Solid solution polymorphs afford two highly soluble co-drug forms of tolbutamide and chlorpropamide

The search for solid solutions of class-two insulin secretagogues, tolbutamide and chlorpropamide, reveals a rare case of monotropic polymorphism for the mixed crystals. At any stoichiometry, two crystal forms are isolated that are kinetically stable at room temperature from a few months to over a year. Dissolution tests certify the solubility advantage of the solid solutions over the pure drugs as well as their physical mixture, suggesting a potential application as a highly soluble co-drug formulation. Tolbutamide and chloropropamide form two co-drug solid solutions that show a rare case of monotropic polymorphism at any composition. Both forms are kinetically stable and with faster dissolution rate than the pure drugs.