Dissolution Rate Studies Research Articles

Intensive leaching of gold from gravity concentrate at low concentration of sodium cyanide

Studies on the intensive leaching of gold gravity concentrate in the drum and conical types at low concentration of sodium cyanide laced with reagent-activator. As a reagent-used organic acid activator with 1.5 and 3.0 kg/t. List the parameters of both devices intensive cyanidation. Tests conducted in comparison with well-known methods of intensive leaching of gold in similar devices with a high concentration of sodium cyanide, in which gold extraction reaches high results. However, there is significant consumption of sodium cyanide, which is an expensive reagent. Similar results can be achieved with a low concentration of sodium cyanide using a reagent-activator, with significant reduction in the consumption of sodium cyanide. It is shown that the use of reagent-activator on the basis of an aliphatic acid significantly intensifies the leaching process. Found that the gold content in the tails of the intensive cyanidation by using reagent-activator on the basis of an aliphatic acids in both vehicles lower than without the use of this reagent. As a result of study of dissolution rate of gold in rolling the unit higher than that of the conical, but for intensive cyanidation gravity concentrates may use both types of machines, drum and conical.

Poly(2-Ethyl-2-Oxazoline) as an Alternative to Poly(Vinylpyrrolidone) in Solid Dispersions for Solubility and Dissolution Rate Enhancement of Drugs

Poly(2-ethyl-2-oxazoline) (PEOX), a biocompatible polymer considered as pseudopolypeptide, was introduced as a potential alternative to the commonly used polymer, poly(vinylpyrrolidone) (PVP) for the preparation of solid dispersion with a poorly soluble drug. Glipizide (GPZ), a Biopharmaceutical Classification System class II model drug, was selected for solubility and dissolution rate study. GPZ-polymer solid dispersions and physical mixtures were characterized and investigated by X-ray diffractometry, differential scanning calorimetry, scanning electron microscopy, and FTIR spectroscopy. The impact of polymers on crystal nucleation kinetics was studied, and PEOX exhibited strong inhibitory effect compared with PVP. Solubility and dissolution behavior of the prepared solid dispersions and their physical blends were in vitro examined and evaluated. A significant enhancement in GPZ solubility was obtained with PEOX compared with the pure drug and solid dispersion with PVP. A big improvement in the intrinsic dissolution rate (45 times) and dissolved amount of GPZ (58 times) was achieved with PEOX in fasted state simulated intestinal fluid, against comparable enhancement observed with PEOX and PVP in phosphate buffer at pH 6.8. Lower molecular weight of PEOX-5K (5000 g/mol) was found to be superior to higher molecular weight PEOX-50K (50,000 g/mol) in the improvement of dissolution behavior. The findings of this study with GPZ as a model drug introduce lower molecular weight PEOX as a promising polymeric carrier toward better oral bioavailability of poorly soluble drugs.

A comparative study between hot-melt extrusion and spray-drying for the manufacture of anti-hypertension compatible monolithic fixed-dose combination products

The purpose of this work was to investigate the application of different advanced continuous processing techniques (hot melt extrusion and spray drying) to the production of fixed-dose combination (FDC) monolithic systems comprising of hydrochlorothiazide and ramipril for the treatment of hypertension. Identical FDC formulations were manufactured by the two different methods and were characterised using powder X-ray diffraction (PXRD) and modulated differential scanning calorimetry (mDSC). Drug dissolution rates were investigated using a Wood’s apparatus, while physical stability was assessed on storage under controlled temperature and humidity conditions. Interestingly both drugs were transformed into their amorphous forms when spray dried, however, hydrochlorothiazide was determined, by PXRD, to be partially crystalline when hot melt extruded with either polymer carrier (Kollidon® VA 64 or Soluplus®). Hot melt extrusion was found to result in significant degradation of ramipril, however, this could be mitigated by the inclusion of the plasticizer, polyethylene glycol 3350, in the formulation and appropriate adjustment of processing temperature. The results of intrinsic dissolution rate studies showed that hot-melt extruded samples were found to release both drugs faster than identical formulations produced via spray drying. However, the differences were attributable to the surface roughness of the compressed discs in the Wood’s apparatus, rather than solid state differences between samples. After a 60-day stability study spray dried samples exhibited a greater physical stability than the equivalent hot melt extruded samples.

