SYNTHESIS, PHARMACOKINETIC AND PHARMACOLOGY OF MUTUAL PRODRUGS OF FENBUFEN AND PROPYPHENAZONEAbstract
Mutual prodrugs of fenbufen and propyphenazone were synthesized with the aim of getting better therapeutic index through avoidance of gastrointestinal problems and to check the efficiency of release of parent drug in the presence of spacer. These mutual pro-drugs were synthesized by direct esterification and by using glycine as a spacer. The title compounds (FP1 & FP2) were characterized by spectral methods and the release of the parent drug from the mutual pro-drug was studied in two different non-enzymatic buffer solutions at pH 1.2 and pH 7.4. The biological activity of the title compounds (FP1 & FP2) was determined by tail-flick method, carrageenan-induced paw edema method, and ulcerogenic potential. From the results obtained it was concluded that these compounds exhibit better biological activity and less gastro-intestinal side effects than parent drug fenbufen. Both mutual prodrugs (FP1 & FP2) exhibited 42 and 32% respectively hydrolysis profile in buffer solutions of pH 7.4 and showed almost negligible hydrolysis i.e., 4.6 and 5.9 % respectively at pH 1.2 over a period of 10 h.
Himanshu, Sucheta *, Ruchita, M. Paliwal, Monika and S. Jain
School of Medical and Allied Sciences, K. R. Mangalam University, Gurugram, Haryana, India.
23 September 2019
15 February 2021
25 February 2021
01 March 2021