A further refinement to the screening process of candidate selection in early drug development is the selection of a polymorphic form on the bases of solid state stability. The Noyes-Whitney titration template method has been used routinely by others to determine the intrinsic solubility of sparingly soluble materials. This method uses potentiometric measurements whilst titrating over a pH range to determine the pH-solubility profile of a drug substance. Using a novel modification to the conventional Noyes-Whitney titration template method, this paper describes an application for the determination of the relative stability between polymorphic forms of materials. Such an assessment can be deduced from the change in Gibbs energy that accompanies the physical changes in materials when going from a solid to a solution phase and will be shown to be derived from the intrinsic solubility measurements. In addition, it will be shown that solution calorimetry was used to good effect to help in the interpretation of the solubility results. Three crystalline polymorphic modifications, a hydrate and two anhydrate forms, and an amorphous form of a pure drug substance currently in development in GSK were ranked in terms of physical stability. Stability measurements were made as a function of temperature and a phase diagram over a narrow temperature range was constructed. (C) 2003 Elsevier B.V. All rights reserved.