In-vitro dissolution rate and molecular docking studies of cabergoline drug with β-cyclodextrin

The physicochemical properties and dissolution profile of cabergoline drug (CAB) with β-cyclodextrin (β-CD) inclusion complex were investigated by the UV spectroscopy. The inclusion complex has used to calculate the stability constant and gives the stoichiometry molar ratio is 1:1 between CAB and β-CD. The phase solubility diagram and the aqueous solubility of CAB (60%) was found to be enhanced by β-CD. In addition, the phase solubility profile of CAB with β-CD was classified as AL-type. Binary systems of CAB with β-CD were prepared by Physical mixture, Kneading and solvent evaporation methods. The solid-state properties of the inclusion complex were characterized by Fourier transformation-infrared spectroscopy, Differential scanning calorimetry, Powder X-ray diffractometric patterns and Scanning electron microscopic techniques. Theoretically, β-CD and CAB inclusion complex obtained by molecular docking studies, it is in good correlation with the results obtained through experimental methods using the Schrödinger software program. In-vitro dissolution profiles of the inclusion complexes were carried out and obvious increase in dissolution rate was observed when compared with pure CAB drug and the complexes.

Crystal Engineering: A Remedy To Tailor the Biopharmaceutical Aspects of Glibenclamide

New cocrystals of glibenclamide (GCM), namely, glibenclamide–hippuric acid, glibenclamide–nicotinic acid, glibenclamide–theophylline, and glibenclamide–succinic acid, were prepared using solvent assisted grinding. The formation of a new crystalline phase was preliminarily characterized by differential scanning calorimetry and powder X-ray diffraction (PXRD), which was further supported by Fourier transform infrared (FT-IR) spectroscopy and 13C solid state NMR analysis. The crystal structures of these cocrystals were determined from PXRD using BIOVIA material studio software. The data revealed the existence of new hydrogen bond interactions between -NH and the oxygen atom of the sulphamoyl group of GCM with carboxylic -C═O, aromatic N (Naromatic), imidazolic -NH, and carboxylic -OH of cocrystal coformers. Equilibrium solubility and intrinsic dissolution rate studies of cocrystals in phosphate buffer of pH 7.4 showed almost 1.5–3.5 times higher solubility as compared to that of pure of GCM. This further led...

PREPARATION AND CHARACTERIZATION OF SOLID DISPERSION FAMOTIDINE – MANNITOL BY CO-GRINDING METHOD

ABSTRACTObjective: This study aims to prepare and characterize solid dispersion of famotidine using mannitol to enhance the solubility and dissolution rate.Methods: Solid dispersions were prepared by co-grinding method in 9 formulas. The ratio of famotidine and mannitol was varied (1:1, 1:2, 2:1 w/w),and each ratio was milled at three different times (30, 60, and 90 minutes). The physical mixture was also prepared as comparison at ratio 1:1 w/w.Solid dispersions were characterized by X-ray diffraction analysis, Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry(DSC) analysis, scanning electron microscopy (SEM), particle size analysis, solubility, and dissolution rate study. The assay of famotidine was doneusing a UV spectrophotometer.Results: The highest solubility of famotidine in solid dispersion was obtained in F2 (ratio 1:2 and grinding time 30 minutes). The solubility of intactfamotidine, physical mixture, and solid dispersion F2 was 1.630±0.027, 2.757±0.096, and 3.272±0.076 mg/ml, respectively. X-ray diffractogram ofsolid dispersion F2 showed a decrease in the peak intensity of famotidine. Thermogram of DSC showed a decrease of famotidine melting point for bothphysical mixture and solid dispersion. Photomicrograph of SEM indicated the changes in morphology solid dispersion compared to intact substances.FTIR analysis showed no chemical interaction between famotidine and mannitol. The particle size analysis showed a reduction in the particle sizeof the solid dispersion. The dissolution result after 60 minutes was 85.029%, 86.166%, 92.057% for intact famotidine, physical mixture, and soliddispersion F2, respectively.Conclusion: Solid dispersion increased solubility and dissolution rate.Keywords: Solid dispersion, Famotidine, Mannitol, Co-grinding, Solubility.

