Quality‐by‐Design Approach to Stability Indicating Method Development for Linagliptin Drug Product

A traditional approach to method development could fail to meet desired separation during validation, transfer, or out of specification studies. A quality‐by‐design (QbD) approach to method development can potentially lead to a more robust/rugged method due to the emphasis on risk management. In a QbD approach, the impact and interactions between critical method variables are understood using a Design of Experiments (DOE) approach, which incorporates statistical multi‐variate analysis and modeling. This study applied a QbD approach to linagliptin stability indicating method development using Fusion AE automated QbD method development software (S‐Matrix) and an Agilent 1200 Infinity Series Method Development Solution. The allowed deviations of the method variables are determined within the design space – the Proven Acceptable Ranges (PARs). The critical method variables in a linagliptin stability‐indicating method are percent organic 90.5 ± 1.5 and pH 7.7 ± 0.1 at a column temperature of 45 °C. The potential interference of method variables in terms of desirable method responses was determined, leading to a better understanding of the method, and achieving desirable method quality. Quality‐by‐Design Approach to Stability Indicating Method Development for Linagliptin Drug Product