Quality-by-design approach for development of sustained-release multiple-unit beads of lamotrigine based on ion-cross-linked composite of pectin and okra mucilage: An in vitro appraisal

Abstract

The main objective of the present study was to develop a sustained release multiple-unit beads of lamotrigine based on ionotropically cross-linked natural polysaccharides such as pectin (PTN) and okra mucilage (OM) and optimize the polymer-concentration, polymer ratio and cross-linker concentration by 2³ full factorial design. Two different levels of three independent variables (total polymer concentration, polymer ratio and [CaCl₂]) were considered for the experimental design. Drug-polymers compatibility was examined by FTIR, DSC, TGA and powder-XRD. The surface morphology of the bead before and after dissolution test was examined by SEM. Effects of the independent variables on bead-size, drug-encapsulation-efficiency (DEE), drug-release along with release similarity and difference factors were examined. The independent variables were then numerically optimized using Design-Expert software (Version 12) with the targets to meet USP-reference release profile after the analysis of variance of all the response parameters such as DEE, percent drug release at 2 h, 5 h, 12 h, Korsmeyer-Peppas rate constant, release similarity and difference factors. The optimized formulation showed excellent DEE of 89.2 ± 4.4% and a sustained release profile with release similarity factor of 94.9. Kinetic modeling of drug release data demonstrated a release mechanism combined of hydration, diffusion and erosion.

Keywords: Multiple-unit; Okra mucilage; Sustained release lamotrigine.