Solid State Behavior of Impurities during “In-Process” Phase Purity Analysis of an API

Manufacturing a specified polymorphic form of an active pharmaceutical ingredient (API) is of immense importance in the pharmaceutical industry. Crystal polymorphism and transformations among different forms of APIs are studied in detail during process development. While associated impurities in API are characterized in depth for their chemical structures and properties, solid state characteristics of impurities are usually overlooked, mainly because of their presence in low levels. Herein, we discuss a case of a process impurity, BrettPhos oxide (BPO), interfering with in-process phase analysis of an API. The impact of changing the workup procedure on the impurity purging and its effect on solid form analysis of the API is highlighted. Complexities encountered due to interplay between different solid forms of BPO and API are presented. Further, phase behavior of BPO in some common process relevant solvents is established.