Ingredient Library
Skin Penetration
Transdermal Delivery
Not every ingredient reaches where it needs to go.
Molecular size, charge, and formulation all determine whether an active stays on the surface or actually reaches its target. This is the science of how ingredients move through skin.
Key Factors
Molecular weight, lipophilicity, vehicle, pH
Barrier Layer
Stratum corneum
Key Measurement
TEWL & flux rate
Penetration Routes
Transcellular, intercellular, follicular
01 — What Is It
The Skin as a Barrier, Not a Sponge
Human skin is built to keep the outside world out. The outermost layer, the stratum corneum, is not a thin film but a dense, highly ordered barrier designed to resist both water loss and external intrusion.
Structurally, the stratum corneum is 10–20 layers of flattened, dead cells (corneocytes) embedded in a continuous lipid matrix. This is the classic “brick-and-mortar” model: protein-rich corneocytes as the bricks, and ceramides, cholesterol, and fatty acids as the mortar.
Because of this architecture, most molecules applied on the surface simply do not penetrate to a meaningful depth. They may hydrate the outer layers or sit within the lipid phase, but reaching the viable epidermis — let alone the dermis — requires very specific physicochemical properties and formulation support.
Why It Matters
Most actives in a product never reach their target tissue. Penetration isn’t a given — it’s a formulation problem.
02 — Mechanism
Three Routes Through the Barrier
Molecules don’t just soak in — they have to find a way through one of three structural pathways.
Transcellular
Direct passage through corneocytes, requiring a molecule to repeatedly partition into and out of lipid bilayers. This route favours very small, sufficiently lipophilic molecules that can cross both aqueous and lipid domains without becoming trapped.
Intercellular (lamellar)
Movement between cells, through the highly ordered lipid lamellae that fill the spaces around corneocytes. This is the dominant route for most cosmetic actives. Both molecular size and lipophilicity determine how easily a molecule can diffuse through this tightly packed lipid matrix.
Follicular (appendageal)
Penetration via hair follicles, sebaceous glands, and sweat glands. These appendages effectively bypass much of the stratum corneum, creating shunt pathways that can be important for larger molecules, particulate systems, and nanoparticle-based delivery.
Why It Matters
Intercellular is the workhorse route. If your active isn’t lipophilic enough — or too large — it likely stalls here and never reaches the viable epidermis.
03 — Penetration Factors
What Actually Determines Depth
Passive penetration is well described by Fick’s law of diffusion: flux across the membrane depends on the concentration gradient, the partition coefficient between formulation and skin, and the diffusion coefficient within the barrier. In practice, this translates to a small set of tractable formulation levers.
Molecular Weight
A practical “sub-500 Da” rule of thumb: below ~500 daltons, molecules have a reasonable chance of crossing the stratum corneum; above this, they are largely confined to surface or very superficial layers. Hyaluronic acid at ~1 MDa stays on top and hydrates the stratum corneum; glycolic acid at 76 Da penetrates readily.
Lipophilicity (logP)
The stratum corneum is lipid-rich, so an intermediate logP (roughly 1–3) is ideal for transcorneal permeation. Too hydrophilic (logP < 0) and the molecule is repelled by the lipid matrix; too lipophilic (logP > 4) and it partitions strongly into the lipids and may become sequestered there instead of progressing into viable tissue.
Vehicle & Formulation
The carrier can modulate penetration as much as the active itself. Solvents like ethanol increase permeation by disrupting lipid organisation. Classic penetration enhancers (for example, oleic acid, propylene glycol) fluidise or disorder the lipid matrix. Encapsulation systems such as liposomes and niosomes can ferry otherwise poorly penetrating actives into and through the stratum corneum.
pH & Ionisation
Uncharged molecules traverse the lipid matrix far more effectively than their ionised counterparts. Many acids (AHAs, BHAs) are most penetration-active in their undissociated form, which is why formulation pH — and the resulting ionisation state — is critical not only for activity at the receptor but for whether the active reaches that site at all.