**Core Concept**
The ability of certain substances to penetrate the skin is influenced by various factors, including the size and lipophilicity of the molecule, the integrity of the stratum corneum, and the presence of specific transport mechanisms. Skin penetration is an important consideration in the development of topical pharmaceuticals and cosmetics.

**Why the Correct Answer is Right**
Substances with a high molecular weight, low lipophilicity, or high water solubility tend to have difficulty penetrating the skin. This is because the stratum corneum, the outermost layer of the epidermis, is a lipid-rich barrier that restricts the passage of polar molecules. Certain substances, such as urea and glycerol, are able to penetrate the skin due to their ability to interact with and disrupt the intercellular lipid bilayers of the stratum corneum.

**Why Each Wrong Option is Incorrect**
**Option A:** This option is incorrect because it lists a substance that is known to penetrate the skin, such as lidocaine. Lidocaine is a small, lipophilic molecule that is able to diffuse through the stratum corneum and interact with nerve fibers to produce local anesthesia.
**Option B:** This option is incorrect because it lists a substance that is known to be used in topical formulations, such as hydrocortisone. Hydrocortisone is a small, lipophilic molecule that is able to penetrate the skin and exert its glucocorticoid effects.
**Option C:** This option is incorrect because it lists a substance that is known to be used in topical formulations, such as retinol. Retinol is a small, lipophilic molecule that is able to penetrate the skin and exert its effects on cell differentiation and proliferation.

**Clinical Pearl / High-Yield Fact**
The stratum corneum is the primary barrier to skin penetration, and substances that are able to interact with and disrupt this barrier are often effective in topical formulations. This is why substances like urea and glycerol are often used in combination with other ingredients to enhance skin penetration.

**Correct Answer:** D.