primary factors (i.e., the presence or absence structural defects) were evaluated for their effects on the dissolution behavior using the biogenic and abiogenic ZnS nanoparticle samples with the largest average particle size. Analysis of the dissolution results (i.e., change in particle radius with time) using the Kelvin equation shows that the defect-bearing biogenic ZnS nanoparticles (γ = 0.799 J/m 2) have a significantly higher surface energy than the abiogenic ZnS nanoparticles (γ = 0.277 J/m 2), suggesting that larger defect-bearing ZnS nanoparticles may be more reactive than the smaller quantum-dot-sized ZnS nanoparticles. These findings provide new insight into the factors that govern the dissolution of metal sulfide nanoparticles in relevant natural and engineered scenarios, and have implication for tracking the fate of zinc at contaminated sites. Moreover, our study exemplified the use of an in situ method (i.e., LCTEM) to investigate nanoparticle behavior (e.g., dissolution) in aqueous solutions.« less

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.

Salt dissolution and sinkhole formation: Results of laboratory experiments

NASA Astrophysics Data System (ADS)

Oz, Imri; Eyal, Shalev; Yoseph, Yechieli; Ittai, Gavrieli; Elad, Levanon; Haim, Gvirtzman

2016-10-01

The accepted mechanism for the formation of thousands of sinkholes along the coast of the Dead Sea suggests that their primary cause is dissolution of a salt layer by groundwater undersaturated with respect to halite. This is related to the drop in the Dead Sea level, which caused a corresponding drop of the freshwater-saltwater interface, resulting in fresher groundwater replacing the brines that were in contact with the salt layer. In this study we used physical laboratory experiments to examine the validity of this mechanism by reproducing the full dynamic natural process and to examine the impact of different hydrogeological characteristics on this process. The experimental results show surface subsidence and sinkhole formation. The stratigraphic configurations of the aquifer, together with the mechanical properties of the salt layer, determine the dynamic patterns of the sinkhole formation (instantaneous versus gradual formation). Laboratory experiments were also used to study the potential impact of future stratification in the Dead Sea, if and when the "Red Sea-Dead Sea Canal" project is carried out, and the Dead Sea level remains stable. The results show that the dissolution rates are slower by 1 order of magnitude in comparison with a nonstratified saltwater body, and therefore, the processes of salt dissolution and sinkhole formation will be relatively restrained under these conditions.

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

PubMed

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

2015-11-03

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

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

PubMed

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

2011-09-01

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

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

PubMed

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

2016-08-01

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

An attempt to stabilize tanshinone IIA solid dispersion by the use of ternary systems with nano-CaCO3 and poloxamer 188.

PubMed

Yan, Hong-Mei; Zhang, Zhen-Hai; Jiang, Yan-Rong; Ding, Dong-Mei; Sun, E; Jia, Xiao-Bin

2014-04-01

Tanshinone IIA (TSIIA) on solid dispersions (SDs) has thermodynamical instability of amorphous drug. Ternary solid dispersions (tSDs) can extend the stability of the amorphous form of drug. Poloxamer 188 was used as a SD carrier. Nano-CaCO3 played an important role in adsorption of biomolecules and is being developed for a host of biotechnological applications. The aim of the present study was to investigate the dissolution behavior and accelerated stability of TSIIA on solid dispersions (SDs) by the use of ternary systems with nano-CaCO3 and poloxamer 188. The TSIIA tSDs were prepared by a spray-drying method. First, the effect of combination of poloxamer 188 and nano-CaCO3 on TSIIA dissolution was studied. Subsequently, a set of complementary techniques (DSC, XRPD, SEM and FTIR) was used to monitor the physical changes of TSIIA in the SDs. Finally, stability test was carried out under the conditions 40°C/75% RH for 6 months. The characterization of tSDs by differential scanning calorimetry analysis (DSC) and X-ray powder diffraction (XRPD) showed that TSIIA was present in its amorphous form. Fourier transforms infrared spectroscopy (FTIR) suggested the presence of interactions between TSIIA and carriers in tSDs. Improvement in the dissolution rate was observed for all SDs. The stability study conducted on SDs with nano-CaCO3 showed stable drug content and dissolution behavior, over the period of 6 months as compared with freshly prepared SDs. SDs preparation with nano-CaCO3 and poloxamer 188 may be a promising approach to enhance the dissolution and stability of TSIIA.

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

PubMed Central

Taneja, Sonali; Mishra, Neha; Malik, Shubhra

2014-01-01

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

Calcium Carbonate Dissolution Above the Lysocline: Implications of Copepod Grazing on Coccolithophores

NASA Astrophysics Data System (ADS)

White, M. M.; Waller, J. D.; Lubelczyk, L.; Drapeau, D.; Bowler, B.; Wyeth, A.; Fields, D.; Balch, W. M.

2016-02-01

Copepod-coccolithophore predator-prey interactions are of great importance because they facilitate the export of particulate inorganic and organic carbon (PIC and POC) from the surface ocean. Coccolith dissolution in acidic copepod guts has been proposed as a possible explanation for the paradox of PIC dissolution above the lysocline, but warrants further investigation. Using a new application of the 14C-microdiffusion technique, we investigated the dissolution of coccoliths in copepod guts. We considered both an estuarine predator-prey model (Acartia tonsa and Pleurochrysis carterae) and an open ocean predator-prey model (Calanus finmarchicus and Emiliania huxleyi). Additionally, we considered the impacts of pCO2 on this process to advance our understanding of the effects of ocean acidification on trophic interactions. In the estuarine predator-prey model, fecal pellets produced immediately after previously-starved copepods grazed on P. carterae had PIC/POC ratios 27-40 % lower than that of the algae, indicating PIC dissolution within the copepod gut, with no impact of pCO2 on this dissolution. Subsequent fecal pellets showed increasing PIC/POC, suggesting that calcite dissolution decreases as the gut fills. The open ocean predator-prey model showed equivocal results, indicating high variability among individual grazing behavior, and therefore no consistent impact of copepod grazing on coccolith dissolution above the lysocline in the open ocean. We will further discuss the effects of fecal pellet PIC/POC ratios on sinking rate.

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.

Two-phase convective CO 2 dissolution in saline aquifers

DOE PAGES

Martinez, Mario J.; Hesse, Marc A.

2016-01-30

Geologic carbon storage in deep saline aquifers is a promising technology for reducing anthropogenic emissions into the atmosphere. Dissolution of injected CO 2 into resident brines is one of the primary trapping mechanisms generally considered necessary to provide long-term storage security. Given that diffusion of CO 2 in brine is woefully slow, convective dissolution, driven by a small increase in brine density with CO 2 saturation, is considered to be the primary mechanism of dissolution trapping. Previous studies of convective dissolution have typically only considered the convective process in the single-phase region below the capillary transition zone and have eithermore » ignored the overlying two-phase region where dissolution actually takes place or replaced it with a virtual region with reduced or enhanced constant permeability. Our objective is to improve estimates of the long-term dissolution flux of CO 2 into brine by including the capillary transition zone in two-phase model simulations. In the fully two-phase model, there is a capillary transition zone above the brine-saturated region over which the brine saturation decreases with increasing elevation. Our two-phase simulations show that the dissolution flux obtained by assuming a brine-saturated, single-phase porous region with a closed upper boundary is recovered in the limit of vanishing entry pressure and capillary transition zone. For typical finite entry pressures and capillary transition zone, however, convection currents penetrate into the two-phase region. As a result, this removes the mass transfer limitation of the diffusive boundary layer and enhances the convective dissolution flux of CO 2 more than 3 times above the rate assuming single-phase conditions.« less

Improving dissolution and oral bioavailability of pranlukast hemihydrate by particle surface modification with surfactants and homogenization

PubMed Central

Ha, Eun-Sol; Baek, In-hwan; Yoo, Jin-Wook; Jung, Yunjin; Kim, Min-Soo

2015-01-01

The present study was carried out to develop an oral formulation of pranlukast hemihydrate with improved dissolution and oral bioavailability using a surface-modified microparticle. Based on solubility measurements, surface-modified pranlukast hemihydrate microparticles were manufactured using the spray-drying method with hydroxypropylmethyl cellulose, sucrose laurate, and water and without the use of an organic solvent. The hydrophilicity of the surface-modified pranlukast hemihydrate microparticle increased, leading to enhanced dissolution and oral bioavailability of pranlukast hemihydrate without a change in crystallinity. The surface-modified microparticles with an hydroxypropylmethyl cellulose/sucrose laurate ratio of 1:2 showed rapid dissolution of up to 85% within 30 minutes in dissolution medium (pH 6.8) and oral bioavailability higher than that of the commercial product, with approximately 2.5-fold and 3.9-fold increases in area under the curve (AUC0→12 h) and peak plasma concentration, respectively. Therefore, the surface-modified microparticle is an effective oral drug delivery system for the poorly water-soluble therapeutic pranlukast hemihydrate. PMID:26150699

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

NASA Astrophysics Data System (ADS)

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

2018-07-01

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

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

NASA Astrophysics Data System (ADS)

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

2017-02-01

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

[Study on solid dispersion of copovidone-based tanshinone II(A)].

PubMed

Jiang, Yan-Rong; Zhang, Zhen-Hai; Xia, Hai-Jiang; Jia, Xiao-Bin

2013-01-01

To apply PVP-S630 in the preparation of tanshinone II(A) (TS II(A)) solid dispersion, in order to improve its dissolution in vitro and reduce the moisture absorption of the solid dispersion. Tanshinone II(A) solid dispersion was prepared by spray drying method. Such analytical methods as SEM, DSC, XRD were used to characterize their phases and detect their dissolution, moisture absorption and stability. In the solid dispersion prepared with tanshinone II(A) and copovidone with proportion of 1:10, tanshinone II(A) was scattered on the surface of the carrier in the amorphous form, with a dissolution in vitro up to 100% at 0.5 h and a lower moisture absorption than PVP-K30 solid dispersion prepared with the same proportion. After a three-month accelerated stability test, it showed no significant change in drug dissolution and content. The solid dispersion prepared with copovidone as the carrier can significantly improve the dissolution of tanshinone II(A), with a relatively low moisture absorption and high stability, thereby having a good prospect of application.

Solid-state, triboelectrostatic and dissolution characteristics of spray-dried piroxicam-glucosamine solid dispersions.

PubMed

Adebisi, Adeola O; Kaialy, Waseem; Hussain, Tariq; Al-Hamidi, Hiba; Nokhodchi, Ali; Conway, Barbara R; Asare-Addo, Kofi

2016-10-01

This work explores the use of both spray drying and d-glucosamine HCl (GLU) as a hydrophilic carrier to improve the dissolution rate of piroxicam (PXM) whilst investigating the electrostatic charges associated with the spray drying process. Spray dried PXM:GLU solid dispersions were prepared and characterised (XRPD, DSC, SEM). Dissolution and triboelectric charging were also conducted. The results showed that the spray dried PXM alone, without GLU produced some PXM form II (DSC results) with no enhancement in solubility relative to that of the parent PXM. XRPD results also showed the spray drying process to decrease the crystallinity of GLU and solid dispersions produced. The presence of GLU improved the dissolution rate of PXM. Spray dried PXM: GLU at a ratio of 2:1 had the most improved dissolution. The spray drying process generally yielded PXM-GLU spherical particles of around 2.5μm which may have contributed to the improved dissolution. PXM showed a higher tendency for charging in comparison to the carrier GLU (-3.8 versus 0.5nC/g for untreated material and -7.5 versus 3.1nC/g for spray dried materials). Spray dried PXM and spray dried GLU demonstrated higher charge densities than untreated PXM and untreated GLU, respectively. Regardless of PXM:GLU ratio, all spray dried PXM:GLU solid dispersions showed a negligible charge density (net-CMR: 0.1-0.3nC/g). Spray drying of PXM:GLU solid dispersions can be used to produce formulation powders with practically no charge and thereby improving handling as well as dissolution behaviour of PXM. Copyright © 2016 Elsevier B.V. All rights reserved.

Pore-scale supercritical CO 2 dissolution and mass transfer under drainage conditions

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

Chang, Chun; Zhou, Quanlin; Oostrom, Mart

Abstract: Recently, both core- and pore-scale imbibition experiments have shown non-equilibrium dissolution of supercritical CO 2 (scCO 2) and a prolonged depletion of residual scCO 2. In this study, pore-scale scCO 2 dissolution and mass transfer under drainage conditions were investigated using a two-dimensional heterogeneous micromodel and a novel fluorescent water dye with a sensitive pH range between 3.7 and 6.5. Drainage experiments were conducted at 9 MPa and 40 °C by injecting scCO 2 into the sandstone-analogue pore network initially saturated by water without dissolved CO 2 (dsCO 2). During the experiments, time-lapse images of dye intensity, reflecting watermore » pH, were obtained. These images show non-uniform pH in individual pores and pore clusters, with average pH levels gradually decreasing with time. Further analysis on selected pores and pore clusters shows that (1) rate-limited mass transfer prevails with slowly decreasing pH over time when the scCO 2-water interface area is low with respect to the volume of water-filled pores and pore clusters, (2) fast scCO 2 dissolution and phase equilibrium occurs when scCO 2 bubbles invade into water-filled pores, significantly enhancing the area-to-volume ratio, and (3) a transition from rate-limited to diffusion-limited mass transfer occurs in a single pore when a medium area-to-volume ratio is prevalent. The analysis also shows that two fundamental processes – scCO 2 dissolution at phase interfaces and diffusion of dsCO 2 at the pore scale (10-100 µm) observed after scCO 2 bubble invasion into water-filled pores without pore throat constraints – are relatively fast. The overall slow dissolution of scCO 2 in the millimeter-scale micromodel can be attributed to the small area-to-volume ratios that represent pore-throat configurations and characteristics of phase interfaces. This finding is applicable for the behavior of dissolution at pore, core, and field scales when water-filled pores and pore clusters of varying size are surrounded by scCO 2 at narrow pore throats.« less

The impact of antibacterial handsoap constituents on the dynamics of triclosan dissolution from dry sand.

PubMed

Koehler, Daniel A; Strevett, Keith A; Papelis, Charalambos; Kibbey, Tohren C G

2017-11-01

Triclosan has been widely used as an antibacterial agent in consumer and industrial products, and large quantities continue to be discharged to natural waters annually. The focus of this work was on studying the dynamics of triclosan dissolution following evaporative drying. Warm weather can cause the water in intermittent streams or the unsaturated zone to evaporate, causing nonvolatile compounds to form solid precipitates. Because dissolution of precipitates is a relatively slow process, the dynamics of dissolution following evaporation may play an important role in controlling the release of contaminants to the environment. The specific purpose of the work was to explore the effects of surfactant co-contaminants from an industrial antibiotic handsoap on the dissolution dynamics of triclosan. The work used a fiber optic-based optical cell to conduct stirred-batch dissolution experiments for sands coated with different mass loadings of triclosan. Results show that the presence of surfactants from the hand soap not only increase the apparent equilibrium solubility, but also increase the rate of approach to equilibrium. A model describing the dissolution process was developed, and was found to be consistent with experimental data. Results of the work suggest that even small solubility enhancement by surfactant co-contaminants may have a significant impact on dissolution dynamics. Because waters containing significant quantities of triclosan are also among those most likely to contain surfactant co-contaminants, it is likely that the release of triclosan to the environment following evaporation may be faster in many cases than would be predicted from experiments based on pure triclosan. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development of paracetamol-caffeine co-crystals to improve compressional, formulation and in vivo performance.

PubMed

Latif, Sumera; Abbas, Nasir; Hussain, Amjad; Arshad, Muhammad Sohail; Bukhari, Nadeem Irfan; Afzal, Hafsa; Riffat, Sualeha; Ahmad, Zeeshan

2018-07-01

Paracetamol, a frequently used antipyretic and analgesic drug, has poor compression moldability owing to its low plasticity. In this study, new co-crystals of paracetamol (PCM) with caffeine (as a co-former) were prepared and delineated. Co-crystals exhibited improved compaction and mechanical behavior. A screening study was performed by utilizing a number of methods namely dry grinding, liquid assisted grinding (LAG), solvent evaporation (SE), and anti-solvent addition using various weight ratios of starting materials. LAG and SE were found successful in the screening study. Powders at 1:1 and 2:1 weight ratio of PCM/CAF by LAG and SE, respectively, resulted in the formation of co-crystals. Samples were characterized by PXRD, DSC, and ATR-FTIR techniques. Compressional properties of PCM and developed co-crystals were analyzed by in-die heckle model. Mean yield pressure (Py), an inverse measure of plasticity, obtained from the heckle plots decreased significantly (p < .05) for co-crystals than pure drug. Intrinsic dissolution profile of co-crystals showed up to 2.84-fold faster dissolution than PCM and physical mixtures in phosphate buffer pH 6.8 at 37 °C. In addition, co-crystals formulated into tablets by direct compression method showed better mechanical properties like hardness and tensile strength. In vitro dissolution studies on tablets also showed enhanced dissolution profiles (∼90-97%) in comparison to the tablets of PCM prepared by direct compression (∼55%) and wet granulation (∼85%) methods. In a single dose sheep model study, co-crystals showed up to twofold increase in AUC and C max . A significant (p < .05) decrease in clearance as compared to pure drug was also recorded. In conclusion, new co-crystals of PCM were successfully prepared with improved tabletability in vitro and in vivo profile. Enhancement in AUC and C max of PCM by co-crystallization might suggest the dose reduction and avoidance of side effects.

Physiochemical Characterization and Release Rate Studies of SolidDispersions of Ketoconazole with Pluronic F127 and PVP K-30

PubMed Central

Kumar, Pankaj; Mohan, Chander; KanamSrinivasan Uma Shankar, Mara; Gulati, Monica

2011-01-01

In the present study solid dispersions of the antifungal drug Ketoconazole were prepared with Pluronic F-127 and PVP K-30 with an intention to improve its dissolution properties. Investigations of the properties of the dispersions were performed using release studies, Differential scanning calorimetery (DSC), X-ray powder diffraction (XRD) and Fourier transform infrared (FTIR). The results obtained showed that the rate of dissolution of Ketoconazole was considerably improved when formulated in solid dispersions with PVP K-30 and Pluronic F-127 as compared with pure drug and physical mixtures. The results from DSC and XRD studies showed the transition of crystalline nature of drug to amorphous form, while FTIR studies demonstrated the absence of drug-carriers interaction. PMID:24250403

Understanding and optimizing the dual excipient functionality of sodium lauryl sulfate in tablet formulation of poorly water soluble drug: wetting and lubrication.

PubMed

Aljaberi, Ahmad; Chatterji, Ashish; Dong, Zedong; Shah, Navnit H; Malick, Waseem; Singhal, Dharmendra; Sandhu, Harpreet K

2013-01-01

To evaluate and optimize sodium lauryl sulfate (SLS) and magnesium stearate (Mg.St) levels, with respect to dissolution and compaction, in a high dose, poorly soluble drug tablet formulation. A model poorly soluble drug was formulated using high shear aqueous granulation. A D-optimal design was used to evaluate and model the effect of granulation conditions, size of milling screen, SLS and Mg.St levels on tablet compaction and ejection. The compaction profiles were generated using a Presster(©) compaction simulator. Dissolution of the kernels was performed using a USP dissolution apparatus II and intrinsic dissolution was determined using a stationary disk system. Unlike kernels dissolution which failed to discriminate between tablets prepared with various SLS contents, the intrinsic dissolution rate showed that a SLS level of 0.57% was sufficient to achieve the required release profile while having minimal effect on compaction. The formulation factors that affect tablet compaction and ejection were identified and satisfactorily modeled. The design space of best factor setting to achieve optimal compaction and ejection properties was successfully constructed by RSM analysis. A systematic study design helped identify the critical factors and provided means to optimize the functionality of key excipient to design robust drug product.

Effects of coformers on phase transformation and release profiles of carbamazepine cocrystals in hydroxypropyl methylcellulose based matrix tablets.

PubMed

Qiu, Shi; Li, Mingzhong

2015-02-01

The aim of this study was to investigate the effects of coformers on phase transformation and release profiles of carbamazepine (CBZ) cocrystals in hydroxypropyl methylcellulose (HPMC) based matrix tablets. It has been found that selection of different coformers of saccharin (SAC) and cinnamic acid (CIN) can affect the stability of CBZ cocrystals in solution, resulting in significant differences in the apparent solubility of CBZ. The dissolution advantage of CBZ-SAC cocrystals can only be shown for a short period during dissolution because of the fast conversion to its dihydrate form (DH). HPMC can partially inhibit the crystallisation of CBZ DH during dissolution of CBZ-SAC cocrystal. However, the increased viscosity of HPMC dissolution medium reduced the dissolution rate of CBZ-SAC cocrystals. Therefore the CBZ-SAC cocrystal formulation did not show any significant advantage in CBZ release rate. In contrast the improved CBZ dissolution rate of CBZ-CIN cocrystal can be realised in both solution and formulation due to its high stability. In conclusion, exploring and understanding the mechanisms of the phase transformation of pharmaceutical cocrystals in aqueous medium for selection of lead cocrystals is the key for success of product development. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of ball milling on the physicochemical properties of atorvastatin calcium sesquihydrate: the dissolution kinetic behaviours of milled amorphous solids.

PubMed

Kobayashi, Makiko; Hattori, Yusuke; Sasaki, Tetsuo; Otsuka, Makoto

2017-01-01

The purposes of this study were to clarify the amorphization by ball milling of atorvastatin calcium sesquihydrate (AT) and to analyse the change in dissolution kinetics. The amorphous AT was prepared from crystal AT by ball milling and analysed in terms of the changes of its physicochemical properties by powder X-ray diffraction analysis (XRD), thermal analysis and infrared spectroscopy (IR). Moreover, to evaluate the usefulness of the amorphous form for pharmaceutical development, intrinsic solubility of the ground product was evaluated using a dissolution kinetic method. The XRD results indicated that crystalline AT was transformed into amorphous solids by more than 30-min milling. The thermal analysis result suggested that chemical potential of the ground AT are changed significantly by milling. The IR spectra of the AT showed the band shift from the amide group at 3406 cm -1 with an intermolecular hydrogen bond to a free amide group at 3365 cm -1 by milling. The dissolution of amorphous AT follows a dissolution kinetic model involving phase transformation. The initial dissolution rate of the ground product increased with the increase in milling time to reflect the increase in the intrinsic solubility based on the amorphous state. © 2016 Royal Pharmaceutical Society.

Evaluation of the impact of sodium lauryl sulfate source variability on solid oral dosage form development.

PubMed

Qiang, Dongmei; Gunn, Jocelyn A; Schultz, Leon; Li, Z Jane

2010-12-01

The objective of this study was to investigate the effects of sodium lauryl sulfate (SLS) from different sources on solubilization/wetting, granulation process, and tablet dissolution of BILR 355 and the potential causes. The particle size distribution, morphology, and thermal behaviors of two pharmaceutical grades of SLS from Spectrum and Cognis were characterized. The surface tension and drug solubility in SLS solutions were measured. The BILR 355 tablets were prepared by a wet granulation process and the dissolution was evaluated. The critical micelle concentration was lower for Spectrum SLS, which resulted in a higher BILR 355 solubility. During wet granulation, less water was required to reach the same end point using Spectrum than Cognis SLS. In general, BILR 355 tablets prepared with Spectrum SLS showed a higher dissolution than the tablets containing Cognis SLS. Micronization of SLS achieved the same improved tablet dissolution as micronized active pharmaceutical ingredient. The observed differences in wetting and solubilization were likely due to the different impurity levels in SLS from two sources. This study demonstrated that SLS from different sources could have significant impact on wet granulation process and dissolution. Therefore, it is critical to evaluate SLS properties from different suppliers, and then identify optimal formulation and process parameters to ensure robustness of drug product manufacture process and performance.

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

NASA Astrophysics Data System (ADS)

Seidel, J.; Ulrich, J.

2017-07-01

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

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

PubMed

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

2007-03-01

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

Single-step preparation and deagglomeration of itraconazole microflakes by supercritical antisolvent method for dissolution enhancement.

PubMed

Sathigari, Sateesh Kumar; Ober, Courtney A; Sanganwar, Ganesh P; Gupta, Ram B; Babu, R Jayachandra

2011-07-01

Itraconazole (ITZ) microflakes were produced by supercritical antisolvent (SAS) method and simultaneously mixed with pharmaceutical excipients in a single step to prevent drug agglomeration. Simultaneous ITZ particle formation and mixing with fast-flo lactose (FFL) was performed in a high-pressure stirred vessel at 116 bar and 40 °C by the SAS-drug excipient mixing (SAS-DEM) method. The effects of stabilizers, such as sodium dodecyl sulfate and poloxamer 407 (PLX), on particle formation and drug dissolution were studied. Drug-excipient formulations were characterized for surface morphology, crystallinity, drug-excipient interactions, drug content uniformity, and drug dissolution rate. Mixture of drug microflakes and FFL formed by the SAS-DEM process shows that the process was successful in overcoming drug-drug agglomeration. PLX produced crystalline drug flakes in loose agglomerates with superior dissolution and flow properties even at higher drug loadings. Characterization studies confirmed the crystallinity of the drug and absence of chemical interactions during the SAS process. The dissolution of ITZ was substantially higher due to SAS and SAS-DEM processes; this improvement can be attributed to the microflake particle structures, effective deagglomeration, and wetting of the drug flakes with the excipients. Copyright © 2011 Wiley-Liss, Inc. and the American Pharmacists Association

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

NASA Astrophysics Data System (ADS)

Seidel, J.; Ulrich, J.

2017-02-01

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

Bioenhanced sublingual tablet of drug with limited permeability using novel surfactant binder and microencapsulated polysorbate: In vitro/in vivo evaluation.

PubMed

El-Setouhy, Doaa Ahmed; Basalious, Emad B; Abdelmalak, Nevine Shawky

2015-08-01

Formulation of sublingual tablets of drugs with limited permeability poses a great challenge due to their poor absorption. In this study, bioenhanced sublingual tablets (BESTs) of zolmitriptan were prepared using novel surfactant binder (Pluronic® p123/Syloid® mixture) to enhance tablet disintegration and dissolution. Microencapsulated polysorbate 80 (Sepitrap™ 80) were included in the composition of BESTs to enhance the drug transport through the sublingual mucosa. Tablets were evaluated for in vitro/in vivo disintegration, in vitro dissolution and ex vivo permeation. Solubility studies confirmed that phosphate buffer; pH 6.8 could be used as dissolution medium for sublingual tablets of zolmitriptan. BEST-5 containing Pluronic® p123/Syloid® mixture and Sepitrap™ 80 exhibited the shortest in vitro/in vivo disintegration times (<30s), the highest dissolution at early time dissolution points and the highest enhancement of drug transport through mucosal membrane. The in vivo pharmacokinetic study using human volunteers showed a significant increase in the rate and extent of sublingual absorption with less variations of Tmax after sublingual administration of both BEST-5 and Zomig-ZMT ODT. Our results proposed that Pluronic® p123/Syloid® mixture and Sepitrap™ 80 could be promising for the development of sublingual tablets for rapid onset of action of drugs with limited permeability. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of taste masking technology on fast dissolving oral film: dissolution rate and bioavailability.

PubMed

Zhu, Ying; You, Xinru; Huang, Keqing; Raza, Faisal; Lu, Xin; Chen, Yuejian; Dhinakar, Arvind; Zhang, Yuan; Kang, Yang; Wu, Jun; Ge, Liang

2018-07-27

Fast dissolving oral film is a stamp-style, drug-loaded polymer film with rapid disintegration and dissolution. This new kind of drug delivery system requires effective taste masking technology. Suspension intermediate and liposome intermediate were prepared, respectively, for the formulation of two kinds of fast dissolving oral films with the aim of studying the effect of taste masking technology on the bioavailability of oral films. Loratadine was selected as the model drug. The surface pH of the films was close to neutral, avoiding oral mucosal irritation or side effects. The thickness of a 2 cm × 2 cm suspension oral film containing 10 mg of loratadine was 100 μm. Electron microscope analysis showed that liposomes were spherical before and after re-dissolution, and drugs with obvious bitterness could be masked by the encapsulation of liposomes. Dissolution of the two films was superior to that of the commercial tablets. Rat pharmacokinetic experiments showed that the oral bioavailability of the suspension film was significantly higher than that of the commercial tablets, and the relative bioavailability of the suspension film was 175%. Liposomal film produced a certain amount of improvement in bioavailability, but lower than that of the suspension film.

Effect of taste masking technology on fast dissolving oral film: dissolution rate and bioavailability

NASA Astrophysics Data System (ADS)

Zhu, Ying; You, Xinru; Huang, Keqing; Raza, Faisal; Lu, Xin; Chen, Yuejian; Dhinakar, Arvind; Zhang, Yuan; Kang, Yang; Wu, Jun; Ge, Liang

2018-07-01

Fast dissolving oral film is a stamp-style, drug-loaded polymer film with rapid disintegration and dissolution. This new kind of drug delivery system requires effective taste masking technology. Suspension intermediate and liposome intermediate were prepared, respectively, for the formulation of two kinds of fast dissolving oral films with the aim of studying the effect of taste masking technology on the bioavailability of oral films. Loratadine was selected as the model drug. The surface pH of the films was close to neutral, avoiding oral mucosal irritation or side effects. The thickness of a 2 cm × 2 cm suspension oral film containing 10 mg of loratadine was 100 μm. Electron microscope analysis showed that liposomes were spherical before and after re-dissolution, and drugs with obvious bitterness could be masked by the encapsulation of liposomes. Dissolution of the two films was superior to that of the commercial tablets. Rat pharmacokinetic experiments showed that the oral bioavailability of the suspension film was significantly higher than that of the commercial tablets, and the relative bioavailability of the suspension film was 175%. Liposomal film produced a certain amount of improvement in bioavailability, but lower than that of the suspension film.

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.

The effect of 8.25% sodium hypochlorite on dental pulp dissolution and dentin flexural strength and modulus.

PubMed

Cullen, James K T; Wealleans, James A; Kirkpatrick, Timothy C; Yaccino, John M

2015-06-01

The purpose of this study was to evaluate the effect of various concentrations of sodium hypochlorite (NaOCl), including 8.25%, on dental pulp dissolution and dentin flexural strength and modulus. Sixty dental pulp samples and 55 plane parallel dentin bars were retrieved from extracted human teeth. Five test groups (n = 10) were formed consisting of a pulp sample and dentin bar immersed in various NaOCl solutions. The negative control group (n = 5) consisted of pulp samples and dentin bars immersed in saline. The positive control group (n = 5) consisted of pulp samples immersed in 8.25% NaOCl without a dentin bar. Every 6 minutes for 1 hour, the solutions were refreshed. The dentin bars were tested for flexural strength and modulus with a 3-point bend test. The time until total pulp dissolution and any changes in dentin bar flexural strength and modulus for the different NaOCl solutions were statistically analyzed. An increase in NaOCl concentration showed a highly significant decrease in pulp dissolution time. The pulp dissolution property of 8.25% NaOCl was significantly faster than any other tested concentration of NaOCl. The presence of dentin did not have a significant effect on the dissolution capacity of NaOCl if the solutions were refreshed. NaOCl concentration did not have a statistically significant effect on dentin flexural strength or modulus. Dilution of NaOCl decreases its pulp dissolution capacity. Refreshing the solution is essential to counteract the effects of dentin. In this study, NaOCl did not have a significant effect on dentin flexural strength or modulus. Published by Elsevier Inc.

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

NASA Astrophysics Data System (ADS)

Adcock, C. T.; Hausrath, E.

2011-12-01

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

Formulation and Evaluation of Mouth Dissolving Tablets of Cinnarizine

PubMed Central

Patel, B. P.; Patel, J. K.; Rajput, G. C.; Thakor, R. S.

2010-01-01

The purpose of this research was to develop mouth dissolve tablets of cinnarizine by effervescent, superdisintegrant addition and sublimation methods. All the three formulations were evaluated for disintegration time, hardness and friability, among these superdisintegrant addition method showed lowest disintegration time; hence it was selected for further studies. Further nine batches (B1-B9) were prepared by using crospovidone, croscarmellose sodium and L-HPC in different concentrations such as 5, 7.5 and 10%. All the formulations were evaluated for weight variation, hardness, friability, drug content, in vitro disintegration time, wetting time, in vitro dissolution. Formulation with 10% L-HPC showed the less disintegration time (25.3 s) and less wetting time (29.1 s). In vitro dissolution studies showed total drug release at the end of 6 min. PMID:21218071

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.

The solid state of rebamipide: preparation, characterization, and dissolution.

PubMed

Jeon, Seong Hyeon; Sohn, Young Taek

2016-04-01

Rebamipide is marketed as a peptic ulcer agent under the trade name Mucosta(R). The objective of this work was to investigate the existence of polymorphs and pseudopolymorphs of rebamipide. Two crystal forms of rebamipide were isolated by recrystallization and characterized by differential thermal analysis (DTA), thermogravimetric analysis (TG), powder X-ray diffractometry, infrared spectrometry, and nuclear magnetic resonance. The DTA curve of Form 1 showed one endothermic peak at 305.2 °C, and that of Form 2 showed one endothermic peak at 307.3 °C. The TG curve of Form 1 showed a single weight loss at 305.2 °C, which corresponded to melting. The TG curve of Form 2 also showed a single weight loss at 307.3 °C, which corresponded to melting. The melting point of Form 2 was higher than that of Form 1. In the dissolution studies in pH 6.8 buffer at 37 ± 0.5 °C, the two crystal forms showed no significant differences in dissolution. After 3 months of storage at 0, 52, and 95% RH, the two crystal forms were not transformed. After milling with a Specamill for 2 h, the two crystal forms were not transformed.

Laboratory study of fungal bioreceptivity of different fractions of composite flooring tiles showing efflorescence.

PubMed

Masaphy, Segula; Lavi, Ido; Sultz, Stephan; Zabari, Limor

2014-06-01

Fungi can grow in extreme habitats, such as natural stone and mineral building materials, sometimes causing deterioration. Efflorescence-concentrated salt deposits-results from water movement through building material; it can damage masonry materials and other bricks. Fungal isolate KUR1, capable of growth on, and dissolution of stone chips composing terrazzo-type floor tiles, was isolated from such tiles showing fiber-like crystalline efflorescence. The isolate's ribosomal DNA sequences were 100 % identical to those of Nigrospora sphaerica. The ability of KUR1 to colonize and degrade the different stone chips composing the tiles was studied in axenic culture experiments. When exposed to each of the different mineral chip types composed of dolomite, calcite, or calcite-apatite mineral in low-nutrition medium, the fungus showed selective nutrient consumption, and different growth and stone mineral dissolution rates. Micromorphological examination of the fungus-colonized chips by electron microscopy showed the production of a fungal biofilm with thin films around the hyphae on the surface of the examined chips and disintegration of the calcite-apatite fraction. More than 70 % dissolution of the introduced powdered (<1 mm particle size) mineral was obtained within 10 days of incubation for the soft calcite-apatite fraction.

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.

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.

In Vitro Dissolution as a Tool for Formulation Selection: Telmisartan Two-Step IVIVC.

