ANALYTICAL QBD APPROACH FIRST ORDER MODEL - ROBUST RP-HPLC METHOD FOR SIMULTANEOUS ASSESSMENT OF ALOGLIPTIN AND METFORMIN

Abstract

Quality by design refers to the achievement of certain predictable quality with desired and predetermined specifications. The objective of this study was to demonstrate an integrated multivariate approach to quantify the constituent concentrations of alogliptin and metformin in combination by simultaneous assessment method using Sigma Tech software with three variables (flow rate, pH of the buffer and % of organic phase) at two levels (first order) and to observe the effectiveness of those variables on response as theoretical plates to optimise the critical method parameters. The method conditions were optimized using a SPOLAR C18 (250 mm × 4.6 mm id, 5 µm particle size) column in an isocratic mode with potassium dihydrogen phosphate buffer, pH 3 and acetonitrile (80:20 % V/V) as mobile phase pumped at a flow rate of 0.5 mL/min and UV detection at 235 nm. The analytical method conditions were verified for robustness and validated as per standard guidelines. The linear regression analysis data for calibration plots showed good linear relationship with r2 =0.999 for both the drugs in the working concentration range of 5-25 µg/mL for alogliptin and 50-250 µg/mL for metformin, with retention times 11.68 and 4.98 min, respectively. The proposed method was applied for quantification of the studied drugs in tablets, spiked human plasma and the results revealed percentage recovery of 99-100 % for both alogliptin and metformin. Moreover, the method was also utilized to study the in vitro dissolution profiles of marketed tablets as per FDA dissolution data base.