Ketorolac-dextran conjugates: synthesis, in vitro and in vivo evaluation.
Ketorolac is a non-steroidal anti-inflammatory drug. Dextran conjugates of ketorolac (KD) were synthesized and characterized to improve ketorolac aqueous solubility and reduce gastrointestinal side effects. An N-acylimidazole derivative of ketorolac (KAI) was condensed with a model carrier polymer, dextran of different molecular masses (40000, 60000, 110000 and 200000). IR spectral data confirmed formation of ester bonding. Ketorolac contents were evaluated by UV-spectrophotometric analysis. The molecular mass was determined by measuring viscosity using the Mark-Howink-Sakurada equation. In vitro hydrolysis studies were performed in aqueous buffers (pH 1.2, 7.4, 9) and in 80% (V/V) human plasma (pH 7.4). At pH 9, a higher rate of ketorolac release from KD was observed as compared to aqueous buffer of pH 7.4 and 80% human plasma (pH 7.4), following first-order kinetics. In vivo biological screening in mice and rats indicated that conjugates retained analgesic and anti-inflammatory activities with significantly reduced ulcerogenicity compared to the parent drug.
Vyas
Savita
S
Department of Pharmacology, M. G. M. Medical College, A. B. Road, Indore-452001, India. vyassavita@yahoo.com
Trivedi
Piyush
P
Chaturvedi
Subhash Chandra
SC
D019342:Acetic Acid; D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002021:Buffers; D002351:Carrageenan; D002626:Chemistry, Pharmaceutical; D003911:Dextrans / Q000737:chemistry*; D004195:Disease Models, Animal; D004337:Drug Carriers; D004339:Drug Compounding; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control; D020910:Ketorolac / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D007700:Kinetics; D008297:Male; D051379:Mice; D008970:Molecular Weight; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control; D010147:Pain Measurement; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002021:Buffers; D003911:Dextrans; D004337:Drug Carriers; D011355:Prodrugs; D002351:Carrageenan; D019342:Acetic Acid; D020910:Ketorolac