The phenomenon whereby a single substance exhibits multiple different crystal structures is known as crystal polymorphism; the structures are known as polymorphic forms. Many active pharmaceutical ingredients (hereinafter referred to as “API”) of pharmaceutical drugs exhibit polymorphism. Differences in crystal type attributable to hydration may sometimes be referred to as pseudopolymorphism. Each crystal form is referred to as a polymorphic form.
In cases in which an API presents multiple polymorphic forms or pseudopolymorphic forms, the forms must be distinguished and controlled during the development and manufacture of pharmaceutical products, due to the potential for different solubilities and absorption rates. APIs can undergo phase transformations to other polymorphic forms or hydration/dehydration due to external factors such as temperature, humidity, pressure, exposure to light or by the addition of additives. This underscores the importance of assessing early in a research project what conditions may prompt phase transformations and which polymorphic forms may result.
Powder X-ray diffraction and differential scanning calorimetry (hereafter abbreviated, respectively, powder XRD and DSC) are fundamental techniques for distinguishing polymorphic forms in APIs. This paper will introduce methods for identifying crystal forms in active pharmaceutical ingredients using powder XRD and DSC, then present a method for examining the polymorphic forms of candidate compounds.