Analytical quality by design approach to RP-HPLC method development and validation for simultaneous estimation of esomeprazole and naproxen in modified-release dosage form

Background The present work describes the development and validation of a new, specific, accurate, and precise stability-indicating RP-HPLC method for the simultaneous estimation of Esomeprazole (ESP) and Naproxen (NAP) in modified-release bi-layer tablet dosage form. Analytical Quality by Design concept was implemented through the method development exercise to establish the robustness of the method. Results Method development was performed on C18, 250 × 4.6 mm ID, and 5 µm particle size column with 10 µl injection volume using a photodiode array (PDA) detector to monitor the detection at 280 nm. The mobile phase consisted of the buffer: methanol at a ratio of 50: 50 (v/v), and the flow rate was maintained at 1.5 ml/min, and the column oven temperature was maintained at 30 °C. The retention times for NAP and ESP were found 5.9 ± 0.1 and 8.9 ± 0.1 min, respectively. The method was validated in terms of system suitability, specificity, accuracy, linearity, precision, and solution stability. Linearity was observed over the range of concentration 8–12 µg/ml for ESP and 200–300 µg/ml for NAP, and the correlation coefficient (R2) was found excellent > 0.999. The method was specific to ESP and NAP, and the peak purity was found 99.97% for ESP and 100.00% for NAP. The method was precise and had %RSD less than 2. Recovery study for accuracy with placebo was found in the range of 99.63–100.36% for ESP and 99.91–100.43% for NAP. Conclusion This proposed fast, reliable, cost-effective method can be used as a quality control tool for the simultaneous determination of Esomeprazole and Naproxen in routine laboratory analysis. Graphical Abstract

DoE-Based Analytical Quality Risk Management for Enhanced AQbD Approach to Economical and Eco-Friendly RP-HPLC Method for Synchronous Estimation of Multiple FDC Products of Antihypertensive Drugs

According to the literature review, numerous chromatographic methods have been published for estimation of fixed-dose combination products of telmisartan but no reverse-phase high-pressure liquid chromatographic (RP-HPLC) method has been published yet for synchronous estimation of fixed-dose combination (FDC) products of telmisartan to save time, cost and solvent for analysis. Hence, an economical and eco-friendly RP-HPLC method has been developed for synchronous estimation of multiple FDC products of antihypertensive drugs using the quality risk management (QRM) and DoE-based enhanced analytical quality by design approach. The analytical-QRM was started with the identification of potential method risk parameters followed by their risk assessment by risk priority number ranking and filtering. The identified critical method parameters were optimized using the DoE-based central composite design. The method operable design range was navigated and the control strategy was framed for control and mitigation of risk throughout the life-cycle of the developed method. The method was developed using Shimpack Octadecyl silane (ODS) C18 column and acetonitrile-1.0%v/v triethylamine in water (pH 6.0; 45 + 55, %v/v). The developed method was validated as per the International Council for Harmonization Q2 (R1) guideline. The developed method was applied for the analysis of seven different antihypertensive dosage forms. The developed RP-HPLC method can be used as an eco-friendly, robust and economical alternative analytical tool to several published methods for estimation of FDC products of antihypertensive drugs in the pharmaceutical industry.