Solubility candidate drug salt selection

Furthermore, pharmacokinetic administration, distribution, metabolism and excretion (ADME) factors affect drug bioavailability, efficacy and safety, and, thus, are a vital consideration in the selection process of oral drug candidates in development pipelines. Since solubility, permeability, and the fraction of dose absorbed are fundamental BCS parameters that affect ADME, these BCS parameters should prove useful in drug discovery and development. In particular, the classification can used to make the development process more efficient.For example, in the case of a drug placed in BCS Class II where dissolution is the rate-limiting step to absorption, formulation principles such as polymorph selection, salt selection, complex formation, and particle size reduction (i.e., nanoparticles) could be applied earlier in development to improve bioavailability. 

Salt formation may be key for the efficient purification of ionizable compounds. Various salts can display different solubilities and tendencies to crystallize and might possess physicochemical differences that can be exploited for convenient processing on scale. Salt forms of drug candidates are selected for desired stability, bioavailability, and formulation characteristics (Chapter 12). A few trends for salt selection are shown in Table 11.4. 

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