QbD based method development forsimultaneous quantification for Amlodipine Besilate, Hydrochlorothiazide and Olmesartan medoxomil Filmcoated tablet dissolutions in different dissolution media by RP-HPLC

摘要

The scientific way to develop a simple and robust analytical HPLC method for the critical separationsis QbD approach. Quality-by-design (QbD) is a systematic approach to product or process development, which begins with predefined objectives, and uses science and risk management approaches to gainproduct and process understanding and ultimately process control. The concept of QbD canbe extended to analytical methods. A simple Analytical method was developed and used to identify and quantify simultaneously the three active pharmaceutical ingredients Amlodipine (AML), Hydrochlorothiazide (HCTZ) and Olmesartan medoxomil (OLM)in presence of major degradants, sample matrix and other extraneous peaks from different dissolution medias, namely pH1.2 Hydrochloric acid ,pH 4.5 Acetate buffer and pH 6.8 Phosphate buffer solutionsby reverse phase HPLC method. The identified CQA (Critical quality attributes) are resolution between acetate peak from HCTZ peak, resolution between HCTZ and Olmesartan (Metabolite of Olmesartan medoxomil) and the resolution between OLM and AML which will effects the quality of the product and Analytical method performance. The CPP (critical process parameters) were identified in initial phase of method development and design space developed for the robust method. The optimized methodology was achieved on C18 (typically 75mm length, 4.6mm ID and 3.5μm) column with optimized conditionsof Mobile phase 0.1% Orthophosphoric acid (pH-2.1): Acetonitrile: Methanol (67:28:5 v/v/v).35°C Column temperature, sampling rate 5pts/sec at 230nm. The method was validated for specificity, reproducibility, accuracy, linearity, robustness and solution stability and can be used for the assessment of quality ofdrug product in development and stability samples of Amlodipine, Hydrochlorothiazide and Olmesartan medoxomil film-coated tablets.