Risk and DoE-Based DMAIC Principle to the Multipurpose-RP-HPLC Method for Synchronous Estimation of Anti-Hypertensive Drugs Using AQbD Approach

Abstract

Abstract Background Hypertension is a major health problem found in people throughout the world and numerous fixed-dose combination (FDC) products of telmisartan are available in the local market for its treatment. Several chromatography methods such as reversed-phase (RP)-HPLC and HPTLC methods have been published for estimation of FDC products of telmisartan with hydrochlorothiazide, atorvastatin, and amlodipine. No RP-HPLC method has been reported yet for synchronous estimation of FDC products of telmisartan, which would save analysis time, cost, and solvent. Objective A multipurpose RP-HPLC method has been developed for synchronous estimation of FDC products of telmisartan using the analytical quality by design approach based on risk- and design of experiment (DoE)-based define, measure, analyse, improve, control (DMAIC) principles. Method The risk-based DMAIC principle was implemented by risk parameter identification and assessment as per the ICH Q9 guideline. The DoE-based DMAIC principle was applied by response surface analysis using a Box-Behnken design. The method operable design ranges were navigated and a control strategy was set for the development of the method as per the analytical target profile (ATP). Results Chromatographic separation was performed using Shimpack ODS C18 column and acetonitrile: 0.1% (v/v) triethylamine (pH 6.5), keeping a flow rate of 1.0 mL/min. The method was validated as per the ICH Q2 (R1) guideline. The developed method was applied for synchronous estimation of seven different anti-hypertensive products. Conclusions The developed method is an eco-friendly and economical alternative to published chromatography methods for the analysis of anti-hypertensive products. Hence, the developed method can be used as a multipurpose RPLC method for quality control of anti-hypertensive products in the pharmaceutical industry. Highlights A multipurpose RPLC method for synchronous estimation of antihypertensive products of telmisartan was developed, saving analysis time, cost, and solvent. The developed method was applied to the synchronous estimation of seven different anti-hypertensive products.