An X-ray Diffraction (XRD) study is conducted to assess the polymorphic form of the Active Pharmaceutical Ingredient (API). This evaluation is critical because different polymorphic forms of an API possess distinct physicochemical properties, such as solubility, melting point, and bioavailability, which directly impact drug performance.
Characteristic peaks (2-theta values) for known polymorphic forms (e.g., alpha, beta, gamma, Form I, Form II, Form III) are referenced from the API's Drug Master File (DMF), API patent.
The XRD analysis involves examining the API, the placebo, and the final formulation. The placebo is analyzed separately to identify and exclude any interfering peaks originating from excipients.
The percentage intensity of a peak is calculated by dividing the intensity of the main peak by the intensity of the given peak, a value typically available in the XRD analysis sheet.
How to determine if the polymorphic form of an API is changed in formulation due to processing?
The polymorphic form of the API in the formulation is considered unchanged if all characteristic peaks listed in the API's DMF/patents are present in the formulation's diffractogram. A shift of ±0.2 in the 2θ value is considered negligible. Major change in 2 theta value in formulation indicates that the polymorphic form of API is changed in the formulation.
Resource Person: Soham Sheta