Factors Affecting Drug Penetration through Skin

Dermal penetration, or the absorption of drugs through the skin, is influenced by several factors. These can be grouped into drug-related factors, skin-related factors, and external factors. Here’s a breakdown of these:

1. Drug-Related Factors

Molecular size plays a significant role in drug penetration through the skin, which is primarily composed of the epidermis and dermis. Here are some key points on how size affects this process:

• Molecular Size: Smaller molecules penetrate the skin more easily. Typically, drugs with a molecular weight below 500 Da have better dermal penetration.
  The outermost layer of the skin, the stratum corneum, acts as the primary barrier to drug penetration. It consists of dead skin cells and lipids, creating a lipid-rich environment. Larger molecules struggle to penetrate this barrier due to physical size constraints.
• Lipophilicity (Oil-Water Solubility): The drug’s affinity for lipids or fats significantly influences its ability to penetrate the skin. More lipophilic drugs tend to cross the skin barrier more easily, but excessive lipophilicity can hinder diffusion. Penetration is largely governed by passive diffusion. Smaller, lipophilic (fat-loving) molecules can move through the lipid layers more efficiently. In contrast, larger or hydrophilic (water-loving) molecules may require specific transport mechanisms or formulations to enhance penetration.
• Concentration of the Drug: Higher concentrations provide a stronger driving force for diffusion through the skin.
• Formulation Type: The vehicle (gel, cream, ointment, patch, etc.) can influence the drug’s release and absorption. For instance, occlusive formulations (ointments, patches) may enhance penetration by increasing skin hydration.
• Chemical Enhancement: Some drugs are formulated with penetration enhancers (e.g., alcohols, surfactants, fatty acids) that increase permeability by disrupting the skin barrier.

2. Skin-Related Factors

• Stratum Corneum Integrity: The outermost layer of the skin (stratum corneum) acts as the primary barrier. Any damage or variation in its thickness can affect drug penetration.
• Skin Hydration: Increased hydration enhances penetration by loosening the stratum corneum. Occlusive dressings or humid environments can increase hydration.
• Skin Condition: Diseases or conditions such as eczema, psoriasis, or abrasions can increase permeability.
• Anatomical Site: Skin thickness and permeability vary across the body. Thin areas (e.g., face, scrotum) allow better penetration compared to thicker areas (e.g., palms, soles).
• Skin Age: The permeability of the skin changes with age. Babies and elderly individuals often have higher skin permeability than young adults.

3. External Factors

• Temperature: Elevated skin temperature can increase the rate of drug diffusion.
• Massaging or Rubbing: Application methods that involve massaging can enhance absorption by improving blood circulation and drug diffusion.
• Duration of Contact: Prolonged exposure to the drug (as seen in transdermal patches) increases penetration.
• pH of Formulation: The pH of both the drug formulation and the skin’s environment affects the ionization state of the drug, which in turn affects its absorption.

4. Environmental Factors

• Occlusion: Covering the skin after applying the drug (occlusion) can enhance penetration by increasing skin hydration and local temperature.
• Humidity: High humidity can improve skin hydration and hence penetration.