Diffusion barriers, pumping

Though drugs appear to cross the blood-brain barrier by passive diffusion, transporter systems in the blood-brain barrier pump drugs back out into the systemic circulation. As in the gut, the Pgp transporter system is the primary active transporter in the blood-brain barrier identified to date. This ATP-dependent transporter system picks up substrates that have crossed the capillary endothelial cells and transports them back to the systemic circulation, limiting their penetration into the CNS. Thus, not only are the physicochemical properties of the drug a determinant for penetration into the CNS but penetration also depends on whether the drug is a substrate for the Pgp transporter system. 

Fig. 3 Pumping cells with different diffusion barriers (a)...

Porous protective layer Outer pumping electrode Pumping sheet ZrO Inner pumping electrode Diffusion barrier Nernst electrode Nernst shsetZrOr Reference electrode Air duct sheet ZrOa Insulation layer Heater... 

For the rich or lean A characteristic, plugging of the diffusion barrier leads to a decreasing pumping current, which rotates the characteristic curve around A= 1. In contrast to this, cracks and delamination within the diffusion barrier layers lead to an increased pumping current causing an opposite rotation of the characteristic curve. 

If two such electrodes are separated by a thin layer of only zirconia, the application of a potential will lead to the pumping of oxygen from the cathode to the anode. This device can be used as an amperometric sensor for oxygen if a diffusion barrier restricts the flux of oxygen to the cathode. Note that similar devices are also often used as potentiometric sensors according to the Nernst equation (i.e., the lambda-probe in cars with catalytic converters). In this case one side of the cell has to act as a reference, e.g., by using ambient air. 

The Sartorius Absorption Model (26), which served as the forerunner to the BCS, simulates concomitant release from the dosage form in the GI tract and absorption of the drug through the lipid barrier. The most important features of Sartorius Absorption Model are the two reservoirs for holding different media at 37°C, a diffusion cell with an artificial lipid barrier of known surface area, and a connecting peristaltic pump which aids the transport of the solution or the media from the reservoir to the compartment of the diffusion cell. The set-up is shown in Figures 7a and b. 

One of the widely used methods of analysis of kinetic data is based on extraction of the distribution of relaxation times or, equivalently, enthalpic barrier heights. In this section, we show that this may be done easily by using the distribution function introduced by Raicu (1999 see Equation [1.16] above). To this end, we use the data reported by Walther and coworkers (Walther et al. 2005) from pump-probe as well as the transient phase grating measurements on trehalose-embedded MbCO. Their pump-probe data have been used without modification herein, while the phase grating data (also reproduced in Figure 1.12) have been corrected for thermal diffusion of the grating using the relaxation time reported above, r,, and Equation (1.25). 

During World War II, plastics and lubricating compounds of unusual chemical and thermal stability were required for many applications, in particular for pumping apparatus used to separate 235U from 23SU by diffusion of corrosive uranium hexafluoride through porous barriers. It was natural to consider the use of substances made only of carbon and fluorine (fluorocarbons) for such purposes, and considerable effort was spent on methods of preparing compounds such as Today, many such substances are in common use. 

Biological membranes present a barrier to the free transport of cations, as the hydrophilic, hydrated cations cannot cross the central hydrophobic region of the membrane which is formed by the hydrocarbon tails of the lipids in the bilayer. Specific mechanisms thus have to be provided for the transport of cations, which therefore allow for the introduction of controls. Such translocation processes may involve the active transport of cations against the concentration gradient with expenditure of energy via the hydrolysis of ATP. These ion pumps involve enzyme activity. Alternatively, facilitated diffusion may occur in which the cation is assisted to cross the hydrophobic barrier. Such diffusion will follow the concentration gradient until concentrations either side of... 

Oils used in mechanical pumps have significantly higher vapor pressures than the oils used within diffusion pumps. Therefore, it is important to prevent backstreaming of mechanical pump oils into the diffusion pump. This barrier can be done either with liquid nitrogen cold traps, molecular sieves, water-cooled thimbles, or chevron baffles. 

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