PubMed

Ruiz Picazo, Alejandro; Martinez-Martinez, Ma Teresa; Colón-Useche, Sarin; Iriarte, Ramon; Sánchez-Dengra, Bárbara; González-Álvarez, Marta; García-Arieta, Alfredo; González-Álvarez, Isabel; Bermejo, Marival

2018-05-17

The purpose of this investigation was to develop an exploratory two-step level A IVIVC for three telmisartan oral immediate release formulations, the reference product Micardis, and two generic formulations (X1 and X2). Correlation was validated with a third test formulation, Y1. Experimental solubility and permeability data were obtained to confirm that telmisartan is a class II compound under the Biopharmaceutic Classification System. Bioequivalence (BE) studies plasma profiles were combined using a previously published reference scaling procedure. X2 demonstrated in vivo BE, while X1 and Y1 failed to show BE due to the lower boundary of the 90% confidence interval for C max being outside the acceptance limits. Average plasma profiles were deconvoluted by the Loo-Riegelman method to obtain the oral fractions absorbed ( f a ). Fractions dissolved ( f diss ) were obtained in several conditions in USP II and USP IV apparatus, and later, the results were compared in order to find the most biopredictive model, calculating the f 2 similarity factor. The apparatus and conditions showing the same rank order than in vivo data were selected for further refinement of conditions. A Levy plot was constructed to estimate the time scaling factor and to make both processes, dissolution and absorption, superimposable. The in vitro dissolution experiment that reflected more accurately the in vivo behavior of the different formulations of telmisartan employed the USP IV dissolution apparatus and a dissolution environment with a flow rate of 8 mL/min and a three-step pH change, from 1.2 to 4.5 and 6.8, with a 0.05% of Tween 80. Thus, these conditions gave rise to a biopredictive dissolution test. This new model is able to predict the formulation differences in dissolution that were previously observed in vivo, which could be used as a risk-analysis tool for formulation selection in future bioequivalence trials.

Influence of acidic and alkaline waste solution properties on uranium migration in subsurface sediments.

PubMed

Szecsody, Jim E; Truex, Mike J; Qafoku, Nikolla P; Wellman, Dawn M; Resch, Tom; Zhong, Lirong

2013-08-01

This study shows that acidic and alkaline wastes co-disposed with uranium into subsurface sediments have significant impact on changes in uranium retardation, concentration, and mass during downward migration. For uranium co-disposal with acidic wastes, significant rapid (i.e., hours) carbonate and slow (i.e., 100 s of hours) clay dissolution resulted, releasing significant sediment-associated uranium, but the extent of uranium release and mobility change was controlled by the acid mass added relative to the sediment proton adsorption capacity. Mineral dissolution in acidic solutions (pH2) resulted in a rapid (<10 h) increase in aqueous carbonate (with Ca(2+), Mg(2+)) and phosphate and a slow (100 s of hours) increase in silica, Al(3+), and K(+), likely from 2:1 clay dissolution. Infiltration of uranium with a strong acid resulted in significant shallow uranium mineral dissolution and deeper uranium precipitation (likely as phosphates and carbonates) with downward uranium migration of three times greater mass at a faster velocity relative to uranium infiltration in pH neutral groundwater. In contrast, mineral dissolution in an alkaline environment (pH13) resulted in a rapid (<10h) increase in carbonate, followed by a slow (10 s to 100 s of hours) increase in silica concentration, likely from montmorillonite, muscovite, and kaolinite dissolution. Infiltration of uranium with a strong base resulted in not only uranium-silicate precipitation (presumed Na-boltwoodite) but also desorption of natural uranium on the sediment due to the high ionic strength solution, or 60% greater mass with greater retardation compared with groundwater. Overall, these results show that acidic or alkaline co-contaminant disposal with uranium can result in complex depth- and time-dependent changes in uranium dissolution/precipitation reactions and uranium sorption, which alter the uranium migration mass, concentration, and velocity. Copyright © 2013 Elsevier B.V. All rights reserved.

Evaluation of SLS: APG mixed surfactant systems as carrier for solid dispersion.

PubMed

Patel, Ashok R; Joshi, Vishal Y

2008-01-01

The present investigation aims at studying the effect of mixed surfactant system of sodium lauryl sulphate (SLS) and alkyl polyglucosides (C(10)APG, C(12)APG and C(12/14)APG) on dissolution rate enhancement of poorly water soluble drug. Aceclofenac--a non-steroidal anti-inflammatory agent was used as a model drug as it has limited water solubility. The influence of the surfactant concentration in various blends on dissolution rate of Solid Dispersion (SD), prepared using solution method with ethanol as the solvent was studied and the advantage of mixed surfactant systems over the individual surfactants was illustrated by differences in the in-vitro dissolution profiles of SD. Physico chemical evaluation (critical micellar concentration, zeta potential and beta-parameter calculations) was carried out to study the mixed surfactant systems. Solid mixtures were characterized by Infrared spectroscopy (FT-IR); X-ray diffraction studies (XRD) and scanning electron microscopy (SEM). It was seen that the dissolution rate of aceclofenac from SD increased with the increase in the APG proportion relative to SLS with the optimum ratio of 0.2 SLS:0.8 APG showing the best effect in all cases. Results obtained from physico-chemical evaluation (the decrease in the value of critical micelle concentration and higher negative value of beta-parameters) suggested the existence of synergism between surfactants blends. The observed results in the dissolution rate enhancement could be attributed to the drug--surfactant interactions as evident from FT-IR, SEM and XRD results.

Influence of cell culture medium composition on in vitro dissolution behavior of a fluoride-containing bioactive glass.

PubMed

Shah, Furqan A; Brauer, Delia S; Wilson, Rory M; Hill, Robert G; Hing, Karin A

2014-03-01

Bioactive glasses are used clinically for bone regeneration, and their bioactivity and cell compatibility are often characterized in vitro, using physiologically relevant test solutions. The aim of this study was to show the influence of varying medium characteristics (pH, composition, presence of proteins) on glass dissolution and apatite formation. The dissolution behavior of a fluoride-containing bioactive glass (BG) was investigated over a period of one week in Eagle's Minimal Essential Medium with Earle's Salts (MEM), supplemented with either, (a) acetate buffer, (b) 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer, (c) HEPES + carbonate, or (d) HEPES + carbonate + fetal bovine serum. Results show pronounced differences in pH, ion release, and apatite formation over 1 week: Despite its acidic pH (pH 5.8 after BG immersion, as compared to pH 7.4-8.3 for HEPES-containing media), apatite formation was fastest in acetate buffered (HEPES-free) MEM. Presence of carbonate resulted in formation of calcite (calcium carbonate). Presence of serum proteins, on the other hand, delayed apatite formation significantly. These results confirm that the composition and properties of a tissue culture medium are important factors during in vitro experiments and need to be taken into consideration when interpreting results from dissolution or cell culture studies. Copyright © 2013 Wiley Periodicals, Inc.

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

PubMed

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

1998-08-01

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

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

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.

Nonlinear dynamics and instability of aqueous dissolution of silicate glasses and minerals

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

Wang, Yifeng; Jove-Colon, Carlos F.; Kuhlman, Kristopher L.

2016-07-22

Aqueous dissolution of silicate glasses and minerals plays a critical role in global biogeochemical cycles and climate evolution. The reactivity of these materials is also important to numerous engineering applications including nuclear waste disposal. The dissolution process has long been considered to be controlled by a leached surface layer in which cations in the silicate framework are gradually leached out and replaced by protons from the solution. This view has recently been challenged by observations of extremely sharp corrosion fronts and oscillatory zonings in altered rims of the materials, suggesting that corrosion of these materials may proceed directly through congruentmore » dissolution followed by secondary mineral precipitation. Here we show that complex silicate material dissolution behaviors can emerge from a simple positive feedback between dissolution-induced cation release and cation-enhanced dissolution kinetics. This self-accelerating mechanism enables a systematic prediction of the occurrence of sharp dissolution fronts (vs. leached surface layers), oscillatory dissolution behaviors and multiple stages of glass dissolution (in particular the alteration resumption at a late stage of a corrosion process). In conclusion, our work provides a new perspective for predicting long-term silicate weathering rates in actual geochemical systems and developing durable silicate materials for various engineering applications.« less

Ligand-controlled Fe mobilization catalyzed by adsorbed Fe(II) on Fe(hydr)oxides

NASA Astrophysics Data System (ADS)

Kang, Kyounglim; Biswakarma, Jagannath; Borowski, Susan C.; Hug, Stephan J.; Hering, Janet G.; Schenkeveld, Walter D. C.; Kraemer, Stephan M.

2017-04-01

Dissolution of Fe(hydr)oxides is a key process in biological iron acquisition. Due to the low solubility of iron oxides in environments with a circumneutral pH, organisms may exude organic compounds catalyzing iron mobilization by reductive and ligand controlled dissolution mechanisms. Recently, we have shown synergistic effects between reductive dissolution and ligand-controlled dissolution that may operate in biological iron acquisition. The synergistic effects were observed in Fe mobilization from single goethite suspensions as well as in suspensions containing calcareous soil[1],[2]. However, how the redox reaction accelerates Fe(hydr)oxide dissolution by ligands is not studied intensively. In our study, we hypothesized that electron transfer to structural Fe(III) labilizes the Fe(hydr)oxide structure, and that this can accelerate ligand controlled dissolution. Systematical batch dissolution experiments were carried out under anoxic conditions at environmentally relevant pH values in which various Fe(hydr)oxides (goethite, hematite, lepidocrocite) interacted with two different types of ligand (desferrioxamine B (DFOB) and N,N'-Di(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid monohydrochloride (HBED)). Electron transfer to the structure was induced by adsorbing Fe(II) to the mineral surface at various Fe(II) concentrations. Our results show a distinct catalytic effect of adsorbed Fe(II) on ligand controlled dissolution, even at submicromolar Fe(II) concentrations. We observed the effect for a range of iron oxides, but it was strongest in lepidocrocite, most likely due to anisotropy in conductivity leading to higher near-surface concentration of reduced iron. Our results demonstrate that the catalytic effect of reductive processes on ligand controlled dissolution require a very low degree of reduction making this an efficient process for biological iron acquisition and a potentially important effect in natural iron cycling. References 1. Wang, Z. M.; Schenkeveld, W. D. C.; Kraemer, S. M.; Giammar, D. E. Environ. Sci. Technol. 2015, 49, (12), 7236-7244. 2. Schenkeveld, W. D. C.; Wang, Z. M.; Giammar, D. E.; Kraemer, S. M. Environ. Sci. Technol. 2016, 50, (12), 6381-6388.

[Dissolution behavior of Fuzi Lizhong pill based on simultaneous determination of two components in Glycyrrhizae Radix et Rhizoma].

PubMed

Jiang, Mao-Yuan; Zhang, Zhen; Shi, Jin-Feng; Zhang, Jin-Ming; Fu, Chao-Mei; Lin, Xia; Liu, Yu-Mei

2018-03-01

To preliminarily investigate the dissolution behavior of Fuzi Lizhong pill, provide the basis for its quality control and lay foundation for in vivo dissolution behavior by determining the dissolution rate of liquiritin and glycyrrhizic acid. High-performance liquid chromatography (HPLC) method for simultaneous content determination of the two active ingredients of liquiritin and glycyrrhizic acid in Fuzi Lizhong pill was established; The dissolution amount of these two active ingredients in fifteen batches of Fuzi Lizhong pill from five manufacturers was obtained at different time points, and then the cumulative dissolution rate was calculated and cumulative dissolution curve was drawn. The similarity of cumulative dissolution curve of different batches was evaluated based on the same factory, and the similarity of cumulative dissolution curve of different factories was evaluated based on the same active ingredients. The dissolution model of Fuzi Lizhong pill based on two kinds of active ingredients was established by fitting with the dissolution data. The best dissolution medium was 0.25% sodium lauryl sulfate. The dissolution behavior of liquiritin and glycyrrhizic acid in Fuzi Lizhong pill was basically the same and sustained release in 48 h. Three batches of the factories (factory 2, factory 3, factory 4 and factory 5) appeared to be similar in dissolution behavior, indicating similarity in dissolution behavior in most factories. Two of the three batches from factory 1 appeared to be not similar in dissolution behavior of liquiritin and glycyrrhizic acid. The dissolution data of the effective ingredients from different factories were same in fitting, and Weibull model was the best model in these batches. Fuzi Lizhong pill in 15 batches from 5 factories showed sustained release in 48 h, proving obviously slow releasing characteristics "pill is lenitive and keeps a long-time efficacy". The generally good dissolution behavior also suggested that quality of different batches from most factories was stable. The dissolution behavior of liquiritin and glycyrrhizic acid in different factories was different, suggesting that the source of medicinal materials and preparation technology parameters in five factories were different. Copyright© by the Chinese Pharmaceutical Association.

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.

Lattice Boltzmann simulation of dissolution-induced changes in permeability and porosity in 3D CO2 reactive transport

NASA Astrophysics Data System (ADS)

Tian, Zhiwei; Wang, Junye

2018-02-01

Dissolution and precipitation of rock matrix are one of the most important processes of geological CO2 sequestration in reservoirs. They change connections of pore channels and properties of matrix, such as bulk density, microporosity and hydraulic conductivity. This study builds on a recently developed multi-layer model to account for dynamic changes of microporous matrix that can accurately predict variations in hydraulic properties and reaction rates due to dynamic changes in matrix porosity and pore connectivity. We apply the model to simulate the dissolution and precipitation processes of rock matrix in heterogeneous porous media to quantify (1) the effect of the reaction rate on dissolution and matrix porosity, (2) the effect of microporous matrix diffusion on the overall effective diffusion and (3) the effect of heterogeneity on hydraulic conductivity. The results show the CO2 storage influenced by factors including the matrix porosity change, reaction front movement, velocity and initial properties. We also simulated dissolution-induced permeability enhancement as well as effects of initial porosity heterogeneity. The matrix with very low permeability, which can be unresolved on X-ray CT, do contribute to flow patterns and dispersion. The concentration of reactant H+ increases along the main fracture paths where the flow velocity increases. The product Ca++ shows the inversed distribution pattern against the H+ concentration. This demonstrates the capability of this model to investigate the complex CO2 reactive transport in real 3D heterogeneous porous media.

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

Yuan, Ke; De Andrade, Vincent; Feng, Zhange

The presence of impurity ions is known to significantly influence mineral surface morphology during crystal growth from aqueous solution, but knowledge on impurity ion-mineral interactions during dissolution under far-from equilibrium conditions remains limited. Here we show that calcite (CaCO 3) exhibits a rich array of dissolution features in the presence of Pb. During the initial stage, calcite exhibits non-classical surface features characterized as micro pyramids developed spontaneously in acidic Pb-bearing solutions. Subsequent pseudomorphic growth of cerussite (PbCO 3) was observed, where nucleation occurred entirely within a pore space created by dissolution at the calcite/substrate interface. Uneven growth rates yielded amore » cerussite shell made of lath- or dendritic-shaped crystals. The cerussite phase was separated from the calcite by pores of less than 200 nm under transmission X-ray microscopy, consistent with the interface-coupled dissolution-precipitation mechanism. These results show that impurity metal ions exert significant control over the microscale dissolution features found on mineral surfaces and provide new insights into interpreting and designing micro structures observed in naturally-occurring and synthetic carbonate minerals by dissolution. In addition, heterogeneous micro-environments created in transport limited reactions under pore spaces may lead to unusual growth forms during crystal nucleation and precipitation.« less

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

PubMed

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

2016-01-01

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

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

DOE PAGES

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

2017-11-21

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

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

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

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

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

In vitro quantitative ((1))H and ((19))F nuclear magnetic resonance spectroscopy and imaging studies of fluvastatin™ in Lescol® XL tablets in a USP-IV dissolution cell.

PubMed

Zhang, Qilei; Gladden, Lynn; Avalle, Paolo; Mantle, Michael

2011-12-20

Swellable polymeric matrices are key systems in the controlled drug release area. Currently, the vast majority of research is still focused on polymer swelling dynamics. This study represents the first quantitative multi-nuclear (((1))H and ((19))F) fast magnetic resonance imaging study of the complete dissolution process of a commercial (Lescol® XL) tablet, whose formulation is based on the hydroxypropyl methylcellulose (HPMC) polymer under in vitro conditions in a standard USP-IV (United States Pharmacopeia apparatus IV) flow-through cell that is incorporated into high field superconducting magnetic resonance spectrometer. Quantitative RARE ((1))H magnetic resonance imaging (MRI) and ((19))F nuclear magnetic resonance (NMR) spectroscopy and imaging methods have been used to give information on: (i) dissolution media uptake and hydrodynamics; (ii) active pharmaceutical ingredient (API) mobilisation and dissolution; (iii) matrix swelling and dissolution and (iv) media activity within the swelling matrix. In order to better reflect the in vivo conditions, the bio-relevant media Simulated Gastric Fluid (SGF) and Fasted State Simulated Intestinal Fluid (FaSSIF) were used. A newly developed quantitative ultra-fast MRI technique was applied and the results clearly show the transport dynamics of media penetration and hydrodynamics along with the polymer swelling processes. The drug dissolution and mobility inside the gel matrix was characterised, in parallel to the ((1))H measurements, by ((19))F NMR spectroscopy and MRI, and the drug release profile in the bulk solution was recorded offline by UV spectrometer. We found that NMR spectroscopy and 1D-MRI can be uniquely used to monitor the drug dissolution/mobilisation process within the gel layer, and the results from ((19))F NMR spectra indicate that in the gel layer, the physical mobility of the drug changes from "dissolved immobilised drug" to "dissolved mobilised drug". Copyright © 2011 Elsevier B.V. All rights reserved.

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.

Efficacy of Magnesium Trihydrate of Ursodeoxycholic Acid and Chenodeoxycholic Acid for Gallstone Dissolution: A Prospective Multicenter Trial.

PubMed

Hyun, Jong Jin; Lee, Hong Sik; Kim, Chang Duck; Dong, Seok Ho; Lee, Seung-Ok; Ryu, Ji Kon; Lee, Don Haeng; Jeong, Seok; Kim, Tae Nyeun; Lee, Jin; Koh, Dong Hee; Park, Eun Taek; Lee, In-Seok; Yoo, Byung Moo; Kim, Jin Hong

2015-07-01

Cholecystectomy is necessary for the treatment of symptomatic or complicated gallbladder (GB) stones, but oral litholysis with bile acids is an attractive alternative therapeutic option for asymptomatic or mildly symptomatic patients. This study was conducted to evaluate the efficacy of magnesium trihydrate of ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) on gallstone dissolution and to investigate improvements in gallstone-related symptoms. A prospective, multicenter, phase 4 clinical study to determine the efficacy of orally administered magnesium trihydrate of UDCA and CDCA was performed from January 2011 to June 2013. The inclusion criteria were GB stone diameter ≤15 mm, GB ejection fraction ≥50%, radiolucency on plain X-ray, and asymptomatic/mildly symptomatic patients. The patients were prescribed one capsule of magnesium trihydrate of UDCA and CDCA at breakfast and two capsules at bedtime for 6 months. The dissolution rate, response rate, and change in symptom score were evaluated. A total of 237 subjects were enrolled, and 195 subjects completed the treatment. The dissolution rate was 45.1% and the response rate was 47.2% (92/195) after 6 months of administration of magnesium trihydrate of UDCA and CDCA. Only the stone diameter was significantly associated with the response rate. Both the symptom score and the number of patients with symptoms significantly decreased regardless of stone dissolution. Adverse events necessitating discontinuation of the drug, surgery, or endoscopic management occurred in 2.5% (6/237) of patients. Magnesium trihydrate of UDCA and CDCA is a well-tolerated bile acid that showed similar efficacy for gallstone dissolution and improvement of gallstone-related symptoms as that shown in previous studies.

Solutal Convection in Porous Media

NASA Astrophysics Data System (ADS)

Liang, Y.; Wen, B.; DiCarlo, D. A.; Hesse, M. A.

2017-12-01

Atmospheric CO2 is one important component of greenhouse gases, which can greatly affect the temperature of the Earth. There are four trapping mechanisms for CO2sequestration, including structural & stratigraphic trapping, residual trapping, dissolution trapping and mineral trapping. Leakage potential is a serious problem for its storage efficiency, and dissolution trapping is a method that can prevent such leakages effectively. Convective dissolution trapping process can be simplified to an interesting physical problem: in porous media, dissolution can initiate convection, and then its dynamics can be affected by the continuous convection conversely. However, it is difficult to detect whether the convective dissolution may take place, as well as how fast and in what pattern it may take place. Previous studies have established a model and related scaling (Rayleigh number and Sherwood number) to describe this physical problem. To testify this model with a large range of Rayleigh numbers, we conducted a series of convective dissolution experiments in porous media. In addition, this large experimental assembly can allow us to quantify relation between wavenumber of the convective motion and the controlling factors of the system for the first time. The result of our laboratory experiments are revolutionary: On one hand, it shows that previous scaling of the convective dissolution becomes invalid once the permeability is large enough; On the other hand, the relation between wavenumber and Rayleigh number demonstrates an opposite trend against the classic model. According to our experimental results, we propose a new model to describe the solutal convection in porous media, and our model can describe and explain our experimental observations. Also, simulation work has been conducted to confirm our model. In the future, our model and relevant knowledge can be unscaled to industrial applications which are relevant to convective dissolution process.

Addressable Direct-Write Nanoscale Filament Formation and Dissolution by Nanoparticle-Mediated Bipolar Electrochemistry.

PubMed

Crouch, Garrison M; Han, Donghoon; Fullerton-Shirey, Susan K; Go, David B; Bohn, Paul W

2017-05-23

Nanoscale conductive filaments, usually associated with resistive memory or memristor technology, may also be used for chemical sensing and nanophotonic applications; however, realistic implementation of the technology requires precise knowledge of the conditions that control the formation and dissolution of filaments. Here we describe and characterize an addressable direct-write nanoelectrochemical approach to achieve repeatable formation/dissolution of Ag filaments across a ∼100 nm poly(ethylene oxide) (PEO) film containing either Ag + alone or Ag + together with 50 nm Ag-nanoparticles acting as bipolar electrodes. Using a conductive AFM tip, formation occurs when the PEO film is subjected to a forward bias, and dissolution occurs under reverse bias. Formation-dissolution kinetics were studied for three film compositions: Ag|PEO-Ag + , Ag|poly(ethylene glycol) monolayer-PEO-Ag + , and Ag|poly(ethylene glycol) monolayer-PEO-Ag + /Ag-nanoparticle. Statistical analysis shows that the distribution of formation times exhibits Gaussian behavior, and the fastest average initial formation time occurs for the Ag|PEO-Ag + system. In contrast, formation in the presence of Ag nanoparticles likely proceeds by a noncontact bipolar electrochemical mechanism, exhibiting the slowest initial filament formation. Dissolution times are log-normal for all three systems, and repeated reformation of filaments from previously formed structures is characterized by rapid regrowth. The direct-write bipolar electrochemical deposition/dissolution strategy developed here presents an approach to reconfigurable, noncontact in situ wiring of nanoparticle arrays-thereby enabling applications where actively controlled connectivity of nanoparticle arrays is used to manipulate nanoelectronic and nanophotonic behavior. The system further allows for facile manipulation of experimental conditions while simultaneously characterizing surface conditions and filament formation/dissolution kinetics.

Development and validation of a dissolution test for lodenafil carbonate based on in vivo data.

PubMed

Codevilla, Cristiane Franco; Castilhos, Tamara dos Santos; Cirne, Carolina Araújo; Froehlich, Pedro Eduardo; Bergold, Ana Maria

2014-04-01

Lodenafil carbonate is a phosphodiesterase type 5 inhibitor used for the treatment of erectile dysfunction. Currently, there is no dissolution test reported for lodenafil carbonate and this drug is not listed in any pharmacopoeia. The present study focused on the development and validation of a dissolution test for lodenafil carbonate tablets, using a simulated absorption profile based on in vivo data. The appropriate conditions were determined after testing sink conditions. Different conditions as medium, surfactant concentration and rotation speed were evaluated. The percentage of dose absorbed was calculated by deconvolution, using the Wagner-Nelson method. According to the obtained results, the use of 0.1 M HCl + 1.5% SLS (900 mL, at 37 + 0.5 °C) as the dissolution medium, paddles at 25 rpm were considered adequate. The samples were quantified by UV spectroscopy at 295 nm and the validation was performed according to international guidelines. The method showed specificity, linearity, accuracy and precision, within the acceptable range. Kinetics of drug release was better described by the first-order model. The proposed dissolution test can be used for the routine quality control of lodenafil carbonate in tablets.

Effect of atmospheric organic complexation on iron-bearing dust solubility

NASA Astrophysics Data System (ADS)

Paris, R.; Desboeufs, K. V.

2013-02-01

Recent studies reported that the effect of organic complexation may be a potentially important process to be considered in models to estimate atmospheric iron flux to the ocean. In this study, we investigated this effect by a series of dissolution experiments on iron-bearing dust in presence or absence of various organic compounds typically found in the atmospheric waters (acetate, formate, oxalate, malonate, succinate, glutarate, glycolate, lactate, tartrate and humic acid as an analogue of humic like substances (HULIS)). Only 4 of tested organic ligands (oxalate, malonate, tartrate and humic acid) caused an enhancement of iron solubility which was associated with an increase of dissolved Fe(II) concentrations. For all of these organic ligands, a positive linear dependence of iron solubility to organic concentrations was observed and showed that the extent of organic complexation on iron solubility decreased in order oxalate > malonate = tartrate > humic acid. This was attributed to the ability of electron donors of organic ligands and implied a reductive ligand-promoted dissolution. This study confirmed that oxalate is the most effective ligand playing on dust iron solubility and showed, for the first time, the potential effect of HULIS on iron dissolution in atmospheric conditions.

Physicochemical properties of protein-modified silver nanoparticles in seawater

NASA Astrophysics Data System (ADS)

Zhong, Hangyue

2013-10-01

This study investigated the physicochemical properties of silver nanoparticles stabilized with casein protein in seawater. UV?vis spectrometry, dynamic light scattering (DLS), and transmission electron microscopy (TEM) were applied to measure the stability of silver nanoparticles in seawater samples. The obtained results show an increased aggregation tendency of silver nanoparticles in seawater, which could be attributed its relatively high cation concentration that could neutralize the negatively charges adsorbed on the surface of silver nanoparticles and reduce the electrostatic repulsion forces between nanoparticles. Similarly, due to the surface charge screening process, the zeta potential of silver nanoparticles in seawater decreased. This observation further supported the aggregation behavior of silver nanoparticles. This study also investigated the dissolution of silver nanoparticles in seawater. Result shows that the silver nanoparticle dissolution in DI water is lower than in seawater, which is attributed to the high Cl? concentration present in seawater. As Cl? can react with silver and form soluble AgCl complex, dissolution of silver nanoparticles was enhanced. Finally, this study demonstrated that silver nanoparticles are destabilized in seawater condition. These results may be helpful in understanding the environmental risk of discharged silver nanoparticles in seawater conditions.

Effects of pore forming agents of potassium bicarbonate and drug loading method against dissolution mechanisms of amoxicillin drugs encapsulated in hydrogel full-Ipn chitosan-poly(N-vinylcaprolactam) as a floating drug delivery system

NASA Astrophysics Data System (ADS)

Aini, Nurul; Rahayu, Dyah Utami Cahyaning; Budianto, Emil

2018-04-01

The limitation of amoxicillin trihydrate in the treatment of H. pylori bacteria is relatively short retention time in the stomach. The FDDS (Floating Drug Delivery System) amoxicillin trihydrate into a chitosan-poly(N-vinylcaprolactam) full-Ipn hydrogel matrix using a pore-forming agent KHCO3 is expected to overcome these limitations. The pore-forming agent to be used is 15% KHCO3 compound. Chemical kinetics approach is performed to determine the dissolution mechanism of amoxicillin trihydrate from K-PNVCL hydrogel in vitro on gastric pH and characterization using SEM performed to confirm the dissolution mechanism. Hydrogels with the addition of pore-forming agents will be loading in situ loading and post loading. Fourier Transform Infra Red (FTIR) spectroscopy was used to characterize K-PNVCL and UV-Vis hydrogels used to calculate the efficiency of encapsulation and drug dissolution rate in K-PNVCL hydrogel. Hydrogel K-PNVCL / KHCO3 that encapsulated by in situ loading method resulted in an encapsulation efficiency of 93.5% and dissolution of 93.4%. While the Hydrogel K-PNVCL / KHCO3 which is drug encapsulation resulted in an encapsulation efficiency of 87.2% with dissolution of 81.5%. Chemical kinetics approach to in situ encapsulation of loading and post loading shows the dissolution mechanism occurring in the K-PNVCL / KHCO3 hydrogel matrix occurs by diffusion. Observation using optical microscope and SEM showed the mechanism of drug dissolution in Hydrogel K-PNVCL occurred by diffusion.

Global charcoal mobilization from soils via dissolution and riverine transport to the oceans

Treesearch

Rudolf Jaffe; Yan Ding; Jutta Niggemann; Anssi V. Vahatalo; Aron Stubbins; Robert G. M. Spencer; John Campbell; Thorsten Dittmar

2013-01-01

Global biomass burning generates 40 million to 250 million tons of charcoal every year, part of which is preserved for millennia in soils and sediments. We have quantified dissolution products of charcoal in a wide range of rivers worldwide and show that globally, a major portion of the annual charcoal production is lost from soils via dissolution and subsequent...

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

PubMed

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

2018-03-06

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

Cidaroids spines facing ocean acidification.

PubMed

Dery, Aurélie; Tran, Phuong Dat; Compère, Philippe; Dubois, Philippe

2018-07-01

When facing seawater undersaturated towards calcium carbonates, spines of classical sea urchins (euechinoids) show traces of corrosion although they are covered by an epidermis. Cidaroids (a sister clade of euechinoids) are provided with mature spines devoid of epidermis, which makes them, at first sight, more sensitive to dissolution when facing undersaturated seawater. A recent study showed that spines of a tropical cidaroid are resistant to dissolution due to the high density and the low magnesium concentration of the peculiar external spine layer, the cortex. The biofilm and epibionts covering the spines was also suggested to take part in the spine protection. Here, we investigate the protective role of these factors in different cidaroid species from a broad range of latitude, temperature and depth. The high density of the cortical layer and the cover of biofilm and epibionts were confirmed as key protection against dissolution. The low magnesium concentration of cidaroid spines compared to that of euechinoid ones makes them less soluble in general. Copyright © 2018 Elsevier Ltd. All rights reserved.

A New Method to Determine the Half-Life for Penicillin Using Microcalorimeter

NASA Astrophysics Data System (ADS)

Li, Z. X.; Zhao, W. W.

2015-01-01

The dissolution process of penicillin in normal saline and isotonic glucose solution was reported using a microcalorimeter. Both the integral and differential heats of solution were measured. The quantitative relationships between the amount of heat released and the quantity of dissolved penicillin were established. Meanwhile, the kinetics and the half-life of the dissolution processes as well as the enthalpy of solution, the entropy of dissolution, and the free energy of dissolution were determined. The results showed that a change of the solvent from normal saline to isotonic glucose solution had little effect on the half-life of penicillin in the dissolution process, and there was no significant difference between the stabilities of penicillin in isotonic glucose solution and normal saline. Moreover, the dissolution process of penicillin in isotonic glucose solution followed the first-order kinetics. These results could provide a theoretical basis for the clinical applications of penicillin.

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

PubMed

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

2017-10-15

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

[Solidification of magnolol phospholipid complex with polyvingypyrrolidone].

PubMed

Dai, Yun-Hao; Wang, Man; Ju, Jian-Ming; Zhang, Zhen-Hai

2016-06-01

In this study, magnolol phospholipid complex (MPC) was prepared and solidified with polyvingypyrrolidone (PVPP). The influence of PVPP on MPC's flowability, dissolution and oral bioavailability was investigated. The results of phase characterization using differential scanning calorimetry (DSC), infrared spectroscopy (IR), and scanning electron microscopy (SEM) showed that magnolol existed in solidified powder and MPC in an amorphous state. In flowability and dissolution experiments, solidified powder showed significant superiority. At the same time, it showed a higher oral bioavailability compared with MPC, with AUC0-∞ of 73.47 μg•h•mL⁻¹ vs. 63.48 μg•h•mL⁻¹. This process for solidifying powder with PVPP is simple and convenient. Copyright© by the Chinese Pharmaceutical Association.

Limacina helicina shell dissolution as an indicator of declining habitat suitability owing to ocean acidification in the California Current Ecosystem

PubMed Central

Bednaršek, N.; Feely, R. A.; Reum, J. C. P.; Peterson, B.; Menkel, J.; Alin, S. R.; Hales, B.

2014-01-01

Few studies to date have demonstrated widespread biological impacts of ocean acidification (OA) under conditions currently found in the natural environment. From a combined survey of physical and chemical water properties and biological sampling along the Washington–Oregon–California coast in August 2011, we show that large portions of the shelf waters are corrosive to pteropods in the natural environment. We show a strong positive correlation between the proportion of pteropod individuals with severe shell dissolution damage and the percentage of undersaturated water in the top 100 m with respect to aragonite. We found 53% of onshore individuals and 24% of offshore individuals on average to have severe dissolution damage. Relative to pre-industrial CO2 concentrations, the extent of undersaturated waters in the top 100 m of the water column has increased over sixfold along the California Current Ecosystem (CCE). We estimate that the incidence of severe pteropod shell dissolution owing to anthropogenic OA has doubled in near shore habitats since pre-industrial conditions across this region and is on track to triple by 2050. These results demonstrate that habitat suitability for pteropods in the coastal CCE is declining. The observed impacts represent a baseline for future observations towards understanding broader scale OA effects. PMID:24789895

Limacina helicina shell dissolution as an indicator of declining habitat suitability owing to ocean acidification in the California Current Ecosystem.

PubMed

Bednaršek, N; Feely, R A; Reum, J C P; Peterson, B; Menkel, J; Alin, S R; Hales, B

2014-06-22

Few studies to date have demonstrated widespread biological impacts of ocean acidification (OA) under conditions currently found in the natural environment. From a combined survey of physical and chemical water properties and biological sampling along the Washington-Oregon-California coast in August 2011, we show that large portions of the shelf waters are corrosive to pteropods in the natural environment. We show a strong positive correlation between the proportion of pteropod individuals with severe shell dissolution damage and the percentage of undersaturated water in the top 100 m with respect to aragonite. We found 53% of onshore individuals and 24% of offshore individuals on average to have severe dissolution damage. Relative to pre-industrial CO2 concentrations, the extent of undersaturated waters in the top 100 m of the water column has increased over sixfold along the California Current Ecosystem (CCE). We estimate that the incidence of severe pteropod shell dissolution owing to anthropogenic OA has doubled in near shore habitats since pre-industrial conditions across this region and is on track to triple by 2050. These results demonstrate that habitat suitability for pteropods in the coastal CCE is declining. The observed impacts represent a baseline for future observations towards understanding broader scale OA effects.

Comparison of three preservation techniques for slowing dissolution of calcareous nannofossils in organic rich sediments

USGS Publications Warehouse

Seefelt, Ellen L.; Self-Trail, Jean; Schultz, Arthur P.

2015-01-01

In an attempt to halt or reduce dissolution of calcareous nannofossils in organic and/or pyrite-rich sediments, three different methods of short-term storage preservation were tested for efficacy: vacuum packing, argon gas replacement, and buffered water. Abundance counts of calcareous nannofossil assemblages over a six month period showed that none of the three preservation methods were consistently effective in reducing assemblage loss due to dissolution. In most cases, the control slides made at the drill site had more abundant calcareous nannofossil assemblages than those slides made from sediments stored via vacuum packing, argon gas replacement, or buffered water. Thin section and XRD analyses showed that in most cases, <1% pyrite was needed to drive the oxidation-reduction reaction that resulted in dissolution, even in carbonate-rich sediments.

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

PubMed

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

2015-11-01

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

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

NASA Astrophysics Data System (ADS)

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

2014-09-01

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

Stirring effect on kaolinite dissolution rate

NASA Astrophysics Data System (ADS)

Metz, Volker; Ganor, Jiwchar

2001-10-01

Experiments were carried out measuring kaolinite dissolution rates using stirred and nonstirred flow-through reactors at pHs 2 to 4 and temperatures of 25°C, 50°C, and 70°C. The results show an increase of kaolinite dissolution rate with increasing stirring speed. The stirring effect is reversible, i.e., as the stirring slows down the dissolution rate decreases. The effect of stirring speed on kaolinite dissolution rate is higher at 25°C than at 50°C and 70°C and at pH 4 than at pHs 2 and 3. It is suggested that fine kaolinite particles are formed as a result of stirring-induced spalling or abrasion of kaolinite. These very fine particles have an increased ratio of reactive surface area to specific surface area, which results in enhancement of kaolinite dissolution rate. A balance between production and dissolution of the fine particles explains both the reversibility and the temperature and pH dependence of the stirring effect. Since the stirring effect on kaolinite dissolution rate varies with temperature and pH, measurement of kinetic parameters such as activation energy may be influenced by stirring. Therefore, standard use of nonagitated reaction vessels for kinetic experiments of mineral dissolution and precipitation is recommended, at least for slow reactions that are surface controlled.

