UWL on Permeability

In in vitro permeability studies conducted in static systems, the UWL adjacent to the membrane can be up to 1500-4000 j,m thick, whereas in vivo the UWL is only 30-300 j,m in the GI tract and is negligible for the BBB [71]. The experimental system is often stirred or shaken to minimize the effects of the UWL. An orbital shaker is often not effective and can be modified by adding beads to enhance the agitation. Recently, it has been clearly demonstrated that the quantitative structure activity relationship was interfered if the UWL limited 

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The UWL permeability is nearly the same for drugs of comparable size, and is characterized by the water diffusivity (Daq) of the drug divided by twice the thickness of the layer (ftaq), Pu = Aiq / (2 h.Aq), in a symmetric permeation cell [40], The unstirred water layer permeability can be determined experimentally in a number of ways based on pH dependency of effective permeability [25,509,535-538], stirring rate dependence [511-514,552,578], and transport across lipid-free microfilters [25,546], 

Figure 6.2 Relationship between the epithelial membrane permeability and the effective intestinal membrane permeability in humans. Based on [6] an recalculated including fold expansion and UWL effect.

It may be assumed that the total resistance to passive transport across the trilamellar (UWU-membrane-UWU) barrier is the sum of the resistances of the membrane and the UWL on each side of it. Resistance is the inverse of permeability. So 

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