Solubility Determination for Carbamazepine and Saccharin in Methanol/Water Mixed Solvent: Basic Data for Design of Cocrystal Production by Antisolvent Crystallization

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 antisolvent based on phase diagram. The objective of this present study is to obtain the basic data for the design of antisolvent cocrystallization operation. The system of carbamazepine (CBZ) and saccharin (SAC) in methanol/water mixed solvent at 303 K 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 obse...