| Title | Optimized prodrug approach: A means for achieving enhanced anti-inflammatory potential in experimentally induced colitis. | | Author(s) | Philip AK, Dabas S, Pathak K | | Institution | Department of Pharmaceutics, Rajiv Academy for Pharmacy, Mathura, Uttar Pradesh, India. | | Source | J Drug Target 2009 Apr; 17(3):235-41. | | Abstract | 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. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 19558362 |
|
