Formulation Development and Evaluation of Paliperidone Nanosuspension for Solubility Enhancement

Abstract

Objective: The main objective of this work is to develop a nanosuspension formulation of paliperidone to overcome its low solubility and bioavailability issues. Stabiliser concentration (X1) and probe ultrasonication duration (X2) at three levels were tested for their effects on particle size (Y1) and saturation solubility (Y2) using a 32-factorial design. Methods: The solvent-antisolvent method, followed by probe ultrasonication was used for the formulation of nanosuspension. The optimised nanosuspension was tested for particle size, saturation solubility, scanning electron microscopy, drug content, thermal analysis, zeta potential, Fourier transform infrared spectroscopy, in vitro dissolution, and in vivo study. Results: The optimised formulation revealed a particle size of 293.4 ± 2.74 nm, saturation solubility of 173.61 ± 3.37 μg/ml, and zeta potential of-23.8 mV. Scanning electron microscope photographs indicated particle size less than 1 μm. Optimised nanosuspension showed 100% drug release within 30 minutes. Studies conducted in Wister rats have shown that the optimised nanosuspension demonstrated a 2.88 times higher maximum concentration and 2 times higher area under the curve. The stability studies demonstrated satisfactory stability over three months. Conclusion: To summarise, this research showed the ability of nanosuspension to enhance the solubility and bioavailability of paliperidone.