A Rapid Method for Screening Crystallization Conditions and Phases of an Active Pharmaceutical Ingredient

Here we present a useful methodology for rapid screening of crystallization conditions and phases in the pharmaceutical industry using a multiwell setup with video-microscopy developed in our laboratory. This methodology which detects, from small quantities of an active pharmaceutical ingredient, crystal habit modification, nucleation and phase transition could be used for rapid and reliable screening of crystallization media, particularly for an early stage of pharmaceutical development

Experimental Demonstration of the Carbamazepine Crystallization from Non-photochemical Laser-Induced Nucleation in Acetonitrile and Methanol

International audienceThis paper reports for the first time the crystallization of the carbamazepine (CBZ) molecule in two solvents (methanol and acetonitrile) using the non-photochemical laser-induced nucleation (NPLIN) technique. The metastable zone of CBZ is first determined experimentally for different temperatures in both solvents. Then, the prepared solutions are irradiated by a 532 nm wavelength nanosecond pulsed laser and permitted to obtain CBZ crystals of phases I and III. The impact of laser power and polarization (circularly (CP) and linearly (LP)) on the CBZ crystallization efficiency in both solvents is determined through experiments. According to the results, the crystallization efficiency is significantly higher in methanol than in acetonitrile, and it is higher in solutions irradiated by CP laser than those by LP laser. Moreover, the irradiation of an acetonitrile solution by a LP laser results in CBZ phases I and III, whereas irradiation by the CP laser leads to CBZ phase III crystals. An ab initio determination of the interaction energy of different pairs of CBZ has been carried-out that enables the explanation of the nucleation in acetonitrile for both polarizations. In methanol, only CBZ phase III is obtained, which is in agreement with the ability of methanol to create noncovalent interactions preventing the CBZ phase I and II nucleation