Transdermal transport partition coefficient

Most structure-permeation evaluations of transdermal transport indicate the strong relationship between a chemical s permeability coefficient across the skin (Aip) and its lipophilicity. Potts and Guy analyzed a diverse database of skin penetration data, comprising 91 compounds and developed a simple relation indicating that Kp depended only on lipophilicity, as measured by the chemical s octanol-water partition coefficient (P), and molecular weight (MW) ... 

This hypothesis also explains why low-frequency ultrasound can induce transdermal transport of drugs which exhibit very low passive transport. Drugs possessing low passive permeabilities are either i) hydrophilic, which makes their partitioning into the SC bilayers difficult or ii) large in molecular size (for example, proteins), which reduces their diffusion coefficients in the SC. Low-frequency ultrasound may overcome both of these limitations by providing aqueous transport channels across the skin. Since these channels are filled with saline, hydrophilic drugs can easily partition into the SC. In addition, diffusion of... 

For transdermal drug transport the active substance should have appropriate physico-chemical and pharmacological properties. Although different requirements are described in literature, in general the molecular weight of the active substance should not exceed about 500 Da, the partition coefficient (log P(octanol/water)) should be between 1.0 and 4.0 and the dose should be low (less than 20 mg/day). Recent research focusses on transdermal delivery of active substances that do not meet these requirements, such as relatively large molecules. 

Medicinal products can be applied on the skin to treat local skin diseases (topical application) or to systemically administer an active substance (transdermal application). In the first case, the active substance should accumulate in or even on the skin and display its effect there. When transdermal administration is intended, the active substance should be transported through the skin followed by absorption into the systemic circulation. In the skin the stratum comeum (the most outer layer of 5-50 layers of dead cells, a homed layer of comeocytes, see Fig. 12.1 and Sect. 12.3.1) forms the major barrier for absorption of active substances. The layer is highly lipophilic in nature and is fully impermeable for hydrophilic active substances. Lipophilic active substances, when adequately formulated, may be absorbed via the skin. Typical characteristics which make an active substance suitable for transdermal transport are an octanol-water partition coefficient (expressed as log Pq/w) between 1 and 3 and a molecular mass below 500 Da [10, 11]. Moreover the dose should not exceed 20 mg per day. Hydrophilic active... 

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