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Development Of Sustained Release Formulations Of Procainamide Hydrochloride For Oral Use (Microcapsules)
Date of Award
Microencapsulated forms of procainamide hydrochloride (PA) were formulated and evaluated for in vitro release against Procan SR('R) tablet. Both ethylcellulose as well as Eudragit-S microcapsules were prepared by a phase separation coacervation technique. The ethylcellulose or Eudragit-S coat-to-core (PA) ratios studied were 1:1, 1:1.33, 1:2 and 1:4, while the coat-to-polyethylene ratios investigated were 3:1, 5:1, 10:1 and 30:1. Treatment of microcapsules with four different concentrations (5, 10, 15 and 20% w/v) of paraffin wax in cyclohexane was also evaluated for effects on drug release. Ethylcellulose microcapsules and Eudragit-S microcapsules with coat to core ratio of 1:4 and 1:2 respectively and a coat-to-polyethylene ratio of 30:1, after treatment with 5% paraffin wax solution, were selected for a biphasic in vitro release study in hydrochloric acid buffer, pH 1.2 for first hour, and phosphate buffer, pH 7.8 for the remaining period. The mixed blends of ethylcellulose and Eudragit-S microcapsules in the proportions of their PA content were also considered for biphasic in vitro release study. While ethylcellulose microcapsules were insensitive to pH changes, Eudragit-S microcapsules gave faster drug release in phosphate buffer pH 7.8 as expected. The time for release of 50% PA was 2.05, 5.85, 2.30, 2.70, 3.00 and 3.90 hours for Procan SR tablets, ethylcellulose microcapsules, Eudragit-S microcapsules, mixed blends MX-1, MX-2 and MX-3 respectively. The ethylcellulose microcapsules (XXI) and mixed blend (MX-3) provided more effective sustained release of PA over several hours than commercially available product Procan SR tablets. Three promising formulations (XXI, XXII and MX-3) were further evaluated for in vivo bioavailability in dogs. On the basis of area under the plasma concentration-time curve (0-10 hrs.) and total cumulative amount of drug excreted (0-30 hrs.), three formulations were found to be bioequivalent to Procan SR('R) tablets. The plasma concentration-time curve data for each formulation was analyzed pharmacokinetically by an open, one-compartment model. Mechanism of drug release from these microcapsules was also studied. The analysis of in vitro release data strongly suggests a diffusion-controlled release of PA from ethylcellulose microcapsules and possibly Procan SR tablets. The release of PA from Eudragit-S microcapsules was shown to be dissolution-controlled.
Sheth, Nitin Vadilal. (1983). Development Of Sustained Release Formulations Of Procainamide Hydrochloride For Oral Use (Microcapsules). University of the Pacific, Dissertation. https://scholarlycommons.pacific.edu/uop_etds/3340