DoE based failure mode effect analysis (FMEA) to development of stability indicating HPTLC method for estimation of apremilast

Abstract

DoE based failure mode effect analysis has been performed for implementation of analytical quality by design approach in development of stability indicating assay method for estimation of apremilast. Failure modes were identified, categorized and listed in Ishikawa diagram on bases of preliminary experimentation and sound science of chromatography. Identified failure modes were analysed by allotting risk priority number according to their effect, severity and detectibility during preliminary experimentation. Seven failure modes were found high RPN scores were screened for their main effect on critical quality attributes by Taguchi OA design. Critical method variables volume of methanol, saturation time and migration distance were further taken to Box–Behnken design to establish relationship between critical method variables and resolution. After response surface methodology method operable design space was obtained by optimization of model and control strategy was developed. The chromatographic separation was performed using aluminium backed pre-coated with silica gel 60F254 as stationary phase and toluene:methanol:ethyl acetate (7:2:1% v/v/v) as mobile phase at wavelength of 241 nm. The method was validated as per ICH Q2(R1) guideline. Developed method was applied for assay of Apremilast in its tablet dosage form and results were found in good agreement with labeled claim.