Optimizing the choice of polymorphs of an active pharmaceutical ingredient (API) has become a significant step in the drug development process. High-throughput combinatorial techniques have been developed to reduce the time required to identify and select the best form of an API. A very important part of the high-throughput crystallization (HTC) workflow is reliable integration of information produced by various analytical instruments and easy access to the information by multiple scientists. Raman spectroscopy has become one of the key analytic techniques used to differentiate between the polymorphs and salts of the API. A Raman microscope has been integrated into an HTC workflow analyzing samples in a 96-well microtiter plate. The control software on the Raman instrument has been modified to open a text file prepared by the HTC software suite to initiate semiautomated analysis of the samples in a specified well plate. All of the data acquisition and spectral analysis is performed by the Raman instrument including various chemometric techniques for classifying and clustering the samples based on their Raman spectra. The final analytical results and spectra are then formatted and saved for easy entry into the central database (SQL LIMS). An HTC software suite has been developed in-house for the HTC laboratory, which includes routines for display and manipulation of the combined information.
