Characterization, Optimization, In Vitro and In Vivo Evaluation of Simvastatin Proliposomes, as a Drug Delivery

Abstract

Simvastatin a cholesterol-lowering agent used to treat hypercholesterolemia, coronary heart disease, and dyslipidemia. However, simvastatin (SV) has shown low oral bioavailability in GIT. The main purpose of the work was to develop proliposomal formulations to increase the oral bioavailability of SV. Film deposition on the carrier method has been used to prepare the proliposomes. The proliposomes were assessed for morphology, particulate size, entrapment efficacy, drug-polymer compatibility, in vitro and in vivo studies. FTIR and DSC results revealed no drug-polymer interaction. SEM and XRD analysis conform; proliposomes are spherical, amorphous in nature, so that it enhances the solubility of SV between 15.01 ± 0.026 and 57.80 ± 0.015 μg/mL in pH 7.4 phosphate buffer. The optimised formulation (PL6) shows drug release up to 12 h (99.78 ± 0.067%). The pharmacokinetics of pure SV and SV proliposomes (SVP) in rats were T_max 2 ± 0.5 and 4 ± 0.7 h, C_max 10.4 ± 2.921 and 21.18 ± 12.321 μg/mL, AUC0-∞ 67.124 ± 0.23 and 179.75 ± 1.541 μg/mL h, respectively. Optimised SVP shows a significant improvement in the rate and absorption of SV. The optimised formulation showed enhanced oral bioavailability of SV in Albino Wister rats and offers a new technique to improve the poor water-soluble drug absorption in the gastrointestinal system.

Keywords: cholesterol; in vivo studies; phospholipid; proliposome; simvastatin.