Preparation and evaluation of Eudragit S 100 microspheres as pH-sensitive release preparations for piroxicam and theophylline using the emulsion-solvent evaporation method.

Abstract

Microencapsulation of the anti-inflammatory drug piroxicam and the anti-asthmatic drug theophylline was investigated as a means of controlling drug release and minimizing or eliminating local side effects. Microspheres of both drugs that are different in the chemical nature and size were successfully encapsulated at a theoretical loading of 25% with the pH sensitive Eudragit S 100 polymer using the emulsion-solvent evaporation method. Solvent composition, stirring rate and the volume of the external phase were adjusted to obtain reproducible, uniform and spherical microspheres. The size distribution of microsphere batches generally ranged from 125-500 microm with geometric means close to 300 microm. Optical light microscopy was used to identify the microsphere shape. Drug loading was determined by completely dissolving the microspheres in an alkaline borate buffer at pH 10. In vitro dissolution studies were carried out on the microspheres at 37 degrees C (+/-0.5 degrees C) at 100 rpm with USP Dissolution Apparatus II using the procedure for enteric-coated products at two successive different pH media (1.2 and 6.5). Both preparations exhibited an initial rapid release in the acidic medium with theophylline showing a larger increase in the amount released during this stage. The drug release was sustained for both preparations at pH 6.5 with theophylline microspheres, showing more extended release. Drug release rate kinetics followed a Higuchi spherical matrix model for both microsphere preparations.