Dissolution Rate Enhancement of Entacapone and Formulation of its Oro- Dispersible Tablets: Applying Statistical Design

Abstract: The major aim of the study was to enhance the solubility and dissolution rate of entacapone by complexation with cyclodextrins (β-CD/HP β-CD). Further the selected cyclodextrin complexes are deigned to formulate oro-dispersible tablets (ODTs) using selected concentration of PEG 4000 as hydrophilic polymer and crospovidone as superdisintegrant. The phase solubility behavior of entacapone in presence of various concentrations of β-CD, HP β-CD, PEG 4000, PVP and Poloxamer 188 (0.25-5% w/v) was studied at 37 ± 2oC. Gibbs free energy (ΔG° tr) values in negative, indicates the spontaneous nature of entacapone solubilization. From dissolution rate studies it was observed β-CD complexes were better over HP β-CD and are formulated to ODTs by direct compression method. Response surface modeling approach (23 full factorial design) was used for design, development and data interpretation. The responses of the design were analyzed using Design Expert 8.0.7.1 (Stat-Ease Inc., USA). The optimized formulation was selected on the basis of software analysis with an overall desirability factor. The optimized formulation showed disintegration time of 40-42s, friability of 0.55% and a release of more than 85% within 45 m. The physicochemical characterizations of inclusion complexes and the optimized tablet formulation were done by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). Key words: Cyclodextrins, Entacapone, Inclusion complexation, Dissolution rate, Disintegration, 23 Factorial design.

CHARACTERIZATION AND INTRINSIC DISSOLUTION RATE STUDY OF MICROWAVE ASSISTED CYCLODEXTRIN INCLUSION COMPLEXES OF GEMFIBROZIL

<p><strong>Objective: </strong>The aim of the present study was to carry out characterization and intrinsic dissolution rate study of microwave assisted inclusion complex of poorly water soluble, lipid lowering agent gemfibrozil [5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid]<strong> </strong>with naturally occurring β-cyclodextrins (CDs) or cycloheptaamylase.</p><p><strong>Methods: </strong>In this work, the phase solubility study was performed to find the ratio of drug and cyclodextrin complexes. Inclusion complexes were prepared by kneading and the prepared complex was subjected to microwave drying and conventional drying techniques. The prepared complexes were evaluated by intrinsic dissolution rate studies and equilibrium solubility study. Further characterization was done by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray powder diffractometry (DSC).</p><p><strong>Results: </strong>The phase solubility studies showed a linear A<sub>L</sub>-type diagram indicating the formation of inclusion complexes in 1:1 molar ratio β-CD-gemfibrozil complex with maximum stability constant of 148.88 M<sup>-1</sup>was selected for preparation of inclusion complex. The microwave dried product was identified as the inclusion complex with maximum IDR when compared to the conventional dried product.</p><p><strong>Conclusion: </strong>This study was concluded that the microwave drying is the most suitable of the previously occurring drying techniques. Since it showed the highest solubility and IDR value.</p>

Solubility and dissolution enhancement of efavirenz hot melt extruded amorphous solid dispersions using combination of polymeric blends: A QbD approach

