Functionally modified polyacrylamide-graft-gum karaya pH-sensitive spray dried microspheres for colon targeting of an anti-cancer drug.

An effort was made to formulate and evaluate pH-sensitive spray dried microspheres using hydrolyzed polyacrylamide-graft-gum karaya (PAAm-g-GK) for colon specific delivery of an anti-cancer agent, capecitabine. The synthesis of pH-sensitive PAAm-g-GK copolymer was done by free radical polymerization followed by alkaline hydrolysis and characterized satisfactorily. The microspheres were spherical in shape; drug entrapment efficiency was found to be in the range of 77.30% to 88.74%. Pulsatile swelling study indicates that the PAAm-g-GK consists of considerable pH-sensitivity. The in-vitro drug release suggested that the microspheres prepared using native GK were incapable to retard the drug release within 5h in the environment of stomach and small intestine. While, those microspheres prepared using pH-sensitive PAAm-g-GK copolymer having crosslinked with glutaraldehyde (GA), released little amount of drug within 5h, but maximum amount of drug was targeted to colonic region in a controlled manner up to 24h. For example, GK10 Microspheres showed only 19.16% drug release at the end of 5th h, while about 80.14% of drug was targeted to colonic region. Cross-linking with GA reduced the early drug release in the upper part of gastrointestinal tract and guaranteed maximum drug release in the colonic region. A rapid enhancement in drug release was witnessed in rat caecal content medium due to the action of colonic bacteria on PAAm-g-GK copolymer.

Novel spray dried pH-sensitive polyacrylamide-grafted-carboxymethylcellulose sodium copolymer microspheres for colon targeted delivery of an anti-cancer drug.

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.