Which is a strategy to improve solubility for BCS II/IV and its rationale?

• A. Salt formation increases ionization and solubility
• B. Co-solvents decrease solubility
• C. Surfactants worsen wetting
• D. Solid dispersions reduce solubility by crystallization

Answer: (A)

When a drug is poorly soluble, converting it into a salt is a powerful way to boost its solubility and dissolution, especially for drugs that are ionizable. Forming a salt introduces a charged species that is more hydrophilic, so it dissolves in water more readily. For a weak base, adding a strong acid creates a positively charged drug salt; for a weak acid, a strong base forms a negatively charged salt. This shift toward ionization lowers lattice energy in the solid and enhances hydration in solution, so the dissolution rate increases. In the context of BCS II/IV, where solubility limits absorption, salt formation often provides a practical and effective route to raise aqueous solubility and improve overall dissolution.

The other ideas described aren’t consistent with how solubility is typically improved. Co-solvents are used to increase solubility rather than decrease it; surfactants generally enhance wetting and solubility rather than worsen them; solid dispersions are designed to improve, not reduce, solubility by maintaining an amorphous form or better dispersion to reduce crystallization.