Injectable long acting chitosan/tripolyphosphate microspheres for the intra-articular delivery of lornoxicam: Optimization and in vivo evaluation

Abstract

Chitosan microspheres were formulated for the intra-articular delivery of lornoxicam in knee osteoarthritis, to minimize associated side-effects after prolonged oral administration. Ionotropic-gelation technique was employed using tripolyphosphate as anionic cross-linker. Full-factorial design experiment was conducted to optimize lornoxicam entrapment-efficiency%. Formulations were assessed for their particle size, in-vitro drug release, Scanning electron microscopy, Differential-scanning-calorimetry and Fourier transform infra-red spectroscopy studies. Changing independent variables, chitosan pH, TPP pH and lornoxicam concentration resulted in different values of entrapment-efficiency% ranging from 13.5%±0.35 to 59.5%±2.2. Particle size ranged from 3.57μm±0.02 to 6.12μm±0.00 and lornoxicam%release was prolonged for up to 8days. SEM results showed spherical shape of the microspheres. FTIR and DSC studies confirmed the crosslinking of chitosan with tripolyphosphate. In-vivo therapeutic effect of lornoxicam microspheres was investigated using Monosodiumiodoacetate (MIA) induced osteoarthritis model in rats. Optimized formula showed long-term in-vivo anti-inflammatory effect relative to lornoxicam solution injected intra-articularly with significant reduction of histological, inflammatory and biochemical parameters of osteoarthritis.