Effect of Water Activity on the Transformation between Hydrate and Anhydrate of Carbamazepine

Abstract

Pharmaceutical hydrates have substantial impact on the bioavailability of drugs, and controlling the formation of hydrates is of significant importance in the pharmaceutical crystallization and formulation processes. The relative stability of carbamazepine anhydrate (CBZA) and dihydrate (CBZD) at room temperature was investigated by using slurry experiments. Optical microscopy, powder X-ray diffraction, Karl Fischer titration, thermogravimetric analysis, and differential scanning calorimetry were used to characterize CBZA and CBZD. The results of slurry experiments showed that the water content at equilibrium plays a vital role in determining the relative stability of CBZA and CBZD. At 20 °C, CBZD is more stable than CBZA when the water content of the solvent mixture in equilibrium (Cwe) is higher than 19.6%, and vice versa. It was also found that CBZD and CBZA can coexist in equilibrium when Cwe is equal to 19.6% or water activity of 0.636 at 20 °C. The three-component phase diagram was established for b...