Synthesis, hydrolysis kinetics and pharmacological evaluation of aceclofenac prodrugs.
The mutual prodrugs of aceclofenac with various naturally available antioxidants; menthol, thymol, eugenol, guiacol and vanillin have been synthesized by the DCC coupling method, purified and characterized by spectral data, as well as, partition coefficient, solubility and hydrolytic studies. The title compounds have more lipophilic character as compared to the parent moieties and good stability in acidic environment, which is prerequisite for the oral absorption of the drug. Under gastric as well as intestinal pH conditions these prodrugs showed variable susceptibility towards hydrolysis. The synthesized derivatives were evaluated for antiinflammatory, analgesic activities and ulcerogenic potential. Prodrug showed improved solubility in organic solvents, which implies lipophilic character of ester prodrugs and were also found to be chemically stable in acidic environment. The aceclofenac mutual prodrugs showed improved analgesic and anti-inflammatory activities with reduced ulcerogenicity.
Department of Pharmaceutical Chemistry, St. John Institute of Pharmacy and Research, Vevoor, Manor Road, Palghar (E), Tal-Palghar, Thane (M.S) 401404, India. bharatpg@gmail.com.
Bharat V
BV
Dhokchawle
Anil B
AB
Bhandari
D019342:Acetic Acid; D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D002351:Carrageenan; D004008:Diclofenac / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D004195:Disease Models, Animal; D015195:Drug Design; D004355:Drug Stability; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D008297:Male; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D017208:Rats, Wistar; D018570:Risk Assessment; D012995:Solubility; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011355:Prodrugs; D004008:Diclofenac; D002351:Carrageenan; D019342:Acetic Acid; C056498:aceclofenac