Formulation and Evaluation of Modified Release Injectable Dosage form of Paliperidone Palmitate Implementing Principles of Quality by Design QbD

Abstract

Objective: The aim of present study was to optimize long-acting injectable newlinemicrospheres of Paliperidone palmitate for treatment of schizophrenia. newlineMethods: In this study, poly lactic-co-glycolic acid was used as release controlling newlinepolymer. Microspheres were manufactured using oil in water emulsion solvent newlineevaporation technique. Box Behnken and face-centered central composite designs newlinewere used for optimization. Independent variables such as drug polymer ratio newline(X1), homogenization speed (X2) and rate of addition (X3) were selected for newlineoptimization. While mean particle size (Y1), drug loading (Y2), entrapment newlineefficiency (Y3), burst release (Y4) and drug release (Y5) were considered as newlinedependent variables. Morphology was studied by using the scanning electron newlinemicroscopy and microscopy technique, while particle size was studied by laser newlinediffraction technique. In vitro drug release studies were performed using shaking newlinewater bath apparatus. Fourier transforms infrared spectroscopy and differential newlinescanning calorimetric study were performed to analyse any changes in crystal newlinebehaviour or to detect any chemical bonding. 13C NMR and 1H NMR used for newlineend-cap and monomer ratio study. newlineResults: The mean particle size of microspheres for 1 month release were found to newlinebe 12 to 152 and#956; and drug loading were found between 19.4 to 46.5%. The mean newlineparticle size of microspheres for 3 month release were found to be 38 to 104 and#956; and newlinedrug loading were found between 27.2 to 47.2%. Mathematical modelling of drug newlinerelease kinetics revealed that near zero-order release. Endcap and molar ratio of newlinemicrospheres were found to be ester end cap and ~75:25, respectively. FTIR data newlineshowed no significant interactions occurred in drugs and excipients. The actual newlineresponses of checkpoint runs were observed within 5% variation of predicted newlinevalues. newlineConclusion: The developed microspheres showed promising results of newlinemorphology, particle size, drug loading, entrapment efficiency, burst release and newlinedrug release.