Dextran carrier macromolecule for colon specific delivery of celecoxib.
The colon specific polymeric conjugates of celecoxib were prepared with dextran of different molecular weight Mr approximately 40 000, 70 000, and 100 000 (CSD-40, CSD-70 and CSD-100). Succinic acid was used as linker between the drug and dextran. The prepared conjugates were characterized by UV, IR, 1H NMR and HPLC. The maximum degree of substitution 3.9+/-0.20 % was found with the dextran CSD-100 conjugates. The percent release of drug obtained by in-vitro hydrolysis studies, was found to be 24.37+/- 0.6, 23.0 +/- 0.5 and 20.13+/- 0.8 in simulated colonic fluid (SCF) pH 6.8 while 17.90 +/- 0.4, 16.8+/- 0.75 and 15.47 +/- 0.5 in simulated intestinal fluid (SIF) pH 7.4 for CSD-40, CSD-70 and CSD-100, respectively, in both medium. The drug release from the conjugates was observed for 24 h in 3% w/v rat caecal content and found to be 41.77 +/- 1.2, 39.03 +/- 1.0 and 35.26 +/- 1.09 for CSD-40, CSD-70 and CSD-100 conjugates, respectively. The half life of conjugates was determined and was found to be short in 3% w/v rat caecal content. No amount of drug was released in simulated gastric fluid pH 1.2 and stomach homogenate in 2 h. The amount of drug released from small intestine homogenate was 3.4+/- 0.1 percent in 12 h for the CSD-40. The above result suggests that dextran could be used as a macromolecular carrier for colon specific drug delivery of celecoxib.
Shrivastava
Prabhat K
PK
Department of Pharmaceutics, Institute of Technology, Banaras Hindu University, Varanasi, U.P., India. skshrivastava.phe@itbhu.ac.in
Shrivastava
Sushant K
SK
D000818:Animals; D000068579:Celecoxib; D003106:Colon / Q000187:drug effects*; D003911:Dextrans / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods*; D045604:Extracellular Fluid / Q000378:metabolism; D006868:Hydrolysis; D066298:In Vitro Techniques; D046911:Macromolecular Substances / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D008970:Molecular Weight; D011720:Pyrazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D019802:Succinic Acid / Q000737:chemistry; D013449:Sulfonamides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics
D003911:Dextrans; D004337:Drug Carriers; D046911:Macromolecular Substances; D011720:Pyrazoles; D013449:Sulfonamides; D019802:Succinic Acid; D000068579:Celecoxib