OBJECTIVES: In this study, the advantages and disadvantages of three salt screening methodologies have been explored, and recommendations are put forward as to when each method is most appropriate. METHODS: Three salt screening methodologies have been investigated: the in-situ salt screen, the saturated solution or rational screen approach, and the cooling-evaporative or high-throughput method. Two Active Pharmaceutical Ingredients (APIs) with significant differences in aqueous solubility have been chosen for this study, namely aripiprazole and desvenlafaxine (see Figure 1). KEY FINDINGS: The in-situ salt formation screen appears to be a good method for early stage salt selection based on aqueous solubility, although this approach does not work for all APIs, as demonstrated in the comparison between aripiprazole and desvenlafaxine. The saturated solution method or rational approach demonstrated a valuable overview of the different salts that can be formed in an efficient and cost-effective manner. The cooling-evaporative screening method involved a complete examination of salt formation, including indication of polymorphism of the salts produced. CONCLUSIONS: The three salt formation approaches are methods that deliver crystalline salts. The choice of salt screen approach depends on the physical properties of the drug substance, development stage and objective of the screen.
OBJECTIVES: In this study, the advantages and disadvantages of three salt screening methodologies have been explored, and recommendations are put forward as to when each method is most appropriate. METHODS: Three salt screening methodologies have been investigated: the in-situ salt screen, the saturated solution or rational screen approach, and the cooling-evaporative or high-throughput method. Two Active Pharmaceutical Ingredients (APIs) with significant differences in aqueous solubility have been chosen for this study, namely aripiprazole and desvenlafaxine (see Figure 1). KEY FINDINGS: The in-situ salt formation screen appears to be a good method for early stage salt selection based on aqueous solubility, although this approach does not work for all APIs, as demonstrated in the comparison between aripiprazole and desvenlafaxine. The saturated solution method or rational approach demonstrated a valuable overview of the different salts that can be formed in an efficient and cost-effective manner. The cooling-evaporative screening method involved a complete examination of salt formation, including indication of polymorphism of the salts produced. CONCLUSIONS: The three salt formation approaches are methods that deliver crystalline salts. The choice of salt screen approach depends on the physical properties of the drug substance, development stage and objective of the screen.