Implementing Analytical Quality by Design (AQbD) Approach for Simultaneous Estimation of Tadalafil and Macitentan by RP-HPLC Method

Abstract

The principle motive behind this work is to develop robust, low cost, and regulatory flexible method for Tadalafil and Macitentan by RP-HPLC using Analytical Quality by Design principles. Failure Mode and Effects Analysis was performed and the risk priority number was calculated, from this analysis independent variables were selected. Optimization of chromatographic condition was performed using Central Composite Design. The separation was achieved using phenomex gemini C18 (150 mm, 4.6 mm, 5μm) column using mobile phase as methanol: 10 mM ammonium formate (74.1 : 25.9 % v/v) (pH: 6.8) at a flow rate 0.94 ml/ min with detection wavelength at 260 nm and 40°C column oven temperature. This method was validated according to ICH Q2 (R1) guideline. Analytical Quality by Design method was numerically optimized with a desirability of 1.0. ANOVA result shows that model was significant for all responses. The method was found to be linear in the range of 0.1-25 μg/ml for Macitentan and 0.4-100 μg/ml for Tadalafil. Percentage recovery was found in the range of 98.6-101.7 % for Macitentan and 98.8-101.8 % for Tadalafil. The RSD of precision and repeatability was found beneath 1 %. AQbD driven method can be highly suitable for analysis of Tadalafil and Macitentan without interference.