Abstract

APPLICATION OF QUALITY BY DESIGN APPROACH FOR DEVELOPMENT AND VALIDATION OF ANALYTICAL RP-HPLC METHOD FOR CELECOXIB IN BULK AND MARKETED FORMULATION

R. S. Kalkotwar and P. S. Vairal*

ABSTRACT

Quality by Design (QbD) is a philosophy that refines the level of knowledge associated with a product that uses process understanding to deliver a product with the desired critical quality attributes. The present study describes the development of a comprehensive science and risk based HPLC method and subsequent validation for the analysis of Celecoxib active pharmaceutical ingredient (API) using a quality by design approach. Optimization was done by response surface methodology, applying a three level Box-Behnken design. Three factors were selected methanol concentration in mobile phase, wavelength and flow rate. The optimized chromatographic method was validated according to the ICH guidelines for linearity, accuracy, limit of detection, limit of quantitation and robustness. The separation was carried on grace C-18 column (4.6×250 mm, 5-μm particle size). Detection was carried out using UV detector at 249nm. The developed method employed mobile phase Methanol adjusted to pH 3 with ortho phosphoric acid and Water in the ratio of 80:20v/v at flow rate 0.8 ml/min and temperature 25°c which was optimized with the help of design expert software. The described method was linear. (r(2)=0.999). The %RSD for accuracy of the method was found to be less than 2%. Peak was obtained at retention time of 5.23min. The proposed method can be successfully used to determine the drug contents of marketed formulation.

Keywords: Quality by design, Design approach, RP-HPLC, Celecoxib.