INTRANASAL FORMULATION AND CHARACTERIZATION OF CHITOSAN MICROSPHERE FOR IMPROVING IN VITRO MUCOADHESION, RESIDENCE TIME AND ABSORPTION RATE OF PREGABALIN

Abstract

Objective: Chitosan-based pregabalin microsphere (CBPM) formulation was prepared to improve in vitro mucoadhesion and absorption of pregabalin via intranasal administration. Methods: The CBPM formulations were prepared using the inotropic gelation method and optimized using the Box-behnken design. The optimized CBPM formulation was physico-chemically characterized using scanning electron microscopy, thermal analysis, Fourier transform infrared spectrometry and powder x-ray diffraction. Additionally, the CBPM formulation was characterized for functional parameters such as in vitro mucoadhesion, in vitro drug release, ex vivo permeability across the sheep nasal mucosa and in vivo anticonvulsant activity in pentylenetetrazol (PTZ)-induced seizures model in mice. Results: The design-optimized CBPM exhibited a 91.45 % inclusion efficiency of pregabalin in the microspheres. The Physico-chemical analysis of the individual components and the optimized formulation confirmed the formation of CBPM. The in vitro mucoadhesion study revealed ~80% mucoadhesive of the CBPM to the sheep nasal mucosa. The in vitro dissolution profiles of CBPM was significantly higher (~97%) than that of pure pregabalin (~70%). The CBPM displayed a higher rate and extent of permeability (~90%) than pure pregabalin (~76%) across the sheep nasal mucosa. The in vivo anticonvulsant activity showed that intranasal administration of CBPM resulted in significant (P<0.01) protection against PTZ-induced convulsions in mice. Conclusion: The chitosan-based microsphere intranasal formulation could be employed as promising delivery for rapid pregabalin absorption.