Polymorphs of a compound can have different characteristics from one another and therefore different pharmaceutical applications, safety concerns, and other implications. During pharmaceutical production, it is important to ensure that the intended polymorph form remains consistent to avoid contamination or unwanted effects. Near-infrared spectroscopy (NIR) can be an ideal technique to qualitatively and quantitatively monitor polymorph structures because it is non-destructive and data can be quickly collected with little to no sample preparation. In this study, NIR was used to 1) distinguish between polymorphic forms of crystalline hydrates, 2) quantitatively determine water content in crystalline active pharmaceutical ingredients (API), and 3) differentiate between types of water in a hydrate. Polymorphs of sodium naproxen and Genentech’s GDC-0941 were prepared and characterized with NIR spectroscopy, powder x-ray diffraction (XRPD), Karl Fischer titrations (KF), and mid-IR spectroscopy to determine structure and water content. Using principal component analysis, polymorphs of sodium naproxen and GDC-0941 were differentiated from one another, including two polymorphs of GDC-0941 that could not be distinguished using XRPD or MIR. Partial least squares regression was used to quantitatively determine the water content in the samples. Analysis of the OH combination region of the NIR spectra for polymorphs of a single form with different water content allowed the peaks due to different types of water interactions to be differentiated from one another. It is especially important to distinguish between water interactions in hygroscopic compounds to determine if the polymorph is changing form or simply absorbing water not contributing to the lattice. The results of this study show that NIR spectroscopy can be used as a complementary technique to conventional characterization methods in the pharmaceutical industry.<br/>

Analysis of crystalline hydrates using near-infrared spectroscopy to differentiate between polymorphic structures and quantitatively determine water content

251st National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.