Identification of Drug Polymorphs in Tablets

Polymorphs of an Active Pharmaceutical Ingredient (API) can have different chemical and physical properties and, thus, a direct impact on the processability of the drug substance and the quality/performance of the drug product, such as stability, dissolution, and bioavailability. Therefore, identification of the crystal phase of an API is of outmost importance. In this work methodologies were developed based on X-ray powder diffraction and IR for the identification of the crystal phase of two APIs (Atorvastatin Calcium and Donepezil HCl) in commercial tablets. INTRODUCTION Polymorphs of an Active Pharmaceutical Ingredient (API) can have different chemical and physical properties and, thus, a direct impact on the processability of the drug substance and the quality/performance of the drug product, such as stability, dissolution, and bioavailability. One polymorph may convert to another during manufacturing and storage, particularly. Therefore, identification of the crystal phase of an API is of outmost importance. Numerous physicochemical measurements and techniques are commonly used to characterize polymorphs, including: melting point, IR, X-ray powder diffraction (XRPD), thermal analysis procedures, Raman spectroscopy, optical microscopy, and NMR. Of them it is mostly Raman spectroscopy and XRPD that have been used for rapid screening of crystal phases. Despite the availability of these techniques polymorph identification in tablets or granules is often very difficult due to: a) the small strength of API in formulation, b) the numerous crystal phases for some APIs and the, as expected, similarity of the respective spectral information and c) the availability in literature of the XRPD patterns only, while information from the other commonly used techniques e.g. IR and Raman spectroscopy are often missing. On the other hand, preparation of polymorphs based on the information mentioned in patents is rarely possible while their acquisition is also difficult and thus the missing spectral information cannot be obtained.