Quantification and Validation of Stability-Indicating RP-HPLC Method for Efavirenz in Bulk and Tablet Dosage Form using Quality by Design (QbD): A Shifting Paradigm.

Abstract

The present study endeavors quality by design (QbD) assisted chromatographic method for the quantification of Efavirenz (ERZ) in bulk and tablet dosage form. Analytical QbD instigated with assignment of analytical target profile (ATP) and critical analytical attributes (CAAs). Risk assessment studies and factor screening studies facilitate to identify the critical method parameters (CMPs). Optimization was performed by employing 32 full factorial design using identified CMPs i.e., flow rate (X1) and pH of buffer (X2) at three different levels and evaluating selected CAAs i.e., retention time (Y1) and peak area (Y2). The individual and interactive influence of CMPs on CAAs were tested by statistical data and response surface plots. Analysis of variance (ANOVA) confirmed that method parameters are significant (P < 0.05). Chromatographic separation was achieved using methanol, 10mM ammonium acetate buffer (70:30v/v), pH adjusted at 3.1 with 0.05% ortho-phosphoric acid as a mobile phase at flow rate 1.0mL/min, and a Nucleosil C18 (4.6mm I.D. × 250mm, 5μm) column with UV detection at 247nm. The method validation and subsequent stresses degradation studies according to ICH guidelines supported the method to be highly efficient for regular drug analysis and its degradation products. The proposed method was successfully demonstrated QbD based approach for the development of highly sensitive, reliable and suitable for routine analysis, and clinical applications.