Zoya Formulates · Science Concepts
Skin Penetration
Not every ingredient reaches where it needs to go. Molecular size, solubility, and formulation all determine how deep an active actually works — and whether it works at all.
The Skin Barrier
What the Skin Is Actually Protecting Against
The stratum corneum is the outermost barrier layer of the skin. It follows a “brick and mortar” structure: flattened, dead keratinocytes called corneocytes are packed like bricks, while a lipid matrix of ceramides, fatty acids, and cholesterol forms the mortar that seals everything together. This structure is intentionally tough and tightly packed to minimise water loss and keep external substances out.
Because of this design, skin penetration is difficult by default. The skin’s primary job is to act as a barrier, not a doorway — it is built to keep microorganisms, pollutants, and most chemicals out. For an active ingredient to reach its target, it has to be small enough, appropriately soluble, and carried in a formula that helps it navigate this barrier without damaging it.
Routes of Entry
How Ingredients Actually Enter the Skin
Transcellular
Through the Cells
In the transcellular route, ingredients pass directly through corneocytes themselves. Because these cells are packed with keratin and low in water, only very small, water-soluble molecules can move efficiently through this pathway.
Intercellular
Between the Cells
The most common route is intercellular: ingredients travel through the lipid-rich channels that weave between corneocytes. Lipophilic (oil-loving) molecules are especially suited to this path, because they can dissolve into and move along the lipid matrix.
Appendageal
Via Hair Follicles & Pores
In the appendageal route, ingredients enter through hair follicles, sebaceous glands, and sweat ducts, partially bypassing the stratum corneum. Oil-soluble ingredients such as beta hydroxy acids (BHAs) can accumulate in these structures, making them especially effective at targeting clogged pores.
Formulation Route
What the Formula Does
Formulas can actively influence which route ingredients take and how far they go. Penetration enhancers such as propylene glycol, ethanol, and oleic acid can temporarily disrupt the lipid matrix and widen the channels between cells. Used carefully, they help actives move through the barrier more efficiently without permanently damaging it.
Molecular Size
Why Size Matters
One of the most useful rules of thumb in dermal delivery is the 500 Dalton rule: molecules larger than roughly 500 Daltons (Da) generally cannot penetrate intact skin in meaningful amounts. The tight packing of the stratum corneum’s lipid matrix simply does not allow bulky structures to slip through.
This explains why classic high molecular weight hyaluronic acid (often 1,000,000+ Da) mostly remains on the surface, where it hydrates and plumps by holding water, while much smaller acids like glycolic acid (~76 Da) can travel deeper into the epidermis. Formulators can use different molecular weights of the same ingredient to target different layers of the skin.
| Ingredient | Molecular Weight | Penetration Depth |
|---|---|---|
| Glycolic acid | ~76 Da | Deep (epidermis/dermis) |
| Salicylic acid | ~138 Da | Pore lining |
| Retinol | ~286 Da | Epidermis |
| Lactic acid | ~90 Da | Surface–epidermis |
| Niacinamide | ~122 Da | Epidermis |
| Hyaluronic acid (high MW) | ~1,000,000 Da | Surface only |
| Hyaluronic acid (low MW) | ~5,000–50,000 Da | Upper epidermis |
pH & Ionisation
How pH Affects Whether an Ingredient Can Penetrate
Many skincare acids — including alpha hydroxy acids (AHAs) and beta hydroxy acids (BHAs) — can exist in two forms depending on pH: an ionised form (charged, more water-loving) and an unionised form (uncharged, more oil-compatible). The lipid matrix of the stratum corneum resists charged molecules, so the ionised form has difficulty crossing it.
At lower pH, a larger fraction of an acid is in its unionised state. This uncharged form can partition more easily into the lipid channels and travel through the barrier. That is why effective AHA exfoliants are typically formulated at pH 3–4: low enough to maintain a meaningful proportion of unionised acid, but not so low as to cause unnecessary irritation for most users.
💡 This is why the same ingredient at a higher pH can feel gentler but also deliver less. pH isn’t just about safety — it directly controls how much of the active actually gets in.
Solubility
Oil-Loving vs Water-Loving Ingredients
Another key property for skin penetration is lipophilicity versus hydrophilicity — how much an ingredient prefers oil over water. This is often expressed as log P (the partition coefficient). A high log P value means the molecule is lipophilic and readily dissolves in oils and lipids; a low log P indicates a more hydrophilic, water-loving character.
Because the stratum corneum’s intercellular spaces are rich in lipids, lipophilic ingredients can move through them more easily. However, once inside the skin, there are more aqueous (water-based) environments. The ideal penetrating molecule therefore has a balance: it is lipophilic enough to cross the barrier, but still sufficiently water-soluble to diffuse through deeper layers.
Retinol is a good example of a lipophilic active that partitions well into the lipid matrix and can reach its receptors in the epidermis. Glycolic acid, in contrast, is strongly hydrophilic — but its very small size compensates, allowing it to penetrate effectively despite its water-loving nature.
Formulation
How the Formula Changes What Gets In
Step 1
Vehicle matters
Creams, serums, and oils deliver ingredients differently. Water-rich serums are well suited to small, water-soluble actives, while oil-based formulas are better carriers for lipophilic ingredients. Emulsions can combine both, helping to transport actives with mixed solubility.
Step 2
Penetration enhancers
Ingredients like ethanol, propylene glycol, and oleic acid can temporarily disrupt the lipid matrix, increasing fluidity and widening the spaces between corneocytes. In controlled amounts, they boost delivery of actives that would otherwise struggle to cross the barrier.
Step 3
Concentration and gradient
Diffusion is driven by a concentration gradient: the higher the concentration of an ingredient on the skin surface compared with inside the skin, the stronger the driving force for it to move inward. Within safe limits, higher concentrations can therefore increase penetration and overall delivery.
Step 4
Occlusion and hydration
Occlusive products or film-forming agents seal the skin, increasing hydration in the stratum corneum. Hydrated corneocytes swell slightly, which can loosen the packing of the lipid matrix and make the barrier more permeable. Applying actives under an occlusive moisturiser can therefore enhance how much reaches its target.
Key Takeaways
The main ideas, in one place.
- The stratum corneum is designed to keep things out — penetration requires the ingredient and formula to work together.
- Most ingredients enter via the intercellular route, moving through the lipid-rich channels between dead skin cells.
- Molecules above ~500 Da generally can’t penetrate intact skin — which is why high-molecular-weight hyaluronic acid stays on the surface.
- Lower pH increases the unionised fraction of acidic actives, directly boosting how much penetrates.
- Lipophilic ingredients move through lipid channels easily; hydrophilic ingredients need to be small to compensate.
- Formulation choices — vehicle, penetration enhancers, concentration, and occlusion — can significantly change how much of an active reaches its target.