Dehydration of risedronate hemi-pentahydrate: analytical and physical characterization.

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 degrees 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.

Structural and analytical characterization of three hydrates and an anhydrate form of risedronate.

Four hydration states are reported for Risedronate monosodium. A single-crystal X-ray structure determination is provided as proof of assignment for the monohydrate, hemi-pentahydrate, and variable hydrate forms. The structure provided for the anhydrate form was determined through simulating annealing calculations and subsequent Reitveld refinement of a high-quality X-ray powder diffraction patterns Favorable comparisons of experimentally obtained X-ray powder patterns are made to those generated from the single crystal data. Characteristic infrared, Raman, and NMR spectra are provided and discussed for each form as are thermal analysis profiles. In addition, photomicrographs are provided for each of the forms isolated for this study. The hemi-pentahydrate is demonstrated to be the equilibrium form at room temperature and 37 degrees C, in the presence of water.