Development and validation of a RP-UPLC method for the determination of betamethasone dipropionate impurities in topical formulations using a multivariate central composite design.

Abstract

The current study presents a specific, accurate, simple, and rapid UPLC method for the determination of impurities present in cream and ointment formulations of betamethasone dipropionate (BMD). The analytical method was optimized using central composite design (CCD) prior to the method validation. Critical Process Parameters (CPPs) and Critical Quality Attributes (CQAs) were identified for the analytical method. A total of 17 experiments were carried out and verified the individual and interaction effects of CPPs. The CPPs were optimized using a numerical method by keeping the CQAs within the desired range (R1-R2: minimize & R3-R5: maximize) as an optimization goal. Optimized chromatographic separation was achieved using a Waters Acquity UPLC BEH C18, 100 mm × 2.1 mm, 1.7 μm column with a gradient mode of elution comprising 20 mM phosphate buffer: ACN 70 : 30, v/v as mobile phase-A and 20 mM phosphate buffer: ACN 30 : 70, v/v as mobile phase-B. The developed method was validated in accordance with ICH guidelines. The validation data conclude that the developed method is specific, accurate, linear, precise, rugged, and robust for the quantification of impurities in BMD topical formulations.