Characterization of Polymorphs in Tablets Using Advanced Analytical Techniques

The identification and quantitation of polymorphic forms in drug substance and drug product is critical because different polymorphic forms may affect the bioavailability and stability of the active pharmaceutical ingredient (API). While the identification of polymorphic forms in drug substance is typically required as part of the specifications for a new drug product, identifying and monitoring the polymorphic forms in a drug product is much more technically challenging. There are several reasons why it is difficult, including: 1) at low drug levels, the excipients can mask the signals from the API; 2) detection of low drug levels in API requires long times to achieve sufficient signal to noise ratio (SNR); 3) preparation of standards for calibration of techniques is difficult. In this proposal we will show how multiple analytical techniques can be used to characterize an API and drug product, including solid-state NMR spectroscopy and powder X-ray diffraction. We will then apply these techniques to the characterization of tableted forms of an API.