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To reach the site of therapeutic action a drug molecule must possess adequate aqueous solubility to deliver an efficacious dose. This chapter gives an overview of aqueous solubility measures and models pertinent to drug discovery, whilst putting these solubility levels into context. Solubility is inexorably linked to other physicochemical properties of molecules and understanding of how these interrelate leads to an understanding of how solubility can be improved, establishing principles to enable this. Various tactics to implement these principles are exemplified.

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