Quetiapine Fumarate Loaded Solid Lipid Nanoparticles for Improved Oral Bioavailability

摘要

Quetiapine fumarate (QF) is an atypical antipsychotic, undergoing extensive first pass metabolism and hence shows lower bioavailability orally. Solid Lipid Nanoparticles (SLNs) of QF were developed using lipid dynasan 114 and surfactant poloxamer 188 and 407 by double microemulsion-solvent evaporation technique. The aim of this study was to develop and evaluate SLNs of QF for enhancement of bioavailability via oral route. A Box-Behnken design has been applied to study the effect of independent variables i.e. lipid concentration, surfactant concentration and homogenization time on dependent variables i.e. particle size and entrapment efficiency. Optimized SLNs were evaluated for morphological characteristics using scanning electron microscopy, and were further evaluated for entrapment efficiency, drug content, fourier transform infrared spectroscopy, differential scanning calorimetry and/? vitro drug release study. The formulation was also subjected to In vivo pharmacokinetic study using a rat model for determination of bioavailability. In vivo study suggested increase in bioavailability of QF SLNs (up to 10 fold increase in Area under curve) as compared to pure drug suspension following oral administration. The enhanced relative bioavailability by the SLNs formulation might be attributed to avoidance of first-pass hepatic metabolism by intestinal lymphatic transport, direct uptake of nanoparticles through the GI tract, increased permeability by surfactants, and decreased degradation of drug. The results suggest that QF SLNs can be used as an approach for enhancement of bioavailability of QF via oral route.