Design and characterization of Methotrextate Mucoadhesive Microspheres

Abstract

Present investigation was to formulate and evaluate mucoadhesive microspheres of Methotrexate using chitosan as a mucoadhesive polymer, prepared by simple emulsification phase separation technique using glutaraldehyde as a crosslinking agent. Nine preliminary trial formulations of mucoadhesive microspheres were prepared using different volume (20 mL to 60 mL) of glutaraldehyde (25 % v/v aqueous solution) as crosslinking agent and different crosslinking time of 1 to 3 hr. Polymer to drug ratio was kept constant (5:1).All the nine formulations were subjected for evaluation of drug content and drug entrapment efficiency, particle size, percentage swelling index, percentage mucoadhesion, in vitro drug release study. From these nine preliminary trial formulations F4, F5 and F6 were selected as optimized formulations based on percentage mucoadhesion, sphericity of microspheres, swelling index and in vitro drug release. The drug polymer compatibility studies were carried out using Fourier transform infrared spectroscopy. The morphology of microspheres were characterised by scanning electron microscopy. The optimized formulation were spherical in shape and free flowing in nature with 72.5 %,70.1 % and 66.2 % mucoadhesion after 1 hour and optimum drug entrapment efficiency of 62.08 %, 69.78 % and 73.26 % with the slow release of 93.57 % , 86.27 % and 78.29 % up to 12 hours. From above three optimised formulations F5 was selected as best formulation based on mucoadhesion, drug content and in vitro drug release. As the concentration of glutaraldehyde increased, the mucoadheasiveness decreases showing more crosslinking between drug and polymer.