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

Influence of Prosolv and Prosolv:Mannitol 200 direct compression fillers on the physicomechanical properties of atorvastatin oral dispersible tablets.

PubMed

Gowda, Veeran; Pabari, Ritesh M; Kelly, John G; Ramtoola, Zebunnissa

2015-06-01

The objective of the present study was to evaluate the influence of Prosolv® and Prosolv®: Mannitol 200 direct compression (DC) fillers on the physicomechanical characteristics of oral dispersible tablets (ODTs) of crystalline atorvastatin calcium. ODTs were formulated by DC and were analyzed for weight uniformity, hardness, friability, drug content, disintegration and dissolution. Three disintegration time (DT) test methods; European Pharmacopoeia (EP) method for conventional tablets (Method 1), a modification of this method (Method 2) and the EP method for oral lyophilisates (Method 3) were compared as part of this study. All ODTs showed low weight variation of <2.5%. Prosolv® only ODTs showed the highest tablet hardness of ∼ 73 N, hardness decreased with increasing mannitol content. Friability of all formulations was <1% although friability of Prosolv®:Mannitol ODTs was higher than for pure Prosolv®. DT of all ODTs was <30 s. Method 2 showed the fastest DT. Method 3 was non-discriminatory giving a DT of 13-15 s for all formulations. Atorvastatin dissolution from all ODTs was >60% within 5 min despite the drug being crystalline. Prosolv® and Prosolv®:Mannitol-based ODTs are suitable for ODT formulations by DC to give ODTs with high mechanical strength, rapid disintegration and dissolution.

The influence of electrolyte additives on the anodic dissolution of aluminum in alkaline solutions

NASA Astrophysics Data System (ADS)

Boehnstedt, W.

1980-09-01

The paper describes the effect of electrolyte additives on the anodic dissolution of aluminum in alkaline solutions. The dissolution is accelerated by the addition of small quantities of gallium or indium ions to the electrolyte indicated by the shift of the zero current potential by about 250 mV on the current-potential curve. Scanning electron microscope studies showed that gallium ions produce many small cracks in the aluminum electrode and collect at the grain boundary areas, increasing the electrode surface; this enlargement, in combination with increased electrolyte agitation due to greater hydrogen evolution, provides higher current densities at the same potential. It is concluded that this process will widen the possibilities of using aluminum and its alloys in high-rate batteries.

The Risk of Divorce as a Barrier to Marriage among Parents of Young Children

PubMed Central

Waller, Maureen R.; Peters, H. Elizabeth

2008-01-01

Using data from the Fragile Families Study, we examine how unmarried parents’ risk of divorce influences their decision to marry. Regression results show that unmarried parents with a high predicted probability of marital dissolution (based on estimates of marital dissolution for a sample of initially married mothers with similar characteristics) had significantly lower odds of marriage to the father of their child even after controlling for individual and relationship characteristics expected to influence marriage transitions. The dissolution propensity we examine also includes a measure of the local divorce climate. As such, our results provide support for the argument that high rates of divorce in the population have led to a fear of divorce among unmarried parents which reduces their probability of marriage. PMID:19227697

The risk of divorce as a barrier to marriage among parents of young children.

PubMed

Waller, Maureen R; Peters, H Elizabeth

2008-12-01

Using data from the Fragile Families Study, we examine how unmarried parents' risk of divorce influences their decision to marry. Regression results show that unmarried parents with a high predicted probability of marital dissolution (based on estimates of marital dissolution for a sample of initially married mothers with similar characteristics) had significantly lower odds of marriage to the father of their child even after controlling for individual and relationship characteristics expected to influence marriage transitions. The dissolution propensity we examine also includes a measure of the local divorce climate. As such, our results provide support for the argument that high rates of divorce in the population have led to a fear of divorce among unmarried parents which reduces their probability of marriage.

Global charcoal mobilization from soils via dissolution and riverine transport to the oceans.

PubMed

Jaffé, Rudolf; Ding, Yan; Niggemann, Jutta; Vähätalo, Anssi V; Stubbins, Aron; Spencer, Robert G M; Campbell, John; Dittmar, Thorsten

2013-04-19

Global biomass burning generates 40 million to 250 million tons of charcoal every year, part of which is preserved for millennia in soils and sediments. We have quantified dissolution products of charcoal in a wide range of rivers worldwide and show that globally, a major portion of the annual charcoal production is lost from soils via dissolution and subsequent transport to the ocean. The global flux of soluble charcoal accounts to 26.5 ± 1.8 million tons per year, which is ~10% of the global riverine flux of dissolved organic carbon (DOC). We suggest that the mobilization of charcoal and DOC out of soils is mechanistically coupled. This study closes a major gap in the global charcoal budget and provides critical information in the context of geoengineering.

DISSOLUTION OF PLUTONIUM METAL IN 8-10 M NITRIC ACID

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

Rudisill, T.; Pierce, R.

2012-02-21

The H-Canyon facility will be used to dissolve Pu metal for subsequent purification and conversion to plutonium dioxide (PuO{sub 2}) using Phase II of HB-Line. To support the new mission, the development of a Pu metal dissolution flowsheet which utilizes concentrated (8-10 M) nitric acid (HNO{sub 3}) solutions containing potassium fluoride (KF) is required. Dissolution of Pu metal in concentrated HNO{sub 3} is desired to eliminate the need to adjust the solution acidity prior to purification by anion exchange. The preferred flowsheet would use 8-10 M HNO{sub 3}, 0.015-0.07 M KF, and 0.5-1.0 g/L Gd to dissolve the Pu upmore » to 6.75 g/L. An alternate flowsheet would use 8-10 M HNO{sub 3}, 0.1-0.2 M KF, and 1-2 g/L B to dissolve the Pu. The targeted average Pu metal dissolution rate is 20 mg/min-cm{sup 2}, which is sufficient to dissolve a 'standard' 2250-g Pu metal button in 24 h. Plutonium metal dissolution rate measurements showed that if Gd is used as the nuclear poison, the optimum dissolution conditions occur in 10 M HNO{sub 3}, 0.04-0.05 M KF, and 0.5-1.0 g/L Gd at 112 to 116 C (boiling). These conditions will result in an estimated Pu metal dissolution rate of {approx}11-15 mg/min-cm{sup 2} and will result in dissolution times of 36-48 h for standard buttons. The recommended minimum and maximum KF concentrations are 0.03 M and 0.07 M, respectively. The maximum KF concentration is dictated by a potential room-temperature Pu-Gd-F precipitation issue at low Pu concentrations. The purpose of the experimental work described in this report was two-fold. Initially a series of screening experiments was performed to measure the dissolution rate of Pu metal as functions of the HNO{sub 3}, KF, and Gd or B concentrations. The objective of the screening tests was to propose optimized conditions for subsequent flowsheet demonstration tests. Based on the rate measurements, this study found that optimal dissolution conditions in solutions containing 0.5-1.0 g/L Gd occurred in 8-10 M HNO{sub 3} with 0.04-0.05 M KF at 112 to 116 C (boiling). The testing also showed that solutions containing 8-10 M HNO{sub 3}, 0.1-0.2 M KF, and 1-2 g/L B achieved acceptable dissolution rates in the same temperature range. To confirm that conditions identified by the dissolution rate measurements for solutions containing Gd or B can be used to dissolve Pu metal up to 6.75 g/L in the presence of Fe, demonstration experiments were performed using concentrations in the optimal ranges. In two of the demonstration experiments using Gd and in one experiment using B, the offgas generation during the dissolution was measured and samples were analyzed for H{sub 2}. The experimental methods used to perform the dissolution rate measurements and flowsheet demonstrations and a discussion of the results are presented.« less

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.

Physical heterogeneity control on effective mineral dissolution rates

NASA Astrophysics Data System (ADS)

Jung, Heewon; Navarre-Sitchler, Alexis

2018-04-01

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

Pb 2+–Calcite Interactions under Far-from-Equilibrium Conditions: Formation of Micropyramids and Pseudomorphic Growth of Cerussite

DOE PAGES

Yuan, Ke; De Andrade, Vincent; Feng, Zhange; ...

2018-01-04

The presence of impurity ions is known to significantly influence mineral surface morphology during crystal growth from aqueous solution, but knowledge on impurity ion-mineral interactions during dissolution under far-from equilibrium conditions remains limited. Here we show that calcite (CaCO 3) exhibits a rich array of dissolution features in the presence of Pb. During the initial stage, calcite exhibits non-classical surface features characterized as micro pyramids developed spontaneously in acidic Pb-bearing solutions. Subsequent pseudomorphic growth of cerussite (PbCO 3) was observed, where nucleation occurred entirely within a pore space created by dissolution at the calcite/substrate interface. Uneven growth rates yielded amore » cerussite shell made of lath- or dendritic-shaped crystals. The cerussite phase was separated from the calcite by pores of less than 200 nm under transmission X-ray microscopy, consistent with the interface-coupled dissolution-precipitation mechanism. These results show that impurity metal ions exert significant control over the microscale dissolution features found on mineral surfaces and provide new insights into interpreting and designing micro structures observed in naturally-occurring and synthetic carbonate minerals by dissolution. In addition, heterogeneous micro-environments created in transport limited reactions under pore spaces may lead to unusual growth forms during crystal nucleation and precipitation.« less

Absorption Study of Genistein Using Solid Lipid Microparticles and Nanoparticles: Control of Oral Bioavailability by Particle Sizes.

PubMed

Kim, Jeong Tae; Barua, Sonia; Kim, Hyeongmin; Hong, Seong-Chul; Yoo, Seung-Yup; Jeon, Hyojin; Cho, Yeongjin; Gil, Sangwon; Oh, Kyungsoo; Lee, Jaehwi

2017-07-01

In this study, the effect of particle size of genistein-loaded solid lipid particulate systems on drug dissolution behavior and oral bioavailability was investigated. Genistein-loaded solid lipid microparticles and nanoparticles were prepared with glyceryl palmitostearate. Except for the particle size, other properties of genistein-loaded solid lipid microparticles and nanoparticles such as particle composition and drug loading efficiency and amount were similarly controlled to mainly evaluate the effect of different particle sizes of the solid lipid particulate systems on drug dissolution behavior and oral bioavailability. The results showed that genistein-loaded solid lipid microparticles and nanoparticles exhibited a considerably increased drug dissolution rate compared to that of genistein bulk powder and suspension. The microparticles gradually released genistein as a function of time while the nanoparticles exhibited a biphasic drug release pattern, showing an initial burst drug release, followed by a sustained release. The oral bioavailability of genistein loaded in solid lipid microparticles and nanoparticles in rats was also significantly enhanced compared to that in bulk powders and the suspension. However, the bioavailability from the microparticles increased more than that from the nanoparticles mainly because the rapid drug dissolution rate and rapid absorption of genistein because of the large surface area of the genistein-solid lipid nanoparticles cleared the drug to a greater extent than the genistein-solid lipid microparticles did. Therefore, the findings of this study suggest that controlling the particle size of solid-lipid particulate systems at a micro-scale would be a promising strategy to increase the oral bioavailability of genistein.

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.

TEM study of a silicate-carbonate-microbe interface prepared by focused ion beam milling

NASA Astrophysics Data System (ADS)

Benzerara, Karim; Menguy, Nicolas; Guyot, François; Vanni, Christian; Gillet, Philippe

2005-03-01

The biogeochemical alteration of an Mg-Fe orthopyroxene, reacted for 70 yr under arid conditions in a desert environment, was studied by transmission electron microscopy. For this purpose, an electron transparent cross-section of the interface between a single microorganism, an orthopyroxene and nanometer-sized calcite crystals, was prepared with a focused ion beam system. X-ray energy dispersive spectrometry and electron energy loss spectroscopy allowed one to clearly distinguish the microorganism en route to fossilization from the nanometer-sized calcite crystals, showing the usefulness of such a protocol for identifying unambiguously traces of life in rocks. A 100-nm-deep depression was observed in the orthopyroxene close to the microorganism, suggesting an enhanced dissolution mediated by the microbe. However, an Al- and Si-rich amorphous altered layer restricted to the area just below the microorganism could be associated with decreased silicate dissolution rates at this location, suggesting complex effects of the microorganism on the silicate dissolution process. The close association observed between silicate dissolution and carbonate formation at the micrometer scale suggests that Urey-type CO 2 sequestration reactions could be mediated by microorganisms under arid conditions.

Comparative study of quality and efficacy of originator's and generic ABZ for the mass treatment of soil-transmitted nematode infections in Nepal

PubMed Central

Albonico, Marco; Mathema P., Pragya; Montresor, Antonio; Khakurel, Balkrishna; Reggi, Valerio; Pandey, Sharada; Savioli, Lorenzo

2017-01-01

Quality and efficacy of two locally-manufactured generic albendazole (ABZ) products (Curex and Royal Drug) used for de-worming children in Nepal since 1999 were tested against the originator product (GSK). The study conducted disintegration and dissolution testing and a randomised controlled clinical trial comparing cure rates (CR) and egg reduction rates (ERR) for Ascaris lumbricoides, Trichuris trichiura and hookworm infections. Stool samples from 1277 children were examined before and 21 days after treatment. For A. lumbricoides GSK's (97.0%) and Royal Drug's (95.0 %) product provided significantly higher CR than Curex's (82.6%); however, all products provided ERR higher than 90%. For T. trichiura Curex's product showed significantly lower ERR (63.2%). For hookworm, GSK's product performed significantly better (CR 74.3%, ERR 87.1%) than Royal Drug's (CR 53.3%, ERR 80.8%) and Curex's (CR 50.7%, ERR 73.1%). Only GSK's product passed both disintegration and dissolution. Both generic products failed dissolution. Curex's product showed poor disintegration. Despite its lower efficacy the cheaper Curex's product achieved good results in controlling morbidity due to soil-transmitted helminth (STH) infections. This study shows that cost-effectiveness of drugs used in mass de-worming campaigns should not be inferred on the basis of one single quality testing parameter. PMID:17129592

Effects of tablet formulation and subsequent film coating on the supersaturated dissolution behavior of amorphous solid dispersions.

PubMed

Sakai, Toshiro; Hirai, Daiki; Kimura, Shin-Ichiro; Iwao, Yasunori; Itai, Shigeru

2018-04-05

The effects of tablet preparation and subsequent film coating with amorphous solid dispersion (ASD) particles that were composed of a drug with poor water solubility and hydrophilic polymers were investigated. ASD particles were prepared with a drug and vinylpyrrolidone-vinyl acetate copolymer (PVPVA) or polyvinylpyrrolidone (PVP) at a weight ratio of 1:1 or 1:2 using a melt extrusion technique. Tablets were prepared by conventional direct compression followed by pan coating. A mathematical model based on the Noyes-Whitney equation assuming that stable crystals precipitated at the changeable surface area of the solid-liquid interface used to estimate drug dissolution kinetics in a non-sink dissolution condition. All the ASD particles showed a maximum dissolution concentration approximately ten times higher than that of the crystalline drug. The ASD particles with PVPVA showed higher precipitation rate with lower polymer ratio, while PVP did not precipitate within 960 min regardless of the polymer ratio, suggesting the ASD particles of 1:1 drug:PVPVA (ASD-1) were the most unstable among the ASD particles considered. The dissolution of a core tablet with ASD-1 showed less supersaturation and a much higher precipitation rate than those of ASD-1 particles. However, a film-coated tablet or core tablet with a trace amount of hydroxypropylmethylcellulose (HPMC) showed a similar dissolution profile to that of the ASD-1 particles, indicating HPMC had a remarkable precipitation inhibition effect. Overall, these results suggest that tablet preparation with ASD may adversely affect the maintenance of supersaturation; however, this effect can be mitigated by adding an appropriate precipitation inhibitor to the formulation. Copyright © 2018 Elsevier B.V. All rights reserved.

Effect of synovial fluid, phosphate-buffered saline solution, and water on the dissolution and corrosion properties of CoCrMo alloys as used in orthopedic implants.

PubMed

Lewis, A C; Kilburn, M R; Papageorgiou, I; Allen, G C; Case, C P

2005-06-15

The corrosion and dissolution of high- and low-carbon CoCrMo alloys, as used in orthopedic joint replacements, were studied by immersing samples in phosphate-buffered saline (PBS), water, and synovial fluid at 37 degrees C for up to 35 days. Bulk properties were analyzed with a fine ion beam microscope. Surface analyses by X-ray photoelectron spectroscopy and Auger electron spectroscopy showed surprisingly that synovial fluid produced a thin oxide/hydroxide layer. Release of ions into solution from the alloy also followed an unexpected pattern where synovial fluid, of all the samples, had the highest Cr concentration but the lowest Co concentration. The presence of carbide inclusions in the alloy did not affect the corrosion or the dissolution mechanisms, although the carbides were a significant feature on the metal surface. Only one mechanism was recognized as controlling the thickness of the oxide/hydroxide interface. The analysis of the dissolved metal showed two mechanisms at work: (1) a protein film caused ligand-induced dissolution, increasing the Cr concentration in synovial fluid, and was explained by the equilibrium constants; (2) corrosion at the interface increased the Co in PBS. The effect of prepassivating the samples (ASTM F-86-01) did not always have the desired effect of reducing dissolution. The release of Cr into PBS increased after prepassivation. The metal-synovial fluid interface did not contain calcium phosphate as a deposit, typically found where samples are exposed to calcium rich bodily fluids. (c) 2005 Wiley Periodicals, Inc.

Experimental Fluidic Investigation of Degradation of Pico-liter Oil Droplets by Physical and Biological Processes

NASA Astrophysics Data System (ADS)

Jalali, Maryam; Sheng, Jian

2016-11-01

This study used laboratory experiments to assess degradation of crude oil by physical and biological processes including dissolution and consumption. To perform this study, we have developed a bioassay that consists of a flow chamber with a bottom glass substrate printed with an array of pico-liter oil droplets using micro-Transfer Printing. The technique allows the printing of highly homogeneous pico-liter droplet array with different dimensions and shapes that can be maintained for weeks. Since the droplets are pinned and stationary on the bottom substrate, the key processes can be evaluated by measuring the change of shape and volume using Atomic Force Microscopy. Parallel microfluidic bioassays are established at the beginning, exposed to abiotic/biotic solutions, and scarified for characterization at given time intervals for each experiment. Two processes, dissolution and consumption, are investigated. In addition, the effects of dispersant on these processes are also studied. The results show that the amount of oil degraded by bacteria accounts for almost 50% of the total volume in comparison to 25% via dissolution. Although dispersant has a subtle effect on dissolution, the effect on rates of consumption and its asymptotic behavior are substantial. Experiments involving different bacterial strains, dispersant concentration, and flow shear rate are on-going.

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.

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

Haste Makes Waste: The Interplay Between Dissolution and Precipitation of Supersaturating Formulations.

PubMed

Sun, Dajun D; Lee, Ping I

2015-11-01

Contrary to the early philosophy of supersaturating formulation design for oral solid dosage forms, current evidence shows that an exceedingly high rate of supersaturation generation could result in a suboptimal in vitro dissolution profile and subsequently could reduce the in vivo oral bioavailability of amorphous solid dispersions. In this commentary, we outline recent research efforts on the specific effects of the rate and extent of supersaturation generation on the overall kinetic solubility profiles of supersaturating formulations. Additional insights into an appropriate definition of sink versus nonsink dissolution conditions and the solubility advantage of amorphous pharmaceuticals are also highlighted. The interplay between dissolution and precipitation kinetics should be carefully considered in designing a suitable supersaturating formulation to best improve the dissolution behavior and oral bioavailability of poorly water-soluble drugs.

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

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.

Comparison of 20 nm silver nanoparticles synthesized with and without a gold core. Structure, dissolution in cell culture media, and biological impact on macrophages

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

Munusamy, Prabhakaran; Wang, Chongmin; Engelhard, Mark H.

Widespread use of silver nanoparticles raises questions of environmental impact and toxicity. Both silver particles and silver ions formed by particle dissolution may impact biological systems. Therefore it is important to understand the characteristics of silver nanoparticles and their stability in relevant media. The synthesis route can impact physical and chemical characteristics of the particles and we report the characterization and solution stability of three types of silver nanoparticles (20 nm particles with and without gold cores and 110 nm particles with gold cores) in cell culture media with serum proteins: FBS10%/RPMI. These nanoparticles were synthesized in aqueous solution andmore » characterized using both in situ and ex situ analysis methods. Dissolution studies were carried at particle concentrations from 1 µg/ml to 50 µg/ml. Particles with gold cores had smaller crystallite size and higher apparent solubility than pure silver particles. A dissolution model was found to describe the time variation of particle size and amount of dissolved silver for particle loadings above 9 µg/ml. An effective solubility product obtained from fitting the data was higher for the 20 nm gold core particles in comparison to the pure silver or 110 nm particles. Dissolution of the nanoparticles was enhanced by presence of serum proteins contained in fetal bovine serum. In addition, the protocol of the dispersion in the medium was found to influence particle agglomeration and dissolution. Results show that particle structure can impact the concentration of dissolved silver and the dose to which cells would be exposed during in vitro studies.« less

Comparison of 20 nm silver nanoparticles synthesized with and without a gold core. Structure, dissolution in cell culture media, and biological impact on macrophages

DOE PAGES

Munusamy, Prabhakaran; Wang, Chongmin; Engelhard, Mark H.; ...

2015-07-15

Widespread use of silver nanoparticles raises questions of environmental impact and toxicity. Both silver particles and silver ions formed by particle dissolution may impact biological systems. Therefore it is important to understand the characteristics of silver nanoparticles and their stability in relevant media. The synthesis route can impact physical and chemical characteristics of the particles and we report the characterization and solution stability of three types of silver nanoparticles (20 nm particles with and without gold cores and 110 nm particles with gold cores) in cell culture media with serum proteins: FBS10%/RPMI. These nanoparticles were synthesized in aqueous solution andmore » characterized using both in situ and ex situ analysis methods. Dissolution studies were carried at particle concentrations from 1 µg/ml to 50 µg/ml. Particles with gold cores had smaller crystallite size and higher apparent solubility than pure silver particles. A dissolution model was found to describe the time variation of particle size and amount of dissolved silver for particle loadings above 9 µg/ml. An effective solubility product obtained from fitting the data was higher for the 20 nm gold core particles in comparison to the pure silver or 110 nm particles. Dissolution of the nanoparticles was enhanced by presence of serum proteins contained in fetal bovine serum. In addition, the protocol of the dispersion in the medium was found to influence particle agglomeration and dissolution. Results show that particle structure can impact the concentration of dissolved silver and the dose to which cells would be exposed during in vitro studies.« less

Role of cellulose ether polymers on ibuprofen release from matrix tablets.

PubMed

Vueba, M L; Batista de Carvalho, L A E; Veiga, F; Sousa, J J; Pina, Maria Eugénia

2005-08-01

Cellulose derivatives are the most frequently used polymers in formulations of pharmaceutical products for controlled drug delivery. The main aim of the present work was to evaluate the effect of different cellulose substitutions on the release rate of ibuprofen (IBP) from hydrophilic matrix tablets. Thus, the release mechanism of IBP with methylcellulose (MC25), hydroxypropylcellulose (HPC), and hydroxypropylmethylcellulose (HPMC K15M or K100M) was studied. In addition, the influence of the diluents lactose monohydrate (LAC) and beta-cyclodextrin (beta-CD) was evaluated. Distinct test formulations were prepared containing: 57.14% of IBP, 20.00% of polymer, 20.29% of diluent, 1.71% of talc lubricants, and 0.86% of magnesium stearate as lubricants. Although non-negligible drug-excipient interactions were detected from DSC studies, these were found not to constitute an incompatibility effect. Tablets were examined for their drug content, weight uniformity, hardness, thickness, tensile strength, friability, porosity, swelling, and dissolution performance. Polymers MC25 and HPC were found to be unsuitable for the preparation of this kind of solid dosage form, while HPMC K15M and K100M showed to be advantageous. Dissolution parameters such as the area under the dissolution curve (AUC), the dissolution efficiency (DE(20 h)), dissolution time (t 50%), and mean dissolution time (MDT) were calculated for all the formulations, and the highest MDT values were obtained with HPMC indicating that a higher value of MDT signifies a higher drug retarding ability of the polymer and vice-versa. The analysis of the drug release data was performed in the light of distinct kinetic mathematical models-Kosmeyer-Peppas, Higuchi, zero-, and first-order. The release process was also found to be slightly influenced by the kind of diluent used.

DSM-IV Alcohol Dependence and Marital Dissolution: Evidence From the National Epidemiologic Survey on Alcohol and Related Conditions

PubMed Central

Cranford, James A

2014-01-01

Objective: The purpose of this study was to examine the cross-sectional and longitudinal associations among alcohol use disorder (AUD), stressful life events, and marital dissolution in a probability sample of adults. Method: The National Epidemiologic Survey on Alcohol and Related Conditions is a prospective, longitudinal study of a probability sample of 43,083 adults 18 years of age and older living in the United States. The interval between Wave 1 (W1) and Wave 2 (W2) was approximately 3 years. Cross-sectional analyses included 32,359 adults ages 18 and older who were ever married at W1, and longitudinal analyses included 17,192 adults who were currently married at W1 and who completed relevant W2 measures. Participants completed inhome surveys conducted with computer-assisted personal interviewing. Results: Rates of lifetime marital dissolution were significantly higher among those with lifetime AUD (48.3%) than in those with no lifetime AUD (30.1%). The incidence of marital dissolution from W1 to W2 was 15.5% for those with a past-12-month AUD at W1, compared to 4.8% among those with no AUD. Proportional hazards regression analyses showed that past-12-month AUD, tobacco use disorder, other substance use disorder, stressful life events, older age at marriage, being married more than once, and being married to an alcoholic at W1 predicted greater hazards of marital dissolution at W2. These associations were not moderated by gender. Conclusions: AUD and stressful life events predict subsequent marital dissolution independently of other substance use disorders, mood and anxiety disorders, and personality disorders. Results were discussed within the framework of the Vulnerability–Stress–Adaptation model of marriage. PMID:24766764

Influence of Coformer Stoichiometric Ratio on Pharmaceutical Cocrystal Dissolution: Three Cocrystals of Carbamazepine/4-Aminobenzoic Acid.

PubMed

Li, Zi; Matzger, Adam J

2016-03-07

Cocrystallization is a technique to optimize solid forms that shows great potential to improve the solubility of active pharmaceutical ingredients (APIs). In some systems, an API can form cocrystals in multiple stoichiometries with the same coformer. However, it remains unclear how coformer stoichiometry influences solubility. This paper investigates the pharmaceutical:coformer pair carbamazepine (CBZ)/p-aminobenzoic acid (PABA); both CBZ/PABA 1:1 and 2:1 cocrystals are known, and a novel 4:1 CBZ/PABA cocrystal is reported here. The 4:1 cocrystal is structurally characterized, and phase stability data suggest that it is a thermodynamically unstable form. Dissolution experiments show that there is no correlation between the cocrystal stoichiometry and dissolution rate in this system. On the other hand, with the relatively weak intermolecular interactions, metastable forms can be beneficial to dissolution rate, which suggests that more effort should be devoted to cocrystal production with kinetic growth methods.

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.

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.

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.

Optimization of Melatonin Dissolution from Extended Release Matrices Using Artificial Neural Networking.

PubMed

Martarelli, D; Casettari, L; Shalaby, K S; Soliman, M E; Cespi, M; Bonacucina, G; Fagioli, L; Perinelli, D R; Lam, J K W; Palmieri, G F

2016-01-01

Efficacy of melatonin in treating sleep disorders has been demonstrated in numerous studies. Being with short half-life, melatonin needs to be formulated in extended-release tablets to prevent the fast drop of its plasma concentration. However, an attempt to mimic melatonin natural plasma levels during night time is challenging. In this work, Artificial Neural Networks (ANNs) were used to optimize melatonin release from hydrophilic polymer matrices. Twenty-seven different tablet formulations with different amounts of hydroxypropyl methylcellulose, xanthan gum and Carbopol®974P NF were prepared and subjected to drug release studies. Using dissolution test data as inputs for ANN designed by Visual Basic programming language, the ideal number of neurons in the hidden layer was determined trial and error methodology to guarantee the best performance of constructed ANN. Results showed that the ANN with nine neurons in the hidden layer had the best results. ANN was examined to check its predictability and then used to determine the best formula that can mimic the release of melatonin from a marketed brand using similarity fit factor. This work shows the possibility of using ANN to optimize the composition of prolonged-release melatonin tablets having dissolution profile desired.

Long-term in situ oxidation of biogenic uraninite in an alluvial aquifer: impact of dissolved oxygen and calcium.

PubMed

Lezama-Pacheco, Juan S; Cerrato, José M; Veeramani, Harish; Alessi, Daniel S; Suvorova, Elena; Bernier-Latmani, Rizlan; Giammar, Daniel E; Long, Philip E; Williams, Kenneth H; Bargar, John R

2015-06-16

Oxidative dissolution controls uranium release to (sub)oxic pore waters from biogenic uraninite produced by natural or engineered processes, such as bioremediation. Laboratory studies show that uraninite dissolution is profoundly influenced by dissolved oxygen (DO), carbonate, and solutes such as Ca(2+). In complex and heterogeneous subsurface environments, the concentrations of these solutes vary in time and space. Knowledge of dissolution processes and kinetics occurring over the long-term under such conditions is needed to predict subsurface uranium behavior and optimize the selection and performance of uraninite-based remediation technologies over multiyear periods. We have assessed dissolution of biogenic uraninite deployed in wells at the Rifle, CO, DOE research site over a 22 month period. Uraninite loss rates were highly sensitive to DO, with near-complete loss at >0.6 mg/L over this period but no measurable loss at lower DO. We conclude that uraninite can be stable over decadal time scales in aquifers under low DO conditions. U(VI) solid products were absent over a wide range of DO values, suggesting that dissolution proceeded through complexation and removal of oxidized surface uranium atoms by carbonate. Moreover, under the groundwater conditions present, Ca(2+) binds strongly to uraninite surfaces at structural uranium sites, impacting uranium fate.

Structural changes in C–S–H gel during dissolution: Small-angle neutron scattering and Si-NMR characterization

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

Trapote-Barreira, Ana, E-mail: anatrapotebarreira@gmail.com; Porcar, Lionel; Large Scale Structure Group, Institut Laue Langevin, Grenoble

2015-06-15

Flow-through experiments were conducted to study the calcium–silicate–hydrate (C–S–H) gel dissolution kinetics. During C–S–H gel dissolution the initial aqueous Ca/Si ratio decreases to reach the stoichiometric value of the Ca/Si ratio of a tobermorite-like phase (Ca/Si = 0.83). As the Ca/Si ratio decreases, the solid C–S–H dissolution rate increases from (4.5 × 10{sup −} {sup 14} to 6.7 × 10{sup −} {sup 12}) mol m{sup −} {sup 2} s{sup −} {sup 1}. The changes in the microstructure of the dissolving C–S–H gel were characterized by small-angle neutron scattering (SANS) and {sup 29}Si magic-angle-spinning nuclear magnetic resonance ({sup 29}Si-MAS NMR). Themore » SANS data were fitted using a fractal model. The SANS specific surface area tends to increase with time and the obtained fit parameters reflect the changes in the nanostructure of the dissolving solid C–S–H within the gel. The {sup 29}Si MAS NMR analyses show that with dissolution the solid C–S–H structure tends to a more ordered tobermorite structure, in agreement with the Ca/Si ratio evolution.« less

Dissolution enhancement of a model poorly water-soluble drug, atorvastatin, with ordered mesoporous silica: comparison of MSF with SBA-15 as drug carriers.

PubMed

Maleki, Aziz; Hamidi, Mehrdad

2016-01-01

The purpose of this study was to develop mesoporous silica materials incorporated with poorly water-soluble drug atorvastatin calcium (AC) in order to improve drug dissolution, and intended to be orally administrated. A comparison between 2D-hexagonal silica nanostructured SBA-15 and mesocellular siliceous foam (MSF) with continuous 3D pore system on drug release rate was investigated. AC-loaded mesoporous silicas were characterized thorough N2 adsorption-desorption analysis, Fourier transform infrared (FT-IR) spectroscopy, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and dynamic light scattering (DLS). Results demonstrated a successful incorporation of AC into the silica-based hosts. The results taken from the drug release tests were also analyzed using different parameters, namely similarity factor (f2), difference factor (f1), dissolution efficiency (DE%), mean dissolution rate (MDR) and dissolution time (tm%). It confirmed a significant enhancement in the release profile of atorvastatin calcium with SBA-15, and MSF as drug carrier. Moreover, in comparison with SBA-15, MSF showed faster release rate of AC in enzyme-free simulated gastric fluid (pH 1.2). We believed that our findings can help the use of mesoporous silica materials in improving bioavailability of poorly water-soluble drugs.

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

NASA Astrophysics Data System (ADS)

Nurjannah, Yanah; Budianto, Emil

2018-04-01

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

Development and optimization of press coated tablets of release engineered valsartan for pulsatile delivery.

PubMed

Shah, Sunny; Patel, Romik; Soniwala, Moinuddin; Chavda, Jayant

2015-01-01

The present work is aimed to develop and optimize pulsatile delivery during dissolution of an improved formulation of valsartan to coordinate the drug release with circadian rhythm. Preliminary studies suggested that β cyclodextrin could improve the solubility of valsartan and showed AL type solubility curve. A 1:1 stoichiometric ratio of valsartan to β cyclodextrin was revealed from phase solubility studies and Job's plot. The prepared complex showed significantly better dissolution efficiency (p < 0.05) compared to pure drug, which could be due to the formation of inclusion complex as revealed from FTIR and DSC studies. Continuous dissolution-absorption studies revealed that absorption of drug from valsartan β cyclodextrin complex was significantly higher (p < 0.05) compared to pure drug, in second part press-coated tablets of valsartan β cyclodextrin complex were subsequently prepared and application of the Plackett-Burman screening design revealed that HPMC K4M and EC showed significant effect on lag time. A 3(2) full factorial design was used to measure the response of HPMC K4M and EC on lag time and time taken for 90% drug release (T90). The optimized batch prepared according to the levels obtained from the desirability function had a lag time of 6 h and consisted of HPMC K4M:ethylcellulose in a 1:1.5 ratio with 180 mg of coating and revealed a close agreement between observed and predicted value (R(2 )= 0.9694).

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.

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

PubMed

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

2017-03-01

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

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

NASA Astrophysics Data System (ADS)

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

2017-03-01

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

Dissolution rate enhancement of gliclazide by ordered mixing.

PubMed

Saharan, Vikas A; Choudhury, Pratim K

2011-09-01

The poorly water soluble antidiabetic drug gliclazide was selected to study the effect of excipients on dissolution rate enhancement. Ordered mixtures of micronized gliclazide with lactose, mannitol, sorbitol, maltitol and sodium chloride were prepared by manual shaking of glass vials containing the drug and excipient(s). Different water soluble excipients, addition of surfactant and superdisintegrant, drug concentration and carrier particle size influenced the dissolution rate of the drug. Dissolution rate studies of the prepared ordered mixtures revealed an increase in drug dissolution with all water soluble excipients. The order of dissolution rate improvement for gliclazide was mannitol > lactose > maltitol > sorbitol > sodium chloride. Composite granules of the particle size range 355-710 μm were superior in increasing the drug dissolution rate from ordered mixtures. Reducing the carrier particle size decreased the dissolution rate of the drug as well as the increase in drug concentration. Kinetic modeling of drug release data fitted best the Hixson-Crowell model, which indicates that all the ordered mixture formulations followed the cube root law fairly well.

NaK pool-boiler solar receiver durability bench test. Volume 2: Metallurgical analysis

NASA Astrophysics Data System (ADS)

Goods, S. H.; Bradshaw, R. W.

