Interaction of pharmaceutical hydrates with supercritical CO2

The aim of this work was to study the solubility in supercritical CO₂ of the hydrated phase of three model drugs, namely theophylline, carbamazepine, and diclofenac sodium, in comparison with the respective anhydrous form. Possible solid-state modifications, stemming from the interaction with supercritical CO₂, were investigated by differential scanning calorimetry, thermogravimetric analysis, hot stage microscopy, Fourier Transform infrared spectroscopy and Karl-Fischer titrimetry. It was found that all three pharmaceutical hydrates exhibited higher solubility in supercritical CO₂ than the relevant anhydrous phases. In the case of theophylline monohydrate, the instability of the crystal phase at the experimental temperature adopted has been evidenced. Diclofenac sodium tetrahydrate represents a peculiar case of chemical interaction with the acid supercritical fluid, mediated by crystal water. This revised version was published online in July 2006 with corrections to the Cover Date.