Quality by design approach to understand the process of optimization of iloperidone nanostructured lipid carriers for oral bioavailability enhancement

Abstract

Context: The current work was carried out by exploring the principles of quality by design approach to develop an optimized nanostructured lipid carrier (NLC) formulation of poorly water soluble active iloperidone (ILO) through systematic statistical study. The potential of NLC for improving the oral bioavailability of ILO was also evaluated.Objective: To understand the effect of formulation variables (critical parameters) on the performance characteristics (critical quality attributes) of NLC.Materials and methods: A 3-factor, 3-level Box–Behnken factorial design was explored to predict the responses such as particle size (Y1) and % entrapment efficiency (EE) (Y2) when concentration of lipid (X1), concentration of drug (X2) and concentration of surfactant (X3) were selected as independent variables.Results and discussion: Particle size analysis revealed that all the batches were within the nanometer range. The % EE was found to be between 63% and 96%. In-vitro release study demonstrated sustained release profile of ILO NLC. The pharmacokinetic study in Wistar rats over the period of 24 h demonstrated 8.30-fold increase in oral bioavailability of ILO NLC as compared with ILO pure drug suspension.Conclusion: The NLC formulation remarkably improved the oral bioavailability of ILO and demonstrated a promising perspective for oral delivery of poorly water-soluble drugs.