Preparation of lovastatin matrix sustained-release pellets by extrusion-spheronization combined with microcrystal dispersion technique

Abstract

The poorly water-soluble drug lovastatin (LVA) is an inhibitor of 3-hydroxy-3-methylglutarylcoenzyme A reductase and has a slow dissolution rate. In this study, a microcrystal dispersion (MCD) technique was used in the preparation of LVA to increase its dissolution rate and then combining with an extrusion-spheronization method, microcrystalline cellulose (MCC) matrix sustained-release pellets containing LVA-MCD were developed and characterized in vitro. Photomicrographs indicated that LVA-MCD existed as fine crystals, of which the mean particle size was reduced from 65.75 μm to 3.97 μm and the dried LVA-MCD powders released completely within 2 hours. SEM results during the release process showed that pellets possessed a matrix structure and after the dissolution test, this matrix structure became loose and porous. The release of LVA was fast and complete, and accumulated release by the optimal formulation was: 0.5 h (20.23 ± 3.40%), 2 h (56.87 ± 2.85%), 4 h (78.71 ± 3.42%), and 8 h (96.81 ± 3.30%). The 3 months accelerating test at 40°C and 75% RH demonstrated that drug release of pellets was not changed and drug degradation was less than 1%. Thus, a novel MCD process with MCC matrix was feasible and effective to get complete release without a lag time for the poorly water soluble drug, LVA, with high stability.