Efavirenz is a non-nucleoside reverse transcriptase inhibitor and categorized in to BCS class II drug. The aim of the present investigation was to apply quality by design approach to enhance the solubility, dissolution and stability of amorphous solid dispersions (ASDs) of efavirenz using a combination of Soluplus® and HPMCAS-HF polymers. In design of experiments, the user defined quadratic model was used to study the effect of variable concentrations of Soluplus® and HPMCAS-HF for the formation of ASDs of efavirenz. Similarly, a prototype ASD was made using Soluplus® as a carrier with efavirenz loading of 30%. The efavirenz ASDs granular extrudates were evaluated for saturation solubility as well as dissolution rate studies. X-ray powder diffraction, Differential scanning calorimetry, Fourier transform infrared, Atomic force microscopy and FTIR imaging to determine the solid state of efavirenz in the ASDs. DSC and XRD data confirmed that bulk crystalline efavirenz transformed to the amorphous form during the hot melt extrusion processing. Prototype ASD batch showed instability upon storage as per ICH guidelines over a period of 6months, observations inferred from DSC, XRD and in vitro dissolution studies. The maximum dissolution rate was observed when Soluplus® and HPMCAS-HF was in ratio of (60:20) as optimized by design of experiments study. Moreover, the optimized ASDs batch were stable at 40°C, 75% RH for a period of 6months without any dissolution rate changes, and remained into amorphous state.

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

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

Steep improvement in dissolution profile of ezetimibe through co-inclusion in urea

The main objective of the present study was to simultaneously improve the dissolution profile and content uniformity of ezetimibe (EZ), a low dose poorly soluble drug, through co-inclusion in urea. EZ, a new category of cholesterol absorption inhibitor used in the treatment of primary hypercholesterolemia and sitosterolemia, reveals extremely poor solubility in water and dissolution rate limited absorption resulting in its low bioavailability. In the current study, EZ—a highly substituted potent compound which is normally non-complexing guest (NNCG) was successfully incorporated in urea lattice in the presence of readily complexing guest (RCG). The modified Zimmerschied calorimetric method was used for the estimation of the minimum amount of RCG required per unit weight of drug for co-inclusion in urea. Ezetimibe urea co-inclusion complexes (EZUCIC) containing varying proportions of RCG and NNCG were prepared and subjected to thermal analysis using DSC. The formation of EZUCIC was confirmed by FTIR, DSC, XRD and 1H-NMR studies. The thermal data was subjected to the regression studies to study the effect of the relative molar fraction of RCG on the heat of decomposition of EZUCIC. Study exhibited improved content uniformity of EZ in EZUCIC. In vitro dissolution rate studies exhibited steep improvement in the dissolution profile of EZ, a BCS class II drug. The dissolution data was subjected to various release kinetic models. Steep improvement in the dissolution profile offer urea co-inclusion technique a promising alternative for formulation of poorly soluble potent drug candidates into immediate release products with improved content uniformity.

A new dosage form of emodin: For solubility and dissolution rate enhancement and application in Alzheimer's disease and bacteriostasis

Emodin (EM), with two pKa values (pKa1 = 8.0 and pKa2 = 10.9), presents low solubility and dissolution rate, which results in low bioavailability. In this report, two EM sodium salts, C15H9O5−·Na+ (EM-1Na) and C15H8O52−·2Na+ (EM-2Na), were prepared by adding various amounts of sodium hydroxide. Salt forms were characterized by FT-IR, XRPD, 1H NMR, DSC, and SEM, as well as solubility and dissolution rate studies in triple-deionized water, buffer at pH 1.2 and pH 6.8, respectively. The aqueous solubility of EM was notably enhanced by more than 20,000 and 50,000 times, corresponding to EM-1Na and EM-2Na. Meanwhile, the dissolution rate exhibited significant enhancement and the dissolution time was shortened. The results showed the dissolution of EM-1Na and EM-2Na was 25 and 35 times greater than EM in 60 min. The results of β-amyloid (Aβ) self-aggregation inhibition and MIC assay did not show apparent difference from those of EM, indicating that the functional groups were not broken down. Moreover, salt formation significantly enhanced the bioavailability of EM, consistent with the ABTS free radical scavenging test results. The significant decrease in IC50 values in the range of 18,394 μg/mL to 29.07 μg/mL indicated a more effective anti-AD action.

