Inclusion compounds with the drug 5-Methoxysulphadiazine: Structures,thermodynamics of decomposition and relationship to polymorphism of the sulphonamide

Abstract

The structures and thermal decompositions of the solvates of 5-methoxysulphadiazine with dioxane, chloroform and tetrahydrofuran have been investigated by X-ray analysis, differential scanning calorimetry and thermogravimetry. These species are clathrates with 1:1 host-guest stoichiometry crystallizing in space group P2₁/c with very similar unit cell parameters. Their structures are based on a common isostructural host framework in which the guest molecules occupy channels with the narrowest constriction being 2 Å. The unusual stability of these species and their decomposition to a common polymorph (Form I) of 5-methoxysulphadiazine are rationalized on the basis of crystal packing analysis, potential energy calculations and estimates of the activation energy for desolvation. Hydrogen bonding patterns between host molecules in the clathrates are compared with those occurring in two polymorphic forms of the parent sulphonamide.