Passive Diffusion

Hydrophobic molecules can pass through the lipid bilayers by random molecular motions. The direction of mass transfer of molecules or substances by passive diffusion depends on the concentration gradient on the two sides of the membrane. Lipophilic compounds are generally absorbed by passive diffusion through the

Intestinal Epithelial cell

Intestinal Epithelial cell

Figure 4.1. Drug transport and site of action (See Color Plate I)

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s

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¡1

BLOOD

Cd jp1 !

1 C2j-

Cr

! h !

Figure 4.2. Fick's first law of diffusion intestinal epithelium. The passive diffusion of the molecules is governed by Fick's first law (Lennernas, 1998; Yoon and Burgess, 1998; Chidambaram and Burgess, 2000).

Fick's first law of diffusion (Fig. 4.2)

where J is the flux (amount of material flowing through a unit cross section); M, the drug mass (g, mol); A, the surface area (cm2); t, the time (s); D, the diffusion coefficient (diffusivity, cm2 s ); Ci, the drug concentration at membrane wall in intestinal lumen (mol l-1); C2, the drug concentration at membrane wall in blood side (mol l-1); and h is the membrane thickness (cm).

The assumptions made by this model are the following: (1) steady state flux. The transfer of drugs reaches to steady state very fast and (2) the steady state follows sink conditions: both sides of the membrane are well stirred and homogenous.

Define partition coefficient K as K = Ci/Cd = C2/Cr (Cd as drug concentration in the gastric intestinal (Gi) lumen, and Cr is the drug concentration in the blood), we can get (4.2)

Cd Cr

Define permeability coefficient P as P = DK/h (unit cm s-1), then

Consider the absorptive surface area, we can get the final (4.4)

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