Determination of Minor Quantities of Polymorph in Drug Substance: Comparison of Near-Infrared Spectroscopy and X-ray Powder Diffraction

摘要

Different polymorphic forms of an API can have substantially different physical properties, e.g., solubility, stability, and ease of compaction. Polymorphism is a "different crystalline phases of a compound, arising from the possibility of at least two crystalline arrangements of that compound in solid state" [1, 3], and has been treated at length in the literature [1-3]. In particular, Brittain [3] has devoted an entire volume to polymorphism as it applies to Pharmaceuticals, both API and formulations of an API. In course of development, change in polymorphic form may occur as a result of change in synthesis or of crystallization method for API, in stressed-stability of API, or in the processing/stability of formulated API. If a particular property, e.g. solubility, of one polymorphic form is desirable, the ability to isolate, characterize, and quantify it becomes a necessary part of the development process. The present work describes techniques used to determine polymorphic purity of an API in development, and to identify the polymorphic form in formulated drug.