Studies on Physico-Chemical and Pharmacokinetic Properties of Olanzapine through Nanosuspension

The increasing frequency of poorly water soluble new chemical entities exhibiting therapeutic activity is of major concern to the pharmaceutical industry. Olanzapine is an atypical antipsychotic used orally in treatment of Schizophrenia. Also, it has poor aqueous solubility (BCS Class II drug) whose oral bioavailability has been reported as only 40%. In this study olanzapine nanosuspension was prepared using Solvent diffusion followed by sonication technique. The nanosuspension was characterized for particle size distribution, poly dispersity index, zeta potential, crystallinity study (DSC), invitro dissolution release profile and pharmacokinetic studies. Average size of the nanoparticles in F6 was 122.2nm. Saturation solubility of optimized batch of nanosuspension and the plain drug were found to be 2851.3±6.3 μg/ml and 251.3 ±6.1 μg/ml, respectively. In vitro cumulative release from the nanosuspension was 83.54% at 45 min when compared to pure drug 22.91% and freeze dried nanosuspension 92.67%. Pharmacokinetic studies in rats revealed that AUC (0–∞) was increased and clearance was decreased when Olanzapine nanosuspensions were administered orally compared with that of Olanzapine suspension which in turn 2 folds increased bioavailability. The enhanced relative bioavailability by the formulation might be attributed to oral bioavailability can be attributed to the adhesiveness of the drug nanosuspension, increased surface area (due to reduction in particle size), increased saturation solubility, leading to an increased concentration gradient between the gastrointestinal tract lumen and blood, and increased dissolution velocity. This enhancement in bioavailability will lead to a subsequent reduction in drug dose, rendering the therapy cost-effective and obliterating any undue drug dumping in the body.Thus, Nanosuspension seems to be a promising approach for bioavailability enhancement because of the simple method of its preparation and its universal applicability.