Physical–chemical properties of furosemide nanocrystals developed using rotation revolution mixer

Recently, several approaches have been reported to improve the dissolution rate and bioavailability of furosemide, a class IV drug. However, to the best of our knowledge, none of them proposed nanocrystals. In the last decade, nanocrystals successfully addressed solubility issues by increasing surface area and saturation solubility, both leading to an increase in the dissolution rate of poor water soluble drugs. The preparation of furosemide nanocrystals was by a rotation revolution mixer method. Size distribution and morphology were performed using laser diffraction and scanning electron microscopy, respectively. In addition, differential scanning calorimetry, thermogravimetry, X-ray powder diffraction (XRD) and low frequency shift-Raman spectroscopy allowed investigating the thermal properties and crystalline state. Solubility saturation and intrinsic dissolution rate (IDR) studies were conducted. The thermal analysis revealed lower melting range for the nanocrystals comparing to furosemide. Moreover, a slight crystalline structure change to the amorphous state was observed by XRD and confirmed by low frequency shift Raman. The particle size was reduced to 231 nm with a polydispersity index of 0.232, a 30-fold reduction from the original powder. Finally, the saturation solubility and IDR showed a significant increase. Furosemide nanocrystals showed potential for development of innovative formulations as an alternative to the commercial products.

Physicochemical properties of tadalafil solid dispersions – Impact of polymer on the apparent solubility and dissolution rate of tadalafil

To improve solubility of tadalafil (Td), a poorly soluble drug substance (3μg/ml) belonging to the II class of the Biopharmaceutical Classification System, its six different solid dispersions (1:1, w/w) in the following polymers: HPMC, MC, PVP, PVP-VA, Kollicoat IR and Soluplus were successfully produced by freeze-drying. Scanning electron microscopy showed a morphological structure of solid dispersions typical of lyophilisates. Apparent solubility and intrinsic dissolution rate studies revealed the greatest, a 16-fold, increase in drug solubility (50μg/ml) and a significant, 20-fold, dissolution rate enhancement for the Td/PVP-VA solid dispersion in comparison with crystalline Td. However, the longest duration of the supersaturation state in water (27μg/ml) over 24h was observed for the Td solid dispersion in HPMC. The improved dissolution of Td from Td/PVP-VA was confirmed in the standard dissolution test of capsules filled with solid dispersions. Powder X-ray diffraction and thermal analysis showed the amorphous nature of these binary systems and indicated the existence of dispersion at the molecular level and its supersaturated character, respectively. Nevertheless, as evidenced by film casting, the greatest ability to dissolve Td in polymer was determined for PVP-VA. The crystallization tendency of Td dispersed in Kollicoat IR could be explained by the low Tg (113°C) of the solid dispersion and the highest difference in Hansen solubility parameters (6.8MPa0.5) between Td and the polymer, although this relationship was not satisfied for the partially crystalline dispersion in PVP. Similarly, no correlation was found between the strength of hydrogen bonds investigated using infrared spectroscopy and the physical stability of solid dispersions or the level of supersaturation in aqueous solution.

Experimental study of dissolution rates of actinolite in CaCl2–HCl–H2O up to 400 °C

