Dehydration of Risedronate Hemi-Pentahydrate: Analytical and Physical Characterization

Abstract

Dehydration of hydrates of pharmaceutical active ingredients (pharmaceutical hydrates) may easily occur during storage or manufacturing. Loss of water may have little effect on the crystal lattice, produce less hydrated forms or possibly amorphous forms. Characterizing the effects of water loss on crystal hydrate forms is important for understanding the behavior of pharmaceutical hydrates throughout the manufacturing and storage processes. This study shows that exposure of the hemi-pentahydrate form of risedronate monosodium to gentle heating (60°C) or conditions of low relative humidity (<10% RH) results in the loss of 1 mole of channel-type water. Upon removal of the channel-type water, the crystal lattice adjusts producing a distinct phase characterized by X-ray, thermal, IR, Raman, and NMR data. Adjustment of the crystal lattice appears to compromise crystal integrity and can result in reduced crystallite and particle sizes.