David J. W. Grant, Principal Investigator

Effects of Impurities Incorporated During Crystallization on the Crystal Properties ofL
Some Therapeutic Agents; Effects of Salt Form and Crystal Habit on Tableting

  Trace amounts of impurities present in the crystallization medium exert profound effects on the nucleation, growth, morphology, and properties of the crystals obtained. Structurally related impurities may be incorporated into the crystal lattice leading to changes in the crystal properties. These researchers set out to investigate:

1. the effects of a diastereomeric impurity on the crystal properties of a chiral compound;
2. the influence of structurally related impurities on the stability of hydrates and on their solid-state reactivity; and
3. the influence of crystallization conditions on impurity uptake and their subsequent effects on crystal properties of the host.

  The observed effects of incorporated impurities on the properties of the host were related to the molecular interaction in the solid-state between the host molecule and the impurity molecule. The molecular modeling tool was applied in these studies to view the crystal structures and hydrogen bond networks, and to calculate the lattice energy and intermolecular interaction energies.

  A related area of study looked at trace amounts of impurities present in the crystallization medium. These exert profound effects on the nucleation, growth, morphology and properties of the crystals obtained. Structurally related impurities may be incorporated into the crystal lattice leading to changes in the crystal properties.

  Another body of research developed by the researchers involved the effects of salt form and crystal habit on tableting. Tableting is an important yet very complex process in the pharmaceutical field. This project studied the effects of salt form and crystal habit on the tableting properties of some pharmaceutical compounds. The Cerius2 program was employed for analyzing the crystal structure, and for calculating the attachment energy, theoretical powder X-ray diffraction patterns, crystal shape, crystallographic planes, and for identifying the slip planes, an important factor in the control of the mechanical (tableting) properties of powders.

  These researchers also worked with eprosartan mesylate. This is used in the treatment of hypertension, and exists as an anhydrate, monohydrate, and dihydrate. The single crystal structures of the anhydrate and dihydrate were visualized and various interatomic distances and intermolecular energies were then calculated in order to assist in understanding, and ultimately in visualizing, the physicochemical properties and phase transitions of eprosartan mesylate.