INTERPOLYMER COMPLEX-BASED MUCOADHESIVE MICROSPHERES OF PREGABALIN: FORMULATION OPTIMISATION, RELEASE KINETICS, AND GASTRORETENTIVE EVALUATION

Abstract

The present study aimed to develop and optimize pregabalin-loaded mucoadhesive microspheres using an interpolymer complexation technique for gastroretentive drug delivery. Microspheres were prepared by combining ionotropic gelation with electrostatic interaction between chitosan and sodium alginate. A Box Behnken Design was employed to systematically investigate the influence of chitosan concentration, alginate concentration, and calcium chloride concentration on critical quality attributes, including particle size, entrapment efficiency, mucoadhesion, and drug release. The optimized formulation exhibited a particle size of 538 ± 22 µm, entrapment efficiency of 85.8 ± 1.7%, and mucoadhesion of 87.6 ± 1.8%, indicating efficient drug encapsulation and strong adhesion potential. In vitro drug release studies demonstrated a sustained release profile, with approximately 85% drug release over 12 hours. Release kinetics analysis revealed that drug release followed the Higuchi model with non-Fickian diffusion behavior. Fourier transform infrared spectroscopy and differential scanning calorimetry confirmed the absence of chemical incompatibility and indicated partial amorphization of the drug within the polymer matrix. Stability studies showed no significant changes in formulation parameters over three months under accelerated conditions. Overall, the developed microspheres represent a promising gastroretentive system for improving the therapeutic performance and patient compliance of pregabalin.