Spectroscopic monitoring of carbamazepine crystallization and phase transformation in ethanol-water solution

The crystallization mechanism of anhydrate/hydrate has to be understood in order to control the hydration state of an active pharmaceutical ingredient. In the present work, the formation of the anhydrous (CBZA) and dihydrate (CBZH) form of carbamazepine (CBZ) in ethanol-water solutions was studied by simultaneous monitoring of both the anhydrate/hydrate phase of the crystals and the CBZ concentration in the mother liquor with the Raman immersion probe. Two different cooling strategies and the effect of one surfactant were studied. The information obtained from the Raman spectroscopy indicated that the thermodynamic factor was dominated in determining the anhydrate/hydrate form of the crystals in the studied system. The thermodynamically stable form was obtained in all studied crystallization conditions. The presence of a surfactant additive showed a slight promotion effect only on the phase transformation of CBZA to CBZH. The results obtained in the present work lead to improved understanding of the formation mechanism of anhydrate/hydrate in aqueous solution.