Optimized prodrug approach: a means for achieving enhanced anti-inflammatory potential in experimentally induced colitis.
In the present study, prodrug of ketoprofen was synthesized and evaluated in vitro to optimize the prodrug, and in vivo to observe the reduction in gastrointestinal disturbance and enhanced colonic anti- inflammatory potential for the prodrug. The prodrug was synthesized by coupling ketoprofen with L-glycine (KET-GLY). In vitro reversion of KET-GLY to ketoprofen was carried out in different pHs and in pH 6.8 containing optimized rat fecal material. In vivo healing potential of KET-GLY was evaluated in acetic acid-induced experimental colitis model. In vitro reversion studies suggested that KET-GLY remained intact in stomach but released the free drug at pH 6.8 containing fresh rat fecal material, where the colonic microfloral enzymes (amidase) hydrolyzed the KET-GLY amide linkage, releasing the free drug. In vivo evaluation indicated KET-GLY to be less toxic in stomach, with enhanced anti-inflammatory potential in the colonic region. These findings suggested KET-GLY to be better in action compared with the parent drug.
Philip
Anil K
AK
Department of Pharmaceutics, Rajiv Academy for Pharmacy, Uttar Pradesh, India. philipanil23@yahoo.co.in
Dabas
Sunny
S
Pathak
Kamla
K
D019342:Acetic Acid / Q000009:adverse effects; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D005998:Glycine / Q000008:administration & dosage* / Q000737:chemistry; D007660:Ketoprofen / Q000008:administration & dosage* / Q000737:chemistry; D011355:Prodrugs / Q000138:chemical synthesis* / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D012460:Sulfasalazine / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011355:Prodrugs; D012460:Sulfasalazine; D007660:Ketoprofen; D019342:Acetic Acid; D005998:Glycine