1995-01-01

The principal materials used in the construction of a NaK based pool-boiler were analyzed. The device, operated for 7500 hours, accumulated 1000 thermal cycles to a peak temperature of 750 C. Haynes 230, used to fabricate the pool-boiler vessel, was found to perform satisfactorily. Air-side corrosion of the pool-boiler vessel was insignificant. Internal surface of the alloy exhibited some NaK-induced elemental dissolution; this dissolution was somewhat more extensive where the alloy was exposed to the liquid metal compared to regions exposed only to NaK vapor; however, the corresponding metal loss in all regions was inconsequential, never exceeding more than a few microns. Autogenous seam welds of the alloy responded in a similar fashion, exhibiting only minimal metal loss over the course of the experiment. While there was 50% loss in ductility of the alloy there remained adequate ductility for the anticipated operating environment. An enhanced boiling nucleation surface comprised of stainless steel powder brazed to the vessel ID showed no change in its structure. It remained intact, showing no cracking after repeated thermal cycling. Other materials used in the experiment showed more extensive degradation after exposure to the NaK. IN 600, used to fabricate thermowells, exhibited extensive surface and intergranular dissolution. Grain boundary dissolution was sufficiently severe in one of the thermowells to cause an air leak, resulting in experiment termination. BNi-3, a brazing alloy used to join the pool-boiler vessel, endcaps and thermowells, showed some dissolution where it was exposed to the NaK as well as thermal aging effects. However, all brazes remained structurally sound. A nickel metal ribbon showed catastrophic dissolution, resulting in the formation of deep (greater than 30 (mu)m) pits and cavities. A zirconium metal foil used to getter oxygen from the NaK became extremely brittle.

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.

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

PubMed Central

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

2018-01-01

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

Reactive transport under stress: Permeability evolution in deformable porous media

NASA Astrophysics Data System (ADS)

Roded, R.; Paredes, X.; Holtzman, R.

2018-07-01

We study reactive transport in a stressed porous media, where dissolution of the solid matrix causes two simultaneous, competing effects: pore enlargement due to chemical deformation, and pore compaction due to mechanical weakening. We use a novel, mechanistic pore-scale model to simulate flooding of a sample under fixed confining stress. Our simulations show that increasing the stress inhibits the permeability enhancement, increasing the injected volume required to reach a certain permeability, in agreement with recent experiments. We explain this behavior by stress concentration downstream, in the less dissolved (hence stiffer) outlet region. As this region is also less conductive, even its small compaction has a strong bottleneck effect that curbs the permeability. Our results also elucidate that the impact of stress depends on the dissolution regime. Under wormholing conditions (slow injection, i.e. high Damkohler number, Da), the development of a sharp dissolution front and high porosity contrast accentuates the bottleneck effect. This reduces transport heterogeneity, promoting wormhole competition. Once the outlet starts eroding, the extreme focusing of transport and hence dissolution-characteristic of wormholing-becomes dominant, diminishing the bottleneck effect and hence the impact of stress at breakthrough. In contrast, at high flow rates (low Da), incomplete reaction upstream allows some of the reactant to traverse the sample, causing a more uniform dissolution. The continuous dissolution and its partial counteraction by compaction at the outlet provides a steady, gradual increase in the effect of stress. Consequently, the impact of stress is more pronounced at high Da during early stages (low permeability), and at low Da close breakthrough. Our work promotes understanding of the interplay between dissolution and compaction and its effect on the hydromechanical property evolution, with important implications for processes ranging from diagenesis and weathering of rocks, to well stimulation and carbon sequestration.

Kinetics of gibbsite dissolution under low ionic strength conditions

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

Ganor, J.; Mogollon, J.L.; Lasaga, A.C.

1999-06-01

Experiments measuring synthetic gibbsite dissolution rates were carried out using both a stirred-flow-through reactor and a column reactor at 25 C, and pH range of 2.5--4.1. All experiments were conducted under far from equilibrium conditions ({Delta}G < {minus}1.1 kcal/mole). The experiments were performed with perchloric acid under relatively low (and variable) ionic strength conditions. An excellent agreement was found between the results of the well-mixed flow-through experiments and those of the (nonmixed) column experiments. This agreement shows that the gibbsite dissolution rate is independent of the stirring rate and therefore supports the conclusion of Bloom and Erich (1987) that gibbsitemore » dissolution reaction is surface controlled and not diffusion controlled. The Brunauer-Emmett-Teller (BET) surface area of the gibbsite increased during the flow-through experiments, while in the column experiments no significant change in surface area was observed. The significant differences in the BET surface area between the column experiments and the flow-through experiments, and the excellent agreement between the rates obtained by both methods, enable the authors to justify the substitution of the BET surface area for the reactive surface area. The dissolution rate of gibbsite varied as a function of the perchloric acid concentration. The authors interpret the gibbsite dissolution rate as a result of a combined effect of proton catalysis and perchlorate inhibition. Following the theoretical study of Ganor and Lasaga (1998) they propose specific reaction mechanisms for the gibbsite dissolution in the presence of perchloric acid. The mathematical predictions of two of these reaction mechanisms adequately describe the experimental data.« less

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

PubMed

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

2018-01-08

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

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

PubMed

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

2017-01-03

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

Coupled alkali feldspar dissolution and secondary mineral precipitation in batch systems: 4. Numerical modeling of kinetic reaction paths

NASA Astrophysics Data System (ADS)

Zhu, Chen; Lu, Peng; Zheng, Zuoping; Ganor, Jiwchar

2010-07-01

This paper explores how dissolution and precipitation reactions are coupled in batch reactor experimental systems at elevated temperatures. This is the fourth paper in our series of "Coupled Alkali Feldspar Dissolution and Secondary Mineral Precipitation in Batch Systems". In our third paper, we demonstrated via speciation-solubility modeling that partial equilibrium between secondary minerals and aqueous solutions was not attained in feldspar hydrolysis batch reactors at 90-300 °C and that a strong coupling between dissolution and precipitation reactions follows as a consequence of the slower precipitation of secondary minerals ( Zhu and Lu, 2009). Here, we develop this concept further by using numerical reaction path models to elucidate how the dissolution and precipitation reactions are coupled. Modeling results show that a quasi-steady state was reached. At the quasi-steady state, dissolution reactions proceeded at rates that are orders of magnitude slower than the rates measured at far from equilibrium. The quasi-steady state is determined by the relative rate constants, and strongly influenced by the function of Gibbs free energy of reaction ( ΔG) in the rate laws. To explore the potential effects of fluid flow rates on the coupling of reactions, we extrapolate a batch system ( Ganor et al., 2007) to open systems and simulated one-dimensional reactive mass transport for oligoclase dissolution and kaolinite precipitation in homogeneous porous media. Different steady states were achieved at different locations along the one-dimensional domain. The time-space distribution and saturation indices (SI) at the steady states were a function of flow rates for a given kinetic model. Regardless of the differences in SI, the ratio between oligoclase dissolution rates and kaolinite precipitation rates remained 1.626, as in the batch system case ( Ganor et al., 2007). Therefore, our simulation results demonstrated coupling among dissolution, precipitation, and flow rates. Results reported in this communication lend support to our hypothesis that slow secondary mineral precipitation explains part of the well-known apparent discrepancy between lab measured and field estimated feldspar dissolution rates ( Zhu et al., 2004). Here we show how the slow secondary mineral precipitation provides a regulator to explain why the systems are held close to equilibrium and show how the most often-quoted "near equilibrium" explanation for an apparent field-lab discrepancy can work quantitatively. The substantiated hypothesis now offers the promise of reconciling part of the apparent field-lab discrepancy.

Effect of atmospheric organic complexation on iron-bearing dust solubility

NASA Astrophysics Data System (ADS)

Paris, R.; Desboeufs, K. V.

2013-05-01

Recent studies reported that the effect of organic complexation may be a potentially important process to be considered by models estimating atmospheric iron flux to the ocean. In this study, we investigated this process effect by a series of dissolution experiments on iron-bearing dust in the presence or the absence of various organic compounds (acetate, formate, oxalate, malonate, succinate, glutarate, glycolate, lactate, tartrate and humic acid as an analogue of humic like substances, HULIS) typically found in atmospheric waters. Only 4 of tested organic ligands (oxalate, malonate, tartrate and humic acid) caused an enhancement of iron solubility which was associated with an increase of dissolved Fe(II) concentrations. For all of these organic ligands, a positive linear dependence of iron solubility to organic concentrations was observed and showed that the extent of organic complexation on iron solubility decreased in the following order: oxalate >malonate = tartrate > humic acid. This was attributed to the ability of electron donors of organic ligands and implies a reductive ligand-promoted dissolution. This study confirms that among the known atmospheric organic binding ligands of Fe, oxalate is the most effective ligand promoting dust iron solubility and showed, for the first time, the potential effect of HULIS on iron dissolution under atmospheric conditions.

Oxidation of platinum nickel nanowires to improve durability of oxygen-reducing electrocatalysts

DOE PAGES

Alia, Shaun M.; Pylypenko, Svitlana; Dameron, Arrelaine; ...

2016-01-12

In this study, the impact of heat treating platinum-coated nickel (Pt-Ni) nanowires in oxygen is examined to determine the effect on oxygen reduction (ORR) activity and durability. Pt-Ni nanowires exhibit promising ORR mass activities (3 times greater than Pt nanoparticles, 1.5 times greater than U.S. Department of Energy target) both before and after potential cycling for all but the highest annealing temperatures explored. The annealing of Pt-Ni nanowires in oxygen with increasing temperature is found to reduce surface area and ORR activity in comparison to the untreated material, but also reduces activity losses following durability testing. Following potential cycling, unannealedmore » Pt-Ni nanowires show significant losses in surface area (23%) and specific activity (18%) while Pt-Ni nanowires annealed at 200°C show modest increases in surface area (2%) and specific activity (6%) after potential cycling. Increasing annealing temperatures also show a clear trend of decreasing Ni dissolution rates. While oxygen annealing has shown the ability to improve durability of Pt-Ni nanowires, significant Ni dissolution was observed in all samples and suggests oxide passivation while showing promise for improved durability, when employed by itself is insufficient to prevent all contamination concerns involving Ni dissolution.« less

The Combination Therapy of Dissolution Using Carbonated Liquid and Endoscopic Procedure for Bezoars: Pragmatical and Clinical Review

PubMed Central

Ogawa, Kohei; Mizuno, Ken-ichi; Shinagawa, Yoko; Kobayashi, Yuji; Abe, Hiroyuki; Watanabe, Yukari; Takahashi, Shunsaku; Hayashi, Kazunao; Yokoyama, Junji; Takeuchi, Manabu; Yamagiwa, Satoshi; Sato, Yuichi; Terai, Shuji

2016-01-01

Bezoars are relatively rare foreign bodies of gastrointestinal tract and often cause ileus and ulcerative lesions in the stomach and subsequent bleeding and perforation due to their size and stiffness. Therefore, the removal of bezoars is essential and recent development of devices, the endoscopic removal procedure, is often applied. However, due to their stiffness, simple endoscopic removal failed in not a few cases, and surgical removal has also been used. Recently, the efficacy of a combination therapy of endoscopic procedure and dissolution using carbonated liquid has been reported. To develop the safe and effective removal procedure, we carefully reviewed a total of 55 reported cases in this study including our 3 additional cases, successfully treated with dissolution with endoscopic fragmentation. In summary, the data showed the efficiency in the combination therapy, treating the larger size of bezoar and reducing the length of hospital stay. To the best of our knowledge, this is the largest pragmatical and clinical review for the combination therapy of dissolution and endoscopic treatment for bezoars. This review should help physicians to manage bezoars more efficiently. PMID:27642293

Characterization and evaluation of miconazole salts and cocrystals for improved physicochemical properties.

PubMed

Tsutsumi, Shunichirou; Iida, Motoo; Tada, Norio; Kojima, Takashi; Ikeda, Yukihiro; Moriwaki, Toshiya; Higashi, Kenjirou; Moribe, Kunikazu; Yamamoto, Keiji

2011-12-15

Miconazole salts and cocrystals were studied to improve the physicochemical properties of miconazole. Maleate, hemifumarate, and hemisuccinate were prepared and characterized by powder X-ray diffractometry, differential scanning calorimetry, and single crystal X-ray diffractometry. The intrinsic dissolution rate and stability of each miconazole crystal form were compared to those of freebase and nitrate to evaluate the optimal crystal form. Crystal structure analysis indicated that maleate was a salt formed by proton transfer from the acid to the imidazole group of miconazole. Hemifumarate and hemisuccinate were determined to be cocrystals formed by hydrogen bonding between the acids and the base in their crystal lattices. Intrinsic dissolution tests showed that the formation of salts and cocrystals improved the dissolution rate of miconazole. Stability tests of preliminary formulations prepared with each crystal form indicated that maleate and hemifumarate were unstable at 80°C and generated a specific degraded product, i.e., a Michael adduct, between miconazole and the acids. Hemisuccinate had a superior intrinsic dissolution rate and stability, and is thus considered a promising crystal form of miconazole. Copyright © 2011 Elsevier B.V. All rights reserved.

[Studies on hydroxyapatite applicatied in coprecipitate of total salvianolic acids phospholipid complex].

PubMed

Chen, Xiao-Yun; Zhang, Zhen-Hai; Liu, Dan; Sun, E; Jia, Xiao-Bin

2014-03-01

The purpose of this research was to prepare total salvianolic acids-phytosome-HA coprecipitate to improve drug dissolution and its micromeritic properties. Firstly, the coprecipitate was prepared by solvent method and in vitro dissolution of tripterine was performed with the salvianolic acid B and danshensu as criteria. At the same time, the micromeritic properties was characterizated, the structure of samples was characterized by TEM, DSC, XRD and FTIR. Results showed that when the ratio of drug to HA was 1:2, it had a better dissolution, the accumulative drug-release percent in vitro at 60 min was over 90%. At the same time, it has good liquidity and low moisture absorption. Its micromeritic properties have improved. It is proved that the drug still existed amorphously by microstructure analysis. The preparation process is simple and feasible, it has practical value.

Influence of Dissolution Media and Presence of Alcohol on the In Vitro Performance of Pharmaceutical Products Containing an Insoluble Drug.

PubMed

Friuli, Valeria; Bruni, Giovanna; Musitelli, Giorgio; Conte, Ubaldo; Maggi, Lauretta

2018-01-01

The purpose of this investigation is to determine how the dissolution media may influence the release rate of an insoluble drug in in vitro conditions. Some oral dosage forms containing ibuprofen, a molecule that shows pH-dependent solubility, are tested. They are evaluated in different media to simulate the gastrointestinal transit at paddle rotation speeds of 50 and 100 rpm. Moreover, the potential effect of different ethanol concentrations on drug release is tested. The dissolution profiles of the tablets show a similar behavior in water (pH 1.0) and phosphate buffer (pH 4.5) where the 2 doses are not completely dissolved. The soft capsules show a different behavior: a certain amount of ibuprofen, which is in solution inside the capsule, reprecipitates in water and in the pH 4.5 buffer. Instead, ibuprofen dissolves rapidly in the pH 6.8 buffer from all the formulations. In the water-ethanol solutions, the dissolution curves show a valuable increase in the drug dissolved at higher ethanol concentrations. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Enhancement of in-vitro drug dissolution of ketoconazole for its optimal in-vivo absorption using Nanoparticles and Solid Dispersion forms of the drug

NASA Astrophysics Data System (ADS)

Syed, Mohammed Irfan

Ketoconazole is one of the most widely prescribed oral antifungal drugs for the systemic treatment of various fungal infections. However, due its hydrophobic nature and poor solubility profiles in the gastro-intestinal fluids, variations in its bioavailability have been documented. Therefore, to enhance its dissolution in the biological fluids, this study was initiated to develop and evaluate Nanoparticles and Solid Dispersion forms of the drug. Nanoparticles of ketoconazole were developed by Wet Bead Milling technique using PVP-10k as the stabilizing material at a weight ratio of (2:1). Solid dispersion powder was prepared by Hot Melt method using PEG-8000 at a weight ratio of (1:2). A commercial product containing 200mg of ketoconazole tablet and pure drug powder were used as the control for comparison purposes. The dissolution studies were carried out in SGF, SIF, USP; and SIF with 0.2% sodium lauryl sulfate using the USP-II method for a 2 hours period. Physical characterizations were carried out using SEM, DSC, XRD and FTIR studies. Wet Bead Milling method yielded nanoparticles in the particles size range of (100-300nm.). First all samples were evaluated for their in-vitro dissolution in SGF at pH=1.2. After 15 minutes, the amounts of drug dissolved were observed to be 27% from both the pure powder and commercial tablet (control), 29% from solid dispersion and 100% from the Nanoparticles dosage form. This supports the fact that Nanoparticles had a strong influence on the dissolution rate of the drug and exhibited much faster dissolution of ketoconazole. When the same formulations were studied in the SIF, USP medium, the control formulation gave 3%, solid dispersion 8% and Nanoparticles 8% drug dissolution after 2 hours period. This could be because the weakly basic ketoconazole drug remained un-dissociated in the alkaline medium. Since this medium was unable to clearly distinguish the dissolution profiles from different formulation of the drug, the SIF solution was modified to include 0.02%, 0.05% and 0.1% sodium lauryl sulfate. Here, after 2 hours, the amount of drug dissolved was calculated to be 10% from controls, 21% from solid dispersion and 36% from nanoparticles in SIF with 0.02% SLS. Drug release was 20% from controls, 41% from solid dispersion and 52% from nanoparticle formulation in SIF with 0.05% SLS. Whereas amount of drug released in SIF with 0.1% SLS showed 21% from the control, 62% from solid dispersion and 85% from Nanoparticles respectively. This data supports that the ketoconazole Nanoparticles and its solid-dispersion exhibit many fold increase in dissolution of the drug, which could lead to a less variable and enhanced in-vivo drug absorption profiles. In addition, the data from the Physical Characterization (DSC, XRD and FTIR) supports that there were no interaction within the ingredients occurred in Nanoparticles and solid-dispersion formulations of the drug sample. Wet Bead Milling and Hot Melt methods proved useful in developing the Nanoparticles and solid dispersion form of ketoconazole. Results from particle size analysis were in correlation with data obtained from Scanning electron Microscopy and size of the nanoparticles was below 100nm. The dissolution studies with the modified simulated intestinal fluid (SIF) exhibited several fold increase in the dissolution of the drug compared to the pure drug powder and the commercial products used as the control. Also, the results from the physical characterization studies clearly support the stability of ketoconazole in both of these formulations.

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.

Study on the influence of the decoking agent on the activity of limestone in wet flue gas desulfurization

NASA Astrophysics Data System (ADS)

Li, Qianjun; Xu, Dongyang; Wu, Yunxia; Yu, Jin

2017-01-01

Influence of the main components of decoking agent (magnesium nitrate, aluminum nitrate, copper nitrate, ammonium nitrate and actual decoking agent) on the activity of limestone is studied in laboratory by MET method. Results show that magnesium nitrate, ammonium nitrate and copper nitrate almost has no effect on the activity of limestone. With the concentration increasing, aluminum nitrate has an increasing inhibition on the dissolution of limestone. Fly ash has inhibition on dissolution of limestone due to the blockage of limestone pore by fly ash. The actual decoking agent has almost no effect on the limestone.

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.

Model of dissolution in the framework of tissue engineering and drug delivery.

PubMed

Sanz-Herrera, J A; Soria, L; Reina-Romo, E; Torres, Y; Boccaccini, A R

2018-05-22

Dissolution phenomena are ubiquitously present in biomaterials in many different fields. Despite the advantages of simulation-based design of biomaterials in medical applications, additional efforts are needed to derive reliable models which describe the process of dissolution. A phenomenologically based model, available for simulation of dissolution in biomaterials, is introduced in this paper. The model turns into a set of reaction-diffusion equations implemented in a finite element numerical framework. First, a parametric analysis is conducted in order to explore the role of model parameters on the overall dissolution process. Then, the model is calibrated and validated versus a straightforward but rigorous experimental setup. Results show that the mathematical model macroscopically reproduces the main physicochemical phenomena that take place in the tests, corroborating its usefulness for design of biomaterials in the tissue engineering and drug delivery research areas.

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.

Dynamic Pore-Scale Imaging of Reactive Transport in Heterogeneous Carbonates at Reservior Conditions

NASA Astrophysics Data System (ADS)

Menke, Hannah; Bijeljic, Branko; Andrew, Matthew; Blunt, Martin

2014-05-01

Sequestering carbon in deep geologic formations is one way of reducing anthropogenic CO2 emissions. Carbon capture, Utilization, and Storage (CCUS) in carbonate reservoirs has the added benefit of mobilizing more oil for extraction, increasing oil reservoir yield, and generating revenue while also mitigating climate change. The magnitude, speed, and type of dissolution are dependent the intrinsic properties of the rock. Understanding how small changes in the pore structure affect dissolution is paramount for successful predictive modelling both on the pore-scale and for up-scaled reservoir simulations. We propose an experimental method whereby both 'Pink Beam' synchrotron radiation and a Micro-CT lab source are used in dynamic X-ray microtomography to investigate the pore structure changes in carbonate rocks of varying heterogeneity at high temperatures and pressures. Four carbonate rock types were studied, two relatively homogeneous carbonates, Ketton and Mt. Gambier, and two very heterogeneous carbonates, Estalliades and Portland Basebed. Each rock type was imaged under the same reservoir and flow conditions to gain insight into the impact of heterogeneity. A 4-mm carbonate core was injected with CO2-saturated brine at 10 MPa and 50oC for 2 hours. Depending on sample heterogeneity and X-ray source, tomographic images were taken at between 30-second and 20-minute time-resolutions and a 4-micron spatial resolution during injection. Changes in porosity, permeability, and structure were obtained by first binning and filtering the images, then binarizing them with watershed segmentation, and finally extracting a pore/throat network. Furthermore, pore-scale flow modelling was performed directly on the binarized image and used to track velocity distributions as the pore network evolved. Significant differences in dissolution type and magnitude were found for each rock type. The most homogeneous carbonate, Ketton, was seen to have predominately uniform dissolution with minor dissolution rate differences between the pores and pore throats. This was not true for the heterogeneous carbonates, Estalliades and Portland Basebed, which formed wormholes. Pore-scale modelling of flow directly on the voxels showed the differences in the evolution of complex flow fields with changes in dissolution regime. The PDFs of normalized velocity for uniform dissolution showed that the maximum pore velocity within the system decreased as dissolution occurred. This is due to dissolution enlarging pores and pore throats. However, in the wormholing regime, there was a large increase in maximum velocity once the wormhole broke through the length of the core and a preferential flow path was created. Additionally, this study serves as a unique benchmark for pore-scale reactive transport modelling directly on the binarized Micro-CT images. This dynamic pore-scale imaging method offers advantages in helping fully explain the dominant physical and chemical processes at the pore scale so that they may be up-scaled to the reservoir scale for increased accuracy in model prediction.

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

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.

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.

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.

Assessing the risk of pH-dependent absorption for new molecular entities: a novel in vitro dissolution test, physicochemical analysis, and risk assessment strategy.

PubMed

Mathias, Neil R; Xu, Yan; Patel, Dhaval; Grass, Michael; Caldwell, Brett; Jager, Casey; Mullin, Jim; Hansen, Luke; Crison, John; Saari, Amy; Gesenberg, Christoph; Morrison, John; Vig, Balvinder; Raghavan, Krishnaswamy

2013-11-04

Weak base therapeutic agents can show reduced absorption or large pharmacokinetic variability when coadministered with pH-modifying agents, or in achlorhydria disease states, due to reduced dissolution rate and/or solubility at high gastric pH. This is often referred to as pH-effect. The goal of this study was to understand why some drugs exhibit a stronger pH-effect than others. To study this, an API-sparing, two-stage, in vitro microdissolution test was developed to generate drug dissolution, supersaturation, and precipitation kinetic data under conditions that mimic the dynamic pH changes in the gastrointestinal tract. In vitro dissolution was assessed for a chemically diverse set of compounds under high pH and low pH, analogous to elevated and normal gastric pH conditions observed in pH-modifier cotreated and untreated subjects, respectively. Represented as a ratio between the conditions, the in vitro pH-effect correlated linearly with clinical pH-effect based on the Cmax ratio and in a non-linear relationship based on AUC ratio. Additionally, several in silico approaches that use the in vitro dissolution data were found to be reasonably predictive of the clinical pH-effect. To explore the hypothesis that physicochemical properties are predictors of clinical pH-effect, statistical correlation analyses were conducted using linear sequential feature selection and partial least-squares regression. Physicochemical parameters did not show statistically significant linear correlations to clinical pH-effect for this data set, which highlights the complexity and poorly understood nature of the interplay between parameters. Finally, a strategy is proposed for implementation early in clinical development, to systematically assess the risk of clinical pH-effect for new molecular entities that integrates physicochemical analysis and in vitro, in vivo and in silico methods.

Dissolution enhancement of chlorzoxazone using cogrinding technique

PubMed Central

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

2015-01-01

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

Dissolution enhancement of atorvastatin calcium by co-grinding technique.

PubMed

Prabhu, Priyanka; Patravale, Vandana

2016-08-01

Atorvastatin calcium (AC) is a BCS class II drug which shows poor bioavailability due to inadequate dissolution. Solid dispersions present a promising option to enhance the solubility of poorly soluble drugs. Co-grinding with hydrophilic excipients is an easy and economical technique to improve the solubility of poorly soluble drugs and is free from usage of organic solvents. The aim of the present study was to explore novel carrier VBP-1 (organosulphur compound) for formulating a solid dispersion by using a simple, commercially viable co-grinding technique to enhance the dissolution of AC and to develop an oral formulation of the same. Composition of the solid dispersion was optimized based on the release profile in pH 1.2 buffer. The optimized solid dispersion was further characterized for flow properties, DSC, FTIR spectroscopy, XRD, contact angle, SEM studies and release profile in phosphate buffer pH 6.8. The developed solid dispersion gave similar release profile as the innovator formulation (Lipitor® tablets) in both pH 1.2 buffer and phosphate buffer pH 6.8. The developed solid dispersion was formulated into hard gelatin capsules (size 3). The developed capsules were found to give similar release as the innovator formulation in both pH 1.2 buffer and phosphate buffer pH 6.8. The developed capsules were found to be stable for a period of 6 months. Anti-hyperlipidemic efficacy studies in rats showed higher reduction in cholesterol and triglyceride levels by the developed capsules in comparison to pure AC. In conclusion, novel carrier VBP-1 was successfully employed to enhance the dissolution of AC using co-grinding technique.

Fabrication of carbonate apatite blocks from set gypsum based on dissolution-precipitation reaction in phosphate-carbonate mixed solution.

PubMed

Nomura, Shunsuke; Tsuru, Kanji; Maruta, Michito; Matsuya, Shigeki; Takahashi, Ichiro; Ishikawa, Kunio

2014-01-01

Carbonate apatite (CO3Ap), fabricated by dissolution-precipitation reaction based on an appropriate precursor, is expected to be replaced by bone according to bone remodeling cycle. One of the precursor candidates is gypsum because it shows self-setting ability, which then enables it to be shaped and molded. The aim of this study, therefore, was to fabricate CO3Ap blocks from set gypsum. Set gypsum was immersed in a mixed solution of 0.4 mol/L disodium hydrogen phosphate (Na2HPO4) and 0.4 mol/L sodium hydrogen carbonate (NaHCO3) at 80-200°C for 6-48 h. Powder X-ray diffraction patterns and Fourier transform infrared spectra showed that CO3Ap block was fabricated by dissolution-precipitation reaction in Na2HPO4-NaHCO3 solution using set gypsum in 48 h when the temperature was 100°C or higher. Conversion rate to CO3Ap increased with treatment temperature. CO3Ap block containing a larger amount of carbonate was obtained when treated at lower temperature.

The Reversal of the Gender Gap in Education and Trends in Marital Dissolution

PubMed Central

Schwartz, Christine R.; Han, Hongyun

2014-01-01

The reversal of the gender gap in education has potentially far-reaching consequences for marriage markets, family formation, and relationship outcomes. One possible consequence of this is the growing number of marriages in which wives have more education than their husbands. Previous studies have found this type of union to be at higher risk of dissolution. Using data on marriages formed between 1950 and 2004 in the United States, we evaluate whether this association has persisted as the prevalence of this relationship type has increased. Our results show a large shift in the association between spouses’ relative education and marital dissolution. In particular, we confirm that marriages in which wives have the educational advantage were once more likely to dissolve, but we show that this association has disappeared in more recent marriage cohorts. Another key finding is that the relative stability of marriages between educational equals has increased. These results are consistent with a shift away from rigid gender specialization toward more flexible, egalitarian partnerships and provide an important counterpoint to claims that progress toward gender equality in heterosexual relationships has stalled. PMID:25364012

Citrus bergamia juice: phytochemical and technological studies.

PubMed

Picerno, Patrizia; Sansone, Francesca; Mencherini, Teresa; Prota, Lucia; Aquino, Rita Patrizia; Rastrelli, Luca; Lauro, Maria Rosaria

2011-07-01

Fresh juice from bergamot (Citrus bergamia Risso) has been studied to evaluate the polyphenolic composition by HPLC-DAD analysis and total polyphenols content by UV method. The main constituent, Naringin, has been selected as analytical and biological marker of the juice. Juice has been loaded onto maltodextrin matrix by spray-drying. The produced maltodextrin/juice powder (BMP) showed neither significant change in total polyphenols content nor decrease in antioxidant properties with respect to fresh juice. Moreover, BMP displayed high in vitro dissolution rate of the bioactive constituents in water and in simulated biological fluids. BMP appears as promising functional raw material for food, nutraceutical and pharmaceutical products. With this aim, a formulation study to develop tablets (BMT) for oral administration has been also performed. The produced solid oral dosage form preserved high polyphenols content, showed complete disaggregation in few minutes and satisfying dissolution rate of the bioactive constituents in simulated biological fluids.

Formulation studies on ibuprofen sodium-cationic dextran conjugate: effect on tableting and dissolution characteristics of ibuprofen.

PubMed

Abioye, Amos Olusegun; Kola-Mustapha, Adeola

2016-01-01

The effect of electrostatic interaction between ibuprofen sodium (IbS) and cationic diethylaminoethyl dextran (Ddex), on the tableting properties and ibuprofen release from the conjugate tablet was investigated. Ibuprofen exhibits poor flow, compaction (tableting) and dissolution behavior due to its hydrophobic structure, high cohesive, adhesive and viscoelastic properties therefore it was granulated with cationic Ddex to improve its compression and dissolution characteristics. Electrostatic interaction and hydrogen bonding between IbS and Ddex was confirmed with FT-IR and DSC results showed a stepwise endothermic solid-solid structural transformation from racemic to anhydrous forms between 120 and 175 °C which melted into liquid form at 208.15 °C. The broad and diffused DSC peaks of the conjugate granules as well as the disappearance of ibuprofen melting peak provided evidence for their highly amorphous state. It was evident that Ddex improved the flowability and densification of the granules and increased the mechanical and tensile strengths of the resulting tablets as the tensile strength increased from 0.67 ± 0.0172 to 1.90 ± 0.0038 MPa with increasing Ddex concentration. Both tapping and compression processes showed that the most prominent mechanism of densification were particle slippage, rearrangement and plastic deformation while fragmentation was minimized. Ddex retarded the extent of dissolution in general, indicating potentials for controlled release formulations. Multiple release mechanisms including diffusion; anomalous transport and super case II transport were noted. It was concluded that interaction between ibuprofen sodium and Ddex produced a novel formulation with improved flowability, tableting and dissolution characteristics with potential controlled drug release characteristics dictated by Ddex concentration.

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...

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.

Preparation of nanocrystalline forsterite by combustion of different fuels and their comparative in-vitro bioactivity, dissolution behaviour and antibacterial studies.

PubMed

Choudhary, Rajan; Manohar, Prasanth; Vecstaudza, Jana; Yáñez-Gascón, Maria Josefa; Sánchez, Horacio Pérez; Nachimuthu, Ramesh; Locs, Janis; Swamiappan, Sasikumar

2017-08-01

This study presents different fuels (Glycine and Urea) that can be used to synthesize nanocrystalline forsterite by the sol-gel combustion method. The weight change of precursor during thermal treatment was studied by thermo-gravimetric analysis (TGA). Pure forsterite was characterized by heating microscopy, Fourier transform infrared spectroscopy, X-ray Diffraction, Brunauer-Emmett-Teller, Scanning Electron Microscopy, and Energy dispersive X-ray spectroscopy. The HAP (hydroxyapatite) deposition ability, degradation and dissolution behaviour of forsterite was examined in simulated body fluid (SBF). The combusted forsterite precursor showed distinct thermal behaviour for each fuel when analyzed by heating microscopy. BET analysis showed that the particle size of forsterite synthesized using glycine was 28nm, specific surface area 65.11m 2 /g and average pore diameter 16.4nm while using urea 1.951μm, 0.939m 2 /g, and 30.5nm are the respective parameters. The dissolution of forsterite pointed to the consumption of Ca and P ions from SBF, the negligible release of Si ion into the SBF and these ionic interactions with SBF can be altered as per the material properties. The forsterite showed good antibacterial activity against S. aureus but lower activity against E. coli. The bactericidal activity of forsterite indicated that it can be used to inhibit biofilm formation in dental, bone implants and bacterial infection during surgical operations. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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

PubMed

Horkovics-Kovats, Stefan

2016-08-25

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

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

PubMed

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

2015-01-01

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

Berberine nanoparticles with enhanced in vitro bioavailability: characterization and antimicrobial activity

PubMed Central

Faidah, Hani S; Khurram, Muhammad; Amin, Muhammad Usman; Haseeb, Abdul; Kakar, Maria

2018-01-01

Background Berberine is an isoquinoline alkaloid widely used in Ayurveda and traditional Chinese medicine to treat illnesses such as hypertension and inflammatory conditions, and as an anticancer and hepato-protective agent. Berberine has low oral bioavailability due to poor aqueous solubility and insufficient dissolution rate, which can reduce the efficacy of drugs taken orally. In this study, evaporative precipitation of nanosuspension (EPN) and anti-solvent precipitation with a syringe pump (APSP) were used to address the problems of solubility, dissolution rate and bioavailability of berberine. Methods Semi-crystalline nanoparticles (NPs) of 90–110 nm diameter for APSP and 65–75 nm diameter for EPN were prepared and then characterized using differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRD). Thereafter, drug content solubility and dissolution studies were undertaken. Berberine and its NPs were evaluated for their antibacterial activity. Results The results indicate that the NPs have significantly increased solubility and dissolution rate due to conversion of the crystalline structure to a semi-crystalline form. Conclusion Berberine NPs produced by both APSP and EPN methods have shown promising activities against Gram-positive and Gram-negative bacteria, and yeasts, with NPs prepared through the EPN method showing superior results compared to those made with the APSP method and the unprocessed drug. PMID:29491706

Berberine nanoparticles with enhanced in vitro bioavailability: characterization and antimicrobial activity.

PubMed

Sahibzada, Muhammad Umar Khayam; Sadiq, Abdul; Faidah, Hani S; Khurram, Muhammad; Amin, Muhammad Usman; Haseeb, Abdul; Kakar, Maria

2018-01-01

Berberine is an isoquinoline alkaloid widely used in Ayurveda and traditional Chinese medicine to treat illnesses such as hypertension and inflammatory conditions, and as an anticancer and hepato-protective agent. Berberine has low oral bioavailability due to poor aqueous solubility and insufficient dissolution rate, which can reduce the efficacy of drugs taken orally. In this study, evaporative precipitation of nanosuspension (EPN) and anti-solvent precipitation with a syringe pump (APSP) were used to address the problems of solubility, dissolution rate and bioavailability of berberine. Semi-crystalline nanoparticles (NPs) of 90-110 nm diameter for APSP and 65-75 nm diameter for EPN were prepared and then characterized using differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRD). Thereafter, drug content solubility and dissolution studies were undertaken. Berberine and its NPs were evaluated for their antibacterial activity. The results indicate that the NPs have significantly increased solubility and dissolution rate due to conversion of the crystalline structure to a semi-crystalline form. Berberine NPs produced by both APSP and EPN methods have shown promising activities against Gram-positive and Gram-negative bacteria, and yeasts, with NPs prepared through the EPN method showing superior results compared to those made with the APSP method and the unprocessed drug.

