Lipophilic dermal solutions

Rapid dermal absorption of trichloroethylene is evident from a study in which peak blood and exhaled air concentrations occurred within 5 minutes after a human subject immersed one hand in a solution of unspecified trichloroethylene concentration for 30 minutes (Sato and Nakajima 1978). Studies on dermal absorption of trichloroethylene in humans, as well as animals, are complicated by the fact that exposure in these studies is usually by direct contact of the skin with the undiluted chemical. Trichloroethylene is a lipophilic solvent that defats the skin and disrupts the stratum comeum, thereby enhancing its own absorption. Thus, the rate of absorption probably increases in a nonlinear fashion with greater epidermal disruption. Although the extent of absorption through the skin may be relatively modest with normal industrial use (Sato and Nakajima 1978 Stewart and Dodd 1964), there is insufficient information to evaluate the effects of chronic, low-level exposure in hiunans, especially when multiple routes may be involved. 

Testosterone (T.) derivatives for clinical use. T. esters for im. depot injection are T. propionate and T. heptanoate (or enanthate). These are given in oily solution by deep intramuscular injection. Upon diffusion of the ester from the depot, esterases quickly split off the acyl residue, to yield free T. With increasing lipophilicity, esters will tend to remain in the depot, and the duration of action therefore lengthens. A T. ester for oral use is the undecanoate. Owing to the fatty acid nature of undecanoic acid, this ester is absorbed into the lymph, enabling it to bypass the liver and enter, via the thoracic duct, the general circulation. 17-0 Methyltestosterone is effective by the oral route due to its increased metabolic stability, but because of the hepatotoxicity of Cl 7-alkylated androgens (cholestasis, tumors) its use should be avoided. Orally active mesterolone is 1 a-methyl-dihydrotestosterone. Trans-dermal delivery systems for T. are also available. 

The stratum corneum basically contains a mixture of cholesterol, free fatty acids, and ceramides, placed in multilayers. They mediate both the epidermal permeability barrier and the transdermal delivery of both lipophilic and hydrophilic molecules. Studies have shown that each of the three key lipid classes is required for normal barrier function (32). These reports also show the potential of certain inhibitors of lipid synthesis to enhance the trans-dermal delivery of drugs like lido-caine or caffeine. Thus, the modulation of stratum corneum lipids is an important determinant of the barrier permeability to both hydrophobic and hydrophilic compounds transport and drug penetration. It has been reported that an inverse correlation exists between solute penetration and stratum corneum lipid content (33). 

Mustard gas is lipophilic and will accumulate in brain and fatty tissue. Mustard gas is soluble in water to less than 0.1% and hydrolyzes in water with a half-life of 3-5 min. It is freely soluble in organic solvents. It has been detected in the blood after dermal or inhalation exposure. Although mustard dissolves slowly in aqueous solution, it must first dissolve in sweat or extracellular fluid to be absorbed. Following dissolution, mustard molecules rapidly rearrange to form extremely reactive cyclic ethylene sulfonium ions that immediately bind to intracellular and extracellular enzymes, proteins, and other cellular components. Mustard binds irreversibly to tissues within several minutes after contact. If decontamination is not done immediately after exposure, injury cannot be prevented. However, later decontamination might prevent a more severe lesion. 

Solutions for dermal use are liquid hydrophilic or lipophilic bases with dissolved active substances and excipients. 

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