Salt Selection and Optimisation Procedures for Pharmaceutical New Chemical Entities

Selection of an appropriate salt form for a new chemical entity provides the pharmaceutical chemist and formulation scientist with the opportunity to modify the characteristics of the potential drug substance and to permit the development of dosage forms with good bioavailability, stability, manufacturability, and patient compliance. Salts are most commonly employed for modifying aqueous solubility, however the salt form selected will influence a range of other properties such as melting point, hygroscopicity, chemical stability, dissolution rate, solution pH, crystal form, and mechanical properties. Where possible, a range of salts should be prepared for each new substance and their properties compared during a suitable preformulation program. Since it is normally possible to fully develop only one salt form, its properties should be appropriate to the primary route of administration and dosage form. An understanding of the influence of drug and salt properties on the finished product is essential to ensure selection of the best salt. The drug properties required for one dosage form may be quite different from those required for another. A well designed salt selection and optimisation study provides a sound base on which to build a rapid and economic product development programme.