Development of Lipid-Polymer combined Oral micelles for Enhanced Oral Delivery of Lovastatin

Abstract

Lovastatin is a Biopharmaceutics Classification System (BCS) Class II drug characterized by poor aqueous solubility and limited oral bioavailability, resulting in variable therapeutic performance. The present study aimed to develop, optimize, and evaluate lovastatin-loaded nanoparticulate carriers for enhancing solubility, dissolution rate, and oral bioavailability. Oral micelles were prepared using a nanoprecipitation technique employing poly(lactic-co-glycolic acid) (PLGA) as the polymeric carrier and Poloxamer 188 as a stabilizer. A Box–Behnken design was utilized to optimize formulation variables including polymer concentration, surfactant concentration, and stirring speed. The optimized formulation was characterized for particle size, polydispersity index, zeta potential, drug entrapment efficiency, surface morphology, in vitro dissolution, stability, and pharmacokinetic performance. The optimized oral micelles exhibited a mean particle size of 145.6 ± 4.2 nm, polydispersity index of 0.221 ± 0.03, zeta potential of −31.4 ± 2.1 mV, and entrapment efficiency of 89.3 ± 1.8%. Scanning electron microscopy revealed spherical and uniformly distributed particles. In vitro dissolution studies demonstrated a significant increase in drug release compared with pure lovastatin, with more than 90% release within 60 min. Pharmacokinetic studies indicated a 2.3-fold increase in oral bioavailability compared with the marketed formulation. Stability studies confirmed the physical stability of oral micelles over three months. The findings suggest that nanoparticulate carriers represent a promising strategy for improving the biopharmaceutical properties and therapeutic efficacy of lovastatin.