Physicochemical characterization and pharmacokinetic evaluation of rosuvastatin calcium incorporated solid lipid nanoparticles.

Abstract

Rosuvastatin calcium (RCa) is a very efficient antihyperlipidemic agent, however, being a BCS class II drug, results in poor oral bioavailability. The present study focused on the enhancement of oral bioavailability of RCa with solid lipid nanoparticles (SLNs). Physicochemical properties of the particles were evaluated by particle size (PS), polidispersity index (PDI), zeta potential (ZP), DSC, FT-IR, XRD, 1H NMR analyses. Entrapment efficiency (EE), drug loading capacity (DL), in vitro release and release kinetics were also analyzed. Safety and efficacy of the formulations were analyzed by cytotoxicity, permeability and pharmacokinetic studies. PS values were ranged between ∼134 and 351 nm with homogenous size distribution (PDI ∼ 0.130-0.33) and ZP data were valued within the range of ∼-17 mV to -41 mV. The SLN2 formulation showed the best cytotoxicity test results and had medium permeability (Papp 5.72 × 10-6 cm sec-1) while pure RCa resulted in low permeability (Papp 3.08 × 10-7 cm sec-1). According to the stability analyses (3 months) 5 ± 3 °C and 25 ± 2 °C were found suitable storage temperatures for SLNs. Pharmacokinetic studies confirmed significant improvement in Cmax (1.4 fold) and AUClast (8.5 fold) by SLNs in comparison with the pure drug indicating the enhanced biopharmaceutical performance of the RCa loaded SLNs.