Evaluation of hydrate formation of a pharmaceutical solid by using diffuse reflectance infrared Fourier-transform spectroscopy.

摘要

Ampicilline and nitrofurantoin, in both anhydrous and hydrate forms, were characterized by powder X-ray diffractometry (PXRD), thermogravimetric and differential thermal analyses (TG/DTA) and diffuse reflectance FT-IR spectroscopy (DRIFTS). Of all the analytical tools applied, only DRIFTS was able to indicate the formation of hydrogen bonds between the molecules of the anhydrous drug substance and crystalline water uptaken from atmospheric moisture as evidenced by the significant absorption at 3500-3700cm(-1) corresponding to crystal water. These results suggested that DRIFTS could provide information on hydration without a standard sample and accurately evaluate the physical stability focusing on the qualification of slight hydration in the early stages of pharmaceutical development. In addition, DRIFTS was applied to the besylate salt of pharmaceutical compound A to identify any possible hydration. This salt had the stable form BSA-I, metastable form BSA-II and hydrate form BSA-III. DRIFTS was able to show the hydration of BSA-II even when stored in a capped bottle, eventually leading to the transformation into BSA-III, which was not detected by PXRD. These findings verify the usefulness of DRIFTS for the solid-state characterization of pharmaceutical substances, especially the monitoring of gradual hydration.