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Abstract
Unique pH-sensitive spray dried microspheres were formulated employing hydrolyzed polyacrylamide-g-carboxymethylcellulose sodium (PAAm-g-NaCMC) co-polymer for colon targeted delivery of an anticancer drug, capecitabine. Synthesis of PAAm-g-NaCMC was carried out through free radical polymerization, which was supported with an inert atmosphere and then the alkaline hydrolysis was performed and subjected for characterization including FTIR spectroscopic analysis, 1H NMR spectroscopic analysis, elemental analysis, viscosity measurement, neutralization equivalent and thermo-gravimetric investigation. The swelling data suggested that the PAAm-g-NaCMC possesses significant pH-sensitive property. The microspheres were in the range of 1.00 to 7.34 μ and the drug entrapment efficiency ranged between 70.98 and 94.41%. In vitro drug release suggested the failure of microspheres formulated using native NaCMC which failed to impede drug release in stomach and small intestine, while those prepared with pH-sensitive PAAm-g-NaCMC copolymer and cross-linked with glutaraldehyde are suitable for colon targeting because they retarded release of drug in physiologic atmosphere of stomach and small intestine. Only 12.97% of drug was released from CMC10 formulation by the end of 5th h and rest of drug has been targeted to colonic region. A sudden increase in release of drug was observed in rat caecal contents media because of colonic bacterial action on PAAm-g-NaCMC copolymer.
Acknowledgements
Authors are grateful to Indian Council of Medical Research (ICMR), New Delhi, India for providing financial assistance (senior research fellowship) vide grant No. 45/65/2013-PHA/BMS. Authors also thank the Management of BLDE Association, Vijayapur, India for providing facilities to carry out the work.