Actinolite dissolution rates in aqueous HCl and aqueous CaCl2–HCl have been measured at temperatures ranging from 25 to 400°C at 23MPa, under conditions far from equilibrium, using a flow-through reactor. The relative release rates for the various elements in actinolite due to breaking of metal–oxygen bonds are all different. All of the release rates vary with temperature and pH. The release rate of Si increases as temperature rises from 20 to 300°C, but then decreases at higher temperatures. Other metallic ions, such as Ca, Mg, Fe, and Al, are all released more rapidly than Si at temperatures between 25 and 300°C, but more slowly at temperatures ⩾300°C. The ratios of mCa/mSi and mMg/mSi in the effluent at 200°C are close to the stoichiometric proportions of these elements in actinolite, but differ from stoichiometric values at temperatures both above and below 200°C. Actinolite dissolution in aqueous HCl at 100°C yields element ratios close to stoichiometric values in the mineral, but again the ratios vary at higher and lower temperatures.Our experiments demonstrate that, under conditions far from equilibrium, dissolution rates depend on both pH and the activity of aqueous MiZi+, where Zi is the valence of the metal Mi in the mineral and MiZi+ refers to Ca2+, Mg2+, or Al3+. The ion-exchange model suggests that metal–hydrogen ion exchange reaction on the surface is a key step for mineral dissolution, and that a Si-rich, Mi-deficient precursor complex is formed on the mineral surface at temperatures <300°C. Using our experimental data, we express the release rate of Si (r) as follows:-r+=Aexp(-EA/RT)((aH+)Zi/aMiZi+)αwhere α is the order with respect to the ratio of activity of hydrogen ions and dissolved metal ions Mi. The Mg–H exchange coefficient, α, is 0.55 at 100°C. The apparent activation energy EA=14.4kJ/mol, and A=0.23×10−3mcm−2s−1.Our results show that water properties vary strongly within the critical region, which affects the dissolution mechanism. Thus, the release rates for various elements at temperatures above 300°C are different from those at temperatures below 300°C. High resolution transmission electron microscopy (HRTEM) and scanning electron microscopy (SEM) studies indicate that a Fe(Al)-rich, Si-deficient layer is formed on the surface at temperatures above 300°C. X-ray photoelectron spectroscopy (XPS) analyses show that the surface layer that formed by reaction with aqueous HCl at 400°C is a hydrated silicate, composed of Si–OH and Mi–OH, as well as Si–O and Mi–O bonds.

Simultaneous improvement in dissolution profile and content uniformity of lafutidine through co-inclusion in urea

In the present study, simultaneous improvement in dissolution profile and content uniformity of Lafutidine (LAF) has been achieved through co-inclusion in urea. LAF, a recently reported histamine H2 receptor antagonist used in the treatment of peptic ulcer, exhibits low aqueous solubility and dissolution rate limited absorption leading to its poor bioavailability. LAF is a potent and normally non-complexing substituted cyclic organic compound. Urea, a well known host for forming inclusion complexes with linear organic compounds was successfully employed for co-inclusion of LAF in the presence of readily complexing guest (RCG). The modified Zimmerschied calorimetric method was employed for the estimation of the minimum amount of RCG required for co-inclusion of lafutidine in urea. The formation of lafutidine urea co-inclusion complexes (LUCIC) was confirmed by DSC, FTIR, XRD and 1H-NMR studies. LUCIC complexes containing varying proportions of guests were prepared and subjected to thermal analysis using DSC. The thermal data was subjected to the regression analysis to study the influence of the relative molar proportion of RCG on the heat of decomposition of LUCIC. Study revealed good content uniformity of lafutidine in LUCIC. In vitro dissolution rate studies demonstrated steep improvement in dissolution profile of LAF—a BCS class II drug. The resulting dissolution data was subjected to various release kinetic models. Studies reveal that urea co-inclusion complex formation may be a promising technique for the formulation of potent poorly soluble drugs into immediate release products with improved content uniformity.

Pluronics f-127/l-81 binary hydrogels as drug-delivery systems: influence of physicochemical aspects on release kinetics and cytotoxicity.

We investigated the structure of the binary mixture of Pluronic F-127 (PL F-127) and Pluronic L-81 (PL L-81), as hydrogels for sumatriptan delivery and investigated the mixture possible use via subcutaneous route for future applications as a long-acting antimigraine formulation. We studied the drug-micelle interaction by dynamic light scattering and differential scanning calorimetry, sol-gel process by rheology, and small-angle X-ray scattering (SAXS). We also employed pharmaceutical formulation aspects by dissolution rate, release profile, and cytotoxicity studies for apoptosis and/or necrosis in fibroblasts (3T3) and neural cells (Neuro 2a). Micellar hydrodynamic diameter studies revealed the formation of binary PL-micelles by association of PL F-127/PL L-81. The mixed micelle and binary hydrogels formation was also verified by only one phase transition temperature for all formulations, even in the presence of sumatriptan. The characterization of the hydrogel supramolecular organization by SAXS, rheology studies, and in vitro dissolution/release results showed a probable relationship between the transition of the lamellar to the hexagonal phase and the lower release constant values observed, indicating that PL L-81 participates in micelle-hydrogel formation and aggregation processes. Furthermore, the reduced cytotoxicity (annexin V-fluorescein isothiocyanate positive staining), with minor PL L-81 concentration, points to its potential use for the development of binary PL-systems containing sumatriptan capable of modulating the gelation process. This use may employ the minimum PL concentration and be interesting for pharmaceutical applications, particularly for migraine treatment.

