title: 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.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Haibing
authors.initials: H
authors.lastname: He
authors.forename: Bo
authors.initials: B
authors.lastname: Shi
authors.forename: Cuifang
authors.initials: C
authors.lastname: Cai
authors.forename: Xing
authors.initials: X
authors.lastname: Tang
mesh_terms: D002482:Cellulose / Q000737:chemistry* / Q000648:ultrastructure; D055598:Chemical Phenomena; D003692:Delayed-Action Preparations / Q000737:chemistry; D004339:Drug Compounding; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D005240:Feasibility Studies; D057927:Hydrophobic and Hydrophilic Interactions; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000032:analysis / Q000737:chemistry*; D065347:Hypromellose Derivatives; D007700:Kinetics; D008148:Lovastatin / Q000032:analysis / Q000737:chemistry*; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D014677:Pharmaceutical Vehicles / Q000737:chemistry; D010784:Photomicrography; D012995:Solubility; D013499:Surface Properties; D013535:Suspensions; D014783:Viscosity
chemical_list: D003692:Delayed-Action Preparations; D005079:Excipients; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014677:Pharmaceutical Vehicles; D013535:Suspensions; D065347:Hypromellose Derivatives; D002482:Cellulose; D008747:Methylcellulose; D008148:Lovastatin; C109691:microcrystalline cellulose