Dissolution Behavior of Solid Drugs. II. Determination of the Transition Temperature of Sulfathiazole Polymorphs by Measuring the Initial Dissolution Rates

Abstract

A new method to determine the polymorphic transition temperature was developed by measuring the initial dissolution rates of polymorphic substances automatically, and was applied to α- and β-forms of sulfathiazole (ST). The transition temperature and the heat of transition between both forms were found to be 102.7° and 1.60 kcal/mole, respectively. It was also confirmed that the dissolution processes for both forms are diffusion controlled. Further, the metastable solubilities of β-crystals were estimated from those of the stable a-form and ratios of dissolution rates of α- and, β-forms at various temperatures. Since practically “stable” β-crystals could successfully obtain after many trials of crystallization, the solubilities of, β-form were also directly measured by solubility equilibrium method. By comparing the solubility data obtained by dissolution rates and solubility equilibrium method, a good agreement was obtained. In addition, thermal methods such as differential thermal analysis and differencial scanning calorimetry will not give accurate transition temperature, because the transition is always suspended by molecular hysteresis. However, the present method will give more correct value, since it utilizes the phenomenon of the delayed transition of the metastable crystals itself. Thus, it will be adopted generally as an universal and less time-consuming one and be applicable even for the determination of the imaginary transition temperature between monotropic polymorphs of organic substances which can not be determined practically by other methods.