Formulation and Evaluation of microspheres of a hypolipidemic drug

Abstract

Simvastatin is a hypolipidemic drug having low oral bioavailability and shorter half life of 3 h. The present investigation was done to combat the low oral bioavailability and shorter half life of simvastatin. Simvastatin microspheres were prepared by emulsion solvent evaporation technique using aerosil 200 as an inert dispersing carrier to improve the dissolution rate of simvastatin and eudragit RS 100 and ethyl cellulose were used as retarding agents to control the release rate. The resultant microspheres were evaluated for percentage yield, drug entrapment efficiency, micromeritic properties, in vitro drug release and release kinetics. Results indicated that the percentage yield, mean particle size, drug entrapment efficiency and the micromeritic properties of the microspheres was influenced by varying drug: polymer: aerosil 200 ratio and emulsifier concentration. The dissolution rate of simvastatin from microspheres was enhanced significantly with increasing the amount of dispersing agents, and sustained by adding retarding agents. The release rate of microspheres could be controlled as desired by adjusting the combination ratio of dispersing agents to retarding agents. IR spectroscopy confirmed the absence of any drug polymer interaction. The in vitro release profiles from microspheres were fitted into various kinetic models and the best fit with the highest correlation coefficient was observed in zero order plots than Higuchi and first order, indicating that the predominant drug release mechanism was controlled release. The release profiles and content of the microspheres stored at temperature of 30° C ± 2° C/65% ± 5% RH and 40° C ± 2° C/75% ± 5% RH were unchanged during 2 months of storage condition. These results indicate that simvastatin microspheres could be prepared providing a sustained release property.