Preparation and characterization of lovastatin polymeric microparticles by coacervation‐phase separation method for dissolution enhancement

Abstract

Dissolution rate of lovastatin is slow, only 30% of the oral dose is absorbed, and it undergoes extensive first-pass extraction resulting in low and variable bioavailability. The objective of this research was to enhance the dissolution rate through preparing polymeric microparticles. Coacervation-phase separation method through the addition of a non-solvent was used to prepare polymeric microparticles. The method was optimized through studying effects of the type of solvent, the type of polymer, drug : polymer ratio and concentration of surfactant on particle size, particle size distribution, and in-vitro drug release. Optimized polymeric microparticles and unprocessed drug were characterized using different techniques (SEM, FTIR, DSC, and PXRD) and their flow properties were evaluated. The optimum microparticles were prepared using ethanol as a solvent, Eudragit V R L 100 as a polymer in a drug:polymer ratio of 1:2 and SDS in a concentration of 0.25%. Characterization techniques indicated a change from the crystalline form to an amorphous form that was molecularly dispersed into the polymer. Flow properties of these microparticles were improved as compared to unprocessed drug. Drug release was enhanced 4-to 5-folds probably due to precipitation of the drug in an amorphous form; wetting enhancement; size reduction and stabilization by polymers and surfactants. In conclusion the selection of proper process parameters enhanced drug release 5 folds. The use of DMSO as a solvent and the preparation of physical mixtures in this research provided a means for controlled or prolonged release.

An Overview of Microparticulate Drug Delivery System and its Extensive Therapeutic Applications in Diabetes

“…In addition, phase separation can be achieved by different techniques such as salt, non-solvent, or incompatible polymer addition. 46 …”