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"…

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.

A Quality by Design approach to investigate tablet dissolution shift upon accelerated stability by multivariate methods.

PubMed

Huang, Jun; Goolcharran, Chimanlall; Ghosh, Krishnendu

2011-05-01

This paper presents the use of experimental design, optimization and multivariate techniques to investigate root-cause of tablet dissolution shift (slow-down) upon stability and develop control strategies for a drug product during formulation and process development. The effectiveness and usefulness of these methodologies were demonstrated through two application examples. In both applications, dissolution slow-down was observed during a 4-week accelerated stability test under 51°C/75%RH storage condition. In Application I, an experimental design was carried out to evaluate the interactions and effects of the design factors on critical quality attribute (CQA) of dissolution upon stability. The design space was studied by design of experiment (DOE) and multivariate analysis to ensure desired dissolution profile and minimal dissolution shift upon stability. Multivariate techniques, such as multi-way principal component analysis (MPCA) of the entire dissolution profiles upon stability, were performed to reveal batch relationships and to evaluate the impact of design factors on dissolution. In Application II, an experiment was conducted to study the impact of varying tablet breaking force on dissolution upon stability utilizing MPCA. It was demonstrated that the use of multivariate methods, defined as Quality by Design (QbD) principles and tools in ICH-Q8 guidance, provides an effective means to achieve a greater understanding of tablet dissolution upon stability. Copyright © 2010 Elsevier B.V. All rights reserved.

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

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

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

2014-07-02

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

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

PubMed

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

2017-11-01

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

Influence of Coformer Stoichiometric Ratio on Pharmaceutical Cocrystal Dissolution: Three Cocrystals of Carbamazepine/4-Aminobenzoic Acid

PubMed Central

Li, Zi; Matzger, Adam J.

2016-01-01

Cocrystallization is a technique to optimize solid forms that shows great potential to improve the solubility of active pharmaceutical ingredients (APIs). In some systems, an API can form cocrystals in multiple stoichiometries with the same coformer. However, it remains unclear how coformer stoichiometry influences solubility. This paper investigates the pharmaceutical:coformer pair carbamazepine (CBZ)/p-aminobenzoic acid (PABA); both CBZ/PABA 1:1 and 2:1 cocrystals are known, and a novel 4:1 CBZ/PABA cocrystal is reported here. The 4:1 cocrystal is structurally characterized, and phase stability data suggest that it is a thermodynamically unstable form. Dissolution experiments show that there is no correlation between the cocrystal stoichiometry and dissolution rate in this system. On the other hand, with the relatively weak intermolecular interactions, metastable forms can be beneficial to dissolution rate, which suggests that more effort should be devoted to cocrystal production with kinetic growth methods. PMID:26837376

Biowaiver extension potential and IVIVC for BCS Class II drugs by formulation design: Case study for cyclosporine self-microemulsifying formulation.

PubMed

Yang, Su-Geun

2010-11-01

The objective of this work was to suggest the biowaiver potential of biopharmaceutical classification system (BCS) Class II drugs in self-microemulsifying drug delivery systems (SMEDDS) which are known to increase the solubility, dissolution and oral absorption of water-insoluble drugs. Cyclosporine was selected as a representative BCS Class II drug. New generic candidate of cyclosporine SMEDDS (test) was applied for the study with brand SMEDDS (reference I) and cyclosporine self-emulsifying drug delivery systems (SEDDS, reference II). Solubility and dissolution of cyclosporine from SMEDDS were critically enhanced, which were the similar behaviors with BCS class I drug. The test showed the identical dissolution rate and the equivalent bioavailability (0.34, 0.42 and 0.68 of p values for AUC₀(→)₂₄(h), C(max) and T(max), respectively) with the reference I. Based on the results, level A in vitro-in vivo correlation (IVIVC) was established from these two SMEDDS formulations. This study serves as a good example for speculating the biowaiver extension potential of BCS Class II drugs specifically in solubilizing formulation such as SMEDDS.

Enhanced oral bioavailability of glycyrrhetinic acid via nanocrystal formulation.

PubMed

Lei, Yaya; Kong, Yindi; Sui, Hong; Feng, Jun; Zhu, Rongyue; Wang, Wenping

2016-10-01

The purpose of this study was to prepare solid nanocrystals of glycyrrhetinic acid (GA) for improved oral bioavailability. The anti-solvent precipitation-ultrasonication method followed by freeze-drying was adopted for the preparation of GA nanocrystals. The physicochemical properties, drug dissolution and pharmacokinetic of the obtained nanocrystals were investigated. GA nanocrystals showed a mean particle size of 220 nm and shaped like short rods. The analysis results from differential scanning calorimetry and X-ray powder diffraction indicated that GA remained in crystalline state despite a huge size reduction. The equilibrium solubility and dissolution rate of GA nanocrystal were significantly improved in comparison with those of the coarse GA or the physical mixture. The bioavailability of GA nanocrystals in rats was 4.3-fold higher than that of the coarse GA after oral administration. With its rapid dissolution and absorption performance, the solid nanocrystal might be a more preferable formulation for oral administration of poorly soluble GA.

SEISMIC-REFLECTION STUDIES OF SINKHOLES AND LIMESTONE DISSOLUTION FEATURES ON THE NORTHEASTERN FLORIDA SHELF.

USGS Publications Warehouse

Popenoe, Peter; Kohout, F.A.; Manheim, F.T.; ,

1984-01-01

High-resolution seismic-reflection profiles show that the shelf off northern Florida is underlain by solution deformed limestone of Oligocene, Eocene, Paleocene and late Cretaceous age. Dissolution and collapse features are widely scattered. They are expressed in three general forms: as sinkholes that presently breach the sea floor, such as Red Snapper Sink and the Crescent Beach submarine spring; as sinkholes that have breached the seafloor in the past but are now filled with shelf sands; and as dissolution collapse structures that originate deep within the section and have caused buckling and folding of overlying Eocene, Oligocene, and to a lesser extent, Neogene strata. Although deformation caused by solution and collapse can be shown to be a continuous process, the major episode of karstification occurred in the late Oligocene and early Miocene when the shelf was exposed to subaerial conditions.

Solid state of CG-400549, a novel FabI inhibitor: characterization, dissolution, transformation.

PubMed

Kim, Bo-Yeon; Sohn, Young-Taek

2011-05-01

The polymorphic and pseudopolymorphic forms of CG-400549, a novel FabI inhibitor with potent in vivo activity were prepared and characterized by differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD) and thermogravimetric analysis (TG). Seven crystal forms of CG-400549, one anhydrate and six solvates, have been isolated by recrystallization and the DSC and PXRD patterns of the seven crystal forms of CG-400549 were different respectively. The dissolution patterns of these seven crystal forms of CG-400549 were studied and they showed significant differences in the dissolution rate. After storage of 1 month at 0% RH (silica gel, 20°C), 52% RH (saturated solution of Na(2)Cr(2)O(7)2H(2)O/20°C) and 95% RH (saturated solution of Na(2)HPO(4)/20°C), all crystal forms were not transformed.

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.

Calcite dissolution rate spectra measured by in situ digital holographic microscopy.

PubMed

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

2017-09-01

Digital holographic microscopy in reflection mode is used to track in situ , real-time nanoscale topography evolution of cleaved (104) calcite surfaces exposed to flowing or static deionized water. The method captures full-field holograms of the surface at frame rates of up to 12.5 s -1 . Numerical reconstruction provides 3D surface topography with vertical resolution of a few nanometers and enables measurement of time-dependent local dissolution fluxes. A statistical distribution, or spectrum, of dissolution rates is generated by sampling multiple area domains on multiple crystals. The data show, as has been demonstrated by Fischer et al. (2012), that dissolution is most fully described by a rate spectrum, although the modal dissolution rate agrees well with published mean dissolution rates ( e.g. , 0.1 µmol m -2 s -1 to 0.3 µmol m -2 s -1 ). Rhombohedral etch pits and other morphological features resulting from rapid local dissolution appear at different times and are heterogeneously distributed across the surface and through the depth. This makes the distribution in rates measured on a single crystal dependent both on the sample observation field size and on time, even at nominally constant undersaturation. Statistical analysis of the inherent noise in the DHM measurements indicates that the technique is robust and that it likely can be applied to quantify and interpret rate spectra for the dissolution or growth of other minerals.

Calcite dissolution rate spectra measured by in situ digital holographic microscopy

NASA Astrophysics Data System (ADS)

Brand, Alexander S.; Feng, Pan; Bullard, Jeffrey W.

2017-09-01

Digital holographic microscopy in reflection mode is used to track in situ, real-time nanoscale topography evolution of cleaved (104) calcite surfaces exposed to flowing or static deionized water. The method captures full-field holograms of the surface at frame rates of up to 12.5 s-1. Numerical reconstruction provides 3D surface topography with vertical resolution of a few nanometers and enables measurement of time-dependent local dissolution fluxes. A statistical distribution, or spectrum, of dissolution rates is generated by sampling multiple area domains on multiple crystals. The data show, as has been demonstrated by Fischer et al. (2012), that dissolution is most fully described by a rate spectrum, although the modal dissolution rate agrees well with published mean dissolution rates (e.g., 0.1 μmol m-2 s-1 to 0.3 μmol m-2 s-1). Rhombohedral etch pits and other morphological features resulting from rapid local dissolution appear at different times and are heterogeneously distributed across the surface and through the depth. This makes the distribution in rates measured on a single crystal dependent both on the sample observation field size and on time, even at nominally constant undersaturation. Statistical analysis of the inherent noise in the DHM measurements indicates that the technique is robust and that it likely can be applied to quantify and interpret rate spectra for the dissolution or growth of other minerals.

Reactivity of Nanoscale Zero-Valent Iron in Unbuffered Systems: Effect of pH and Fe(II) Dissolution.

PubMed

Bae, Sungjun; Hanna, Khalil

2015-09-01

While most published studies used buffers to maintain the pH, there is limited knowledge regarding the reactivity of nanoscale zerovalent iron (NZVI) in poorly buffered pH systems to date. In this work, the effect of pH and Fe(II) dissolution on the reactivity of NZVI was investigated during the reduction of 4-nitrophenol (4-NP) in unbuffered pH systems. The reduction rate increased exponentially with respect to the NZVI concentration, and the ratio of dissolved Fe(II)/initial NZVI was related proportionally to the initial pH values, suggesting that lower pH (6-7) with low NZVI loading may slow the 4-NP reduction through acceleration of the dissolution of NZVI particles. Additional experiments using buffered pH systems confirmed that high pH values (8-9) can preserve the NZVI particles against dissolution, thereby enhancing the reduction kinetics of 4-NP. Furthermore, reduction tests using ferrous ion in suspensions of magnetite and maghemite showed that surface-bound Fe(II) on oxide coatings can play an important role in enhancing 4-NP reduction by NZVI at pH 8. These unexpected results highlight the importance of pH and Fe(II) dissolution when NZVI technology is applied to poorly buffered systems, particularly at a low amount of NZVI (i.e., <0.075 g/L).

Enhanced dissolution and oral bioavailability of valsartan solid dispersions prepared by a freeze-drying technique using hydrophilic polymers.

PubMed

Xu, Wei-Juan; Xie, Hong-Juan; Cao, Qing-Ri; Shi, Li-Li; Cao, Yue; Zhu, Xiao-Yin; Cui, Jing-Hao

2016-01-01

This study aimed to improve the dissolution rate and oral bioavailability of valsartan (VAL), a poorly soluble drug using solid dispersions (SDs). The SDs were prepared by a freeze-drying technique with polyethylene glycol 6000 (PEG6000) and hydroxypropylmethylcellulose (HPMC 100KV) as hydrophilic polymers, sodium hydroxide (NaOH) as an alkalizer, and poloxamer 188 as a surfactant without using any organic solvents. In vitro dissolution rate and physicochemical properties of the SDs were characterized using the USP paddle method, differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and Fourier transform-infrared (FT-IR) spectroscopy, respectively. In addition, the oral bioavailability of SDs in rats was evaluated by using VAL (pure drug) as a reference. The dissolution rates of the SDs were significantly improved at pH 1.2 and pH 6.8 compared to those of the pure drug. The results from DSC, XRD showed that VAL was molecularly dispersed in the SDs as an amorphous form. The FT-IR results suggested that intermolecular hydrogen bonding had formed between VAL and its carriers. The SDs exhibited significantly higher values of AUC 0-24 h and Cmax in comparison with the pure drug. In conclusion, hydrophilic polymer-based SDs prepared by a freeze-drying technique can be a promising method to enhance dissolution rate and oral bioavailability of VAL.

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

PubMed

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

2012-07-15

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

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.

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.

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.

Use of Mixer Torque Rheometer to Clarify the Relationship between the Kneading States of Wet Mass and the Dissolution of Final Product in High Shear Granulation.

PubMed

Otsuka, Tomoko; Kuroiwa, Yosuke; Sato, Kazunari; Yamashita, Kazunari; Hakomori, Tadashi; Kimura, Shin-Ichiro; Iwao, Yasunori; Itai, Shigeru

2018-01-01

The properties of wet mass, which indicate the progress of high shear granulation processes, usually have an effect on final product properties, such as tablet dissolution. The mixer torque rheometer (MTR) is a useful tool for quantitatively measuring the 'kneading state' of wet mass and detecting differences in granules. However, there have been no studies of the relationship between the MTR torque and the final product properties to date. In this study, we measured the MTR torque of wet granules at different kneading states, which were prepared by changing the granulation conditions. We then evaluated the relationship between the MTR torque and the dissolution rate of the final product properties. The amperage of the high shear granulator is usually monitored during granulation, but we could not detect a difference in the kneading state through the amperage. However, using MTR torque we were able to quantify the difference of the wet mass. Moreover, MTR torque showed a high correlation with dissolution, compared with the correlations with other intermediate properties, such as granules particle size and tablet hardness. These other properties are affected by following processes and are not properties that directly relate to the kneading state. Thus, MTR torque is a property of wet mass after granulation, and it can be used to directly evaluate differences of the kneading state, and as a result, dissolution. These results indicate the importance of controlling the kneading state, i.e., the progress of granulation, and the utility of MTR for detecting differences in wet mass.

The contribution of human activities to dissolved inorganic carbon fluxes in a karst underground river system: evidence from major elements and δ¹³C(DIC) in Nandong, Southwest China.

PubMed

Jiang, Yongjun

2013-09-01

Generally, the DIC in karst groundwater is dominantly derived from carbonate dissolution by carbonic acid. However, recently increases in the inorganic carbon flux have been linked to human activities, which nitric and sulfuric acids may contribute to carbonate dissolution. In order to quantify the sources and fluxes of DIC, and evaluate the carbon isotopic evolution of groundwater in Southwest China, the carbonate dissolution by carbonic, sulfuric and nitric acids was evaluated by hydrochemistry and δ¹³C(DIC)of groundwater. The results show that: (1) groundwater collected from residential and agricultural areas, showed higher DIC concentrations and δ¹³C(DIC) than those in groundwater collected from forested and grass land areas; (2) the contributions of carbonate dissolution by carbonic acid to total DIC concentrations in groundwater collected from forested and grass land areas averaged 99%; (3) the contributions of carbonate dissolution by carbonic acid to total DIC concentrations in groundwater, collected from residential and agricultural areas, varied from 40% to 77% with a mean percentage of 62%; (4) while the contributions of carbonate dissolution by sulfuric and nitric acids to total DIC concentrations in groundwater, collected from residential and agricultural areas, varied from 23% to 60% with a mean percentage of 38%; and (5) the δ¹³C(DIC) approaching a value of around -14‰, with a molar ratio between (Ca²⁺+Mg²⁺) and HCO₃⁻ of around 0.5 in groundwater, indicated that the carbonate was dissolved by soil CO₂ from C₃ vegetation under open system conditions. While the δ¹³C(DIC) varying from -5‰ to -11‰, with a variational molar ratio between (Ca²⁺+Mg²⁺) and HCO₃⁻ of 0.5 to 0.8 in groundwater, indicated that carbonate dissolution was controlled by soil CO₂ (from C₃ vegetation), HNO₃ and H₂SO₄. Also, this study indicated that the amount of soil or atmospheric CO₂ consumed during carbonate weathering should be critically evaluated when sulfuric or nitric acids are involved. Thus, not only the exports of inorganic carbon have been enhanced, but also the concentrations of nitrate and sulfate in karst groundwater have been elevated due to carbonate dissolution by sulfuric or nitric acid. Copyright © 2013 Elsevier B.V. All rights reserved.

Atmospheric Dissolved Iron Depostiion to the Global Oceans: Effects of Oxalate-Promoted Fe Dissolution, Photochemical Redox Cycling, and Dust Mineralogy

NASA Technical Reports Server (NTRS)

Johnson, M. S.; Meskhidze, N.

2013-01-01

Mineral dust deposition is suggested to be a significant atmospheric supply pathway of bioavailable iron (Fe) to Fe-depleted surface oceans. In this study, mineral dust and dissolved Fe (Fed) deposition rates are predicted for March 2009 to February 2010 using the 3-D chemical transport model GEOS-Chem implemented with a comprehensive dust-Fe dissolution scheme. The model simulates Fed production during the atmospheric transport of mineral dust taking into account inorganic and organic (oxalate)-promoted Fe dissolution processes, photochemical redox cycling between ferric (Fe(III)) and ferrous (Fe(II)) forms of Fe, dissolution of three different Fe-containing minerals (hematite, goethite, and aluminosilicates), and detailed mineralogy of windblown dust from the major desert regions. Our calculations suggest that during the yearlong simulation is approximately 0.26 Tg (1 Tg = 1012 g) of Fed was deposited to global oceanic regions. Compared to simulations only taking into account proton-promoted Fe dissolution, the addition of oxalate to the dust-Fe mobilization scheme increased total annual model-predicted Fed deposition to global oceanic regions by approximately 75%. The implementation of Fe(II)/Fe(III) photochemical redox cycling in the model allows for the distinction between different oxidation states of deposited Fed. Our calculations suggest that during the daytime, large fractions of Fed deposited to the global oceans is likely to be in Fe(II) form, while nocturnal fluxes of Fed are largely in Fe(III) form. Model simulations also show that atmospheric fluxes of Fed can be strongly influenced by the mineralogy of Fe-containing compounds. This study shows that Fed deposition to the oceans is controlled by total dust-Fe mass concentrations, mineralogy, the surface area of dust particles, atmospheric chemical composition, cloud processing, and meteorological parameters and exhibits complex and spatiotemporally variable patterns. Our study suggests that the explicit model representation of individual processes leading to Fed production within mineral dust are needed to improve the understanding of the atmospheric Fe cycle, and quantify the effect of dust-Fe on ocean biological productivity, carbon cycle, and climate.

Solubility and dissolution improvement of ketoprofen by emulsification ionic gelation

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

Modelling karst aquifer evolution in fractured, porous rocks

NASA Astrophysics Data System (ADS)

Kaufmann, Georg

2016-12-01

The removal of material in soluble rocks by physical and chemical dissolution is an important process enhancing the secondary porosity of soluble rocks. Depending on the history of the soluble rock, dissolution can occur either along fractures and bedding partings of the rock in the case of a telogenetic origin, or within the interconnected pore space in the case of eogenetic origin. In soluble rocks characterised by both fractures and pore space, dissolution in both flow compartments is possible. We investigate the dissolution of calcite both along fractures and within the pore space of a limestone rock by numerical modelling. The limestone rock is treated as fractured, porous aquifer, in which the hydraulic conductivity increases with time both for the fractures and the pore spaces. We show that enlargement of pore space by dissolution will accelerate the development of a classical fracture-dominated telogenetic karst aquifer, breakthrough occurs faster. In the case of a pore-controlled aquifer as in eogenetic rocks, enlargement of pores results in a front of enlarged pore spaces migrating into the karst aquifer, with more homogeneous enlargement around this dissolution front, and later breakthrough.

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).

Revisiting classical silicate dissolution rate laws under hydrothermal conditions

NASA Astrophysics Data System (ADS)

Pollet-Villard, Marion; Daval, Damien; Saldi, Giuseppe; Knauss, Kevin; Wild, Bastien; Fritz, Bertrand

2015-04-01

In the context of geothermal energy, the relative intensities of primary mineral leaching and secondary mineral precipitation can affect porosity and permeability of the reservoir, thereby influencing its hydraulic performance and the efficiency of the geothermal power station. That is why the prediction of reaction kinetics of fluid/rock interactions represents a critical issue in this context. Moreover, in several geothermal systems such as the one of Soultz-sous-Forêts (Alsace, France), the circulation of aqueous fluids induces only modest modifications of their chemical composition. Therefore, fluid-rock interactions take place at close-to-equilibrium conditions, where the rate-affinity relations are poorly known and intensively debated [1]. To describe more precisely the dissolution processes, our strategy consists in investigating the dissolution of the main cleavages of K-spar minerals (one of the prevalent primary minerals in the reservoir of Soultz-sous-Forêts geothermal system) over a wide range of Gibbs free energy (ΔG) conditions. The aims are to decipher the impact of crystallographic orientation and microstructural surface modifications on the dissolution kinetics and to propose a relation between K-spar dissolution rate and ΔG. Our experimental work relies on a coupled approach which combines classical experiments of K-spar dissolution monitored by aqueous chemical analyses (ICP-AES) and innovative techniques of nm- to μm-scale characterization of solid surface (SEM, AFM, VSI) [2]. Our results confirm that K-spar dissolution is an anisotropic process: we measure a tenfold factor between the slowest and the fastest-dissolving surfaces. Moreover, the formation of etch pits on surfaces during their alteration has been evidenced on all of the different faces that have been studied. This complex evolution of the surface topography casts doubt of the relevance of a surface model based on shrinking particles and represents a possible cause of an apparent modification of silicate dissolution rate over time. In addition, we evidenced that the relation between K-spar dissolution rate and ΔG depends on the crystallographic orientation of the altered surface, and differs from the transition state theory currently implemented into geochemical codes. Importantly, this theoretical curve overestimates the dissolution rates measured in close-to-equilibrium conditions. Taken together, the new findings show promise as a means for improving the accuracy of geochemical simulations. [1] Schott, J., Pokrovsky, O. S., and Oelkers, E. H., 2009. The Link Between Mineral Dissolution/Precipitation Kinetics and Solution Chemistry. Rev Mineral Geochem 70, 207-258. [2] Daval, D., Hellmann, R., Saldi, G. D., Wirth, R., and Knauss, K. G., 2013. Linking nm-scale measurements of the anisotropy of silicate surface reactivity to macroscopic dissolution rate laws: New insights based on diopside. Geochim Cosmochim Acta 107, 121-134.

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.

Dynamic Pore-Scale Imaging of Reactive Transport in Heterogeneous Carbonates at Reservoir Conditions Across Multiple Dissolution Regimes

NASA Astrophysics Data System (ADS)

Menke, H. P.; Bijeljic, B.; Andrew, M. G.; Blunt, M. J.

2014-12-01

Sequestering carbon in deep geologic formations is one way of reducing anthropogenic CO2 emissions. When supercritical CO2 mixes with brine in a reservoir, the acid generated has the potential to dissolve the surrounding pore structure. However, the magnitude and type of dissolution are condition dependent. Understanding how small changes in the pore structure, chemistry, and flow properties affect dissolution is paramount for successful predictive modelling. Both 'Pink Beam' synchrotron radiation and a Micro-CT lab source are used in dynamic X-ray microtomography to investigate the pore structure changes during supercritical CO2 injection in carbonate rocks of varying heterogeneity at high temperatures and pressures and various flow-rates. Three carbonate rock types were studied, one with a homogeneous pore structure and two heterogeneous carbonates. All samples are practically pure calcium carbonate, but have widely varying rock structures. Flow-rate was varied in three successive experiments by over an order of magnitude whlie keeping all other experimental conditions constant. A 4-mm carbonate core was injected with CO2-saturated brine at 10 MPa and 50oC. Tomographic images were taken at 30-second to 20-minute time-resolutions during a 2 to 4-hour injection period. A pore network was extracted using a topological analysis of the pore space and pore-scale flow modelling was performed directly on the binarized images with connected pathways and used to track the altering velocity distributions. Significant differences in dissolution type and magnitude were found for each rock type and flowrate. At the highest flow-rates, the homogeneous carbonate was seen to have predominately uniform dissolution with minor dissolution rate differences between the pores and pore throats. Alternatively, the heterogeneous carbonates which formed wormholes at high flow rates. At low flow rates the homogeneous rock developed wormholes, while the heterogeneous samples showed evidence of compact dissolution. This study serves as a unique benchmark for pore-scale reactive transport modelling directly on the binarized Micro-CT images. Dynamic pore-scale imaging methods offer advantages in helping explain the dominant processes at the pore scale so that they may be up-scaled for accurate model prediction.

What Happens during Natural Protein Fibre Dissolution in Ionic Liquids.

PubMed

Chen, Jingyu; Vongsanga, Kylie; Wang, Xungai; Byrne, Nolene

2014-08-28

Here, we monitor the dissolution of several natural protein fibres such as wool, human hair and silk, in various ionic liquids (ILs). The dissolution of protein-based materials using ILs is an emerging area exploring the production of new materials from waste products. Wool is a keratin fibre, which is extensively used in the textiles industry and as a result has considerable amounts of waste produced each year. Wool, along with human hair, has a unique morphology whereby the outer layer, the cuticle, is heavily cross linked with disulphide bonds, whereas silk does not have this outer layer. Here we show how ILs dissolve natural protein fibres and how the mechanism of dissolution is directly related to the structure and morphology of the wool fibre.

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.

Enhancement in in vitro anti-angiogenesis activity and cytotoxicity in lung cancer cell by pectin-PVP based curcumin particulates.

PubMed

Gaikwad, Dinanath; Shewale, Rajnita; Patil, Vinit; Mali, Dipak; Gaikwad, Uday; Jadhav, Namdeo

2017-11-01

The aim of this work was to prepare pectin-poly (vinyl pyrrolidone) [PVP] based curcumin particulates to enhance the anticancer potential of curcumin, solubility and allow its localized controlled release. Pectin-PVP based curcumin particulates (PECTIN-PVP CUR) were prepared by spray drying technique in different ratios and were evaluated for surface morphology, micromeritics, flowability, particle size, drug content, in vitro dissolution, inhalable fraction, anti-angiogenesis/angiolysis and cytotoxicity. Results of micromeritic properties, Carr's index, Hausner's ratio and angle of repose were satisfactory. The batch CP3 was considered as optimum, due to excellent flowability, acceptable aggregation and enhanced solubility. The particle size and size distribution data of selected batch CP3 showed 90% of curcumin particulates having size less than 2.74μm, which may deposit to lungs. Twin Impinger studies showed that 29% of respirable fraction was generated, which could be directly delivered to lungs. The in vitro dissolution data showed many fold increase in dissolution rate. Angiolytic activity and MTT assay of PECTIN-PVP CUR have demonstrated enhancement in the anti-tumor potential, compared to curcumin alone. Altogether, PECTIN-PVP CUR were found suitable for local delivery and enhance its anticancer potential of curcumin. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2018-01-15

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

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.

The combined effect of wet granulation process parameters and dried granule moisture content on tablet quality attributes.

PubMed

Gabbott, Ian P; Al Husban, Farhan; Reynolds, Gavin K

2016-09-01

A pharmaceutical compound was used to study the effect of batch wet granulation process parameters in combination with the residual moisture content remaining after drying on granule and tablet quality attributes. The effect of three batch wet granulation process parameters was evaluated using a multivariate experimental design, with a novel constrained design space. Batches were characterised for moisture content, granule density, crushing strength, porosity, disintegration time and dissolution. Mechanisms of the effect of the process parameters on the granule and tablet quality attributes are proposed. Water quantity added during granulation showed a significant effect on granule density and tablet dissolution rate. Mixing time showed a significant effect on tablet crushing strength, and mixing speed showed a significant effect on the distribution of tablet crushing strengths obtained. The residual moisture content remaining after granule drying showed a significant effect on tablet crushing strength. The effect of moisture on tablet tensile strength has been reported before, but not in combination with granulation parameters and granule properties, and the impact on tablet dissolution was not assessed. Correlations between the energy input during granulation, the density of granules produced, and the quality attributes of the final tablets were also identified. Understanding the impact of the granulation and drying process parameters on granule and tablet properties provides a basis for process optimisation and scaling. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Ocean acidification accelerates dissolution of experimental coral reef communities

NASA Astrophysics Data System (ADS)

Comeau, S.; Carpenter, R. C.; Lantz, C. A.; Edmunds, P. J.

2015-01-01

Ocean acidification (OA) poses a severe threat to tropical coral reefs, yet much of what is know about these effects comes from individual corals and algae incubated in isolation under high pCO2. Studies of similar effects on coral reef communities are scarce. To investigate the response of coral reef communities to OA, we used large outdoor flumes in which communities composed of calcified algae, corals, and sediment were combined to match the percentage cover of benthic communities in the shallow back reef of Moorea, French Polynesia. Reef communities in the flumes were exposed to ambient (~ 400 μatm) and high pCO2 (~ 1300 μatm) for 8 weeks, and calcification rates measured for the constructed communities including the sediments. Community calcification was reduced by 59% under high pCO2, with sediment dissolution explaining ~ 50% of this decrease; net calcification of corals and calcified algae remained positive but was reduced by 29% under elevated pCO2. These results show that, despite the capacity of coral reef calcifiers to maintain positive net accretion of calcium carbonate under OA conditions, reef communities might transition to net dissolution as pCO2 increases, particularly at night, due to enhanced sediment dissolution.

Ocean acidification accelerates dissolution of experimental coral reef communities

NASA Astrophysics Data System (ADS)

Comeau, S.; Carpenter, R. C.; Lantz, C. A.; Edmunds, P. J.

2014-08-01

Ocean acidification (OA) poses a severe threat to tropical coral reefs, yet much of what is know about these effects comes from individual corals and algae incubated in isolation under high pCO2. Studies of similar effects on coral reef communities are scarce. To investigate the response of coral reef communities to OA, we used large outdoor flumes in which communities composed of calcified algae, corals, and sediment were combined to match the percentage cover of benthic communities in the shallow back reef of Moorea, French Polynesia. Reef communities in the flumes were exposed to ambient (~400 μatm) and high pCO2 (~1300 μatm) for 8 weeks, and calcification rates measured for the constructed communities including the sediments. Community calcification was depressed 59% under high pCO2, with sediment dissolution explaining ~50% of this decrease; net calcification of corals and calcified algae remained positive, but was reduced 29% under elevated pCO2. These results show that despite the capacity of coral reef calcifiers to maintain positive net accretion of calcium carbonate under OA conditions, reef communities might switch to net dissolution as pCO2 increases, particularly at night, due to enhanced sediment dissolution.

Effects of ocean acidification on the dissolution rates of reef-coral skeletons.

PubMed

van Woesik, Robert; van Woesik, Kelly; van Woesik, Liana; van Woesik, Sandra

2013-01-01

Ocean acidification threatens the foundation of tropical coral reefs. This study investigated three aspects of ocean acidification: (i) the rates at which perforate and imperforate coral-colony skeletons passively dissolve when pH is 7.8, which is predicted to occur globally by 2100, (ii) the rates of passive dissolution of corals with respect to coral-colony surface areas, and (iii) the comparative rates of a vertical reef-growth model, incorporating passive dissolution rates, and predicted sea-level rise. By 2100, when the ocean pH is expected to be 7.8, perforate Montipora coral skeletons will lose on average 15 kg CaCO3 m(-2) y(-1), which is approximately -10.5 mm of vertical reduction of reef framework per year. This rate of passive dissolution is higher than the average rate of reef growth over the last several millennia and suggests that reefs composed of perforate Montipora coral skeletons will have trouble keeping up with sea-level rise under ocean acidification. Reefs composed of primarily imperforate coral skeletons will not likely dissolve as rapidly, but our model shows they will also have trouble keeping up with sea-level rise by 2050.

Solubilization, Solution Equilibria, and Biodegradation of PAH's under Thermophilic Conditions

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

Viamajala, S.; Peyton, B. M.; Richards, L. A.

Biodegradation rates of PAHs are typically low at mesophilic conditions and it is believed that the kinetics of degradation is controlled by PAH solubility and mass transfer rates. Solubility tests were performed on phenanthrene, fluorene and fluoranthene at 20 C, 40 C and 60 C and, as expected, a significant increase in the equilibrium solubility concentration and of the rate of dissolution of these polycyclic aromatic hydrocarbons (PAHs) was observed with increasing temperature. A first-order model was used to describe the PAH dissolution kinetics and the thermodynamic property changes associated with the dissolution process (enthalpy, entropy and Gibb's free energymore » of solution) were evaluated. Further, other relevant thermodynamic properties for these PAHs, including the activity coefficients at infinite dilution, Henry's law constants and octanol-water partition coefficients, were calculated in the temperature range 20-60 C. In parallel with the dissolution studies, three thermophilic Geobacilli were isolated from compost that grew on phenanthrene at 60 C and degraded the PAH more rapidly than other reported mesophiles. Our results show that while solubilization rates of PAHs are significantly enhanced at elevated temperatures, the biodegradation of PAHs under thermophilic conditions is likely mass transfer limited due to enhanced degradation rates.« less

Retention and clearance of inhaled ceramic fibres in rat lungs and development of a dissolution model.

PubMed Central

Yamato, H; Hori, H; Tanaka, I; Higashi, T; Morimoto, Y; Kido, M

1994-01-01

Male Wistar rats were exposed to aluminium silicate ceramic fibres by inhalation to study pulmonary deposition, clearance, and dissolution of the fibres. Rats were killed at one day, one month, three months, and six months after the termination of exposure. After exposure, fibres greater than 50 microns in length were seen with a scanning electron microscope in the alveolar region of the lung. Fibres were recovered from the lungs with a low temperature ashing technique and their number, diameter, and length were measured by scanning electron microscopy. The number of fibres remaining in the lungs declined exponentially with time after exposure and their silicon content also fell. The geometric median diameter of fibres decreased linearly with time. By six months after exposure, the surface of fibres recovered from the lungs had an eroded appearance. The results suggest that ceramic fibres are physically cleared from the lung and that they show signs of dissolution. Finally, the results were used to develop a theoretical model of fibre dissolution that gives a satisfactory fit to the experimental data. Images Figure 1 Figure 2 Figure 5 PMID:8199672

Theoretical study of the influence of chemical reactions and physical parameters on the convective dissolution of CO2 in aqueous solutions

NASA Astrophysics Data System (ADS)

Loodts, Vanessa; Rongy, Laurence; De Wit, Anne

2014-05-01

Subsurface carbon sequestration has emerged as a promising solution to the problem of increasing atmospheric carbon dioxide (CO2) levels. How does the efficiency of such a sequestration process depend on the physical and chemical characteristics of the storage site? This question is emblematic of the need to better understand the dynamics of CO2 in subsurface formations, and in particular, the properties of the convective dissolution of CO2 in the salt water of aquifers. This dissolution is known to improve the safety of the sequestration by reducing the risks of leaks of CO2 to the atmosphere. Buoyancy-driven convection makes this dissolution faster by transporting dissolved CO2 further away from the interface. Indeed, upon injection, the less dense CO2 phase rises above the aqueous layer where it starts to dissolve. The dissolved CO2 increases the density of the aqueous solution, thereby creating a layer of denser CO2-rich solution above less dense solution. This unstable density gradient in the gravity field is at the origin of convection. In this framework, we theoretically investigate the effect of CO2 pressure, salt concentration, temperature, and chemical reactions on the dissolution-driven convection of CO2 in aqueous solutions. On the basis of a linear stability analysis, we assess the stability of the time-dependent density profiles developing when CO2 dissolves in an aqueous layer below it. We predict that increasing CO2 pressure destabilizes the system with regard to buoyancy-driven convection, because it increases the density gradient at the origin of the instability. By contrast, increasing salt concentration or temperature stabilizes the system via effects on CO2 solubility, solutal expansion coefficient, diffusion coefficient and on the viscosity and density of the solution. We also show that a reaction of CO2 with chemical species dissolved in the aqueous solution can either enhance or decrease the amplitude of the convective dissolution compared to the non reactive one. On the basis of a reaction-diffusion-convection model, we classify the various possible cases and show that the difference between the solutal expansion coefficients of the reactant and of the product governs the type of density profile building up in the aqueous solution and thus the stability of the system. By contrast to non reactive density profiles, reactive density profiles can feature a minimum that induces a delay of the buoyancy-driven convection. This work identifies the parameters that could influence the dissolution-driven convection in the aquifers, and thus impact the safety of the sequestration. In other words, this theoretical study shows that it is crucial to analyse the composition and reactivity of potential storage sites to choose those that will be most efficient for long-term CO2 sequestration.

