title: Synthesis and evaluation of mutual prodrugs of ibuprofen with menthol, thymol and eugenol.
abstract: The present works deals with simple and efficient method of improving therapeutic efficacy of racemic ibuprofen by retarding gastrointestinal side effects through masking of carboxylic group chemically. This is achieved by synthesis and evaluation of ester derivatives of ibuprofen as mutual prodrugs with naturally occurring phenolic and alcoholic compounds. Promoieties like menthol; thymol and eugenol were selected with the aim of getting synergistic effect as these are natural analgesic having traditional medicinal values. Prodrugs are found to be highly lipophilic as compared to parent drug. All the prodrugs are found to be highly stable at acidic pH while undergoes hydrolysis at neutral and alkaline pH as indicated by their t(1/2) values. Synthesized prodrugs derivatives show increased anti-inflammatory activity that might be attributed to synergistic effect as ibuprofen conjugates to natural analgesics. Ulcer index shows much reduction in gastric ulceration compared to ibuprofen concluding the successful masking of acidic group.
authors.affiliation: Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Dhule 425 405 MS, India. vivek.redasani@gmail.com
authors.forename: Vivekkumar K
authors.initials: VK
authors.lastname: Redasani
authors.forename: Sanjay B
authors.initials: SB
authors.lastname: Bari
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000138:chemical synthesis / Q000627:therapeutic use*; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D005054:Eugenol / Q000009:adverse effects / Q000138:chemical synthesis / Q000627:therapeutic use; D005260:Female; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000009:adverse effects / Q000138:chemical synthesis / Q000627:therapeutic use*; D008297:Male; D008610:Menthol / Q000009:adverse effects / Q000138:chemical synthesis / Q000627:therapeutic use; D011355:Prodrugs / Q000009:adverse effects / Q000138:chemical synthesis / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000188:drug therapy*; D013943:Thymol / Q000009:adverse effects / Q000138:chemical synthesis / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011355:Prodrugs; D008610:Menthol; D013943:Thymol; D005054:Eugenol; D002351:Carrageenan; D007052:Ibuprofen