STRUCTURE AND THERMAL-STABILITY OF ALPRAZOLAM AND SELECTED SOLVATES

Five forms of the drug alprazolam have been identified by thermal anal ysis and X-ray powder diffraction (XRD), The single crystal X-ray stru ctures of two of these species, a polymorph 1 and a dihydrate 2, were determined. The dihydrate crystallized from a solution of alprazolam i n methanol containing traces of water. Species 3 and 4 are nonstoichio metric solvates with ethanol and acetonitrile, respectively, The diffe rential scanning calorimetric curves for the solvates 2-4 are similar, showing a desolvation endotherm, followed by an exotherm associated w ith recrystallization, and a final endotherm for the fusion of alprazo lam, The solvates 3 and 4 were shown to be isomorphous by XRD, The pro ducts of desolvation of 2-4 were identified by their XRD traces, Solva tes 2 and 3 yield polymorph 1 on desolvation, whereas solvate 4 yields a different polymorph.