Which form of a drug is water soluble?

• A. Ionized
• B. Unionized
• C. Both
• D. Neither

Answer: (A)

Water solubility is greatly enhanced when a drug carries a charge. The ionized form has a net positive or negative charge, which enables strong interactions with water molecules through ion-dipole forces, making it much more soluble in aqueous environments like GI fluids. The unionized form is neutral and typically less polar, so it interacts less with water and tends to be more lipophilic, leading to poorer water solubility. In practice, forming salts often converts a drug to its ionized form to improve dissolution in water. Keep in mind that while the ionized form dissolves well in water, it may cross membranes less easily due to lower lipophilicity, whereas the unionized form can permeate membranes more readily.