Some medications are applied topically for a local skin effect, such as:

  • Topical corticosteroids for eczema or psoriasis, of which approx 2% is absorbed systemically.
  • Topical tretinoin for acne, of which approximately 1 to 2% is absorbed systemically.
  • Topical minoxidil for hair loss, of which approx 1 to 2% is absorbed systemically.

Some medications are applied topically for a regional effect on underlying anatomy, such as:

  • Topical diclofenac (NSAID) for pain relief and anti-inflammatory treatment of muscle strain or arthritis, of which approximately 6% is absorbed systemically.
  • Topical lidocaine for local pain control (the percentage of systemic absorption varies dramatically depending on formulation and application method).

Some medications are applied topically for systemic effects, such as:

  • Topical nicotine patch to aid in smoking cessation.
  • Topical birth control patch (estrogen/progesterone) for contraception.
  • Topical fentanyl patch for pain control in hospice / cancer patients.

The bioavailability of topically applied medications is complex, including pH, hydrophobicity, vehicle (gel vs cream vs injection vs patch), and other drug factors - plus the skin factors at the site applied such as thickness of stratum corneum and blood supply.

But of all these factors, which have the largest effect of increasing bioavailability, ie systemic absorption of a medication?

  • Comments are not for extended discussion; this conversation has been moved to chat.
    – Carey Gregory
    Sep 16 '19 at 14:15
  • 3
    Rewrote for site guidelines as the fundamental question itself has some great points that are useful for students and professionals
    – DoctorWhom
    Sep 18 '19 at 22:32
  • Thanks for the edit. It is an interesting topic. Pretty sure there must have been someone that attempted to do some design of experimetns to try predict the % absorption.
    – Pherdindy
    Sep 20 '19 at 3:52

I would suggest the Noyes-Whitney equation:

dW\dt = DA(C_s - C)\L


  • dW\dt is the rate of dissolution.
  • A is the surface area of the solid.
  • C is the concentration of the solid in the bulk dissolution medium.
  • C_s is the concentration of the solid in the diffusion layer surrounding the solid.
  • D is the diffusion coefficient.
  • L is the diffusion layer thickness.

can easily be adapted into a dermal equation.

(Sourced from Wikipedia)

I would believe that the normal rules of physics for absorption, e.g. water\towel, apply.

Wikipedia also suggests several formula that are applicable to skin only:

Dermally absorbed dose rate = concentration in water x surface area exposed x exposure time x permeability coefficient x conversion factors.

for one.

  • But the question is which of those factors has the greatest effect of increasing absorption?
    – Carey Gregory
    Sep 27 '19 at 4:54
  • Initially I was eyeing something like this formula that can possibly approximate absorption. But perhaps it is still limited due to factors such as using other solvents or drying time among others.
    – Pherdindy
    Sep 28 '19 at 11:35

I don't think that it is possible for anyone "at home" to calculate or otherwise accurately predict the absorption percent and therefore systemic effectiveness or side effect of a topically applied drug from its physio-chemical properties, but it is possible to measure these parameters for every single drug during its development.

Drug and skin factors (roughly from more to less important) that increase systemic drug bioavailability are listed below.


1) Molecular weight

Drugs with molecular weight greater than 400-500 Daltons are hardly absorbed (Experimental Dermatology and here).

Molecular weight of some transdermal drugs (Pharmaceutical Science & Technology Today, 2000, Table 1):

  • Scopolamine: 303
  • Clonidine: 230
  • Glyceryl trinitrate: 227
  • Estradiol: 272
  • Fentanyl: 337
  • Testosterone: 288

The molecular weight of minoxidil is 212 Daltons (Replacement of Renal Function by Dialysis: A textbook of dialysis).

Insulin, for example, has a molecular weight ~6,000 Daltons and is not absorbed through intact skin.

2) Ionization

Non-ionized (pH neutral) drugs are absorbed better than ionized ones.

3) Lipid vs water solubility

Lipid-soluble (lipophilic) drugs tend to be absorbed better than water soluble (hydrophilic) ones (PubMed). Molecules, that are not lipid-soluble (at least a bit), such as water, may not be absorbed in any meaningful amounts, despite their low molecular weight.

Minoxidil... is used orally as a systemic antihypertensive drug with vasodilatory activity. Topically, it is used in cases of androgenetic alopecia and other types of baldness. The ingredient is lipophylic, and the resorption rate is 2–3%. The concentrations in the serum are far below therapeutic levels (to treat hypertension) in adults (ScienceDirect).

4) Vehicle

Drugs that are mainly water-soluble can be absorbed better in water-based vehicles. Occlusive vehicles (that keep the water in the skin) can greatly increase absorption of certain drugs (Inchem).

Lipid-soluble drugs can be absorbed better in lipid vehicles. Lipid solvents (acetone) increase drug permeation after prolonged use (PubMed).

A vehicle can increase the absorption of a drug for at least 6 times (as shown in the table 124.3 in this article.

Oleic acid (a fatty acid) and ethanol in the vehicle can increase the absorption of minoxidil into the skin (not into the blood) by 10 fold (Medicines, 2018).


1) Anatomical site

Dermal absorption rate can greatly depend on the anatomical site - a study with hydrocortisone (mst.dk):

Here the skin on the scrotum had the highest permeability and the increasing rate over the areas was as follows: plantar < palmar < back < scalp < axilla < forehead < scrotum. The penetration rate from the foot to the scrotum varied 42-fold.

2) Skin hydration

Skin hydration through soaking, moisturizing or humidity can increase the absorption of hydrophylic drugs (Molecules).

3) Tape striping

Stripping the uppermost layer of the skin (stratum corneum) by a tape can greatly improve the absorption of some drugs (here).

4) Skin disease

The impairment of stratum corneum in skin diseases, such as eczema and psoriasis, can increase drug absorption (BJD, PubMed).

5) Contact time

One study about minoxidil showed that the absorption percent can increase with the duration of a drug being applied on the skin (J Pharm Sci).

Factors that decease dermal absorption:

  • Binding. Some substances get trapped (to various extents) in the skin due to binding, for example, certain metal ions (Hg2+), quaternary ammonium ions, heterocyclic ammonium ions, sulfonium salts and quinines (Inchem, p.26).
  • Thanks for the answer. It's possible that there is some data with regards to the concentration to absorption of several drugs and can possibly be approximated for a certain set of solutions but that is probably a deep study as well. But interesting if someone found a relationship
    – Pherdindy
    Sep 28 '19 at 11:28
  • @Pherdindy, by concentration, do you mean the concentration of a drug in the actual preparation? The amount of the drug that is absorbed increases with the amount of the drug applied on the skin, but the percent of the drug may actually decrease with the amount applied.
    – Jan
    Sep 28 '19 at 11:34
  • Yes the concentration of the drug in the solution. But thinking about it, most likely it cannot be compared due to difference in drug property such as size which may affect absorption. Instead a relationship with size, mass, or concentration, solvent, and others would be more complete
    – Pherdindy
    Sep 28 '19 at 11:39
  • @Pherdindy, yes, it is a combination of drug properties, which makes it nearly impossible to predict the percent of drug absorption. A small drug particle that should be theoretically well absorbed can "bind" in the skin because of some other property and won't be well absorbed.
    – Jan
    Sep 28 '19 at 11:41
  • Right maybe it would be difficult to predict and that there is no approximation formula if there are too many interactions between factors that make results vary too much
    – Pherdindy
    Sep 28 '19 at 11:46

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