Application note: Low frequency/THz-Raman®: real-time monitoring of structural forms in pharmaceutical applications

In this application note Ondax discuss how Polymorphism is a major concern in the pharmaceutical industry…

Polymorphism is a major concern in the pharmaceutical industry, since as many as 90% of all active pharmaceutical ingredients (APIs) will exist in more than one structural form, and usually only one specific form is approved by the US Food and Drug Administration (FDA) for use. This is because the structural form will affect multiple properties of the API, including the dissolution rate (and thus bioavailability and dosage), the stability (shelf life and storage conditions), and other key material properties that affect its performance or manufacturing process (e.g. melting point, solubility, density, hardness, etc.).

Furthermore, APIs may spontaneously convert from a metastable or amorphous form, to a more stable, but less soluble crystalline form under different environmental conditions, such as temperature, pressure, atmosphere, light and humidity. Pseudopolymorphism, where different crystal types are obtained through differences in co-solvents or the level of hydration, will also have an impact on both the API and excipients1 contained in the final drug product. Characterising and understanding these form changes is critical not only during the initial drug development, but for determining optimum formulation methods, especially during real-time processing (milling, blending, tableting) of the API.