An experimental study of tremolite dissolution rates as a function of pH and temperature: Implications for tremolite toxicity and its use in carbon storage

Steady-state tremolite dissolution rates, at far-from-equilibrium conditions, were measured as a function of aqueous silica and magnesium activity, pH from 1.9 to 6.7, and temperature from 25 to 150ºC. Calcium is released from tremolite faster than either Mg or Si throughout most of the experiments even after these latter elements attained steady-state release rates. The preferential removal of Ca releases fine Mg-Si rich needle-like fibres from the tremolite, probably promoting its toxicity. In contrast, Mg was released in stoichiometric or near to stoichiometric proportion to Si once steady-state was attained. Measured steady-state tremolite dissolution rates based on Si release can be described using where r+ signifies the BET surface area-normalized forward tremolite steady-state dissolution rate, AA refers to a pre-exponential factor = 6610–3 mol cm–2 s–1, EA designates an activation energy equal to 80 kJ mol–1, R represents the gas constant, T denotes absolute temperature, and ai refers to the activity of the subscripted aqueous species. This rate expression is consistent with tremolite dissolution rates at acidic pH being controlled by the detachment of partially liberated silica tetrahedra formed from the exchange of Mg2+ for two protons near the mineral surface after the near-surface Ca has been removed. Nevertheless, Mg release rates from tremolite are ~3 orders of magnitude slower than those from forsterite and enstatite suggesting that tremolite carbonation will be far less efficient than the carbonation of these other Mg-silicate minerals.

Studies on urea co-inclusion complexes of simvastatin for improvement of pharmaceutical characteristics

Urea is a well known molecular host for forming inclusion complexes with linear long chain organic compounds. In the present study, simvastatin (SMV), a highly substituted, potent and non-complexing cyclic organic compound, was successfully incorporated in urea lattice in the presence of a suitable readily complexing guest (RCG). The formation of simvastatin urea co-inclusion complex (SMVIC) was confirmed by DSC, FTIR, XRD and 1H-NMR studies. A modified Zimmerschied calorimetric method was utilized to estimate the minimum amount of RCG required for inclusion of simvastatin in urea. Urea-SMV-RCG co-inclusion complexes containing varying proportions of guests were prepared and their thermal behaviour was studied by DSC. Regression analysis revealed an excellent r2 value with regard to the influence of the relative proportion of RCG on the heat of decomposition of SMVIC. The inclusion complexes were found to exhibit good content uniformity. In vitro dissolution rate studies revealed significant improvement in dissolution profile of SMV which is a potent BCS class II drug with poor solubility in water and dissolution rate limited absorption. Studies reveal that urea co-inclusion complex formation can be exploited as a promising approach for the development of improved pharmaceutical formulation of SMV.

Design of a New Reactor to Work at Low Volume Liquid/Surface Solid Ratio and High Pressure and Temperature: Dissolution Rate Studies of UO2Under Both Anoxic and Reducing Conditions.

ABSTRACTA flow-through experimental reactor has been designed in order to perform studies at both high pressure and high temperature conditions. A chromatographic pump is used to impulse the leachant throughout the reactor in order to work at very low flows but high pressures. Therefore, high surface solid to volume leachant ratios, similar to the ones predicted in the final repository, can be obtained. The reactor allows working at different atmospheres at pressures up to 50 bars. The temperature inside the reactor can be set using a jacket.Using this new reactor the evolution of uranium concentrations released from an UO2sample was studied at different conditions.The results show that at hydrogen pressures between 5 and 7 bars, hydrogen peroxide does not seem to significantly oxidize the uranium (IV) oxide. Uranium concentrations in those experiments remain between 10-8mol·l-1and 10-9mol·l-1.