Molecular properties determine the systemic absorption of topical medications
Molecular properties such as size, lipophilicity, and weight directly dictate how effectively topical medications can penetrate the skin barrier and enter systemic circulation.
The retrieved papers consistently support the fundamental pharmacological principle that molecular properties—such as molecular weight (e.g., the 500 Dalton rule), hydrophilicity, and physicochemical structure—determine the penetration and systemic absorption of topically applied medications. None of the papers refute this claim.
Jan D. Bos, Marcus M. H. M. Meinardi. The 500 Dalton rule for the skin penetration of chemical compounds and drugs. 2000. https://doi.org/10.1034/j.1600-0625.2000.009003165.x
The 500 Dalton rule demonstrates how molecular weight and properties restrict skin penetration and absorption of compounds.
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Ing EB, Lim K, Davies NM, Lobenberg R, Harunur Rashid M, Le TS, Rullo J. Topical pyridostigmine for ocular myasthenia gravis: a translational hypothesis.. 2026. https://doi.org/10.51329/mehdiophthal1540
Discusses how the small, hydrophilic molecular properties of pyridostigmine favor specific permeability profiles like conjunctival penetration.
Ahn J, Jin G, Cho M, Do M, Ahn J, Ko J, Bang S. Engineering skin microphysiological systems for transdermal drug screening based on strategic model selection and quantitative prediction roadmaps.. 2026. https://doi.org/10.1016/j.mtbio.2026.103223
Examines physiological determinants and physicochemical properties governing transdermal absorption and transport.
Eltaib L, Alotaibi H, Hamod MA, Alfuraih S, Hamood NA, Balkhair AM, Aljasser AA. Nanotechnologies for Skin Drug Delivery: Polymeric, Bio-Based, and Hybrid Nanocarriers with Clinical and Translational Perspectives.. 2026. https://doi.org/10.3390/ph19071057
Notes that extent of systemic delivery varies widely depending on drug physicochemical properties and molecular weight.
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