Thermal Dehydration of Nafagrel Hydrochloride Hydrate at Controlled Water Vapor Partial Pressures.

Nafagrel hydrochloride exists as both a hemihydrate and monohydrate. Conversion from the hemihydrate to the monohydrate is not reversible, and both hydrates can coexist in stable equilibrium between 23% relative humidity (RH) and 64% RH. In order to clarify the dehydration behavior, the kinetics of the thermal dehydration of the hydrates was studied by means of isothermal gravimetry at atmospheric pressure with a controlled water vapor pressure. This revealed that dehydration did not depend on absolute humidity but on RH. The dehydration of the hemihydrate proceeded by two-dimensional gorwth of the nuclei, A2, but the mechanism of monohydrate dehydration changed from A2 to a two-dimensional phase boundary, R2, with an increase in RH. The dehydration of the monohydrate proceeded by R2, resulting in the production of the hemihydrate at 6.5% RH or above. These kinetic analyses showed that the monohydrate dehydrated faster than the hemihydrate.