Passive diffusion gastrointestinal membrane

Chemicals have to pass through either the skin or mucous membranes lining the respiratory airways and gastrointestinal tract to enter the circulation and reach their site of action. This process is called absorption. Different mechanisms of entry into the body also greatly affect the absorption of a compound. Passive diffusion is the most important transfer mechanism. According to Pick s law, diffusion velocity v depends on the diffusion constant (D), the surface area of the membrane (A), concentration difference across the membrane (Ac), and thickness of the membrane (L)... 

Absorption of some highly ionized compounds (e.g., sulfonic acids and quaternary ammonium compounds) from the gastrointestinal tract cannot be explained in terms of the transport mechanisms discussed earUer. These compounds are known to penetrate the Upid membrane despite their low Upid-water partition coefficients. It is postulated that these highly lipophobic drugs combine reversibly with such endogenous compounds as mucin in the gastrointestinal lumen, forming neutral ion pair complexes it is this neutral complex that penetrates the Upid membrane by passive diffusion. 

Most substances that can be absorbed enter cells by passive diffusion, but the extent to which a substance is or can be absorbed from the skin, gastrointestinal tract, or lung is not necessarily uniform among these sites and, in fact, may vary substantially. Typically for a substance well absorbed from one site, less is absorbed (if absorbed at all) from one or both of the other possible sites of exposure. For example, a substance may be completely absorbed from the gastrointestinal tract, moderately absorbed from the lung, and poorly absorbed from the skin. On the other hand, there are some substances are well absorbed from each of the sites of exposure, and others are poorly absorbed from each site. Whether a given substance can be absorbed depends on its physicochemical properties, their effect on the substance s ability to cross cellular membranes, and the site s anatomical and physiological characteristics. 

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... 

Facilitated diffusion is very similar to passive diffusion with the difference that transfer across membranes is assisted by the participation of carrier proteins embedded in the membrane bilayer. Again, the direction of passage will be from the side of the membrane with high concentration of a chemical to the side with low concentration this also occurs without energy expenditure by the cell. Such a process is somewhat specific in the sense that it applies to molecules that are able to bind to a carrier protein. Absorption of nutrients such as glucose and amino acids across the epithelial membrane of the gastrointestinal tract occurs by facilitated diffusion. Since a finite number of carriers are available for transport, the process is saturable at high concentrations of the transported molecules and competition for transport may occur between molecules of similar structure. 

Similar to the solid dosage forms containing chiral excipients, biological membranes may provide chiral environments (see Chapter 3). Most drugs cross the gastrointestinal membrane through simple passive diffusion thus, no stereoselectivity in the process is expected. It appears. 

Because there were no pubUshed reports of the local effects of vitamin E on the periarticular tissue, it is necessary to determine local toxicity using animal studies. Tocopherols that are orally from food or supplements are transported across the gastrointestinal membrane by passive diffusion after solubilization by mixing with chyme and bile salts in the stomach and small intestine [8]. Tocopherols are then incorporated in chylomicrons, which are taken up by the liver. After secretion from the liver, low density lipoproteins (LDLs) and high density lipoproteins (HDLs) are the major carriers of tocopherols in humans [101]. 

Only the more lipid-soluble un-ionised form of the drug traverses biological membranes by passive diffusion. A log P value of about 2 appears to be optimal for gastrointestinal absorption if dissolution phenomena are not rate-limiting. 

Two distinguishing features of gastrointestinal active and facilitated transport processes are that they are capacity-limited and inhibitable. Passive transcellular solute flux is proportional to mucosal solute concentration (C), where the proportionality constant is the ratio of the product of membrane diffusion coefficient (Dm) and distribution coefficient (Kd) to the length of the transcellular pathway (Lm). 

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