Hydrophilic drugs passive diffusion

For most topically applied drugs, passive diffusion along the concentration gradient, either transcellularly or paracellularly, is the main permeation mechanism across the cornea. Occasionally, a carrier-mediated active transport mechanism is indicated (Liaw et al. 1992). Lipophilic drugs tend to favour the transcellular route, whereas hydrophilic drugs usually permeate via the paracellular route through intercellular spaces (Borchardt 1990). 

The outer membrane of gram-negative bacteria is a permeability barrier that allows the passive diffusion of small hydrophilic antibiotics only through aqueous channels, the porins. Drugs larger than 800 Da are... 

Computational models for blood-brain-barrier penetration have been well reviewed in detail by Clark [36]. Penetration of the blood-brain-barrier (BBB) via passive diffusion is dependent upon the hydrophilicity and lipophilicity of a molecule. However, the BBB is a thicker, more lipophilic membrane than the intestinal membrane. Kelder et al. [37] showed that very few of 776 orally administered CNS drugs had PSA >90, while a substantial fraction of 1590 orally administered non-CNS had PSA >90. These results demonstrate the poor BBB penetration by hydrophilic molecules. 

Ester prodrugs are employed to enhance membrane permeation and transepithelial transport of hydrophilic drugs by increasing the lipophilicity of the parent compound, resulting in enhanced transmembrane transport by passive diffusion. For example, pivampicillin, a pival-oyloxymethyl ester of ampicillin, is more lipophilic than its parent ampicillin and has demonstrated increased membrane permeation and transepithelial transport in in vivo studies.103... 

Absorption barriers are related to the permeability of drug molecules across the gastrointestinal membrane including the colonic membrane. There are two distinct mechanisms for molecules to cross the membrane via paracellular transport and transcellular transport (Fig. 5). Para-cellular transport involves only passive diffusion where the molecules pass through the tight junctions between the epithelial cells. In contrast, transcellular transport can occur by passive diffusion as well as by active transport, or endocytosis. In general, the hydrophilic molecules diffuse predominantly through the paracellular route, whereas the lipophilic... 

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... 

Most body tissues are protected by lipophilic barriers that serve as the body s primary protection against absorption of chemicals. It is well established that lipophilic chemicals can penetrate lipophilic barriers (including mucous membranes) much more readily than can hydrophilic chemicals by passively diffusing across lipid-rich cell membranes. 2 4l The lipid-rich mucous membranes also serve as barriers to the absorption of hydrophilic species. Lipophilic chemicals, however, promote the permeation of hydrophilic chemicals that are dissolved in the lipophiles. Lipophiles are routinely used, for example, in drug delivery systems (see Section 3.3). 

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