A method for the rapid evaluation of the physical stability of pharmaceutical hydrates

The object of this project was to develop a simple kinetic method to rapidly assess the physical stability of pharmaceutical hydrates. Humidity controlled thermogravimetric analysis (TGA) and X-ray powder diffractometry (XRD) were used to study the dehydration of amoxicillin trihydrate. Dehydration resulted in a poorly crystalline phase and could be described by the phase boundary controlled model at all the conditions studied. The relationship between the dehydration rate constant, k, and water vapor pressure, p, was described by the equation: k=k₀×(1-p/p_t), where k₀ is the rate constant when the water vapor pressure is 0 Torr and p_t is the transition water vapor pressure at the temperature studied. When the dehydration rate constant was plotted as a function of water vapor pressure, the intercept on the x-axis was the transition water vapor pressure, p_t. Using this relationship, the transition water vapor pressure of amoxicillin trihydrate was determined to be ~10.5 Torr at 68°C. At water vapor pressures>p_t, the hydrate is the stable phase.