Irin Dewan

Characterization and Compatibility Studies of Different Rate Retardant Polymer Loaded Microspheres by Solvent Evaporation Technique: In Vitro-In Vivo Study of Vildagliptin as a Model Drug.

The present study has been performed to microencapsulate the antidiabetic drug of Vildagliptin to get sustained release of drug. The attempt of this study was to formulate and evaluate the Vildagliptin loaded microspheres by emulsion solvent evaporation technique using different polymers like Eudragit RL100, Eudragit RS100, Ethyl cellulose, and Methocel K100M. In vitro dissolution studies were carried out in 0.1 N HCl for 8 hours according to USP paddle method. The maximum and minimum drug release were observed as 92.5% and 68.5% from microspheres, respectively, after 8 hours. Release kinetics were studied in different mathematical release models to find out the linear relationship and release rate of drug. The SEM, DSC, and FTIR studies have been done to confirm good spheres and smooth surface as well as interaction along with drug and polymer. In this experiment, it is difficult to explain the exact mechanism of drug release. But the drug might be released by both diffusion and erosion as the correlation coefficient (R 2) best fitted with Korsmeyer model and release exponent (n) was 0.45–0.89. At last it can be concluded that all in vitro and in vivo experiments exhibited promising result to treat type II diabetes mellitus with Vildagliptin microspheres.

Evaluation of In Vitro Equivalence for Tablets Containing the Poorly WaterSoluble Compound Atorvastatin

This paper describes the evaluation of the in vitro equivalence of tablets containing a poorly water-soluble compound, atorvastatin, marketed in Bangladesh under biowaiver conditions. Drug release was compared with that of a reference product. The in vitro equivalence test was carried out in three different media (pH 1.2, pH 4.5, and pH 6.8). Test results were subjected to statistical analysis to compare the dissolution profiles. Model-independent approaches of difference factor (f1), similarity factor (f2), and dissolution efficiency (%DE) were employed. Dissolution profiles of test and reference (innovator) atorvastatin are equivalent at pH 6.8 without statistical treatment. The test products are equivalent at pH 4.5 (f1 50) and not equivalent at pH 1.2 (f1 > 15 and f2 < 50). Other general quality parameters of these tablets (e.g., weight variation, crushing strength, friability, and disintegration time) were also determined according to established protocols, and test results were within limit. INTRODUCTION Some drugs that have a good clinical therapeutic effect often show low systemic availability because of poor water solubility. Up to 40 percent of new chemical entities discovered by the pharmaceutical industry today are poorly soluble or lipophilic compounds. The solubility issues complicate the delivery of these new drugs and many existing drugs (1). Poorly water-soluble drugs show unpredictable absorption and high intrasubject and intersubject variability (2–4). Therefore, constant surveillance of marketed, poorly water-soluble drugs by the government, manufacturers, and independent research groups is essential to ensure availability of quality medicines. Atorvastatin, a synthetic lipid-lowering agent, is an inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMGCoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, an early rate-limiting step in cholesterol biosynthesis (5). The calcium salt of atorvastatin is currently used for the treatment of hypercholesterolemia (6). The intestinal permeability of atorvastatin is high at the physiologically relevant intestinal pH (7, 8). However, it has been reported that the absolute bioavailability of atorvastatin is only 12% after a 40-mg oral dose (9). The low systemic availability is attributed to low dissolution, presystemic clearance in gastrointestinal mucosa, and hepatic first-pass metabolism (10). Atorvastatin calcium is a crystalline powder and is insoluble in aqueous solution at pH 4 and below. It is very slightly soluble in water. The solubility in aqueous solution at pH 2.1 is about 0.0204 mg /mL, while the solubility in pH 6.0 aqueous solution is about 1.23mg/mL (11). The dose/ solubility (D/S) ratio for atorvastatin is greater than 250 mL for the 10-mg dose at pH 1.2, although the drug dissolves in 250 mL of buffer solution at pH 6.8. Therefore, atorvastatin is a low solubility drug according to WHO Guidance (12). Atorvastatin is not listed in the WHO Model list and is not classified according to BCS by WHO (13). Because of its solubility (low) and permeability (high), atorvastatin is assigned to BCS Class 2 according to WHO guidance. We selected atorvastatin tablets to evaluate the quality of locally available, lipid-lowering drugs with special emphasis on the study of disintegration and dissolution properties of the test samples due to their immense importance in predicting drug bioavailability as well as product quality. We used USP buffer solutions of pH 1.2 (hydrochloric acid solution), pH 4.5 (acetate buffer solution), and pH 6.8 (phosphate buffer solution). Six units were tested for dissolution. Other general quality parameters of these tablets like weight variation, crushing strength, friability, disintegration time were also determined according to established protocols. The test results were subjected to statistical analysis to compare the dissolution profile. Model independent approaches of difference factor (f1), similarity factor (f2), and dissolution efficiency (%DE) were employed. MATERIALS AND METHODS Chemicals Standard atorvastatin calcium was a kind gift from Incepta Pharmaceuticals Ltd., Bangladesh. Three brands *Corresponding author. e-mail: ashraf@uap-bd.edu dx.doi.org/10.14227/DT190412P30

Surface Deposition and Coalescence and Coacervation Phase Separation Methods: In Vitro Study and Compatibility Analysis of Eudragit RS30D, Eudragit RL30D, and Carbopol-PLA Loaded Metronidazole Microspheres

Metronidazole (MTZ) has extremely broad spectrum of protozoal and antimicrobial activity and is clinically effective in trichomoniasis, amoebic colitis, and giardiasis. This study was performed to formulate and evaluate the MTZ loaded microspheres by coacervation phase separation and surface deposition and coalescence methods using different polymers like Gelatin, Carbopol 934P, Polylactic Acid (PLA), Eudragit RS30D, and Eudragit RL30D to acquire sustained release of drug. In vitro dissolution studies were carried out in phosphate buffer (pH 7.4) for 8 hours according to USP paddle method. The maximum and minimum release of MTZ from microspheres observed were 84.81% and 76.6% for coacervation and 95.07% and 80.07% for surface deposition method, respectively, after 8 hours. Release kinetics was studied in different mathematical release models. The SEM and FTIR studies confirm good spheres and smooth surface as well as interaction between drug and polymers. Though release kinetic is uncertain, the best fit was obtained with the Korsmeyer kinetic model with release exponent (n) lying between 0.45 and 0.89. In vitro studies showed that MTZ microspheres with different polymers might be a good candidate as sustained drug delivery system to treat bacterial infections.