Synthesis and evaluation of mutual prodrugs of some NSAIDs
Department of Pharmaceutical Chemistry, Bhupal Nobles Institute of Pharmaceutical Sciences, Udaipur, Rajasthan, India.
Research Article
International Journal of Frontiers in Chemistry and Pharmacy Research, 2023, 03(01), 032–041.
Article DOI: 10.53294/ijfcpr.2023.3.1.0049
Publication history:
Received on 04 July 2023; revised on 29 August 2023; accepted on 01 September 2023
Abstract:
The therapeutic efficacy of NSAIDs can be improved by reducing their gastrointestinal side effects by modifying their carboxyl group. Anti-inflammatory drugs Ibuprofen, Ketoprofen were chosen for the preparation of mutual prodrugs with paracetamol. The compounds were synthesized with the aim of achieving a synergistic effect and reducing the gastric irritation of anti-inflammatory drugs. Compounds were confirmed by characterization. The synthesis involved an esterification reaction between the carboxyl group of selected NSAIDs and the hydroxyl group of paracetamol. Mutual prodrugs were evaluated for hydrolysis study in acidic medium and phosphate buffer. Compounds were found to hydrolyze at a controlled rate in the environment, and thus this study found that a mutual prodrug approach can be effectively used to achieve the goals of enhancing the effectiveness of NSAIDs in two ways. First, by masking the carboxyl group of NSAIDs to reduce GI effects and achieve synergistic effects using paracetamol as a pro moiety. Both IP and KP prodrugs were retaining anti-inflammatory activity intact and exhibited much-reduced gastric irritant activity. Prodrug IP however, showed better activity and negligible ulcerogenic tendency than KP.
Keywords:
Mutual prodrugs; NSAIDs; Paracetamol; Esters; Hydrolysis; In vivo evaluation
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