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.

The Impact of Amorphisation and Spheronization Techniques on the Improved in Vitro & in Vivo Performance of Glimepiride Tablets

PubMed Central

Makar, Rana Refaat; Latif, Randa; Hosni, Ehab Ahmed; El Gazayerly, Omaima Naim

2017-01-01

Purpose: Triple solid dispersion adsorbates (TSDads) and spherical agglomerates (SA) present new techniques that extensively enhance dissolution of poorly soluble drugs. The aim of the present study is to hasten the onset of hypoglycemic effect of glimepiride through enhancing its rate of release from tablet formulation prepared from either technique. Methods: Drug release from TSDads or SA tablets with different added excipients was explored. Scanning electron microscopy (SEM) and effect of compression on dissolution were illustrated. Pharmacodynamic evaluation was performed on optimized tablets. Results: TSDads & SA tablets with Cross Povidone showed least disintegration times of 1.48 and 0.5 min. respectively. Kinetics of drug release recorded least half-lives (54.13 and 59.83min for both techniques respectively). Cross section in tablets displayed an organized interconnected matrix under SEM, accounting for the rapid access of dissolution media to the tablet core. Components of tablets filled into capsules showed a similar release profile to that of tablets after compression as indicated by similarity factor. The onset time of maximum reduction in blood glucose in male albino rabbits was hastened to 2h instead of 3h for commercial tablets. Conclusion: After optimization of tablet excipients that interacted differently with respect to their effect on drug release, we could conclude that both amorphisation and spheronization were equally successful in promoting in vitro dissolution enhancement as well as providing a more rapid onset time for drug action in vivo. PMID:29399545

Comparison and Characterisation of Regenerated Chitosan from 1-Butyl-3-methylimidazolium Chloride and Chitosan from Crab Shells

PubMed Central

Arnold, Lyndon

2015-01-01

Chitosan is a biopolymer derived from chitin which is naturally occurring in the exoskeleton of crustaceans. This paper reports dissolution and regeneration of chitosan by directly dissolving in an ionic liquid solvent, 1-butyl-3-methylimidazolium chloride (BMIMCl). This will provide an ideal platform to solubilise these kinds of polymers to achieve the dissolution. The current study dissolved chitosan from crab shell utilising BMIMCl as a solvent and characterised the resultant regenerated polymer. The regenerated chitosan showed increased hydrogen bonding when characterised by Fourier transform infrared (FTIR) spectral analysis. In addition, the study also compared the characteristics of regenerated and generic chitosan. The regenerated chitosan was also evaluated for antimicrobial properties and showed to possess antibacterial features similar to the commercial grade. This method can be utilised in future for blending of polymers with chitosan in a dissolved phase. PMID:26090452

Dissolution Flowsheet for High Flux Isotope Reactor Fuel

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

Daniel, W. E.; Rudisill, T. S.; O'Rourke, P. E.

2016-09-27

As part of the Spent Nuclear Fuel (SNF) processing campaign, H-Canyon is planning to begin dissolving High Flux Isotope Reactor (HFIR) fuel in late FY17 or early FY18. Each HFIR fuel core contains inner and outer fuel elements which were fabricated from uranium oxide (U 3O 8) dispersed in a continuous Al phase using traditional powder metallurgy techniques. Fuels fabricated in this manner, like other SNF’s processed in H-Canyon, dissolve by the same general mechanisms with similar gas generation rates and the production of H 2. The HFIR fuel cores will be dissolved and the recovered U will be down-blendedmore » into low-enriched U. HFIR fuel was previously processed in H-Canyon using a unique insert in both the 6.1D and 6.4D dissolvers. Multiple cores will be charged to the same dissolver solution maximizing the concentration of dissolved Al. The objective of this study was to identify flowsheet conditions through literature review and laboratory experimentation to safely and efficiently dissolve the HFIR fuel in H-Canyon. Laboratory-scale experiments were performed to evaluate the dissolution of HFIR fuel using both Al 1100 and Al 6061 T6 alloy coupons. The Al 1100 alloy was considered a representative surrogate which provided an upper bound on the generation of flammable (i.e., H 2) gas during the dissolution process. The dissolution of the Al 6061 T6 alloy proceeded at a slower rate than the Al 1100 alloy, and was used to verify that the target Al concentration in solution could be achieved for the selected Hg concentration. Mass spectrometry and Raman spectroscopy were used to provide continuous monitoring of the concentration of H 2 and other permanent gases in the dissolution offgas, allowing the development of H 2 generation rate profiles. The H 2 generation rates were subsequently used to evaluate if a full HFIR core could be dissolved in an H-Canyon dissolver without exceeding 60% of the calculated lower flammability limit (LFL) for H 2 at a given Hg concentration. Complete dissolution of the Al 1100 and Al 6061 T6 alloys up to a final Al concentration of 2 M was obtained using a 7 M HNO 3 solution containing a 0.002 M Hg catalyst. However, following the dissolutions, solids were observed in the solution. The solids were amorphous, but likely originated from the Si present in the alloys. No crystalline materials, such as Al(NO 3) 3 were observed. During the course of the dissolution experiments, it was determined that delaying the addition of Hg once the HNO 3 solution reached the boiling point can reduce the total offgas and H 2 generation rates. The delay in starting the Hg addition is not necessary for HFIR fuel dissolution, but could be useful in other research reactor dissolution campaigns. The potential to generate flammable concentrations of H 2 in the offgas during a HFIR fuel dissolution was evaluated using the experimental data. The predicted H 2 concentration in the dissolver offgas stream was compared with 60% of the calculated H 2 LFL at 200 °C using several prototypical experiments. The calculations showed that a full HFIR core can be dissolved using nominally 0.002 M Hg to catalyze the dissolution. The margin between the predicted H 2 concentration and the calculated LFL was greater when the solution was allowed to boil for 45 min prior to initiating the Hg addition. When the Hg was increased to 0.004 M, the predicted H 2 concentration exceeded the calculated LFL early in the dissolution. The dissolution experiments also demonstrated that additional Hg (beyond the initial 0.002 M) could be added as the Al concentration increases. The ability to add more Hg during a HFIR fuel dissolution could be beneficial if slow dissolution rates are observed at high Al concentrations. Experimental data were used to demonstrate that the predicted H 2 concentration in a dissolver was below 60% of the calculated LFL at 200 °C when 0.004 M Hg was used to catalyze the dissolution if the Al concentration is conservatively greater than 0.5 M. Data also show that the Hg concentration during a HFIR fuel dissolution can be increased from 0.002 to 0.008 M at an Al concentration of 1.3 M.« less

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.

Development and Validation of Discriminating and Biorelevant Dissolution Test for Lornoxicam Tablets

PubMed Central

Anumolu, P. D.; Sunitha, G.; Bindu, S. Hima; Satheshbabu, P. R.; Subrahmanyam, C. V. S.

2015-01-01

The establishment of biorelevant and discriminating dissolution procedure for drug products with limited water solubility is a useful technique for qualitative forecasting of the in vivo behavior of formulations. It also characterizes the drug product performance in pharmaceutical development. Lornoxicam, a BCS class-II drug is a nonsteroidal antiinflammatory drug of the oxicam class, has no official dissolution media available in the literature. The objective of present work was to develop and validate a discriminating and biorelevant dissolution test for lornoxicam tablet dosage forms. To quantify the lornoxicam in dissolution samples, UV spectrophotometric method was developed using 0.01M sodium hydroxide solution as solvent at λma×376 nm. After evaluation of saturation solubility, dissolution, sink conditions and stability of lornoxicam bulk drug in different pH solutions and biorelevant media, the dissolution method was optimized using USP paddle type apparatus at 50 rpm rotation speed and 500 ml simulated intestinal fluid as discriminating and biorelevant dissolution medium. The similarity factor (f2) were investigated for formulations with changes in composition and manufacturing variations, values revealed that dissolution method having discriminating power and method was validated as per standard guidelines. The proposed dissolution method can be effectively applied for routine quality control in vitro dissolution studies of lornoxicam in tablets and helpful to pharmacopoeias. PMID:26180277

Development and Validation of Discriminating and Biorelevant Dissolution Test for Lornoxicam Tablets.

PubMed

Anumolu, P D; Sunitha, G; Bindu, S Hima; Satheshbabu, P R; Subrahmanyam, C V S

2015-01-01

The establishment of biorelevant and discriminating dissolution procedure for drug products with limited water solubility is a useful technique for qualitative forecasting of the in vivo behavior of formulations. It also characterizes the drug product performance in pharmaceutical development. Lornoxicam, a BCS class-II drug is a nonsteroidal antiinflammatory drug of the oxicam class, has no official dissolution media available in the literature. The objective of present work was to develop and validate a discriminating and biorelevant dissolution test for lornoxicam tablet dosage forms. To quantify the lornoxicam in dissolution samples, UV spectrophotometric method was developed using 0.01M sodium hydroxide solution as solvent at λma×376 nm. After evaluation of saturation solubility, dissolution, sink conditions and stability of lornoxicam bulk drug in different pH solutions and biorelevant media, the dissolution method was optimized using USP paddle type apparatus at 50 rpm rotation speed and 500 ml simulated intestinal fluid as discriminating and biorelevant dissolution medium. The similarity factor (f2) were investigated for formulations with changes in composition and manufacturing variations, values revealed that dissolution method having discriminating power and method was validated as per standard guidelines. The proposed dissolution method can be effectively applied for routine quality control in vitro dissolution studies of lornoxicam in tablets and helpful to pharmacopoeias.

Path Selection in the Growth of Wormholes

NASA Astrophysics Data System (ADS)

Yang, Yi; Bruns, Stefan; Stipp, Susan; Sørensen, Henning

2017-04-01

Spontaneous growth of wormholes in natural porous media often leads to generation of highly complex flow systems with fractal morphologies. Despite extensive investigations, the underpinning mechanism for path selection during wormholing remains elusive. Here we introduce the concept of cumulative surface (CS) and show that the trajectory of a growing wormhole is one with minimum CS. Theoretical analysis shows that the CS determines the position of the dissolution front. We then show, using numerical simulation based on greyscale data of the fine grained carbonate rock chalk, that the tip of an advancing pore always follows the migration of the most far reaching dissolution front determined from the CS. The predicted dissolution behavior was verified by experimental observation of wormhole growth in chalk using in situ microtomography. The results suggest that wormholing is deterministic in nature rather than stochastic. This insight sheds light on engineering of artificial flow systems in geologic formations by exploiting self-organization in natural porous materials.

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.

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.

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.

Improving the API dissolution rate during pharmaceutical hot-melt extrusion I: Effect of the API particle size, and the co-rotating, twin-screw extruder screw configuration on the API dissolution rate.

PubMed

Li, Meng; Gogos, Costas G; Ioannidis, Nicolas

2015-01-15

The dissolution rate of the active pharmaceutical ingredients in pharmaceutical hot-melt extrusion is the most critical elementary step during the extrusion of amorphous solid solutions - total dissolution has to be achieved within the short residence time in the extruder. Dissolution and dissolution rates are affected by process, material and equipment variables. In this work, we examine the effect of one of the material variables and one of the equipment variables, namely, the API particle size and extruder screw configuration on the API dissolution rate, in a co-rotating, twin-screw extruder. By rapidly removing the extruder screws from the barrel after achieving a steady state, we collected samples along the length of the extruder screws that were characterized by polarized optical microscopy (POM) and differential scanning calorimetry (DSC) to determine the amount of undissolved API. Analyses of samples indicate that reduction of particle size of the API and appropriate selection of screw design can markedly improve the dissolution rate of the API during extrusion. In addition, angle of repose measurements and light microscopy images show that the reduction of particle size of the API can improve the flowability of the physical mixture feed and the adhesiveness between its components, respectively, through dry coating of the polymer particles by the API particles. Copyright © 2014. Published by Elsevier B.V.

Pharmacokinetics of a slow-release formulation of soybean isoflavones in healthy postmenopausal women.

PubMed

Setchell, Kenneth D R; Brzezinski, Amnon; Brown, Nadine M; Desai, Pankaj B; Melhem, Murad; Meredith, Trevor; Zimmer-Nechimias, Linda; Wolfe, Brian; Cohen, Yoram; Blatt, Yoav

2005-03-23

Pharmacokinetic studies of soybean isoflavones have shown that following oral ingestion, the two major isoflavones, daidzin and genistin, are hydrolyzed in the intestine, rapidly absorbed into the peripheral circulation, and eliminated from the body with a terminal half-life of 7-8 h. These characteristics make maintenance of steady-state plasma isoflavone concentrations difficult to attain unless there is repeated daily ingestion of foods or supplements containing isoflavones. In an attempt to sustain more constant plasma isoflavone concentrations, a new slow-release formulation of a soybean isoflavone extract was prepared by microencapsulation with a mixture of hydroxypropylcellulose and ethylcellulose to alter its dissolution characteristics. In vitro experiments confirmed slow aqueous dissolution of isoflavones from this formulation when compared with the conventional isoflavone extract. The pharmacokinetics of this slow-release isoflavone extract was studied in 10 healthy postmenopausal women after oral administration of a single capsule containing the equivalent of 22.3 mg of genistein and 7.47 mg of daidzein expressed as aglycons. A comparison of the key pharmacokinetic parameters obtained in this study with those established in extensive studies performed previously in this laboratory indicated that the mean residence time of genistein and daidzein increased 2-fold with microencapsulation. These findings are indicative of a decreased rate of absorption, consistent with the observed slow in vitro dissolution rate. These findings show that it is feasible to employ polymer matrices that slow the aqueous dissolution for preparing sustained-release formulations of soy isoflavones. Further studies to optimize such formulations are warranted.

Discoloration of titanium alloy in acidic saline solutions with peroxide.

PubMed

Takemoto, Shinji; Hattori, Masayuki; Yoshinari, Masao; Kawada, Eiji; Oda, Yutaka

2013-01-01

The objective of this study was to compare corrosion behavior in several titanium alloys with immersion in acidulated saline solutions containing hydrogen peroxide. Seven types of titanium alloy were immersed in saline solutions with varying levels of pH and hydrogen peroxide content, and resulting differences in color and release of metallic elements determined in each alloy. Some alloys were characterized using Auger electron spectroscopy. Ti-55Ni alloy showed a high level of dissolution and difference in color. With immersion in solution containing hydrogen peroxide at pH 4, the other alloys showed a marked difference in color but a low level of dissolution. The formation of a thick oxide film was observed in commercially pure titanium showing discoloration. The results suggest that discoloration in titanium alloys immersed in hydrogen peroxide-containing acidulated solutions is caused by an increase in the thickness of this oxide film, whereas discoloration of Ti-55Ni is caused by corrosion.

Formation of itraconazole-succinic acid cocrystals by gas antisolvent cocrystallization.

PubMed

Ober, Courtney A; Gupta, Ram B

2012-12-01

Cocrystals of itraconazole, an antifungal drug with poor bioavailability, and succinic acid, a water-soluble dicarboxylic acid, were formed by gas antisolvent (GAS) cocrystallization using pressurized CO(2) to improve itraconazole dissolution. In this study, itraconazole and succinic acid were simultaneously dissolved in a liquid solvent, tetrahydrofuran, at ambient conditions. The solution was then pressurized with CO(2), which decreased the solvating power of tetrahydrofuran and caused crystallization of itraconazole-succinic acid cocrystals. The cocrystals prepared by GAS cocrystallization were compared to those produced using a traditional liquid antisolvent, n-heptane, for crystallinity, chemical structure, thermal behavior, size and surface morphology, potential clinical relevance, and stability. Powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy analyses showed that itraconazole-succinic acid cocrystals with physical and chemical properties similar to cocrystals produced using a traditional liquid antisolvent technique can be prepared by CO(2) antisolvent cocrystallization. The dissolution profile of itraconazole was significantly enhanced through GAS cocrystallization with succinic acid, achieving over 90% dissolution in less than 2 h. The cocrystals appeared stable against thermal stress for up to 4 weeks under accelerated stability conditions, showing only moderate decreases in their degree of crystallinity but no change in their crystalline structure. This study shows the utility of an itraconazole-succinic acid cocrystal for improving itraconazole bioavailability while also demonstrating the potential for CO(2) to replace traditional liquid antisolvents in cocrystal preparation, thus making cocrystal production more environmentally benign and scale-up more feasible.

Pore-scale supercritical CO 2 dissolution and mass transfer under drainage conditions

DOE PAGES

Chang, Chun; Zhou, Quanlin; Oostrom, Mart; ...

2016-12-05

Recently, both core- and pore-scale imbibition experiments have shown non-equilibrium dissolution of supercritical CO 2 (scCO 2) and a prolonged depletion of residual scCO 2. In this paper, pore-scale scCO 2 dissolution and mass transfer under drainage conditions were investigated using a two-dimensional heterogeneous micromodel and a novel fluorescent water dye with a sensitive pH range between 3.7 and 6.5. Drainage experiments were conducted at 9 MPa and 40 °C by injecting scCO 2 into the sandstone-analogue pore network initially saturated by water without dissolved CO 2 (dsCO 2). During the experiments, time-lapse images of dye intensity, reflecting water pH,more » were obtained. These images show non-uniform pH in individual pores and pore clusters, with average pH levels gradually decreasing with time. Further analysis on selected pores and pore clusters shows that (1) rate-limited mass transfer prevails with slowly decreasing pH over time when the scCO 2-water interface area is low with respect to the volume of water-filled pores and pore clusters, (2) fast scCO 2 dissolution and phase equilibrium occurs when scCO 2 bubbles invade into water-filled pores, significantly enhancing the area-to-volume ratio, and (3) a transition from rate-limited to diffusion-limited mass transfer occurs in a single pore when a medium area-to-volume ratio is prevalent. The analysis also shows that two fundamental processes – scCO 2 dissolution at phase interfaces and diffusion of dsCO 2 at the pore scale (10–100 µm) observed after scCO 2 bubble invasion into water-filled pores without pore throat constraints – are relatively fast. The overall slow dissolution of scCO 2 in the millimeter-scale micromodel can be attributed to the small area-to-volume ratios that represent pore-throat configurations and characteristics of phase interfaces. Finally, this finding is applicable for the behavior of dissolution at pore, core, and field scales when water-filled pores and pore clusters of varying size are surrounded by scCO 2 at narrow pore throats.« less

Pore-scale supercritical CO 2 dissolution and mass transfer under drainage conditions

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

Chang, Chun; Zhou, Quanlin; Oostrom, Mart

Recently, both core- and pore-scale imbibition experiments have shown non-equilibrium dissolution of supercritical CO 2 (scCO 2) and a prolonged depletion of residual scCO 2. In this paper, pore-scale scCO 2 dissolution and mass transfer under drainage conditions were investigated using a two-dimensional heterogeneous micromodel and a novel fluorescent water dye with a sensitive pH range between 3.7 and 6.5. Drainage experiments were conducted at 9 MPa and 40 °C by injecting scCO 2 into the sandstone-analogue pore network initially saturated by water without dissolved CO 2 (dsCO 2). During the experiments, time-lapse images of dye intensity, reflecting water pH,more » were obtained. These images show non-uniform pH in individual pores and pore clusters, with average pH levels gradually decreasing with time. Further analysis on selected pores and pore clusters shows that (1) rate-limited mass transfer prevails with slowly decreasing pH over time when the scCO 2-water interface area is low with respect to the volume of water-filled pores and pore clusters, (2) fast scCO 2 dissolution and phase equilibrium occurs when scCO 2 bubbles invade into water-filled pores, significantly enhancing the area-to-volume ratio, and (3) a transition from rate-limited to diffusion-limited mass transfer occurs in a single pore when a medium area-to-volume ratio is prevalent. The analysis also shows that two fundamental processes – scCO 2 dissolution at phase interfaces and diffusion of dsCO 2 at the pore scale (10–100 µm) observed after scCO 2 bubble invasion into water-filled pores without pore throat constraints – are relatively fast. The overall slow dissolution of scCO 2 in the millimeter-scale micromodel can be attributed to the small area-to-volume ratios that represent pore-throat configurations and characteristics of phase interfaces. Finally, this finding is applicable for the behavior of dissolution at pore, core, and field scales when water-filled pores and pore clusters of varying size are surrounded by scCO 2 at narrow pore throats.« less

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

The Effect of Micrite on Velocity, Its Sensitivity to Pressure, and Dissolution of Carbonates

NASA Astrophysics Data System (ADS)

El Husseiny, A.; Vanorio, T.

2014-12-01

This study investigates the effect of micrite on the acoustic properties of well-controlled microstructures created in the laboratory to closely mimic carbonate rocks. In particular, we examine the effect of micrite content on the elastic stiffness rock, its sensitivity to pressure, and induced dissolution upon saturation with a reactive fluid. We followed Dunham's classification and fabricated the samples by mixing coarse (sand size) and very fine (micrite size) calcite grains in different ratios, with the addition of cement and then cold-compressing the mixture. The acoustic velocities were measured under bench-top conditions and as functions of confining pressure before and after the injection of a CO2aqueous solution. Our bench-top measurements indicated that micrite makes the frame of the carbonate samples stiffer. Since the sensitivity of the elastic stiffness to pressure decreases as the content of micrite increases (see figure 1), we hypothesize a stiffer pore structure (i.e., rounder pores) in micrite-richer fabrics. Furthermore, the presence of micrite makes the carbonate sample more reactive upon dissolution. The concentration of Ca+2 cations in the fluid measured at the outlet after the injection of the CO2 aqueous solution shows larger dissolution in the micrite-rich samples likely due to the higher surface area of the micrite aggregates. The content of micrite also seems to affect the evolution of stiffness as dissolution proceeds. As the content of micrite increases, the enhanced dissolution translates into a marked softening of the rock frame. We conclude that the content of micrite can play an important role in the complex rock-fluid interaction of carbonates as well as when comparing Gassmann's predictions to velocity measurements of saturated carbonates.

Near Surface Geophysical Investigations of Potential Direct Recharge Zones in the Biscayne Aquifer within Everglades National Park, Florida.

NASA Astrophysics Data System (ADS)

Mount, G.; Comas, X.

2017-12-01

The karstic Miami Limestone of the Biscayne aquifer is characterized as having water flow that is controlled by the presence of dissolution enhanced porosity and mega-porous features. The dissolution features and other high porosity areas create horizontal preferential flow paths and high rates of ground water velocity, which may not be accurately conceptualized in groundwater flow models. In addition, recent research suggests the presence of numerous vertical dissolution features across Everglades National Park at Long Pine Key Trail, that may act as areas of direct recharge to the aquifer. These vertical features have been identified through ground penetrating radar (GPR) surveys as areas of velocity pull-down which have been modeled to have porosity values higher than the surrounding Miami Limestone. As climate change may induce larger and longer temporal variability between wet and dry times in the Everglades, a more comprehensive understanding of preferential flow pathways from the surface to the aquifer would be a great benefit to modelers and planners. This research utilizes near surface geophysical techniques, such as GPR, to identify these vertical dissolution features and then estimate the spatial variability of porosity using petrophysical models. GPR transects that were collected for several kilometers along the Long Pine Key Trail, show numerous pull down areas that correspond to dissolution enhanced porosity zones within the Miami Limestone. Additional 3D GPR surveys have attempted to delineate the boundaries of these features to elucidate their geometry for future modelling studies. We demonstrate the ability of near surface geophysics and petrophysical models to identify dissolution enhanced porosity in shallow karstic limestones to better understand areas that may act as zones of direct recharge into the Biscayne Aquifer.

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.

Can accurate kinetic laws be created to describe chemical weathering?

NASA Astrophysics Data System (ADS)

Schott, Jacques; Oelkers, Eric H.; Bénézeth, Pascale; Goddéris, Yves; François, Louis

2012-11-01

Knowledge of the mechanisms and rates of mineral dissolution and growth, especially close to equilibrium, is essential for describing the temporal and spatial evolution of natural processes like weathering and its impact on CO2 budget and climate. The Surface Complexation approach (SC) combined with Transition State Theory (TST) provides an efficient framework for describing mineral dissolution over wide ranges of solution composition, chemical affinity, and temperature. There has been a large debate for several years, however, about the comparative merits of SC/TS versus classical growth theories for describing mineral dissolution and growth at near-to-equilibrium conditions. This study considers recent results obtained in our laboratory on oxides, hydroxides, silicates, and carbonates on near-equilibrium dissolution and growth via the combination of complementary microscopic and macroscopic techniques including hydrothermal atomic force microscopy, hydrogen-electrode concentration cell, mixed flow and batch reactors. Results show that the dissolution and precipitation of hydroxides, kaolinite, and hydromagnesite powders of relatively high BET surface area closely follow SC/TST rate laws with a linear dependence of both dissolution and growth rates on fluid saturation state (Ω) even at very close to equilibrium conditions (|ΔG| < 500 J/mol). This occurs because sufficient reactive sites (e.g. at kink, steps, and edges) are available at the exposed faces for dissolution and/or growth, allowing reactions to proceed via the direct and reversible detachment/attachment of reactants at the surface. In contrast, for magnesite and quartz, which have low surface areas, fewer active sites are available for growth and dissolution. Such minerals exhibit rates dependencies on Ω at near equilibrium conditions ranging from linear to highly non-linear functions of Ω, depending on the treatment of the crystals before the reaction. It follows that the form of the f(ΔG) function describing the growth and dissolution of minerals with low surface areas depends on the availability of reactive sites at the exposed faces and thus on the history of the mineral-fluid interaction and the hydrodynamic conditions under which the crystals are reacted. It is advocated that the crystal surface roughness could serve as a proxy of the density of reactive sites. The consequences of the different rate laws on the quantification of loess weathering along the Mississippi valley for the next one hundred years are examined.

A Novel Approach to Experimental Studies of Mineral Dissolution Kinetics

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

Chen Zhu; William E. Seyfried

2005-01-01

Currently, DOE is conducting pilot CO{sub 2} injection tests to evaluate the concept of geological sequestration. One strategy that potentially enhances CO{sub 2} solubility and reduces the risk of CO{sub 2} leak back to the surface is dissolution of indigenous minerals in the geological formation and precipitation of secondary carbonate phases, which increases the brine pH and immobilizes CO{sub 2}. Clearly, the rates at which these dissolution and precipitation reactions occur directly determine the efficiency of this strategy. However, one of the fundamental problems in modern geochemistry is the persistent two to five orders of magnitude discrepancy between laboratory-measured andmore » field derived feldspar dissolution rates. To date, there is no real guidance as to how to predict silicate reaction rates for use in quantitative models. Current models for assessment of geological carbon sequestration have generally opted to use laboratory rates, in spite of the dearth of such data for compositionally complex systems, and the persistent disconnect between lab and field applications. Therefore, a firm scientific basis for predicting silicate reaction kinetics in CO{sub 2} injected geological formations is urgently needed to assure the reliability of the geochemical models used for the assessments of carbon sequestration strategies. The funded experimental and theoretical study attempts to resolve this outstanding scientific issue by novel experimental design and theoretical interpretation to measure silicate dissolution rates and iron carbonate precipitation rates at conditions pertinent to geological carbon sequestration. In the first year of the project, we have successfully developed a sample preparation method and completed three batch feldspar dissolution experiments at 200 C and 300 bars. The changes of solution chemistry as dissolution experiments progressed were monitored with on-line sampling of the aqueous phase at the constant temperature and pressure. These data allow calculating overall apparent feldspar dissolution rates and secondary mineral precipitation rates as a function of saturation states. State-of-the-art atomic resolution transmission electron microscopy (TEM), scanning electron microscopy, and electron microprobe was used to characterize the reactants (feldspars before experiments). We experimented with different sample preparation methods for TEM study, and found excellent images and chemical resolution with reactants, which shows promise of the technology and establishes the baseline for comparison with products (feldspars after the experiments). Preliminary electron microscopic characterization shows that the reacted feldspars have etch pits and are covered with secondary sheet silicate phases. Reaction-path geochemical modeling is used to interpret the experimental results. We have established the software and database, and are making great progress. Also during the first year, our education goal of graduate student training has been achieved. A Ph. D. student at Indiana University is progressing well in the degree program and has taken geochemical modeling, SEM, and TEM courses, which will facilitate research in the second and third year. A Ph. D. student at University of Minnesota is progressing well in conducting the experiments, and is near graduation. With the success of training of graduate students and excellent experimental data in the first year, we anticipate a more fruitful year in the second year.« less

Solid formulation of a supersaturable self-microemulsifying drug delivery system for valsartan with improved dissolution and bioavailability

PubMed Central

Yeom, Dong Woo; Chae, Bo Ram; Kim, Jin Han; Chae, Jun Soo; Shin, Dong Jun; Kim, Chang Hyun; Kim, Sung Rae; Choi, Ji Ho; Song, Seh Hyon; Oh, Dongho; Sohn, Se Il; Choi, Young Wook

2017-01-01

In order to improve the dissolution and oral bioavailability of valsartan (VST), and reduce the required volume for treatment, we previously formulated a supersaturable self-microemulsifying drug delivery system (SuSMEDDS) composed of VST (80 mg), Capmul® MCM (13.2 mg), Tween® 80 (59.2 mg), Transcutol® P (59.2 mg), and Poloxamer 407 (13.2 mg). In the present study, by using Florite® PS-10 (119.1 mg) and Vivapur® 105 (105.6 mg) as solid carriers, VST-loaded solidified SuSMEDDS (S-SuSMEDDS) granules were successfully developed, which possessed good flow properties and rapid drug dissolution. By introducing croscarmellose sodium (31 mg) as a superdisintegrant, S-SuSMEDDS tablets were also successfully formulated, which showed fast disintegration and high dissolution efficiency. Preparation of granules and tablets was successfully optimized using D-optimal mixture design and 3-level factorial design, respectively, resulting in percentage prediction errors of <10%. In pharmacokinetic studies in rats, the relative bioavailability of the optimized granules was 107% and 222% of values obtained for SuSMEDDS and Diovan® powder, respectively. Therefore, we conclude that novel S-SuSMEDDS formulations offer great potential for developing solid dosage forms of a liquefied formulation such as SuSMEDDS, while improving oral absorption of drugs with poor water solubility. PMID:29212229

Solid formulation of a supersaturable self-microemulsifying drug delivery system for valsartan with improved dissolution and bioavailability.

PubMed

Yeom, Dong Woo; Chae, Bo Ram; Kim, Jin Han; Chae, Jun Soo; Shin, Dong Jun; Kim, Chang Hyun; Kim, Sung Rae; Choi, Ji Ho; Song, Seh Hyon; Oh, Dongho; Sohn, Se Il; Choi, Young Wook

2017-11-07

In order to improve the dissolution and oral bioavailability of valsartan (VST), and reduce the required volume for treatment, we previously formulated a supersaturable self-microemulsifying drug delivery system (SuSMEDDS) composed of VST (80 mg), Capmul ® MCM (13.2 mg), Tween ® 80 (59.2 mg), Transcutol ® P (59.2 mg), and Poloxamer 407 (13.2 mg). In the present study, by using Florite ® PS-10 (119.1 mg) and Vivapur ® 105 (105.6 mg) as solid carriers, VST-loaded solidified SuSMEDDS (S-SuSMEDDS) granules were successfully developed, which possessed good flow properties and rapid drug dissolution. By introducing croscarmellose sodium (31 mg) as a superdisintegrant, S-SuSMEDDS tablets were also successfully formulated, which showed fast disintegration and high dissolution efficiency. Preparation of granules and tablets was successfully optimized using D-optimal mixture design and 3-level factorial design, respectively, resulting in percentage prediction errors of <10%. In pharmacokinetic studies in rats, the relative bioavailability of the optimized granules was 107% and 222% of values obtained for SuSMEDDS and Diovan ® powder, respectively. Therefore, we conclude that novel S-SuSMEDDS formulations offer great potential for developing solid dosage forms of a liquefied formulation such as SuSMEDDS, while improving oral absorption of drugs with poor water solubility.

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

PubMed

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

2013-07-01

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

Solubility and Diffusivity: Important Metrics in the Search for the Root Cause of Light- and Elevated Temperature-Induced Degradation

DOE PAGES

Jensen, Mallory A.; Morishige, Ashley E.; Chakraborty, Sagnik; ...

2018-02-02

Light- and elevated temperature-induced degradation (LeTID) is a detrimental effect observed under operating conditions in p-type multicrystalline silicon (mc-Si) solar cells. In this paper, we employ synchrotron-based techniques to study the dissolution of precipitates due to different firing processes at grain boundaries in LeTID-affected mc-Si. The synchrotron measurements show clear dissolution of collocated metal precipitates during firing. We compare our observations with degradation behavior in the same wafers. The experimental results are complemented with process simulations to provide insight into the change in bulk point defect concentration due to firing. Several studies have proposed that LeTID is caused by metal-richmore » precipitate dissolution during contact firing, and we find that the solubility and diffusivity are promising screening metrics to identify metals that are compatible with this hypothesis. While slower and less soluble elements (e.g., Fe and Cr) are not compatible according to our simulations, the point defect concentrations of faster and more soluble elements (e.g., Cu and Ni) increase after a high-temperature firing process, primarily due to emitter segregation rather than precipitate dissolution. Finally, these results are a useful complement to lifetime spectroscopy techniques, and can be used to evaluate additional candidates in the search for the root cause of LeTID.« less

Solubility and Diffusivity: Important Metrics in the Search for the Root Cause of Light- and Elevated Temperature-Induced Degradation

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

Jensen, Mallory A.; Morishige, Ashley E.; Chakraborty, Sagnik

Light- and elevated temperature-induced degradation (LeTID) is a detrimental effect observed under operating conditions in p-type multicrystalline silicon (mc-Si) solar cells. In this paper, we employ synchrotron-based techniques to study the dissolution of precipitates due to different firing processes at grain boundaries in LeTID-affected mc-Si. The synchrotron measurements show clear dissolution of collocated metal precipitates during firing. We compare our observations with degradation behavior in the same wafers. The experimental results are complemented with process simulations to provide insight into the change in bulk point defect concentration due to firing. Several studies have proposed that LeTID is caused by metal-richmore » precipitate dissolution during contact firing, and we find that the solubility and diffusivity are promising screening metrics to identify metals that are compatible with this hypothesis. While slower and less soluble elements (e.g., Fe and Cr) are not compatible according to our simulations, the point defect concentrations of faster and more soluble elements (e.g., Cu and Ni) increase after a high-temperature firing process, primarily due to emitter segregation rather than precipitate dissolution. Finally, these results are a useful complement to lifetime spectroscopy techniques, and can be used to evaluate additional candidates in the search for the root cause of LeTID.« less

Rapidly absorbed orodispersible tablet containing molecularly dispersed felodipine for management of hypertensive crisis: development, optimization and in vitro/in vivo studies.

