Thermodynamics Research Center / ThermoML | Journal of Chemical and Engineering Data

ABSTRACT

In the pharmaceutical industry, selection of the crystal form of active pharmaceutical ingredients (APIs) is one of the ways for improvement of drug solubility. Recently, cocrystal form is attracting lots of attention, and production methods for cocrystalline particles are being studied. One of the production methods for cocrystal is solution cocrystallization method with anti-solvent based on phase diagram. The objective of this present study is to obtain the basic data for the design of anti-solvent cocrystallization operation. The system of carbamazepine (CBZ) and saccharin (SAC) in methanol/water mixed solvent at 303K was selected. Equilibrium slurry with various compositions was prepared and analyzed to measure the phase diagram. The compositions of CBZ and SAC were determined by HPLC measurement, and the solvent composition of the equilibrium solutions were determined based on SAC and CBZ composition, and mass balance. By XRD measurement, CBZ III, CBZ dihydrate, SAC and CBZ/SAC cocrystal I were observed as the solid phases co-existing with equilibrium solution. From these measurements, the concentration region in which cocrystal is stable was shown clearly. Therefore, the basic data for operation design of anti-solvent cocrystallization operation was obtained for CBZ/SAC cocrystal in MeOH/water mixed solvent system at 303 K.