Aqueous boundary layer permeability coefficient

The release of steroids such as progesterone from films of PCL and its copolymers with lactic acid has been shown to be rapid (Fig. 10) and to exhibit the expected (time)l/2 kinetics when corrected for the contribution of an aqueous boundary layer (68). The kinetics were consistent with phase separation of the steroid in the polymer and a Fickian diffusion process. The release rates, reflecting the permeability coefficient, depended on the method of film preparation and were greater with compression molded films than solution cast films. In vivo release rates from films implanted in rabbits was very rapid, being essentially identical to the rate of excretion of a bolus injection of progesterone, i. e., the rate of excretion rather than the rate of release from the polymer was rate determining. 

Karlsson, J. P. Artursson, P., A method for the determination of cellular permeability coefficients and aqueous boundary layer thickness in monolayers of intestinal epithelial (Caco-2) cells grown in permeable filter chambers, Int. J. Pharm. 7, 55-64 (1991). 

Figure 21 Linearized double reciprocal plot of the effective permeability coefficients and corresponding stirring rates to determine the power dependency of the stirring rate and mass transfer resistances for the aqueous boundary layers and the Caco-2 cell monolayer in the Transwell system. 

Table 12 Effective Permeability Coefficients and Thicknesses of the Aqueous Boundary Layer of the Caco-2 Cell Monolayer/ Transwell System as a Function of Stirring by Planar Rotating Shaker3...

Figure 31 Scheme for the protein-binding, diffusional, and partitioning processes and barriers that are encountered by a highly lipophilic and membrane-interactive drug (D) as it permeates through a cell within a continuous monolayer, h and h, thicknesses of the aqueous boundary layers. kd and ka, dissociation and association binding constants, respectively. P, protein molecule. Permeability coefficients Effective, Pe aqueous boundary layer, PABL and PW apical membrane, Pap basolateral membrane, Pbl. 

Figure 35 Relationship between the uptake permeability coefficient and the free drug concentration. PAEL is the permeability of the free drug across the aqueous boundary layer, and P BL is the same for the drug-albumin complex. [Redrawn from Raub et al. (1993) with permission from the publisher.]...

The identification and characterization of cell culture systems (e.g., Caco-2-cells) that mimic in vivo biological barriers (e.g., intestinal mucosa) have afforded pharmaceutical scientists the opportunity to rapidly and efficiently assess the permeability of drugs through these barriers in vitro. The results generated from these types of in vitro studies are generally expressed as effective permeability coefficients (Pe). If Pe is properly corrected to account for the barrier effects of the filter (PF) and the aqueous boundary layer (PAbl) as previously described in Section II.C, the results provide the permeability coefficient for the cell monolayer... 

It was postulated that the aqueous pores are available to all molecular species, both ionic and non-ionic, while the lipoidal pathway is accessible only to un-ionised species. In addition, Ho and co-workers introduced the concept of the aqueous boundary layer (ABL) [9, 10], The ABL is considered a stagnant water layer adjacent to the apical membrane surface that is created by incomplete mixing of luminal contents near the intestinal cell surface. The influence of drug structure on permeability in these domains will be different for example ABL permeability (Paq) is inversely related to solute size, whereas membrane permeability (Pm) is dependent on both size and charge. Using this model, the apparent permeability coefficient (Papp) through the biomembrane may therefore be expressed as a function of the resistance of the ABL and... 

When the permeabilities of the aqueous boundary layer and membrane are relatively large, reduced blood flow becomes the rate-limiting step. For example, the apparent permeability coefficient is approximately 85% controlled by blood flow when Pgq and Pmembrane are each approxi-mately 10 times greater than Pbiood-... 

Assuming no significant aqueous boundary layer on the blood side, the apparent permeability coefficient (Papp) in Eq. (1) is expressed by ... 

If the drug stratum corneum/product partition coefficient K is defined as Csc(o)/C)>, CJc is assumed to be much less than Csc(o), and the permeability coefficient (kp) is KD/h, equation 4 is equivalent to equation 3. The lag time is normally defined by Fick s law as h2/6D. The importance of equation 4 is well illustrated by the work of Rougier and Lotte (1993) in which it was shown that the in vivo percutaneous absorption (= Js) of a series of compounds was directly related to their concentration in stripped stratum corneum, irrespective of their structure, concentration or site of application. In theory, drug transport could go via a polar pathway, with a permeability coefficient kp pojar, as well as through the intercellular lipid pathway, with a permeability coefficient kp iipi(1, although the existence of a polar pathway remains controversial. As indicated previously, for lipophilic drugs, an aqueous boundary layer is likely to be present at the stratum corneum-viable epidermis interface... 

Various parameters in Equation 31.17 have been defined earlier. Danesi et al. [92] described a simple correlation between permeability coefficient in FSSLM and HFSLM configuration. At very large values of ( ) (as compared to 1), Equation 31.17 is transformed into the one used for FSSLM by Danesi et al. [92]. Hence, the smaller the value of ( ), the higher will be the negative value of the left-hand side of Equation 31.17, which suggests the higher rate of mass transfer. Later on, D Elia et al. [93] considered the resistance in series model where they have studied the mass transport across hollow-fiber contactors in NDSX mode. They showed that the overall mass transfer resistance is equal to the sum of individual mass transfer resistances across the aqueous boundary layer and membrane phase. Mathematically, it can be written as follows ... 

A Effective membrane area C, Concentration of metal ion in bulk feed at time t Co Initial concentration of metal ion in bulk feed Membrane thickness Thickness of aqueous boundary layer Membrane diffusion coefficient Aqueous diffusion coefficient Aqueous feed film mass transfer coefficient Organic membrane phase mass transfer coefficient Overall mass transfer coefficient Distribution ratio Two-phase extraction constant Aqueous feed mass transfer coefficient Membrane mass transfer coefficient Aqueous strip mass transfer coefficient Length of the fiber Molecular weight of the complex Number of fibers Permeability coefficient (cm/s)... 

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