Quantitation of a polymorphic mixture of an active pharmaceutical ingredient with solid state 13C CPMAS NMR spectroscopy

Active pharmaceutical ingredients (API) often crystallise in several forms with significant differences in their physical properties. In pharmaceutical applications it is very important to be able to identify these polymorphs during drug manufacturing and storaging, also quantitative information about polymorphs is often required. Solid state 13C cross-polarisation (CP), magic angle spinning (MAS), nuclear magnetic resonance (NMR) spectroscopy was utilised in studying polymorphisity of an API with two polymorphic forms. Quantitative information was obtained from polymorphic mixtures, and a formulated product was also studied in order to determine the possibility of distinguishing between the two polymorphs in a low-dose formulation. Quantitative data was obtained using two methods: integration of signals from the dipolar dephased spectra, and a chemometric method known as Direct Exponential Curve Resolution Algorithm (DECRA). We concluded that the two polymorphs are easily identifiable based on their spectral differences. Quantitative results showed reasonable accuracy, and while identification of the polymorph present in formulation was not possible, traces of the API are detectable in as low dosage as 0.7% by weight using solid state NMR methods.