PubMed

Basalious, Emad B; El-Sebaie, Wessam; El-Gazayerly, Omaima

2013-01-01

A liquisolid orodispersible tablet of felodipine, a BCS Class II drug, was developed to improve drug dissolution and absorption through the buccal mucosa for management of hypertensive crisis. A 24 full-factorial design was applied to optimize felodipine liquisolid systems (FLSs) having acceptable flow properties and possessing enhanced drug dissolution rates. Four formulation variables; The liquid type, X1 (PG or PEG), drug concentration, X2 (10% and 20%), type of coat, X3 (Aerosil® and Aeroperl®) and excipients ratio, X4 (10 and 20) were included in the design. The systems were assessed for dissolution and flow properties. Following optimization, the formulation components (X1, X2, X3 and X4) were PEG, 10%, Aerosil® and 20, respectively. The optimized FLS was compressed into felodipine liquisolid orodispersible tablet using Prosolv® as carrier material (FLODT-2). The in vitro and in vivo disintegration times of FLODT-2 were 9 and 7 s, respectively. The in vivo pharmacokinetic study using human volunteers showed a significant increase in dissolution and absorption rates of the formulation of FLODT-2 compared to soft gelatin capsules filled with felodipine solution in PEG under the same conditions. Our results proposed that the optimized FLODT formulation could be promising to manage hypertensive crisis.

Development and characterization of lecithin stabilized glibenclamide nanocrystals for enhanced solubility and drug delivery.

PubMed

Kumar, B Sajeev; Saraswathi, R; Kumar, K Venkates; Jha, S K; Venkates, D P; Dhanaraj, S A

2014-05-01

Novel LNCs (lipid nanocrystals) were developed with an aim to improve the solubility, stability and targeting efficiency of the model drug glibenclamide (GLB). PEG 20000, Tween 80 and soybean lecithin were used as polymer, surfactant and complexing agent, respectively. GLB nanocrystals (NCs) were prepared by precipitation process and complexed using hot and cold melt technique. The LNCs were evaluated by drug loading, saturation solubility (SL), optical clarity, in vitro dissolution, solid state characterization, in vivo and stability analysis. LNCs exhibited a threefold increase in SL and a higher dissolution rate than GLB. The percentage dissolution efficiency was found to decrease with increase in PEG 20000. The average particle size was in the range of 155-842 nm and zeta potential values tend to increase after complexation. X-ray powder diffractometry and differential scanning calorimetry results proved the crystallinity prevailed in the samples. Spherical shaped particles (<1000 nm) with a lipid coat on the surface were observed in scanning electron microscopy analysis. Fourier transform infrared results proved the absence of interaction between drug and polymer and stability study findings proved that LNCs were stable. In vivo study findings showed a decrease in drug concentration to pancreas in male Wistar rats. It can be concluded that LNCs are could offer enhanced solubility, dissolution rate and stability for poorly water soluble drugs. The targeting efficiency of LNCs was decreased and further membrane permeability studies ought to be carried out.

Investigating the Effects of Loading Factors on the In Vitro Pharmaceutical Performance of Mesoporous Materials as Drug Carriers for Ibuprofen

PubMed Central

Lai, Junmin; Lin, Wu; Scholes, Peter; Li, Mingzhong

2017-01-01

The aim of the study was to investigate the effects of the loading factors, i.e., the initial drug loading concentration and the ratio of the drug to carriers, on the in vitro pharmaceutical performance of drug-loaded mesoporous systems. Ibuprofen (IBU) was used as a model drug, and two non-ordered mesoporous materials of commercial silica Syloid® 244FP (S244FP) and Neusilin® US2 (NS2) were selected in the study. The IBU-loaded mesoporous samples were prepared by a solvent immersion method with a rotary evaporation drying technique and characterized by polarized light microscopy (PLM), Fourier transform infrared (FTIR) spectroscopy, X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). Dissolution experiments were performed in simulated gastric media at 37 °C under non-sink conditions. The concentration of IBU in solution was determined by HPLC. The study showed that the dissolution rate of IBU can be improved significantly using the mesoporous S224FP carriers due to the conversion of crystalline IBU into the amorphous form. Both of the loading factors affected the IBU dissolution kinetics. Due to the molecular interaction between the IBU and NS2 carriers, the loading factors had little effects on the drug release kinetics with incomplete drug desorption recovery and insignificant dissolution enhancement. Care and extensive evaluation must therefore be taken when mesoporous materials are chosen as carrier delivery systems. PMID:28772509

Autogenous teeth used for bone grafting: a comparison with traditional grafting materials.

PubMed

Kim, Young-Kyun; Kim, Su-Gwan; Yun, Pil-Young; Yeo, In-Sung; Jin, Seung-Chan; Oh, Ji-Su; Kim, Heung-Joong; Yu, Sun-Kyoung; Lee, Sook-Young; Kim, Jae-Sung; Um, In-Woong; Jeong, Mi-Ae; Kim, Gyung-Wook

2014-01-01

This study evaluated the surface structures and physicochemical characteristics of a novel autogenous tooth bone graft material currently in clinical use. The material's surface structure was compared with a variety of other bone graft materials via scanning electron microscope (SEM). The crystalline structure of the autogenous tooth bone graft material from the crown (AutoBT crown) and root (AutoBT root), xenograft (BioOss), alloplastic material (MBCP), allograft (ICB), and autogenous mandibular cortical bone were compared using x-ray diffraction (XRD) analysis. The solubility of each material was measured with the Ca/P dissolution test. The results of the SEM analysis showed that the pattern associated with AutoBT was similar to that from autogenous cortical bones. In the XRD analysis, AutoBT root and allograft showed a low crystalline structure similar to that of autogenous cortical bones. In the CaP dissolution test, the amount of calcium and phosphorus dissolution in AutoBT was significant from the beginning, while displaying a pattern similar to that of autogenous cortical bones. In conclusion, autogenous tooth bone graft materials can be considered to have physicochemical characteristics similar to those of autogenous bones. Copyright © 2014 Elsevier Inc. All rights reserved.

A comparative study of first-derivative spectrophotometry and column high-performance liquid chromatography applied to the determination of repaglinide in tablets and for dissolution testing.

PubMed

AlKhalidi, Bashar A; Shtaiwi, Majed; AlKhatib, Hatim S; Mohammad, Mohammad; Bustanji, Yasser

2008-01-01

A fast and reliable method for the determination of repaglinide is highly desirable to support formulation screening and quality control. A first-derivative UV spectroscopic method was developed for the determination of repaglinide in tablet dosage form and for dissolution testing. First-derivative UV absorbance was measured at 253 nm. The developed method was validated for linearity, accuracy, precision, limit of detection (LOD), and limit of quantitation (LOQ) in comparison to the U.S. Pharmacopeia (USP) column high-performance liquid chromatographic (HPLC) method. The first-derivative UV spectrophotometric method showed excellent linearity [correlation coefficient (r) = 0.9999] in the concentration range of 1-35 microg/mL and precision (relative standard deviation < 1.5%). The LOD and LOQ were 0.23 and 0.72 microg/mL, respectively, and good recoveries were achieved (98-101.8%). Statistical comparison of results of the first-derivative UV spectrophotometric and the USP HPLC methods using the t-test showed that there was no significant difference between the 2 methods. Additionally, the method was successfully used for the dissolution test of repaglinide and was found to be reliable, simple, fast, and inexpensive.

[Effect of stability and dissolution of realgar nano-particles using solid dispersion technology].

PubMed

Guo, Teng; Shi, Feng; Yang, Gang; Feng, Nian-Ping

2013-09-01

To improve the stability and dissolution of realgar nano-particles by solid dispersion. Using polyethylene glycol 6000 and poloxamer-188 as carriers, the solid dispersions were prepare by melting method. XRD, microscopic inspection were used to determine the status of realgar nano-particles in solid dispersions. The content and stability test of As(2)0(3) were determined by DDC-Ag method. Hydride generation atomic absorption spectrometry was used to determine the content of Arsenic and investigated the in vitro dissolution behavior of solid dispersions. The results of XRD and microscopic inspection showed that realgar nano-particles in solid dispersions were amorphous. The dissolution amount and rate of Arsenic from realgar nano-particles of all solid dispersions were increased significantly, the reunion of realgar nano-particles and content of As(2)0(3) were reduced for the formation of solid dispersions. The solid dispersion of realgar nano-particles with poloxamer-188 as carriers could obviously improve stability, dissolution and solubility.

Improved oral bioavailability of probucol by dry media-milling.

PubMed

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

2017-09-01

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

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.

Nanocomposite formation between alpha-glucosyl stevia and surfactant improves the dissolution profile of poorly water-soluble drug.

PubMed

Uchiyama, Hiromasa; Tozuka, Yuichi; Nishikawa, Masahiro; Takeuchi, Hirofumi

2012-05-30

The formation of a hybrid-nanocomposite using α-glucosyl stevia (Stevia-G) and surfactant was explored to improve the dissolution of flurbiprofen (FP). As reported previously, the dissolution amount of FP was enhanced in the presence of Stevia-G, induced by the formation of an FP and Stevia-G-associated nanostructure. When a small amount of sodium dodecyl sulfate (SDS) was present with Stevia-G, the amount of dissolved FP was extremely enhanced. This dissolution-enhancement effect was also observed with the cationic surfactant of dodecyl trimethyl ammonium bromide, but not with the non-ionic surfactant of n-octyl-β-D-maltopyranoside. To investigate the dissolution-enhancement effect of Stevia-G/SDS mixture, the pyrene I(1)/I(3) ratio was plotted versus the Stevia-G concentration. The pyrene I(1)/I(3) ratio of Stevia-G/SDS mixture had a sigmoidal curve at lower Stevia-G concentrations compared to the Stevia-G solution alone. These results indicate that the Stevia-G/SDS mixture provides a hydrophobic core around pyrene molecules at lower Stevia-G concentrations, leading to nanocomposite formation between Stevia-G and SDS. The nanocomposite of Stevia-G/SDS showed no cytotoxicity to Caco-2 cells at a mixture of 0.1% SDS and 1% Stevia-G solution, whereas 0.1% SDS solution showed high toxicity. These results suggest that the nanocomposite formation of Stevia-G/SDS may be useful way to enhance the dissolution of poorly water-soluble drugs without special treatment. Copyright © 2012 Elsevier B.V. All rights reserved.

Sodium sulfate - Deposition and dissolution of silica

NASA Technical Reports Server (NTRS)

Jacobson, Nathan S.

1989-01-01

The hot-corrosion process for SiO2-protected materials involves deposition of Na2SO4 and dissolution of the protective SiO2 scale. Dew points for Na2SO4 deposition are calculated as a function of pressure, sodium content, and sulfur content. Expected dissolution regimes for SiO2 are calculated as a function of Na2SO4 basicity. Controlled-condition burner-rig tests on quartz verify some of these predicted dissolution regimes. The basicity of Na2SO4 is not always a simple function of P(SO3). Electrochemical measurements of an (Na2O) show that carbon creates basic conditions in Na2SO4, which explains the extensive corrosion of SiO2-protected materials containing carbon, such as SiC.

What Happens during Natural Protein Fibre Dissolution in Ionic Liquids

PubMed Central

Chen, Jingyu; Vongsanga, Kylie; Wang, Xungai; Byrne, Nolene

2014-01-01

Here, we monitor the dissolution of several natural protein fibres such as wool, human hair and silk, in various ionic liquids (ILs). The dissolution of protein-based materials using ILs is an emerging area exploring the production of new materials from waste products. Wool is a keratin fibre, which is extensively used in the textiles industry and as a result has considerable amounts of waste produced each year. Wool, along with human hair, has a unique morphology whereby the outer layer, the cuticle, is heavily cross linked with disulphide bonds, whereas silk does not have this outer layer. Here we show how ILs dissolve natural protein fibres and how the mechanism of dissolution is directly related to the structure and morphology of the wool fibre. PMID:28788183

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

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.

[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.

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.

Influence of design parameters in Water-Alternating-Gas Injection on enhancement of CO2 trapping in heterogeneous formations: A numerical study

NASA Astrophysics Data System (ADS)

Joodaki, S.; Yang, Z.; Niemi, A. P.

2016-12-01

CO2 trapping in saline aquifers can be enhanced by applying specific injection strategies. Water-alternating-gas (WAG) injection, in which intermittent slugs of CO2 and water are injected, is one of the suggested methods to increase the trapping of CO2 as a result of both capillary forces (residual trapping) and dissolution into the ambient water (dissolution trapping). In this study, 3D numerical modeling was used to investigate the importance of parameters needed to design an effective WAG injection sequence including (i) CO2 and water injection rates, (ii) WAG ratio, (iii) number of cycles and their duration. We employ iTOUGH2-EOS17 model to simulate the CO2 injection and subsequent trapping in heterogeneous formations. Spatially correlated random permeability fields are generated using GSLIB based on available data at the Heletz, a pilot injection site in Israel, aimed for scientifically motivated CO2 injection experiments. Hysteresis effects on relative permeability and capillary pressure function are taken into account based on the Land model (1968). The results showed that both residual and dissolution trapping can be enhanced by increasing in CO2 injection rate due to the fact that higher CO2 injection rate reduces the gravity segregation and increases the reservoir volume swept by CO2. Faster water injection will favor the residual and dissolution trapping due to improved mixing. Increasing total amount of water injection will increase the dissolution trapping but also the cost of the injection. It causes higher pressure increases as well. Using numerical modeling, it is possible to predict the best parameter combination to optimize the trapping and find the balance between safety and cost of the injection process.

Structure and reactivity of oxalate surface complexes on lepidocrocite derived from infrared spectroscopy, DFT-calculations, adsorption, dissolution and photochemical experiments

NASA Astrophysics Data System (ADS)

Borowski, Susan C.; Biswakarma, Jagannath; Kang, Kyounglim; Schenkeveld, Walter D. C.; Hering, Janet G.; Kubicki, James D.; Kraemer, Stephan M.; Hug, Stephan J.

2018-04-01

Oxalate, together with other ligands, plays an important role in the dissolution of iron(hdyr)oxides and the bio-availability of iron. The formation and properties of oxalate surface complexes on lepidocrocite were studied with a combination of infrared spectroscopy (IR), density functional theory (DFT) calculations, dissolution, and photochemical experiments. IR spectra measured as a function of time, concentration, and pH (50-200 μM oxalate, pH 3-7) showed that several surface complexes are formed at different rates and in different proportions. Measured spectra could be separated into three contributions described by Gaussian line shapes, with frequencies that agreed well with the theoretical frequencies of three different surface complexes: an outer-sphere complex (OS), an inner-sphere monodentate mononuclear complex (MM), and a bidentate mononuclear complex (BM) involving one O atom from each carboxylate group. At pH 6, OS was formed at the highest rate. The contribution of BM increased with decreasing pH. In dissolution experiments, lepidocrocite was dissolved at rates proportional to the surface concentration of BM, rather than to the total adsorbed concentration. Under UV-light (365 nm), BM was photolyzed at a higher rate than MM and OS. Although the comparison of measured spectra with calculated frequencies cannot exclude additional possible structures, the combined results allowed the assignment of three main structures with different reactivities consistent with experiments. The results illustrate the importance of the surface speciation of adsorbed ligands in dissolution and photochemical reactions.

Solid-state flurbiprofen and methyl-β-cyclodextrin inclusion complexes prepared using a single-step, organic solvent-free supercritical fluid process.

PubMed

Rudrangi, Shashi Ravi Suman; Kaialy, Waseem; Ghori, Muhammad U; Trivedi, Vivek; Snowden, Martin J; Alexander, Bruce David

2016-07-01

The aim of this study was to enhance the apparent solubility and dissolution properties of flurbiprofen through inclusion complexation with cyclodextrins. Especially, the efficacy of supercritical fluid technology as a preparative technique for the preparation of flurbiprofen-methyl-β-cyclodextrin inclusion complexes was evaluated. The complexes were prepared by supercritical carbon dioxide processing and were evaluated by solubility, differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy, practical yield, drug content estimation and in vitro dissolution studies. Computational molecular docking studies were conducted to study the possibility of molecular arrangement of inclusion complexes between flurbiprofen and methyl-β-cyclodextrin. The studies support the formation of stable molecular inclusion complexes between the drug and cyclodextrin in a 1:1 stoichiometry. In vitro dissolution studies showed that the dissolution properties of flurbiprofen were significantly enhanced by the binary mixtures prepared by supercritical carbon dioxide processing. The amount of flurbiprofen dissolved into solution alone was very low with 1.11±0.09% dissolving at the end of 60min, while the binary mixtures processed by supercritical carbon dioxide at 45°C and 200bar released 99.39±2.34% of the drug at the end of 30min. All the binary mixtures processed by supercritical carbon dioxide at 45°C exhibited a drug release of more than 80% within the first 10min irrespective of the pressure employed. The study demonstrated the single step, organic solvent-free supercritical carbon dioxide process as a promising approach for the preparation of inclusion complexes between flurbiprofen and methyl-β-cyclodextrin in solid-state. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

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.

Concentration gradients at the mineral-solution interface: implications for understanding dissolution mechanisms

NASA Astrophysics Data System (ADS)

Ruiz-Agudo, Encarnacion; Patiño-López, Luis David; Putnis, Christine V.; Rodriguez-Navarro, Carlos; Putnis, Andrew

2014-05-01

Dissolution is a key process in fluid-rock interactions, such as in chemical weathering, CO2 carbonation reactions, metasomatism, and metamorphism. Many multicomponent rock-forming minerals are reported to dissolve incongruently, because the elemental molar ratios, measured in the fluid during dissolution experiments, that differ from those in the solid. This frequently results in the formation of chemically and structurally altered zones at the fluid-solid interface of varying thickness that are depleted in some elements relative to the bulk mineral composition. Although the mechanisms of the formation of these altered layers is still a matter of debate (see e.g. Ruiz-Agudo et al. 2012 and Schott et al. 2012), recent AFM studies on the dissolution of two multicomponent minerals, dolomite, Ca0.5Mg0.5CO3 (Urosevic et al. 2012), and wollastonite, CaSiO3 (Ruiz-Agudo et al. 2012), provide experimental evidence showing that these layers are formed in a two-step process: (i) stoichiometric dissolution of the pristine mineral surfaces and (ii) precipitation of a secondary phase. This occurs despite the fact that the bulk solution is undersaturated with respect to such a phase. It has been suggested that after stoichiometric dissolution of the mineral, a boundary layer of fluid in contact with the surface becomes supersaturated with respect to a secondary phase that then precipitates. Here we present in situ observations of the evolution of the fluid composition at the interface during dissolution in acidic solutions (pH 1.5) of dolomite and wollastonite using real-time phase-shift interferometry. We show that immediately when the sparingly soluble dolomite or wollastonite crystals are in contact with the solution, the refractive index of the solution at the crystal surface sharply increases. A steep refractive index gradient (i.e., concentration gradient) develops as a consequence of mineral dissolution producing an interfacial fluid with a different composition to the bulk. Similar observations have been made during the replacement of KBr by KCl (Putnis et al. 2005). Thus, it seems that incongruent dissolution is essentially similar to any other mineral-fluid equilibration process: when a fluid interacts with a mineral with which it is out of equilibrium the mineral will tend to dissolve. Depending on the fluid composition, the interfacial fluid may become supersaturated with respect to a secondary phase that will eventually nucleate on the parent mineral surface. Ruiz-Agudo E., Putnis, C.V., Rodríguez-Navarro, C. and Putnis A. (2012) Geology 40, 947-950 (2012) Urosevic M., Rodríguez-Navarro C., Putnis C.V., Cardell C., Putnis A. and Ruiz Agudo, E. (2012) In Geochimica et Cosmochimica Acta 80, 1-13 Schott J., Pokrovsky O.S., Spalla O., Devreux F., Gloter A. and Mielczarski J.A. (2012) Geochimica et Cosmochimica Acta 98, 259-281 Putnis C.V., Tsukamoto K. and Nishimura Y. (2005) American Mineralogist 90, 1909-1912

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…

Improved oral absorption of cilostazol via sulfonate salt formation with mesylate and besylate

PubMed Central

Seo, Jae Hong; Park, Jung Bae; Choi, Woong-Kee; Park, Sunhwa; Sung, Yun Jin; Oh, Euichaul; Bae, Soo Kyung

2015-01-01

Objective Cilostazol is a Biopharmaceutical Classification System class II drug with low solubility and high permeability, so its oral absorption is variable and incomplete. The aim of this study was to prepare two sulfonate salts of cilostazol to increase the dissolution and hence the oral bioavailability of cilostazol. Methods Cilostazol mesylate and cilostazol besylate were synthesized from cilostazol by acid addition reaction with methane sulfonic acid and benzene sulfonic acid, respectively. The salt preparations were characterized by nuclear magnetic resonance spectroscopy. The water contents, hygroscopicity, stress stability, and photostability of the two cilostazol salts were also determined. The dissolution profiles in various pH conditions and pharmacokinetic studies in rats were compared with those of cilostazol-free base. Results The two cilostazol salts exhibited good physicochemical properties, such as nonhygroscopicity, stress stability, and photostability, which make it suitable for the preparation of pharmaceutical formulations. Both cilostazol mesylate and cilostazol besylate showed significantly improved dissolution rate and extent of drug release in the pH range 1.2–6.8 compared to the cilostazol-free base. In addition, after oral administration to rats, cilostazol mesylate and cilostazol besylate showed increases in Cmax and AUCt of approximately 3.65- and 2.87-fold and 3.88- and 2.94-fold, respectively, compared to cilostazol-free base. Conclusion This study showed that two novel salts of cilostazol, such as cilostazol mesylate and cilostazol besylate, could be used to enhance its oral absorption. The findings warrant further preclinical and clinical studies on cilostazol mesylate and cilostazol besylate at doses lower than the usually recommended dosage, so that it can be established as an alternative to the marketed cilostazol tablet. PMID:26251575

Rapid disintegrating tablets of simvastatin dispersions in polyoxyethylene–polypropylene block copolymer for maximized disintegration and dissolution

PubMed Central

Balata, Gehan F; Zidan, Ahmad S; Abourehab, Mohamad AS; Essa, Ebtessam A

2016-01-01

The objective of this research was to improve the dissolution of simvastatin and to incorporate it in rapid disintegrating tablets (RDTs) with an optimized disintegration and dissolution characteristics. Polyoxyethylene–polypropylene block copolymer (poloxamer 188) was employed as a hydrophilic carrier to prepare simvastatin solid dispersions (SDs). Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC) and X-ray diffractometry were employed to understand the interaction between the drug and the carrier in the solid state. The results obtained from Fourier transform infrared spectroscopy showed absence of any chemical interaction between the drug and poloxamer. The results of differential scanning calorimetry and X-ray diffractometry confirmed the conversion of simvastatin to distorted crystalline state. The SD of 1:2 w/w drug to carrier ratio showed the highest dissolution; hence, it was incorporated in RDT formulations using a 32 full factorial design and response surface methodology. The initial assessments of RDTs demonstrated an acceptable flow, hardness, and friability to indicate good mechanical strength. The interaction and Pareto charts indicated that percentage of croscarmellose sodium incorporated was the most important factor affecting the disintegration time and dissolution parameter followed by the hardness value and their interaction effect. Compression force showed a superior influence to increase RDT’s porosity and to fasten disintegration rather than swelling action by croscarmellose sodium. On the other hand, croscarmellose sodium was most important for the initial simvastatin release. The results suggest the potential use of poloxamer 188-based SD in RDT for the oral delivery of poor water-soluble antihyperlipidemic drug, simvastatin. PMID:27757012

Design of a potential colonic drug delivery system of mesalamine.

PubMed

Gohel, Mukesh C; Parikh, Rajesh K; Nagori, Stavan A; Dabhi, Mahesh R

2008-01-01

The aim of the present investigation was to develop a site-specific colonic drug delivery system, built on the principles of the combination of pH and time sensitivity. Press-coated mesalamine tablets with a coat of HPMC E-15 were over-coated with Eudragit S100. The in vitro drug release study was conducted using sequential dissolution technique at pH 1.2, 6.0, 7.2 and 6.4 mimicking different regions of gastrointestinal tract. The optimized batch (F2) showed less than 6% of drug release before reaching colonic pH 6.4 and complete drug release was obtained thereafter within 2 hr. A short-term dissolution stability study demonstrated statistical insignificant difference in drug release.

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.

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.

Variable-focus microscopy and UV surface dissolution imaging as complementary techniques in intrinsic dissolution rate determination.

PubMed

Ward, Adam; Walton, Karl; Box, Karl; Østergaard, Jesper; Gillie, Lisa J; Conway, Barbara R; Asare-Addo, Kofi

2017-09-15

This work reports a novel approach to the assessment of the surface properties of compacts used in Surface Dissolution Imaging (SDI). SDI is useful for determining intrinsic dissolution rate (IDR), an important parameter in early stage drug development. Surface topography, post-compaction and post-SDI run, have been measured using a non-contact, optical, three-dimensional microscope based on focus variation, the Alicona Infinite Focus Microscope, with the aim of correlating the IDRs to the surface properties. Ibuprofen (IBU) was used as a model poorly-soluble drug. DSC and XRD were used to monitor possible polymorphic changes that may have occurred post-compaction and post-SDI run. IBUs IDR decreased from 0.033mg/min/cm 2 to 0.022mg/min/cm 2 from 10 to 20min, respectively, during the experiment. XRD and DSC showed no form changes during the SDI run. The surface topography images showed that a distinct imprint was embossed on the surfaces of some compacts which could affect IDRs. Surface parameter values were associated with the SDI experiments which showed strong correlations with the IDR values. The variable-focus microscope can be used as a complimentary tool in the determination of IDR values from the SDI. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

The effect of superdisintegrants on the properties and dissolution profiles of liquisolid tablets containing rosuvastatin.

PubMed

Vraníková, Barbora; Gajdziok, Jan; Doležel, Petr

2017-03-01

The preparation of liquisolid systems (LSS) represents a promising method for enhancing a dissolution rate and bioavailability of poorly soluble drugs. The release of the drug from LSS tablets is affected by many factors, including the disintegration time. The evaluation of differences among LSS containing varying amounts and types of commercially used superdisintegrants (Kollidon® CL-F, Vivasol® and Explotab®). LSS were prepared by spraying rosuvastatin solution onto Neusilin® US2 and further processing into tablets. Varying amounts of superdisintegrants were used and the differences among LSS were evaluated. The multiple scatter plot method was used to visualize the relationships within the obtained data. All disintegrants do not showed negative effect on the flow properties of powder blends. The type and concentration of superdisintegrant had an impact on the disintegration time and dissolution profiles of tablets. Tablets with Explotab® showed the longest disintegration time and the smallest amount of released drug. Fastest disintegration and dissolution rate were observed in tablets containing Kollidon® CL-F (≥2.5% w/w). Also tablets with Vivasol® (2.5-4.0% w/w) showed fast disintegration and complete drug release. Kollidon® CL-F and Vivasol® in concentration ≥2.5% are suitable superdisintegrants for LSS with enhanced release of drug.

The Personality of Children Prior to Divorce: A Prospective Study.

ERIC Educational Resources Information Center

Block, Jeanne H.; And Others

1986-01-01

Reports on a longitudinal study that provides a prospective view of children's personality functioning prior to their subsequent experiencing of divorce. Shows the behavior of boys as early as 11 years prior to parental separation or formal dissolution of marriage to be consistently affected by predivorce familial stress. (HOD)

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.

Microstructure and mechanical properties of 2024-T3 and 7075-T6 aluminum alloys and austenitic stainless steel 304 after being exposed to hydrogen peroxide

NASA Astrophysics Data System (ADS)

Sofyan, Nofrijon Bin Imam

The effect of hydrogen peroxide used as a decontaminant agent on selected aircraft metallic materials has been investigated. The work is divided into three sections; bacterial attachment behavior onto an austenitic stainless steel 304 surface; effect of decontamination process on the microstructure and mechanical properties of aircraft metallic structural materials of two aluminum alloys, i.e. 2024-T3 and 7075-T6, and an austenitic stainless steel 304 as used in galley and lavatory surfaces; and copper dissolution rate into hydrogen peroxide. With respect to bacterial attachment, the results show that surface roughness plays a role in the attachment of bacteria onto metallic surfaces at certain extent. However, when the contact angle of the liquid on a surface increased to a certain degree, detachment of bacteria on that surface became more difficult. In its relation to the decontamination process, the results show that a corrosion site, especially on the austenitic stainless steel 304 weld and its surrounding HAZ area, needs more attention because it could become a source or a harborage of bio-contaminant agent after either incidental or intentional bio-contaminant delivery. On the effect of the decontamination process on the microstructure and mechanical properties of aircraft metallic structural materials, the results show that microstructural effects are both relatively small in magnitude and confined to a region immediately adjacent to the exposed surface. No systematic effect is found on the tensile properties of the three alloys under the conditions examined. The results of this investigation are promising with respect to the application of vapor phase hydrogen peroxide as a decontaminant agent to civilian aircraft, in that even under the most severe circumstances that could occur; only very limited damage was observed. The results from the dissolution of copper by concentrated liquid hydrogen peroxide showed that the rate of copper dissolution increased for the first 15 minutes of the reaction time with an activation energy of 19 kJ/mol, and then the fraction of copper dissolved became constant. This constant dissolution was expected to be due to the formation of copper hydroxide, which was observed to precipitate after the solution settled for some time. However, because the final consumption of hydrogen peroxide was not controlled, the exact reason for this constant dissolution cannot be determined at this time. The value of activation energy is within the range of activation energy found in the literature for other dissolution process. The low activation energy for dissolution of pure copper correlates with the observation of dissolution of copper from intermetallic particles in the aluminum alloys.

Dissolution of uranophane: An AFM, XPS, SEM and ICP study

NASA Astrophysics Data System (ADS)

Schindler, Michael; Freund, Michael; Hawthorne, Frank C.; Burns, Peter C.; Maurice, Patricia A.

2009-05-01

Dissolution experiments on single crystals of uranophane and uranophane-β, Ca(H 2O) 5[(UO 2)(SiO 3(OH)] 2, from the Shinkolobwe mine of the Democratic Republic of Congo, were done in an aqueous HCl solution of pH 3.5 for 3 h, in HCl solutions of pH 2 for 5, 10 and 30 min, and in Pb 2+-, Ba-, Sr-, Ca- and Mg-HCl solutions of pH 2 for 30 min. The basal surfaces of the treated uranophane crystals were examined using atomic-force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). Solutions after dissolution experiments on single crystals and synthetic powders were analysed with inductively coupled plasma-optical emission spectroscopy (ICP-OES) and mass spectroscopy (ICP-MS). The morphology of the observed etch pits (measured by AFM) were compared to the morphology, predicted on the basis of the bond-valence deficiency of polyhedron chains along the edges of the basal surface. Etch pits form in HCl solutions of pH 2. Their decrease in depth with the duration of the dissolution experiment is explained with the stepwave dissolution model, which describes the lowering of the surrounding area of an etch pit with continuous waves of steps emanated from the etch pit into the rest of the crystal surface. Hillocks form in an HCl solution of pH 3.5, and the chemical composition of the surface (as indicated by XPS) shows that these hillocks are the result of the precipitation of a uranyl-hydroxy-hydrate phase. Well-orientated hillocks form on the surface of uranophane in a SrCl 2-HCl solution of pH 2. They are part of an aged silica coating of composition Si 2O 2(OH) 4(H 2O) n. An amorphous layer forms on the surface of uranophane in a MgCl 2-HCl solution of pH 2, which has a composition and structure similar to silicic acid. Small crystallites of uranyl-hydroxy-hydrate phases form on the surface of uranophane after treatment in Pb(NO 3) 2-HCl and BaCl 2-HCl solutions of pH 2. Dissolution experiments on synthetic uranophane powders show that in the early stage of the experiments, the dissolution rate of uranophane increase in the sequence Pb(NO 3) 2-HCl < BaCl 2-HCl < CaCl 2-HCl < HCl < SrCl 2-HCl < MgCl 2-HCl, indicating that the dissolution of uranophane is more enhanced in solutions containing divalent cations of small ionic radii and high Lewis acidity (Mg, MgCl +).

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.

Investigation of the effect of solubility increase at the main absorption site on bioavailability of BCS class II drug (risperidone) using liquisolid technique.

PubMed

Khames, Ahmed

2017-11-01

BCS class II drugs usually suffer inadequate bioavailability as dissolution step is the absorption rate limiting step. In this work, the effect of solubility increase at the main absorption site for these drugs was investigated using risperidone as a drug model. Liquisolid technique was applied to prepare risperidone per-oral tablets of high dissolution rate at intestinal pH (6.8) using versatile nonionic surfactants of high solubilizing ability [Transcutol HP, Labrasol and Labrasol/Labrafil (1:1) mixture] as liquid vehicles at different drug concentrations (10-30%) and fixed (R). The prepared liquisolid tablets were fully evaluated and the dissolution rate at pH 6.8 was investigated. The formulae that showed significantly different release rate were selected and subjected to mathematical modeling using DE 25 , MDT and similarity factor (f2). Depending on mathematical modeling results, formula of higher dissolution rate was subjected to solid state characterization using differential scanning calorimetric (DSC), infrared spectroscopy (IR) and X-ray diffraction (XRD). Finally, the drug bioavailability was studied in comparison to conventional tablets in rabbits. Results showed that liquisolid tablet prepared using Labrasol/Labrafil (1:1) mixture as liquid vehicle containing 10% risperidone is a compatible formula with law drug crystallinity and higher dissolution rate (100% in 25 min). The drug bioavailability was significantly increased in comparison to the conventional tablets (1441.711 μg h/mL and 137.518 μg/mL in comparison to 321.011 μg h/mL and 38.673 μg/mL for AUC and Cp max , respectively). This led to the conclusion that liquisolid technique was efficiently improved drug solubility and solubility increase of BCS class II drugs at their main absorption site significantly increases their bioavailability.

Mathematical model to analyze the dissolution behavior of metastable crystals or amorphous drug accompanied with a solid-liquid interface reaction.

PubMed

Hirai, Daiki; Iwao, Yasunori; Kimura, Shin-Ichiro; Noguchi, Shuji; Itai, Shigeru

2017-04-30

Metastable crystals and the amorphous state of poorly water-soluble drugs in solid dispersions (SDs), are subject to a solid-liquid interface reaction upon exposure to a solvent. The dissolution behavior during the solid-liquid interface reaction often shows that the concentration of drugs is supersaturated, with a high initial drug concentration compared with the solubility of stable crystals but finally approaching the latter solubility with time. However, a method for measuring the precipitation rate of stable crystals and/or the potential solubility of metastable crystals or amorphous drugs has not been established. In this study, a novel mathematical model that can represent the dissolution behavior of the solid-liquid interface reaction for metastable crystals or amorphous drug was developed and its validity was evaluated. The theory for this model was based on the Noyes-Whitney equation and assumes that the precipitation of stable crystals at the solid-liquid interface occurs through a first-order reaction. Moreover, two models were developed, one assuming that the surface area of the drug remains constant because of the presence of excess drug in the bulk and the other that the surface area changes in time-dependency because of agglomeration of the drug. SDs of Ibuprofen (IB)/polyvinylpyrrolidone (PVP) were prepared and their dissolution behaviors under non-sink conditions were fitted by the models to evaluate improvements in solubility. The model assuming time-dependent surface area showed good agreement with experimental values. Furthermore, by applying the model to the dissolution profile, parameters such as the precipitation rate and the potential solubility of the amorphous drug were successfully calculated. In addition, it was shown that the improvement in solubility with supersaturation was able to be evaluated quantitatively using this model. Therefore, this mathematical model would be a useful tool to quantitatively determine the supersaturation concentration of a metastable drug from solid dispersions. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2015-09-01

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

Dissolution kinetics and biodurability of tremolite particles in mimicked lung fluids: Effect of citrate and oxalate

NASA Astrophysics Data System (ADS)

Rozalen, Marisa; Ramos, M. Elena; Huertas, F. Javier; Fiore, Saverio; Gervilla, Fernando

2013-11-01

The effect of citrate and oxalate on tremolite dissolution rate was measured at 37 °C in non-stirred flow-through reactors, using modified Gamble's solutions at pH 4 (macrophages), 7.4 (interstitial fluids) and 5.5 (intermediate check point) containing 0, 0.15, 1.5 and 15 mmol L-1 of citrate or oxalate. The dissolution rates calculated from Si concentration in the output solutions without organic ligands depend on pH, decreasing when the pH increases from -13.00 (pH 4) to -13.35 (pH 7.4) mol g-1 s-1 and following a proton-promoted mechanism. The presence of both ligands enhances dissolution rates at every pH, increasing this effect when the ligand concentration increases. Citrate produces a stronger effect as a catalyst than oxalate, mainly at more acidic pHs and enhances dissolution rates until 20 times for solutions with 15 mmol L-1 citrate. However, at pH 7.4 the effect is lighter and oxalate solutions (15 mmol L-1) only enhances dissolution rates eight times respect to free organic ligand solutions. Dissolution is promoted by the attack to protons and organic ligands to the tremolite surface. Magnesium speciation in oxalate and citrate solutions shows that Mg citrate complexes are more effective than oxalate ones during the alteration of tremolite in magrophages, but this tendency is the opposite for interstitial fluids, being oxalate magnesium complexes stronger. The biodurability estimations show that the destruction of the fibers is faster in acidic conditions (macrophages) than in the neutral solutions (interstitial fluid). At pH 4, both ligands oxalate and citrate reduce the residence time of the fibers with respect to that calculated in absence of ligands. Nevertheless, at pH 7.4 the presence of ligands does not reduce significantly the lifetime of the fibers.

