Passive diffusion of drugs occurs in what layer of the skin?

• A. Dermis
• B. Epidermis
• C. Hypodermis
• D. Stratum corneum

Answer: (D)

The main factor governing passive diffusion across the skin is the stratum corneum, the outermost layer of the epidermis. This layer is composed of dead keratin-filled cells (corneocytes) embedded in a dense, lipid-rich matrix, forming the primary barrier to permeation. For a drug to diffuse passively, it must partition into and navigate through this lipid barrier, which is why molecules with appropriate lipophilicity and small size penetrate most readily.

Beneath the stratum corneum lie the viable epidermis and dermis, which are more aqueous and vascularized. While drugs can move into these layers after crossing the stratum corneum, they are not the principal barrier; the diffusion rate is typically limited at the stratum corneum. The hypodermis (subcutaneous tissue) is largely adipose tissue and does not determine the diffusion barrier.

So, passive diffusion primarily occurs through the stratum corneum.