Use of pharmaceutical salts and cocrystals to address the issue of poor solubility

Salt and cocrystal formation are the most commonly used method of increasing solubility and dissolution rate of pharmaceutical compounds, and are of particular interest for compounds with an intermediate to low aqueous solubility. However, selection of the most appropriate form does not necessarily equate to selection of the salt/cocrystal with the optimal aqueous solubility, but rather a balance between the best solubility and the best physicochemical properties. This review provides a presentation of salt and cocrystal selection, from a high throughput screening perspective and then an assessment of counter ion properties, common ion effects and the potential impact on the biopharmaceutical performance of the compound. In addition, there is a brief discussion of the impact on polymorphism, the potential use of salts and stoichiometric amorphous mixtures to stabilise amorphous forms and other potential issues for consideration from a pharmaceutical development perspective. (c) 2012 Elsevier B.V. All rights reserved.