IMPROVED ORAL BIOAVAILABILITY OF PLGA-NANOPARTICLES CONTAINING A TYPICAL ANTIPSYCHOTIC AGENT
Olanzapine, a lipophilic antipsychotic drug, has poor oral bioavailability due to first-pass effect. The objective of this study was to prepare PLGA (poly (lactic-co-glycolic acid) nanoparticles of Olanzapine that will improve the oral bioavailability of Olanzapine and sustain the release to avoid the first pass effect and to prolong the effect of the drug. Nanoparticles of Olanzapine were formulated using PLGA and poloxamer 188 by Nanoprecipitation technique. Prepared nanoparticles were examined for physicochemical characteristics, in vitro release kinetics and pharmacokinetic studies. Average size of the nanoparticles were in range of 122-155nm. The drug encapsulation efficiency was 56.10 % at 5.61 mg of drug loading. In vitro cumulative release from the nanoparticles was 72% at 24hr. pharmacokinetic studies in rats revealed that AUC (0–∞) was increased (5.59 - fold) and clearance was decreased when Olanzapine entrapped particles were administered orally compared with that of Olanzapine suspension. The enhanced relative bioavailability by the 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 and clearance. These results indicate that Olanzapine can be loaded into PLGA nanoparticles for improvement of its relative oral bioavailability