Abstract

Analytical Quality by Design (AQbD) Approach in RP-HPLC Method Development for the Assay of Etofenamate in Dosage Forms by Central Composite Deign (CCD)

Ramalingam Peraman, Assistant Professor , Gulf Medical University

By considering the current regulatory requirement for an analytical method development, a reversed phase high performance liquid chromatographic method (RP-HPLC) for routine analysis of etofenamate (ETF) in dosage form has been optimized from method operable design region (MODR) using analytical quality by design (AQbD) approach. Unlike routine approach, the present study was initiated with understanding of method performance on quality target product profile (QTPP), Analytical target profile (ATP) and various critical parameters related to the improvement of chromatographic performance using fewer experiments, without additional cost for column and other reagents. Sigma Tech software was used to obtain polynomial process model as a predictive solution for retention time (Y). The statistical analysis model revealed that two factor interactions were quite significant and hence central composite design (CCD) was used. The non-linear process model was used to construct contour diagrams, two dimensional response surface plots. Optimum values for critical parameters (pH (X1), % aqueous in mobile phase composition (X2) and flow rate (X3)) were obtained through contour diagrams for the targeted values of retention time. The predicted data from contour diagram for retention time were verified actually and it satisfied with actual experimental data. A LC system equipped with a C18 column (250mm × 4.6mm, 5µ), a binary pump and photodiode array detector were used in this work. The optimized method was achieved at 1.2 mL/min flow rate using mobile phase composition of methanol and 0.2 % triethylamine in water at 85:15, % v/v, pH adjusted to 6.5. The method was validated and verified for robustness and system suitability during method transfer and also compared with routine reported method.