Use of Humidity Controlled DSC (HC-DSC) as a Technique to Generate Rapid Physical Stability Phase Diagrams of Hydrates

摘要

Humidity controlled differential scanning calorimetry (HC-DSC) has been developedrnwith an overall objective of process control of pharmaceutical hydrates. Saturated salt solutionsrnwith stable water activities over the desired temperature range served as suitablernmicrohygrostats. Dehydration temperatures as a function of water activity were obtained forrncopper sulfate pentahydrate (CuSO_4·5H_2O), the model compound. Slow scanning rates permittedrnassumption of equilibrium conditions, enabling application of a van't Hoff-based theoreticalrnmodel developed earlier. Dehydration onset temperatures were used to generate a stability phaserndiagram, which was verified at ambient temperature. HC-DSC is convenient, rapid and fairlyrnaccurate in generating stability phase diagrams. The technique has been successful inrnconstructing phase diagrams of two pharmaceutical hydrates as well.