Enhancement of the dissolution rate and bioavailability of fenofibrate by a melt-adsorption method using supercritical carbon dioxide

PubMed Central

Cha, Kwang-Ho; Cho, Kyung-Jin; Kim, Min-Soo; Kim, Jeong-Soo; Park, Hee Jun; Park, Junsung; Cho, Wonkyung; Park, Jeong-Sook; Hwang, Sung-Joo

2012-01-01

Background: The aim of this study was to enhance the bioavailability of fenofibrate, a poorly water-soluble drug, using a melt-adsorption method with supercritical CO2. Methods: Fenofibrate was loaded onto Neusilin® UFL2 at different weight ratios of fenofibrate to Neusilin UFL2 by melt-adsorption using supercritical CO2. For comparison, fenofibrate-loaded Neusilin UFL2 was prepared by solvent evaporation and hot melt-adsorption methods. The fenofibrate formulations prepared were characterized by differential scanning calorimetry, powder x-ray diffractometry, specific surface area, pore size distribution, scanning electron microscopy, and energy-dispersive x-ray spectrometry. In vitro dissolution and in vivo bioavailability were also investigated. Results: Fenofibrate was distributed into the pores of Neusilin UFL2 and showed reduced crystal formation following adsorption. Supercritical CO2 facilitated the introduction of fenofibrate into the pores of Neusilin UFL2. Compared with raw fenofibrate, fenofibrate from the prepared powders showed a significantly increased dissolution rate and better bioavailability. In particular, the area under the drug concentration-time curve and maximal serum concentration of the powders prepared using supercritical CO2 were 4.62-fold and 4.52-fold greater than the corresponding values for raw fenofibrate. Conclusion: The results of this study highlight the usefulness of the melt-adsorption method using supercritical CO2 for improving the bioavailability of fenofibrate. PMID:23118538

Comparison of the In Vivo Pharmacokinetics and In Vitro Dissolution of Raltegravir in HIV Patients Receiving the Drug by Swallowing or by Chewing

PubMed Central

Baldelli, Sara; Cerea, Matteo; Landonio, Simona; Meraviglia, Paola; Simioni, Emanuela; Cozzi, Valeria; Fucile, Serena; Gazzaniga, Andrea; Clementi, Emilio; Galli, Massimo; Rizzardini, Giuliano; Gervasoni, Cristina

2012-01-01

The pharmacokinetics of raltegravir (RAL) in HIV patients is characterized by high interpatient/intrapatient variability. We investigated the potential contribution of the drug pharmaceutical formulation to RAL pharmacokinetics. We first compared in vivo the pharmacokinetics of RAL for 67 patients to whom the drug was administered by swallowing the intact tablet with those obtained from 13 HIV-infected patients who chewed the RAL tablet due to swallowing difficulties. Subsequently, we evaluated in vitro the dissolution of RAL tablets under different conditions. In the in vivo study, we found that patients given RAL by chewing the tablets presented pharmacokinetic profiles characterized by significantly higher RAL absorption than did patients receiving the drug by swallowing. The in vitro studies showed that when the whole tablets were exposed to an acidic medium, the release of RAL was very low, whereas when the tablets were crushed, the profiles presented significantly higher concentrations of RAL. Crushed tablets tested in water or in a pH 6.8 buffer exhibited prompt and complete dissolution of RAL. HIV-infected patients receiving RAL by chewing the tablet showed higher drug absorption and reduced pharmacokinetic variability compared with patients swallowing the intact tablet. This is related to problems in tablet disintegration and to erratic drug absorption. The amelioration of the RAL pharmaceutical formulation could improve drug pharmacokinetics. PMID:22964253

Study of thermochemical sulfate reduction mechanism using compound specific sulfur isotope analysis

USGS Publications Warehouse

Meshoulam, Alexander; Ellis, Geoffrey S.; Ahmad, Ward Said; Deev, Andrei; Sessions, Alex L.; Tang, Yongchun; Adkins, Jess F.; Liu, Jinzhong; Gilhooly, William P.; Aizenshtat, Zeev; Amrani, Alon

2016-01-01

Experiments involving sparingly soluble CaSO4 show that during the second catalytic phase of TSR the rate of sulfate reduction exceeds that of sulfate dissolution. In this case, there is no apparent isotopic fractionation between source sulfate and generated H2S, as all of the available sulfate is effectively reduced at all reaction times. When CaSO4 is replaced with fully soluble Na2SO4, sulfate dissolution is no longer rate limiting and significant S-isotopic fractionation is observed. This supports the notion that CaSO4dissolution can lead to the apparent lack of fractionation between H2S and sulfate produced by TSR in nature. The S-isotopic composition of individual OSCs record information related to geochemical reactions that cannot be discerned from the δ34S values obtained from bulk phases such as H2S, oil, and sulfate minerals, and provide important mechanistic details about the overall TSR process.

Poly (amidoamine) dendrimer-mediated hybrid formulation for combination therapy of ramipril and hydrochlorothiazide.

PubMed

Singh, Mayank Kumar; Pooja, Deep; Kulhari, Hitesh; Jain, Sanjay Kumar; Sistla, Ramakrishna; Chauhan, Abhay Singh

2017-01-01

We present a dendrimer-based hybrid formulation strategy to explore the potential of poly (amidoamine) PAMAM dendrimers to be used as drug carriers for combination therapy of an anti-hypertensive drug ramipril (RAPL) and a diuretic hydrochlorothiazide (HCTZ). The drug-dendrimer complexes were prepared by phase-equilibration method. The results showed that the solubility of RAPL and HCTZ was dependent on dendrimer concentration and pH of dendrimer solution. The solubility profile of both RAPL and HCTZ dendrimer complexes illustrated a non-linear relationship with dendrimer concentration. At 0.8% (w/v) dendrimer concentration, solubility of RAPL was increased 4.91 folds with amine-terminated while for HCTZ, solubility enhancement was highest (3.72 folds) with carboxy-terminated. The complexes were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance analysis and high performance liquid chromatography. In-vitro drug dissolution performance of pure drugs, individual drug loaded dendrimer formulations and hybrid formulations was studied in USP dissolution medium (pH7.0) and in simulated gastric fluid (pH1.2). Dendrimer mediated formulations showed faster and complete dissolution compared to pure RAPL or HCTZ. Surprisingly, similar pattern of dissolution profile was established with hybrid formulations as compared to individual drug loaded dendrimers. The dendrimer-based hybrid formulations were found to be stable at dark and refrigerated conditions up to 5weeks. Conclusively, the proposed formulation strategy establishes a novel multitasking platform using dendrimer for simultaneous loading and delivery of multiple drugs for pharmaceutical applications. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Experimental Study on the Behavior of TiN and Ti2O3 Inclusions in Contact with CaO‐Al2O3‐SiO2‐MgO Slags

PubMed Central

Bernhard, C.

2017-01-01

TiN and Ti2O3 are the predominant inclusion types in Ti-alloyed ferritic chromium stainless steels. In order to ensure the required steel cleanness level, an effective removal of such inclusions in the slag during secondary metallurgy is essential. This inclusion removal predominantly takes place via dissolution of the inclusion in the slag. The dissolution behavior of TiN and Ti2O3 in CaO-SiO2-Al2O3-MgO slags as well as their agglomeration behavior in the liquid steel is investigated using High Temperature Laser Scanning Confocal Microscopy and Tammann Furnace experiments. Thermodynamic calculations are performed using FactSage 7.0. The behavior of TiN is observed to be completely different to that of oxides. Ti2O3 dissolves quickly in slags, and its dissolution behavior is comparable to that of other already well examined oxides. In contrast, TiN shows a very intense gas reaction which is attributed to the release of nitrogen during contact with slag. Slags with higher SiO2 content show a significantly higher ability for the dissolution of TiN as compared to Al2O3-rich slags. The gas reaction is found to also significantly influence the final steel cleanness. Despite the easy absorption of TiN in the slag, the formed nitrogen supports the formation of pinholes in the steel. PMID:29109805

Preliminary Investigation of the Dissolution Behavior, Cytocompatibility, Effects of Fibrinogen Conformation and Platelet Adhesion for Radiopaque Embolic Particles

PubMed Central

Kehoe, Sharon; Tremblay, Marie-Laurence; Coughlan, Aisling; Towler, Mark R.; Rainey, Jan K.; Abraham, Robert J.; Boyd, Daniel

2013-01-01

Experimental embolic particles based on a novel zinc-silicate glass system have been biologically evaluated for potential consideration in transcatheter arterial embolization procedures. In addition to controlling the cytotoxicity and haemocompatibility for such embolic particles, its glass structure may mediate specific responses via dissolution in the physiological environment. In a 120 h in-vitro dissolution study, ion release levels for silicon (Si4+), sodium (Na+), calcium (Ca2+), zinc (Zn2+), titanium (Ti4+), lanthanum (La3+), strontium (Sr2+), and magnesium (Mg2+), were found to range from 0.04 to 5.41 ppm, 0.27–2.28 ppm, 2.32–8.47 ppm, 0.16–0.20 ppm, 0.12–2.15 ppm, 0.16–0.49 ppm and 0.01–0.12 ppm, respectively for the series of glass compositions evaluated. Initial release of Zn2+ (1.93–10.40 ppm) was only evident after 120 h. All compositions showed levels of cell viabilities ranging from 61.31 ± 4.33% to 153.7 ± 1.25% at 25%–100% serial extract dilutions. The conformational state of fibrinogen, known to induce thrombi, indicated that no changes were induced with respect of the materials dissolution by-products. Furthermore, the best-in-class experimental composition showed equivalency to contour PVA in terms of inducing platelet adhesion. The data generated here provides requisite evidence to continue to in-vivo pre-clinical evaluation using the best-in-class experimental composition evaluated. PMID:24956083

Coral reefs will transition to net dissolving before end of century

NASA Astrophysics Data System (ADS)

Eyre, Bradley D.; Cyronak, Tyler; Drupp, Patrick; De Carlo, Eric Heinen; Sachs, Julian P.; Andersson, Andreas J.

2018-02-01

Ocean acidification refers to the lowering of the ocean’s pH due to the uptake of anthropogenic CO2 from the atmosphere. Coral reef calcification is expected to decrease as the oceans become more acidic. Dissolving calcium carbonate (CaCO3) sands could greatly exacerbate reef loss associated with reduced calcification but is presently poorly constrained. Here we show that CaCO3 dissolution in reef sediments across five globally distributed sites is negatively correlated with the aragonite saturation state (Ωar) of overlying seawater and that CaCO3 sediment dissolution is 10-fold more sensitive to ocean acidification than coral calcification. Consequently, reef sediments globally will transition from net precipitation to net dissolution when seawater Ωar reaches 2.92 ± 0.16 (expected circa 2050 CE). Notably, some reefs are already experiencing net sediment dissolution.

Positively Charged Nanostructured Lipid Carriers and Their Effect on the Dissolution of Poorly Soluble Drugs.

PubMed

Choi, Kyeong-Ok; Choe, Jaehyeog; Suh, Seokjin; Ko, Sanghoon

2016-05-20

The objective of this study is to develop suitable formulations to improve the dissolution rate of poorly water soluble drugs. We selected lipid-based formulation as a drug carrier and modified the surface using positively charged chitosan derivative (HTCC) to increase its water solubility and bioavailability. Chitosan and HTCC-coated lipid particles had higher zeta-potential values than uncoated one over the whole pH ranges and improved encapsulation efficiency. In vitro drug release showed that all NLC formulations showed higher in vitro release efficiency than drug particle at pH 7.4. Furthermore, NLC formulation prepared with chitosan or HTCC represented good sustained release property. The results indicate that chitosan and HTCC can be excellent formulating excipients of lipid-based delivery carrier for improving poorly water soluble drug delivery.

Collaborative Discourse and the Modeling of Solution Chemistry with Magnetic 3D Physical Models--Impact and Characterization

ERIC Educational Resources Information Center

Warfa, Abdi-Rizak M.; Roehrig, Gillian H.; Schneider, Jamie L.; Nyachwaya, James

2014-01-01

A significant body of the literature in science education examines students' conceptions of the dissolution of ionic solids in water, often showing that students lack proper understanding of the particulate nature of dissolving materials as well as holding numerous misconceptions about the dissolution process. Consequently, chemical educators have…

Electric current density imaging of tablet dissolution.

PubMed

Mikac, Ursa; Demsar, Alojz; Sersa, Igor; Demsar, Franci

2002-01-01

The Electric current density imaging technique (CDI) was used to monitor the dissolution of and ion migration from tablets of different acids in agar-agar gel. Conventional MRI cannot monitor these processes, since it can only show changes in the size of the tablet during the dissolving process. CDI traces the dissolved ions thanks to changes in conductivity.

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

Kinetics of carbonate dissolution in CO2-saturated aqueous system at reservoir conditions

NASA Astrophysics Data System (ADS)

Peng, Cheng; Crawshaw, John P.; Maitland, Geoffrey; Trusler, J. P. Martin

2014-05-01

In recent years, carbon capture and storage (CCS) has emerged as a key technology for limiting anthropogenic CO2 emissions while allowing the continued utilisation of fossil fuels. The most promising geological storage sites are deep saline aquifers because the capacity, integrity and injection economics are most favourable, and the environmental impact can be minimal. Many rock-fluid chemical reactions are known to occur both during and after CO2 injection in saline aquifers. The importance of rock-fluid reactions in the (CO2 + H2O) system can be understood in terms of their impact on the integrity and stability of both the formation rocks and cap rocks. The chemical interactions between CO2-acidified brines and the reservoir minerals can influence the porosity and permeability of the formations, resulting in changes in the transport processes occurring during CO2 storage. Since carbonate minerals are abundant in sedimentary rocks, one of the requirements to safely implement CO2 storage in saline aquifers is to characterise the reactivity of carbonate minerals in aqueous solutions at reservoir conditions. In this work, we reported measurements of the intrinsic rate of carbonate dissolution in CO2-saturated water under high-temperature high-pressure reservoir conditions extending up to 373 K and 14 MPa. The rate of carbonate dissolution in CO2-free HCl(aq) was also measured at ambient pressure at temperatures up to 353 K. Various pure minerals and reservoir rocks were investigated in this study, including single-crystals of calcite and magnesite, and samples of dolomite, chalks and sandstones. A specially-designed batch reactor system, implementing the rotating disc technique, was used to obtain the intrinsic reaction rate at the solid/liquid interface, free of mass transfer effects. The effective area and mineralogy of the exposed surface was determined by a combination of surface characterisation techniques including XRD, SEM, EDX and optical microscopy. The results of the study indicate that the rotating disc technique can allow accurate measurement of the carbonate dissolution rate under surface-reaction-controlled conditions, and that the carbonate dissolution rate typically increases with the increase of temperature, CO2 partial pressure and solution acidity. The study shows that the dissolution of carbonate in CO2-free acidic solutions can be described as a first order heterogeneous reaction; however, this model is not sufficient to describe the reaction kinetics of carbonate minerals in the (CO2 + H2O) system, particularly for high reactivity carbonates, such as calcite, at reservoir conditions. For these systems, both pH and the activity of CO2(aq) influence the dissolution rate. Based on the experimental results, kinetic models have been developed and parameterised to describe the dissolution of different carbonate minerals. The results of this study should facilitate more rigorous modelling of mineral dissolution in deep saline aquifers used for CO2 storage. We gratefully acknowledge the funding of QCCSRC provided jointly by Qatar Petroleum, Shell, and the Qatar Science & Technology Park. Keywords: Carbon Dioxide, Carbonate, High Pressure, High Temperature, Reaction Kinetics.

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.

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

The toxicity of zinc oxide nanoparticles to Lemna minor (L.) is predominantly caused by dissolved Zn.

PubMed

Chen, Xiaolin; O'Halloran, John; Jansen, Marcel A K

2016-05-01

Nano-ZnO particles have been reported to be toxic to many aquatic organisms, although it is debated whether this is caused by nanoparticles per sé, or rather dissolved Zn. This study investigated the role of dissolved Zn in nano-ZnO toxicity to Lemna minor. The technical approach was based on modulating nano-ZnO dissolution by either modifying the pH of the growth medium and/or surface coating of nano-ZnO, and measuring resulting impacts on L. minor growth and physiology. Results show rapid and total dissolution of nano-ZnO in the medium (pH 4.5). Quantitatively similar toxic effects were found when L. minor was exposed to nano-ZnO or the "dissolved Zn equivalent of dissolved nano-ZnO". The conclusion that nano-ZnO toxicity is primarily caused by dissolved Zn was further supported by the observation that phytotoxicity was absent on medium with higher pH-values (>7), where dissolution of nano-ZnO almost ceased. Similarly, the reduced toxicity of coated nano-ZnO, which displays a slower Zn dissolution, is also consistent with a major role for dissolved Zn in nano-ZnO toxicity. Copyright © 2016 Elsevier B.V. All rights reserved.

INVESTIGATING THE PREFERENTIAL DISSOLUTION OF LEAD FROM SOLDER PARTICULATES

EPA Science Inventory

During a building corrosion control study, bottles containing acid-preserved water samples with high levels of lead often had particulate material on the bottom. Scanning electron microscope analysis of the particles showed the presence of tin and the absence of lead, indicating ...

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.

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.

Density Functional Theory Study of Oxygen Reduction Activity on Ultrathin Platinum Nanotubes

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

Matanovic, Ivana; Kent, Paul; Garzon, Fernando

2012-07-13

The structure, stability, and catalytic activity of a number of single- and double-wall platinum (n,m) nanotubes ranging in diameter from 0.3 to 2.0 nm were studied using plane-wave based density functional theory in the gas phase and water environment. The change in the catalytic activity toward the oxygen reduction reaction (ORR) with the size and chirality of the nanotube was studied by calculating equilibrium adsorption potentials for ORR intermediates and by constructing free energy diagrams in the ORR dissociative mechanism network. In addition, the stability of the platinum nanotubes is investigated in terms of electrochemical dissolution potentials and by determiningmore » the most stable state of the material as a function of pH and potential, as represented in Pourbaix diagrams. Our results show that the catalytic activity and the stability toward electrochemical dissolution depend greatly on the diameter and chirality of the nanotube. On the basis of the estimated overpotentials for ORR, we conclude that smaller, approximately 0.5 nm in diameter single-wall platinum nanotubes consistently show a huge, up to 400 mV larger overpotential than platinum, indicating very poor catalytic activity toward ORR. This is the result of substantial structural changes induced by the adsorption of any chemical species on these tubes. Single-wall n = m platinum nanotubes with a diameter larger than 1 nm have smaller ORR overpotentials than bulk platinum for up to 180 mV and thus show improved catalytic activity relative to bulk. We also predict that these nanotubes can endure the highest cell potentials but dissolution potentials are still for 110 mV lower than for the bulk, indicating a possible corrosion problem.« less

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.

Quality-by-design approach for the development of telmisartan potassium tablets.

PubMed

Oh, Ga-Hui; Park, Jin-Hyun; Shin, Hye-Won; Kim, Joo-Eun; Park, Young-Joon

2018-05-01

A quality-by-design approach was adopted to develop telmisartan potassium (TP) tablets, which were bioequivalent with the commercially available Micardis ® (telmisartan free base) tablets. The dissolution pattern and impurity profile of TP tablets differed from those of Micardis ® tablets because telmisartan free base is poorly soluble in water. After identifying the quality target product profile and critical quality attributes (CQAs), drug dissolution, and impurities were predicted to be risky CQAs. To determine the exact range and cause of risks, we used the risk assessment (RA) tools, preliminary hazard analysis and failure mode and effect analysis to determine the parameters affecting drug dissolution, impurities, and formulation. The range of the design space was optimized using the face-centered central composite design among the design of experiment (DOE) methods. The binder, disintegrant, and kneading time in the wet granulation were identified as X values affecting Y values (disintegration, hardness, friability, dissolution, and impurities). After determining the design space with the desired Y values, the TP tablets were formulated and their dissolution pattern was compared with that of the reference tablet. The selected TP tablet formulated using design space showed a similar dissolution to that of Micardis ® tablets at pH 7.5. The QbD approach TP tablet was bioequivalent to Micardis ® tablets in beagle dogs.

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

PubMed

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

2018-02-01

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

[Studies on six heavy metal elements dissolution characteristics of Andrographis herb by ICP-OES].

PubMed

Tang, Rui; Li, Tian-Peng; Gu, Xue-Shi; Li, Yong-Jian; Yang, Yi

2010-02-01

A simple and accurate method for the simultaneous determination of As, Ba, Cd, Cr, Cu and Pb in andrographis herb by inductively coupled plasma optical emission spectrometry (ICP-OES) was developed. The samples were digested by HNO3-HClO4. The digestion-determination method was evaluated with the relative standard deviations for all these elements between 2.1% and 4.6%, and the recoveries were between 92.0% and 103.2%. The measuring method was proved to be simple, reliable and highly sensitive. The dissolution characteristics of the 6 heavy metal elements in different solvents and with different extraction methods such as refluxing, soaking, and ultrasonic assisted extraction were studied. The experimental results showed that Ba was in the highest concentration followed by Cu and Cr, and the concentration of As, Pb and Cd was relatively lower in the herb. With the increase in ethanol concentration, the dissolution amount of Ba decreased but that of Cu and Cr increased, and the highest concentration of Cd was dissolved in acidic solution. Overall, Cd and Pb were difficult to dissolve out with 85% ethanol refluxing, but As dissolved comparatively more under the same condition. Comparing the extraction methods, the higher concentration of these 6 metals was obtained by refluxing water or alkaline water than that by 85% ethanol maceration. These differences might be related to the existent forms of these six elements in the herb. The determination and study on dissolution characteristics of these elements by using ICP-OES was important for rational using medicinal resources and ensuring the safety of drugs.

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.

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.

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.

Electrochemical way of molybdenum extraction from the Bimetallic systems of Mo-W

NASA Astrophysics Data System (ADS)

Kudreeva, L. K.; Nauryzbaev, M. K.; Kurbatov, A. P.; Kamysbaev, D. H.; Adilbekova, A. O.; Mukataeva, Z. S.

2015-12-01

Electrochemical dissolution of molybdenum and tungsten was investigated in water- dimethylsulfoxide (DMSO) media at different concentrations of lithium chloride and magnesium perchlorate. The terms of efficient extraction of molybdenum from bimetallic systems of Mo-W have been determined. The polarization curves of the electrooxidation of molybdenum in the solution of 0.25 M LiCl in the DMSO at the different rates of rotations and the scan rate equal to 50 mV/s were obtained. In the presence of the addition of water at the potential of 0.1-0.75 V the small area of polarizability occurs, then with increasing potentials above 1.5 V there is a sharp increase of the oxidation current. Comparison of the current values of anodic dissolution of molybdenum and tungsten showed that the rate of anodic dissolution of molybdenum significantly exceeds the rate of anodic dissolution of tungsten. In the case of molybdenum, the dissolution process is limited by diffusion, in the case of tungsten - by the passive film formation on the electrode surface.

Dissolution characteristics of sericite in chalcopyrite bioleaching and its effect on copper extraction

NASA Astrophysics Data System (ADS)

Dong, Ying-bo; Li, Hao; Lin, Hai; Zhang, Yuan

2017-04-01

The effects of sericite particle size, rotation speed, and leaching temperature on sericite dissolution and copper extraction in a chalcopyrite bioleaching system were examined. Finer particles, appropriate temperature and rotation speed for Acidithiobacillus ferrooxidans resulted in a higher Al3+ dissolution concentration. The Al3+ dissolution concentration reached its highest concentration of 38.66 mg/L after 48-d leaching when the sericite particle size, temperature, and rotation speed were -43 μm, 30°C, and 160 r/min, respectively. Meanwhile, the sericite particle size, rotation speed, and temperature can affect copper extraction. The copper extraction rate is higher when the sericite particle size is finer. An appropriately high temperature is favorable for copper leaching. The dissolution of sericite fitted the shrinking core model, 1-(2/3) α-(1- α)2/3 = k 1 t, which indicates that internal diffusion is the decision step controlling the overall reaction rate in the leaching process. Scanning electron microscopy analysis showed small precipitates covered on the surface of sericite after leaching, which increased the diffusion resistance of the leaching solution and dissolved ions.

Trends in the economic consequences of marital and cohabitation dissolution in the United States.

PubMed

Tach, Laura M; Eads, Alicia

2015-04-01

Mothers in the United States use a combination of employment, public transfers, and private safety nets to cushion the economic losses of romantic union dissolution, but changes in maternal labor force participation, government transfer programs, and private social networks may have altered the economic impact of union dissolution over time. Using nationally representative panels from the Survey of Income and Program Participation (SIPP) from 1984 to 2007, we show that the economic consequences of divorce have declined since the 1980s owing to the growth in married women's earnings and their receipt of child support and income from personal networks. In contrast, the economic consequences of cohabitation dissolution were modest in the 1980s but have worsened over time. Cohabiting mothers' income losses associated with union dissolution now closely resemble those of divorced mothers. These trends imply that changes in marital stability have not contributed to rising income instability among families with children, but trends in the extent and economic costs of cohabitation have likely contributed to rising income instability for less-advantaged children.

Superconcentrated electrolytes for a high-voltage lithium-ion battery

PubMed Central

Wang, Jianhui; Yamada, Yuki; Sodeyama, Keitaro; Chiang, Ching Hua; Tateyama, Yoshitaka; Yamada, Atsuo

2016-01-01

Finding a viable electrolyte for next-generation 5 V-class lithium-ion batteries is of primary importance. A long-standing obstacle has been metal-ion dissolution at high voltages. The LiPF6 salt in conventional electrolytes is chemically unstable, which accelerates transition metal dissolution of the electrode material, yet beneficially suppresses oxidative dissolution of the aluminium current collector; replacing LiPF6 with more stable lithium salts may diminish transition metal dissolution but unfortunately encounters severe aluminium oxidation. Here we report an electrolyte design that can solve this dilemma. By mixing a stable lithium salt LiN(SO2F)2 with dimethyl carbonate solvent at extremely high concentrations, we obtain an unusual liquid showing a three-dimensional network of anions and solvent molecules that coordinate strongly to Li+ ions. This simple formulation of superconcentrated LiN(SO2F)2/dimethyl carbonate electrolyte inhibits the dissolution of both aluminium and transition metal at around 5 V, and realizes a high-voltage LiNi0.5Mn1.5O4/graphite battery that exhibits excellent cycling durability, high rate capability and enhanced safety. PMID:27354162

The dissolution of calcite in CO2-saturated solutions at 25°C and 1 atmosphere total pressure

USGS Publications Warehouse

Plummer, Niel; Wigley, T.M.L.

1976-01-01

The dissolution of Iceland spar in CO2-saturated solutions at 25°C and 1 atm total pressure has been followed by measurement of pH as a function of time. Surface concentrations of reactant and product species have been calculated from bulk fluid data using mass transport theory and a model that accounts for homogeneous reactions in the bulk fluid. The surface concentrations are found to be close to bulk solution values. This indicates that calcite dissolution under the experimental conditions is controlled by the kinetics of surface reaction. The rate of calcite dissolution follows an empirical second order relation with respect to calcium and hydrogen ion from near the initial condition (pH 3.91) to approximately pH 5.9. Beyond pH 5.9 the rate of surface reaction is greatly reduced and higher reaction orders are observed. Calculations show that the rate of calcite dissolution in natural environments may be influenced by both transport and surface-reaction processes. In the absence of inhibition, relatively short times should be sufficient to establish equilibrium.

Understanding effect of formulation and manufacturing variables on the critical quality attributes of warfarin sodium product.

PubMed

Rahman, Ziyaur; Korang-Yeboah, Maxwell; Siddiqui, Akhtar; Mohammad, Adil; Khan, Mansoor A

2015-11-10

Warfarin sodium (WS) is a narrow therapeutic index drug and its product quality should be thoroughly understood and monitored in order to avoid clinical performance issues. This study was focused on understanding the effect of manufacturing and formulation variables on WS product critical quality attributes (CQAs). Eight formulations were developed with lactose monohydrate (LM) or lactose anhydrous (LA), and were either wet granulated or directly compressed. Formulations were granulated either with ethanol, isopropyl alcohol (IPA) and IPA-water mixture (50:50). Formulations were characterized for IPA, water content, hardness, disintegration time (DT), assay, dissolution and drug physical forms (scanning electron microscopy (SEM), near infrared chemical imaging (NIR-CI), X-ray powder diffraction (XRPD) and solid state nuclear magnetic resonance (ssNMR)), and performed accelerated stability studies at 40°C/75% RH for three days. The DT and dissolution of directly compressed formulations were faster than wet granulated formulations. This was due to phase transformation of crystalline drug into its amorphous form as indicated by SEM, NIR-CI, XRPD and ssNMR data which itself act as a binder. Similarly, LM showed faster disintegration and dissolution than LA containing formulations. Stability results indicated an increase in hardness and DT, and a decrease in dissolution rate and extent. This was due to phase transformation of the drug and consolidation with particles' bonding. In conclusion, the CQAs of WS product were significantly affected by manufacturing and formulation variables. Published by Elsevier B.V.

The effect of dentin on the pulp tissue dissolution capacity of sodium hypochlorite and calcium hydroxide.

PubMed

Slutzky-Goldberg, Iris; Hanut, Aiham; Matalon, Shlomo; Baev, Valery; Slutzky, Hagay

2013-08-01

Sodium hypochlorite (NaOCl) and calcium hydroxide (Ca[OH]2) have tissue dissolution capacity. The aim of this study was to evaluate the potential effect of dentin on their tissue dissolution capacity in a novel dentin model. Dentin models were prepared from 25 freshly extracted human molar teeth; the crowns were separated from the roots, and a rectangular inner shape was prepared. Pulp tissue samples adjusted to similar weights of 6.5 ± 0.2 mg were randomly divided into 6 groups: NaOCl groups in test tubes or dentin models for 1 hour, Ca(OH)2 groups in test tubes or dentin models for 1 week, and control groups saline in test tubes or dentin models for 1 week. The final weights after the experimental period were checked and compared with the initial weights. The differences were statistically analyzed. The tissue dissolution capacity of Ca(OH)2 was affected by the presence of dentin. Similarly, NaOCl lost its effect on the pulp tissue after incubation in dentin. Comparison between all test groups showed highly significant differences (P < .001). Dentin has a detrimental effect on the ability of NaOCl and Ca(OH)2 to dissolve pulp tissue. The dentin model appears to be an efficient tool for the study of interactions between local endodontic medicaments, dentin, and pulp tissue. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Time-dependent Enhanced Corrosion of Ti6Al4V in the Presence of H2O2 and Albumin.

PubMed

Zhang, Yue; Addison, Owen; Yu, Fei; Troconis, Brendy C Rincon; Scully, John R; Davenport, Alison J

2018-02-16

There is increasing concern regarding the biological consequences of metal release from implants. However, the mechanisms underpinning implant surface degradation, especially in the absence of wear, are often poorly understood. Here the synergistic effect of albumin and H 2 O 2 on corrosion of Ti6Al4V in physiological saline is studied with electrochemical methods. It is found that albumin induces a time-dependent dissolution of Ti6Al4V in the presence of H 2 O 2 in physiology saline. Potentiostatic polarisation measurements show that albumin supresses dissolution in the presence of H 2 O 2 at short times (<24 h) but over longer time periods (120 h) it significantly accelerates corrosion, which is attributed to albumin-catalysed dissolution of the corrosion product layer resulting in formation of a thinner oxide film. Dissolution of Ti6Al4V in the presence of albumin and H 2 O 2 in physiological saline is also found to be dependent on potential: the titanium ion release rate is found to be higher (0.57 µg/cm 2 ) at a lower potential (90 mV), where the oxide capacitance and resistance inferred from Electrochemical Impedance Spectroscopy also suggests a less resistant oxide film. The study highlights the importance of using more realistic solutions, and considering behaviour over longer time periods when testing corrosion resistance of metallic biomaterials.

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.

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.

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.

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

PubMed

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

2018-07-01

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

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

PubMed

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

2014-11-20

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

Quantification of temperature impacts on the dissolution of chlorinated hydrocarbons into groundwater

NASA Astrophysics Data System (ADS)

Koproch, Nicolas; Popp, Steffi; Köber, Ralf; Beyer, Christof; Bauer, Sebastian; Dahmke, Andreas

2016-04-01

Shallow thermal energy storage has great potential for heat storage especially in urban and industrial areas. However, frequently existing organic groundwater contaminations in such areas were currently seen as exclusion criteria for thermal use of the shallow subsurface, since increased contaminant discharge is feared as consequence of heating. Contaminant discharge is influenced by a complex interaction of processes and boundary conditions as e.g. solubility, dispersion, viscosity and degradation, where there is still a lack of experimental evidence of the temperature dependent interaction. Even existing studies on basic influencing factors as e.g. temperature dependent solubilities show contradictory results. Such knowledge gaps should be reduced to improve the basis and liability of numerical model simulations and the knowledge base to enable a more differentiated and optimized use of resources. For this purpose batch as well as 1- and 2-dimensional experimental studies concerning the temperature dependent release of TCE (trichloroethylene) from a NAPL (non aqueous phase liquid) source are presented and discussed. In addition, this experimental studies are accompanied by a numerical model verification, where extensions of existing numerical model approaches on basis of this obtained experimental results are developed. Firstly, temperature dependent TCE solubility data were collected using batch experiments with significantly better temperature resolution compared to earlier studies, showing a distinct minimum at 35°C and increased solubility towards 5°C and 70°C. Secondly, heated 1-dimensional stainless steel columns homogenously filled with quartz sand were used to quantify source zone depletion and contaminant discharge at 10-70°C. Cumulative mass discharge curves indicated two blob categories with distinct differences in dissolution kinetics. Increasing the temperature showed here an increase of the amount of fast dissolving blobs indicating higher NAPL-water contact areas. Thirdly, heatable 2D-tanks (40 cm x 25 cm x 10 cm) homogenously filled with quartz sand and percolated by distilled H2O were used to investigate the dissolution behavior and plume development of TCE from a residual source zone (5 cm x 5 cm x 10 cm) at 10-70°C. Using NAPL source zone saturation of 5% (Case A) and 20% (Case B) two exemplary cases of a depleted and a fresh source zone were investigated. TCE outflow concentrations in case A increased continuously with increasing temperature, but were controlled by the temperature-dependent solubility in Case B. The experimental results showed that the TCE mass transfer rate has a minimum at about 40°C, if dissolution is non-rate limited and a continuous increase with increasing temperature for rate-limited systems. Implementation of temperature dependent NAPL dissolution and two different blob categories with different mass transfer rate coefficients in the OpenGeoSys code proved successful in reproducing the experimental results. Acknowledgments: The presented work is part of the ANGUS+ project (03EK3022) funded by the German Ministry of Education and Research (BMBF).

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.