What features of lidocaine's structure allow it to penetrate the stratum corneum?

• A. Hydrophobic features only
• B. Hydrophilic features only
• C. Hydrophilic and lipophilic features
• D. Large molecular weight

Answer: (C)

The ability to penetrate the stratum corneum relies on a molecule being amphiphilic—able to interact with both the lipid-rich barrier and the aqueous environments beneath it. Lidocaine has this balance: a lipophilic aromatic portion that partitions into the lipid matrix of the stratum corneum, and polar amide/tertiary amine groups that provide hydrophilicity and allow diffusion through the aqueous regions. Because lidocaine is a weak base with a pKa around 7.9, a fraction is uncharged at skin pH, which enhances its ability to cross the barrier. Purely hydrophobic only would struggle to move through aqueous pathways, while purely hydrophilic would not readily partition into the lipid barrier; lidocaine combines both features, making penetration efficient. Its molecular weight is reasonable for diffusion, unlike a large molecule that would hinder entry.