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.
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).
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).
SKIN and OTHER FACTORS
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
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).