Quality risk assessment and DoE-based analytical quality by design approach to stability-indicating assay method for acidic degradation kinetic study of apremilast

Abstract

Quality risk assessment and design of experiment (DoE)-based quality by design (QbD) approach has been applied for the development of a stability-indicating assay method for acidic degradation kinetic study of apremilast. Quality risk assessment started with the identification of risk factors for method development by preliminary experimentation, prior knowledge of chromatography, and brainstorming process. The identified risk factors were properly categorized and listed in fishbone diagram. Risk assessment was done by allotment of risk priority number (RPN) score to each risk factor based on preliminary experimentation. From the assessment of risk factors, the identified risk factors were checked for their main effects on resolution and tailing factors by Taguchi design. Critically identified risk factors were studied for effect on critical quality attributes by DoE-based Box–Behnken design. Method operable design region (MODR) was navigated for optimization if risk factors and control strategy were set for desired output. The separation was performed using toluene–ethyl acetate–methanol (7:1:2, v/v) on aluminum plate pre-coated with silica gel G F254. The method was validated as per the International Conference on Harmonization (ICH) Q2R1 guideline. The developed method was applied for forced degradation and acidic degradation kinetic study at different stress conditions. The degradation kinetics was found to follow the first order.