Skin absorption, also known as dermal absorption or skin permeation, begins at the skin surface and involves passage through the stratum corneum, epidermis, and dermis. The outermost layer—the stratum corneum—forms the primary skin barrier. Its structure and hydration affect skin permeability and systemic absorption. Formulations that respect skin barrier function support healthy dermal delivery without irritation or skin sensitization.

Role of formulation chemistry and formulation type

Cosmetics formulation and pharmaceutical formulation categories—creams, gels, lotions, microencapsulated formulations, and transdermal formulations—affect skin penetration. Formulation type influences steady-state flux, receptor compartment uptake, and diffusion cell performance in franz-type diffusion cells and other diffusion cell methods. Finite dose skin permeation models and cutaneous distribution studies rely on these variables.

Influence of molecular characteristics

Molecular weight and molecular size determine permeation pathways through the stratum corneum. Smaller molecules generally penetrate more easily, impacting skin permeability coefficient and permeability coefficients measured in in vitro dermal absorption studies. Other molecular characteristics, studied via molecular dynamics simulations and attenuated total reflectance fourier-transform infrared spectroscopy (ATR-FTIR spectroscopy), also play roles.

Enhancers, vehicles, and chemical enhancers

Penetration enhancers such as oleic acid, fatty acids, hyaluronic acid, alcohols, glycols, and permeation enhancers help disrupt skin barrier to temporarily increase skin permeation rates. Chemical enhancers and penetrant vehicles modify receptor medium or receptor fluid uptake in franz diffusion cell assays and in vitro models.

Experimental models and assay methods

- Franz diffusion cell and franz-type diffusion cells: gold standard for dermal permeation studies

- In vitro dermal absorption and skin permeation assays using full thickness skin, rat skin, minipig skin, or frozen skin

- 3D skin model, transdermal cell culture, in silico skin penetration models for cutaneous absorption prediction

- Assessment of skin integrity tests to ensure viable barrier prior to testing

- Use of receptor fluid or receptor compartment for accurate permeability coefficients

Regulatory, safety, and analytical considerations

Dermal exposure safety relies on skin absorption rate data and OECD guidelines and criteria. Studies follow OECD guidelines and default dermal absorption values to determine systemic exposure dose or systemic exposure dosage. Skin irritation, skin sensitization, skin metabolism, and cutaneous bioavailability are evaluated through cutaneous administration studies. Methods like raman spectroscopy, ATR‑FTIR spectroscopy, and diffusion cell device monitoring contribute to compliance and safety.

Key factors summary

For any topical formulations or cosmetics formulation, the following influence skin absorption:

- Skin physiology, hydration, skin layers, and skin source site (e.g., face, forearm)

- Formulation chemistry, formulation category, formulation type

- Molecular weight, molecular size, and molecular dynamics

- Penetration enhancers, chemical enhancers, and receptor medium selection

- Experimental model (rat skin, minipig skin, frozen skin, full thickness skin) and assay method (franz diffusion cell, in vitro models)

These parameters determine dermal permeation, steady-state flux, and systemic absorption through the skin barrier. Reliable skin permeability data require proper diffusion cell method, skin permeation assays, receptor fluid, and skin integrity tests. Combining in vitro dermal absorption with in silico skin penetration models ensures comprehensive risk assessment and effective formulation.

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