Application of Box Behnken Design for Development of Paliperidone Solid Dispersion using Fluid Bed Processing: Formulation and Characterization

Abstract

Background: In order to enhance the solubility of Paliperidone, a solid dispersion was formulated. The investigation outlines the application of the Box-Behnken design to optimize the processing variables of a fluid bed processor, aiming to achieve the most efficient results with the minimum number of tests. Poor water solubility, limited bioavailability, and effective manufacturing techniques serve as the foundation for formulation development. Methods: A solid dispersion was prepared through a combination of fluid bed processing and solvent evaporation. The study explored into the impacts of various independent factors viz. spray rate, atomization pressure, and inlet temperature on the compressibility index, particle size, solubility and dissolution of the pure drug, physical mixture and solid dispersion. Furthermore, scanning electron microscopy was employed to assess the melting state, internal structure and surface morphology of the solid dispersion. The Fourier transform infrared spectroscopy, powder x-ray diffractometry, and differential scanning calorimetry, were conducted to provide comprehensive insights into the characteristics of the formulation. Results: The solid dispersion of paliperidone prepared by a fluid bed processor, exhibited a smooth and spherical structure. The saturation solubility reached 261.25 µg/ml of paliperidone by adjusting the independent variables namely inlet temperature (57.50°C), spray rate (1.75 rpm), and atomization air pressure (2.25 Mpa). Notably, the drug release study revealed that 96.78% of paliperidone was released from solid dispersion within 60 minutes Conclusion: Solid dispersion of paliperidone prepared by using Boxbehken design showed improved solubility.