SYNTHESIS AND CHARACTERIZATION OF NOVEL DI-AZO CROSS-LINKED POLYMER FOR COLON SPECIFIC DELIVERY

摘要

The aim of the current study was to synthesize di-azo polymers for colon targeted drug delivery and to characterize these polymers for the same. The novel azo crosslinking agents; diallyl ester of 4,4"-azobenzene dicarboxylic acid from p-Nitro benzoic acid & diallyl ester of 4,4"-azobenzene di-acetic acid from p-Nitro phenyl acetic acid were synthesized. These cross linkers were analyzed by spectral analysis like IR, Proton-NMR, GC-MS. Bulk polymerization method was used to synthesize azo polymers using different acrylate monomers viz. methyl methacrylate, butyl methacrylate. While synthesizing, the cross-linker concentration was varied. These di-azo polymers were characterized for organoleptic properties, solubility, film forming property, biodegradation study in rat caecal content, IR analysis. The polymers PMB 1:1:2:A and PMB 1:1:2:B were found to degrade completely in rat caecal content in anaerobic conditions only and further used to coat budesonide capsules. The drug release study revealed that the capsules coated with azo aromatic polymers PMB 1:1:2:A and PMB 1:1:2:B released 6.76% & 5.68% drug in pH 6.8 phosphate buffer respectively within 3 hrs. At the same time the release in media containing pH 6.8 phosphate buffer with 2% rat caecal content with anaerobic conditions was 36.98% and 25.03% drug within 3 hrs for polymer PMB 1:1:2:A and PMB 1:1:2:B respectively. There was significant (P=0.0269) (P 0.05) difference between cumulative percent drug release (within 3 hrs) in presence and absence of colonic contents. The drug release data was fitted to various kinetic models; results revealed that capsules coated with both co-polymers i.e. PMB 1:1:2:A and PMB 1:1:2:B shown higher correlation coefficient (R) values for zero order equation, indicating zero order release kinetics and the value of "n" was higher than 1.0 (n 1.0) indicating that, drug release occur by both diffusion of drug (non-fickian diffusion or super case II transport) & polymer degradation. This confirms the polymers releases drug only in presence of colonic contents in anaerobic conditions mainly due to azoreductase enzyme from colonic bacteria which cleaved azo bond in amines through amide intermediates. This gave finally bursting or erosion of polymer & release of drug in formulation.