Process Development and Optimization of Linagliptin Aided by the Design of Experiments (DoE)

A design of experiments (DoE) approach was applied to the development and optimization of the manufacturing process to prepare linagliptin. DoE techniques such as a central composite face-centered design and a fractional factorial design were applied to obtain the critical process parameters and establish the optimal reaction conditions. With process-related impurities determined and successfully removed, a robust high-yielding and high-purity procedure was identified, which has been successfully demonstrated at a 100 g scale level to prepare the desired product in a 68% overall isolated yield and high-performance liquid chromatography (HPLC) purity of around 99.9%.

Automated summary

A design of experiments approach was used to optimize the manufacturing process of linagliptin. Through determining critical process parameters and optimal reaction conditions, process-related impurities were successfully removed, resulting in a high-yield and high-purity procedure.