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Dissolution Medium (dissolution + medium)
Selected AbstractsMicroenvironmental pH modulation in solid dosage formsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 5 2007Sherif I. Farag Badawy Abstract There are many reports in the literature referring to the effect of ,microenvironmental pH' on solid dosage form performance, particularly stability and dissolution profiles. Several techniques have been proposed for the measurement of the microenvironmental pH. Those techniques use certain assumptions and approximations and many of them employ a solution calibration curve of a probe to predict hydrogen ion activity in a substantially dry solid. Despite the limitation of the methodology, it is clear from the literature that microenvironmental pH has a significant impact on stability of compounds which demonstrate pH dependent stability in solution. Degradation kinetics of such compounds, and in some cases degradation profile as well, are dependent on the microenvironmental pH of the solid. Modulation of the microenvironmental pH through the use of pH modifiers can hence prove to be a very effective tool in maximizing solid dosage form stability. Judicial selection of the appropriate pH modifier, its concentration and the manufacturing process used to incorporate the pH modifier is necessary to enhance stability. Control of microenvironmental pH to maximize stability can be achieved without the use of pH modifier in some cases if an appropriate counter ion is used to provide an inherently optimal pH for the salt. Microenvironmental pH modulation was also shown to control the dissolution profile of both immediate and controlled release dosage forms of compounds with pH dependent solubility. The pH modifiers have been used in conjunction with high energy or salt forms in immediate release formulations to minimize the precipitation of the less soluble free form during initial dissolution. Additionally, pH modifiers were utilized in controlled release dosage forms of weakly basic drugs which exhibit diminished release in dissolution media with high pH. The incorporation of acidic pH modifiers in the controlled release formulation increases the solubility of the basic drug even as the high pH dissolution medium enters into the dosage form hence increasing drug release rate. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 948,959, 2007 [source] In situ measurement of solvent-mediated phase transformations during dissolution testingJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2006Jaakko Aaltonen Abstract In this study, solvent-mediated phase transformations of theophylline (TP) and nitrofurantoin (NF) were measured in a channel flow intrinsic dissolution test system. The test set-up comprised simultaneous measurement of drug concentration in the dissolution medium (with UV-Vis spectrophotometry) and measurement of the solid-state form of the dissolving solid (in situ with Raman spectroscopy). The solid phase transformations were also investigated off-line with scanning electron microscopy. TP anhydrate underwent a transformation to TP monohydrate, and NF anhydrate (form ,) to NF monohydrate (form II). Transformation of TP anhydrate to TP monohydrate resulted in a clear decrease in the dissolution rate, while the transformation of NF anhydrate (form ,) to NF monohydrate (form II) could not be linked as clearly to changes in the dissolution rate. The transformation of TP was an order of magnitude faster than that of NF. The presence of a water absorbing excipient, microcrystalline cellulose, was found to delay the onset of the transformation of TP anhydrate. Combining the measurement of drug concentration in the dissolution medium with the solid phase measurement offers a deeper understanding of the solvent-mediated phase transformation phenomena during dissolution. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:2730,2737, 2006 [source] Characterization of crosslinking effects on the physicochemical and drug diffusional properties of cationic hydrogels designed as bioactive urological biomaterialsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2005David S. Jones This study examined the effects of concentration and type of crosslinker (tetraethyleneglycol diacrylate, TEGDA; diethyleneglycol dimethacrylate, DEGDMA; and polyethyleneglycol dimethacrylate, PEGDMA) on the mechanical and drug diffusional properties of hydrogels that had been selected as candidate coatings for bioactive medical devices. Hydrogels (dimethylaminoethylmethacrylate-covinylpyrrolidone; 1:1) were prepared by free radical polymerization and characterized using tensile analysis, dynamic contact angle analysis and analysis of swelling at pH 6.0. The release of fusidic acid and chlorhexidine was evaluated using buffered medium at pH 6.0 and, in addition, using dissolution medium that had been buffered to pH 9 in the presence and absence of elevated concentrations of calcium, representative of urinary encrustation. Crosslinker concentration, but not type, affected the advancing and receding contact angles. Conversely, both crosslinker type and concentration affected the mechanical and swelling properties of the hydrogels. Maximum swelling and elongation at break were associated with the PEGDMA-crosslinked hydrogels whereas TEGDA-crosslinked hydrogels exhibited the maximum ultimate tensile strength and Young's modulus. Drug release from all systems occurred by diffusion. The mass of chlorhexidine and fusidic acid released was dependent on crosslinker type and concentration, with hydrogels crosslinked with PEGDMA offering the greatest mass of drug released at each sampling period. The mass of fusidic acid but not chlorhexidine released at pH 9.0 in a calcium augmented medium was lower than that released in the same medium devoid of elevated calcium, due to the formation of the poorly soluble calcium salt. In conclusion, this study has uniquely examined the effects of crosslinker type and concentration on physicochemical and drug release properties essential to the clinical and non-clinical performance of bioactive hydrogels for medical device application. [source] Investigation on different levels of in vitro,in vivo correlation: gemfibrozil immediate release capsuleBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 6 2008Mohammad-Reza Rouini Abstract Gemfibrozil is a practically water-insoluble, high-dose drug. It represents a typical drug with dissolution rate controlled bioavailability. The aim of this study was to select a dissolution condition for gemfibrozil immediate release capsules, resulting in the best in vitro/in vivo correlation (IVIVC). Five 300,mg gemfibrozil products, including the innovator and four generic products were selected. In vitro dissolution test methods with a standard paddle, round-bottomed vessel of 1,l capacity, and potassium phosphate buffer as the dissolution medium (referred to as conditions I, II and III, respectively) were developed. The products were administered to 12 healthy volunteers and thereby different pharmacokinetic parameters were calculated. Correlations between the in vitro and in vivo calculated parameters were investigated. Of the single point parameters investigated, the best results were seen in the relation between the percent dissolved in 10, 20 and 45,min and the time to 90% dissolution from the in vitro side and the AUCs and Cmax from the in vivo side. The correlation between MRT and MDT was also investigated, and no significant correlation was found in the three above-mentioned conditions. The Wagner-Nelson method was used to calculate the percent remaining to be absorbed. Superimposition of the percent in vivo absorption and the in vitro dissolution curves was used to investigate a multiple point correlation. A remarkable superimposition between in vivo and in vitro curves in conditions I and II was observed. Copyright © 2008 John Wiley & Sons, Ltd. [source] | ||||||||||