A novel approach towards therapeutic optimization of diclofenac

Authors

  • MR YADAV Pharmacy Department, Faculty of Technology and Engineering, Kalabhavan, The M.S. University of Baroda, Vadodara-390001. India
  • PK HALEN Pharmacy Department, Faculty of Technology and Engineering, Kalabhavan, The M.S. University of Baroda, Vadodara-390001. India
  • KK CHAGTI Pharmacy Department, Faculty of Technology and Engineering, Kalabhavan, The M.S. University of Baroda, Vadodara-390001. India
  • B HEMALATHA Pharmacy Department, Faculty of Technology and Engineering, Kalabhavan, The M.S. University of Baroda, Vadodara-390001. India
  • R GIRIDHAR Pharmacy Department, Faculty of Technology and Engineering, Kalabhavan, The M.S. University of Baroda, Vadodara-390001. India

Keywords:

Diclofenac, Direct contact effect, Gastrointestinal toxicity, Mucosal injury, Prodrugs, Ulcerogenicity

Abstract

In an effort for obtaining compounds with lower gastric toxicity than diclofenac, five different N,Ndisubstitutedaminoethylester derivatives of diclofenac were synthesized and evaluated. These esterswere designed so as to satisfy the structural requirement for them to possess the anticholinergic activityin intact form before cleavage. Besides blocking the acidic carboxyl group by esterification this activitywas incorporated into the synthesized esters with an expected additional benefit of having reduced gastricacid secretion and thereby abolishing the local irritation by a dual mechanism. This report describes thesynthesis, hydrolysis kinetics and the biological activity of these esters. All the ester derivatives werefound to be stable in buffers (pH 2.0 and 7.4) for sufficient time period, assuring them to be absorbedintact and to successfully overcome the local gastric irritation of the parent drug. A fast enzymatichydrolysis was observed for all the derivatives in 80% pooled human serum. The synthesized esters werefound to possess the proposed anticholinergic activity. The anti-inflammatory activity for most of thecompounds was retained with a significant reduction in the ulcerogenic potential compared to diclofenac.

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Published

2005-06-16

How to Cite

1.
YADAV M, HALEN P, CHAGTI K, HEMALATHA B, GIRIDHAR R. A novel approach towards therapeutic optimization of diclofenac. Ars Pharm [Internet]. 2005 Jun. 16 [cited 2024 Jul. 22];46(3):263-77. Available from: https://revistaseug.ugr.es/index.php/ars/article/view/5079

Issue

Vol. 46 No. 3 (2005)

Section

Original Articles

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