Scalable Process Development of Ceritinib: Application of Statistical Design of Experiments

A convenient and commercially viable cost-effective, safe manufacturing process was developed to manufacture ceritinib. This work describes the implementation of the quality by design approach through the identification of critical quality attributes (CQAs), critical material attributes (CMAs), and critical process parameters (CPPs). Application of the statistical design of experimentation for an experimental plan to find the relationship between CQAs, CMAs, and CPPs. This work also describes a superior process for large-scale manufacturing of ceritinib in terms of process safety, handling, scalability, and enhanced throughput. Work captured here addressed the challenges in reported procedures such as sodium hydride’s explosive hazard, high-temperature microwave conditions, nitro to amine reduction under high pressure using a palladium catalyst, and column chromatography to purify the finished product.