SYNTHESIS, PHARMACOLOGICAL ACTIVITY AND HYDROLYTIC BEHAVIOUR OF MUTUAL PRODRUGS OF IBUPROFENAbstract
For reducing the gastrointestinal (GI) toxicity associated with ibuprofen (IBU), its carboxylic group was masked by synthesizing its mutual prodrugs with propyphenazone by direct coupling and by using spacer technique (amino acid was taken as a spacer). The structures of synthesized prodrugs were confirmed by 1H-NMR, 13C-NMR, Mass and FT-IR spectral methods, and their purity were established by elemental analysis. The mutual prodrugs were evaluated for their drug release behavior in enzyme-free simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.4). The release of free ibuprofen from prodrugs showed negligible hydrolysis at gastric pH in SGF as compared to SIF where they undergo significant hydrolysis and thus release IBU in adequate amounts following first-order kinetics. Both IBU prodrugs were retaining anti-inflammatory activity intact and exhibited better analgesic activity along with much-reduced ulcerogenic. Prodrug IP1, however, showed better analgesic activity and negligible ulcerogenic tendency than IP2, and hence it could be considered as a better candidate for prodrug among the two.
Sucheta, S. Nanda * and D. P. Pathak
Department of Pharmaceutical Sciences, M. D. University, Rohtak, Haryana, India.
25 March 2014
20 May 2014
25 September 2014
01 October 2014