Abstract

DEVELOPMENT OF VALIDATED RP- HPLC METHOD FOR BOSENTAN IN FORMULATION AND ITS APPLICATION TO IN-VITRO INTERACTION STUDY WITH ACECLOFENAC

A.Suganthi*, Sai Lakshmi.C.H, Sruthi Vinod and T.K. Ravi

ABSTRACT

A simple, specific and selective internal standard method using RPHPLC – PDA was developed for the determination of bosentan in its tablet dosage form. Chromatographic method was achieved on C18 column using a mobile phase system consisting of methanol: 0.1% formic acid pH 6.4 (70:30, v/v). Linearity was found in the concentration range of 1-6μg/mL. Low relative standard deviation and good % recovery values of the method showed that the developed method was highly precise, accurate and free from interference present in formulation. The method was successfully applied to the in-vitro interaction study because protein binding is one of the important pharmacokinetic parameters of a drug. Simultaneous administration of two or more drugs can modify the interaction of the drug to plasma protein and in turn percentage of protein binding. Drug-drug interaction alters the known therapeutic response of the drug and there may be enhanced or diminished effects of one or both drugs. The binding interaction of bosentan with aceclofenac was studied under simulated physiological condition using RP-HPLC. The study involved development and validation RP-HPLC for the determination of bosentan in presence of aceclofenac, finding the saturation concentration of bosentan determination of equilibration period and in-vitro interaction of bosentan with aceclofenac. Highest percentage protein binding of bosentan at saturation level was found to be 89.45%. From the interaction study it was observed that there is significant decrease in bosentan may lead to increase in their plasma concentration. Therefore, it may be concluded that bosentan should not be coadministered with aceclofenac.

Keywords: Bosentan, RP- HPLC, Analysis of formulation, Interaction, Aceclofenac, ICH guidelines.