Abstract

DEGRADATION AND KINETIC STUDY OF TADALAFIL AND CHIRAL SEPARATION BY RP-HPLC

Dr. Dhrubo Jyoti Sen and Amee K. Patel*

ABSTRACT

A simple, precise and accurate isocratic RP–HPLC method was developed. The method has shown adequate separation for Tadalafil and degradation products. Separation was achieved on a ACE C18 (150mm×4.6 mm i.d., 5μm particle size) column using mobile phase consisting of Acetonitrile – Water (70:30v/v) at flow rate of 1mL/min and UV detection at 284nm. This drug was subjected to acid hydrolysis, alkali hydrolysis and oxidation by applying stress conditions. The linearity was investigated in the range of 20– 120μg/mL (r2=0.999) for Tadalafil. The intraday and intraday % RSD values were 0.93%. The LOD and LOQ were 0.167μg/mL and 0.5064μg/mL Tadalafil was degraded in acid (1N HCl), alkali (1N NaOH) and oxidative medium in different temperature conditions. Tadalafil was more degraded in alkaline condition compared to acidic. For the degradation kinetic in acidic and alkaline conditions the best fit was obtained for first-order reaction rate. The rate constant (k) is in the alkaline medium, 0.0089min-1 for 40°0C NaOH, 0.042min-1 for 60°C NaOH, 0.1896min-1 for 80°C NaOH and in acid medium, 0.0072min-1 for 40°C HCl, 0.0342min-1 for 60°C HCl, 0.1812min-1 for 80°C HCl and in oxidative medium 0.010min-1 for room temperature. The t1/2 was found to be less in alkaline condition compared to acidic conditions which shows, the drug has lower stability in alkaline medium. The t1/2 for alkaline condition was 77.87mins at 400C, 16.50mins at 600C and 3.655mins at 800C. The t1/2 is 96.250mins at 400C, 20.263mins at 600C and 3.825mins at 800C for acidic condition. The activation energy of Tadalafil in alkaline medium was found to be 5.103KJ/mole and acidic medium was found to be 4.841KJ/mole.

Keywords: Tadalafil, Rate constant, Alkali hydrolysis, Acid hydrolysis, oxidation, Half life, Shelf life, RP – HPLC, Retention time, Chromatogram, Linearity, Correlation coefficient, Arrhenius plot, Calibration curve, Interday and intraday precision, LOD, LOQ.