Stability candidate drug salt selection

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. 

Additional preformulation and physicochemical characterization of the candidate compound are performed and stress stability studies may be initiated. Ideally, the optimal solid state (polymorphic) and chemical (salt) form of the molecule are identified as part of clinical candidate selection. Selection of the most stable and bioavailable form will expedite subsequent development. The methods for testing the drug substance are refined and additional methods may be developed. 

A variety of factors need to be considered when selecting the optimum chemical form of a new drug candidate. These include all physicochemical properties which would influence physical and chemical stability, processability under manufacturing conditions, dissolution rate, and bioavailability. Such selection of chemical form must be done at the initial stages of development, when material and time are limited. Often the medicinal and process chemists select salt forms based on a practical basis, such as previous experience with the salt type, ease of synthesis, reaction yield, etc. Pharmaceutical considerations such as stability, handleability, hygroscopicity, and suitability for a specific dosage form may be secondary considerations. 

---