Development of extended release coevaporates and coprecipitates of promethazine HCl with acrylic polymers: Formulation considerations

Abstract

The present investigation studied a novel extended release system of promethazine hydrochloride (PHC) with acrylic polymers Eudragit RLPO and Eudragit RS100 in different weight ratios (1:1 and 1:5) using coevaporation and coprecipitation techniques. Solid dispersions were characterized by Fourier-transformed infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC), Powder X-ray diffractometry (PXRD), Nuclear magnetic resonance (NMR), Scanning electron microscopy (SEM) as well as solubility and in vitro dissolution studies in 0.1 N HCl (pH 1.2), double distilled water and phosphate buffer (pH 7.4). Adsorption test from drug solution to solid polymers were also performed. Selected solid dispersion system was subjected to direct compression and compressed tablets were evaluated for in vitro dissolution studies. The progressive disappearance of drug peaks in thermotropic profiles of coevaporates were related to increasing amount of polymers while SEM studies suggested homogenous dispersion of drug in polymer. Eudragit RLPO had a greater adsorptive capacity than Eudragit RS100 and thus its coevaporates in 1:5 ratio exhibited higher dissolution rate with 91.90% drug release for 12 h. Among different formulations, tablets prepared by Eudragit RLPO coevaporates (1:5) displayed extended release of drug for 12 h with 90.87% release followed by zero order kinetics (r2=0.9808). © 2008 Pharmaceutical Society of Japan.