A Systematic QbD Approach for Developing a Robust Stability – Indicating RP-HPLC Method for Antihypertensive Formulations

Abstract

A quality by design (QbD) approach can potentially lead to a more robust/rugged method development due to emphasis on the risk assessment and management. Aim of present investigation was to develop a new simple, rapid and sensitive RP-HPLC method by employing Box- Behnken design (BBD) approach for determination of telmisartan and azelnidipine in prepared tablets. Box-Behnken design (BBD) was employed to optimize the chromatographic conditions for HPLC method development, taking mobile phase composition (% methanol), flow rate and λmax as independent variables and retention time and tailing factor as the measured responses. The mobile phase composition was methanol: water (80:20 v/v) on a Cosmosil C18 (250mm x 4.6 ID, Particle size: 5 µm) column. In isocratic mode, it had a flow rate 0.9 mL/min and eluted analyte was detected at 256 nm. Analysis of variance (ANOVA) confirmed that the three factors were significant. Validation parameters followed the International Council for Harmonization (ICH) guidelines for the new HPLC method. Forced degradation (acid, base, oxidation, thermal and photolytic) studies were also performed according to ICH guidelines. The developed method was validated as per recommended ICH guidelines which revealed the high degree of linear, precise, accurate, sensitive and robust method over the existing RP-HPLC method. The developed BBD-based method helped in generating a design space and operating space with knowledge of all method performance characteristics, and RP-HPLC method takes less time and can be used in routine for quality control of bulk and marketed formulation of TELM and AZEL.