Gregory A. Stephenson from Eli Lilly & Company, Indianapolis used Accelrys' analytical instrument products to demonstrate that lattice relaxation processes are exothermic and result in increased packing efficiency. Originally performed using the diffraction tools of the Cerius2 environment, this work employed capabilities now available via the Reflex product in Materials Studio.
The figure depicts sample experimental results: the comparison of the X-ray powder diffraction pattern of erythromycin A dihydrate, versus time of exposure to P2O5 .
Desolvates, produced by desolvation of hydrated crystalline pharmaceutical compounds, retain most of the three dimensional order of the solvated lattice. This is demonstrated by similarities in their diffraction patterns before and after desolvation. The desolvated lattice is physically less stable relative to the solvated lattice. If the sample is re-exposed to atmospheric moisture it is extremely hygroscopic, gaining several percent water at rates in excess of one percent per minute. Processing properties, chemical stability, and our ability to develop reproducible analytical methods may be adversely impacted by these properties. If properly characterized, controls on drying and storage processes can ensure that the optimal crystalline form is produced and maintained.
In studying such "isomorphic desolvates" we found that, if the desolvate is maintained in an environment of less than 20% relative humidity, its lattice relaxes with time to a more efficiently packed structure. This gives rise to subtle differences in X-ray powder diffraction patterns. We used the DBWS  Rietveld refinement  program in Cerius2 to calculate changes in the crystal lattice parameters as it contracted. Changes in packing efficiency were readily monitored as a function of time using Cerius2's Connolly surface algorithm . The fractional volume of the unit cell occupied by drug molecules was calculated relative to the unit cell volume computed through Rietveld refinement. We were able to demonstrate that lattice relaxation processes are exothermic and result in increased packing efficiency. We related these changes to the crystallographic packing of the molecular crystals investigated .
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