European Journal of Biomedical and Pharmaceutical Sciences

CORRELATION APPROACH OF IN-VIVO AND IN-VITRO HYDROLYTIC METABOLISM OF ESTER LINKAGE OF PRODRUG MADE OF INDOMETHACIN AND PARACETAMOL IN RP-HPLC IN ACIDIC AND ALKALINE MEDIUM

*Prof. Dr. Dhrubo Jyoti Sen

ABSTRACT

The desired prodrug made of indomethacin and paracetamol has been synthesized in which ester and amide linkages both have been present and in-vitro and in-vivo biotransformation by hydrolysis pattern has been correlated for this prodrug. This prodrug has two amide linkages (–CONH–) and one ester linkage (–COO–). Since the ester and amide both are susceptible for hydrolysis but in amide (–CONH–) three lone pairs of electrons are present [two for oxygen and one for nitrogen] and in ester (–COO–) four lone pairs of electrons are present [four for two oxygens]. So the electron density of ester is greater than amide and electronegativity of oxygen is 3.44 and for nitrogen is 3.04. So total electronegativity of ester (–COO–) is 3.44+3.44=6.88 and for amide (–CONH–) is 3.44+3.04=6.44. Hence possibility of hydrolytic biotransformation of this prodrug having ester and amide linkages, the ester linkage hydrolyses prior to amide so the prodrug produces two fractions: indomethacin and paracetamol both in acidic as well as in alkaline medium. The release of free drug both in in-vitro and in-vivo so it will be implemented as a prodrug which can show prolong action on pain and fever after getting release into free parent drug by biotransformation. The HPLC (High Performance Liquid Chromatography) study reports the retention time (Rt) and release kinetics of prodrug by taking HPLC degradation datas of three samples of Prodrug and individual HPLC data of parent drugs separately to compare the Rt value of release of two drugs from Prodrug in both acidic and alkaline pH. logP of prodrug=3.94 releases indomethacin (logP=3.10) and paracetamol (logP=0.34) both in acidic and alkaline pH. This is a comparison study of drug release in in-vitro gastric as well as intestinal pH focusing on in-vivo biotransformation.

Keywords: Prodrug, Indomethacin, Paracetamol, Molecular weight, logP, UV ?max, IR, Mobile phase, TLC-Rf value, HPLC-Rt value, LOD, LOC.