Preparation and physicochemical properties of niclosamide anhydrate and two monohydrates.

The intent of the study was to prepare and characterize three crystal forms of niclosamide namely the anhydrate and the two monohydrates and to investigate the moisture adsorption and desorption behavior of these crystal forms. The crystal forms were prepared by recrystallization and were characterized by differential scanning calorimetry, thermogravimetric analysis, isoperibol solution calorimetry, Karl Fischer titration, and X-ray powder diffractometry. Moisture adsorption by the anhydrate at increased relative humidities and two temperatures, 30 and 40 degrees C, was measured while the desorption from the monohydrates was determined at 45, 55, and 65 degrees C for monohydrate H(A) and 75, 90, and 100 degrees C for monohydrate H(B). Thermal analysis and solution calorimetry showed that monohydrate H(B) is more stable than monohydrate H(A) and solubility measurements showed the solubility of the crystal forms decreased in the order: anhydrate>>monohydrate H(A)>monohydrate H(B). With an increase in temperature and relative humidity niclosamide anhydrate adsorbed moisture to form monohydrate H(A) by a random nucleation process. Dehydration of monohydrate H(A) at increased temperatures followed zero order kinetics and resulted in a change to the anhydrate. Monohydrate H(B) was transformed to the anhydrate at higher temperatures by a three-dimensional diffusion mechanism.