Structure and thermal stability of alprazolam and selected solvates
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M R Caira1, B Easter, S Honiball
1Department of Chemistry, University of Cape Town, Western Cape, South Africa.
Abstract:
Five forms of the drug alprazolam have been identified by thermal analysis and X-ray powder diffraction (XRD). The single crystal X-ray structures of two of these species, a polymorph 1 and a dihydrate 2, were determined. The dihydrate crystallized from a solution of alprazolam in methanol containing traces of water. Species 3 and 4 are nonstoichiometric solvates with ethanol and acetonitrile, respectively. The differential scanning calorimetric curves for the solvates 2-4 are similar, showing a desolvation endotherm, followed by an exotherm associated with recrystallization, and a final endotherm for the fusion of alprazolam. The solvates 3 and 4 were shown to be isomorphous by XRD. The products of desolvation of 2-4 were identified by their XRD traces. Solvates 2 and 3 yield polymorph 1 on desolvation, whereas solvate 4 yields a different polymorph.
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