ABSTRACT
Objective Enzyme triggered multi unit colon targeting mini tablet of indomethacin were prepared,in order to improve the target treatment of colon disease.Methods Different proportion of enteric layer and chitosan layer were screened to optimize the prescription.The colon targeting mini tablets were prepared by direct compression method.The drug release properties were investigated in different release medium.Rats were used to investigate the distribution of tissue in vivo.The Beagle dogs were used to study the pharmacokinetics and bioavailability.Results The optimum chitosan layer prescription:coating liquid concentration was 2％,plasticizer three citric acid ethyl ester (TEC) was 15％,an anti sticking agent amount of talc was 30％,coating weight was 5％;Enteric layer prescription:coating liquid solid content was 20％,plasticizer content of TEC was 5％,anti sticking agent talc powder dosage was 40％,coating weight was 3％.The chitosan multi unit colon targeted preparation seldom released in rat stomach and small intestine,released slowly in colon.The pharmacokinetics parameters in Beagle dogs were:Cmax =(3.25 + 0.672) mg·L-1,tmax =(2.00 + 0.014) h,AUC(0.∞) =(10.2 +0.871) mg·L-1 ·h,MRT (0-∞) =(2.82 + 0.180) h,CL =(2.46 + 0.202) L·h-1 ·kg-1.The release time of mini tablets for colon targeted was significantly prolonged and preserved stable blood concentration.Conclusion The enzyme triggered multi unit colon targeting mini tablet of indomethacin showed good target to colon and sustained release effect,providing an important reference for the development of preparation of indomethacin for the treatment of colon disease.
ABSTRACT
OBJECTIVE: To develop colon-targeting multi-dosage oral delivery system (mini tablet) using chitosan as the material for treatment of colon cancer. METHODS: Indomethacin (IN) was chosen as a model drug. Firstly, IN solid dispersion was prepared, then Eudragit-chitosan bilayer coated colon targeting mini tablets were prepared by direct compression method and coating technology. The release profiles of the targeting mini tablets in different release media were studied. Small animal in vivo fluorescence imaging investigation was used to sudy the transport and absorption in rats. Beagle dogs were used as animal model to study the pharmacokinetics and bioavailability of the mini tablets. RESULTS: The Eugragit-chitosan bilayer coated mini tablets maintained complete form when passing through the stomach and small intestine of rats, and targeted to the colon. The pharmacokinetic data in Beagle dogs showed that the mini tablets had delayed release and preserved steady absorption. CONCLUSION: The prepared Eudragit-chitosan bilayer coated multi dosage oral colon mini tablets showed good colon targeting effect and sustained release, which can provide important reference for the treatment of colon diseases.