Chapter 4 - Salt Screening and Selection: New Challenges and Considerations in the Modern Pharmaceutical Research and Development Paradigm

Abstract

This chapter reviews salt screening and selection strategies, taking into account the new challenges, and considerations of modern drug discovery, and development processes. Solubility prediction may be useful in early drug discovery phases when solubility measurement is not yet possible. The predicted solubility data may provide guidance in screening of computer designed combinatorial libraries and in lead optimization. The solubility of the salt depends largely on the counterion. The hydrophobicity of the counterion and the melting point of the salt both play a significant role in the solubility of the salt form. Since melting point data are difficult to obtain without making the actual salt, predicting salt solubility remains difficult. One way to get a quick assessment of the solubilities of possible salts is to use an in situ screening method. In this method the solubility of a basic drug is determined in the presence of various salt-forming acids. The risks associated with salt and crystal form issues must be assessed as early as possible in the development process, so that the appropriate experiments can be completed in a timely fashion. Various considerations such as physico-chemical properties, biopharmaceutical properties, and the potential for scale-up should be considered as part of the screening and selection process.