Permeability studies, hairless mouse

Table 8—Permeability rate of propranolol hydrochloride from Methocel matrix diffusion study through hairless mouse skin (comparative data)...

Permeability Studies. A two-chamber diffusion cell procedure (8. 12) was employed with freshly excised hairless mouse skin. The diffusion cell consisted of two half cells or compartments (2 ml volume/half cell) and the area for diffusion between the two half cells was approximately 0.6 cm2. The full-thickness skin membrane was prepared by sacrificing the mouse as previously described and excising two square sections of the left and right abdominal skin. A skin membrane was mounted between the two compartments of the diffusion cell with the dermis side facing the receiver compartment, clamped and excess skin trimmed. The assembled diffusion cells were immersed in a water bath at the selected temperature between 10 and 60°C. Glycerine baths were used for temperatures between 60 and 90°C. Each compartment was filled with PBS adjusted to 7.3 pH at the specific experimental temperatures. 

Thermally induced permeability enhancement of the more lipophilic solutes (butanol, octanol and hydrocortisone) through hairless mouse stratum corneum occurred in the temperature range also associated with lipid transitions in the calorimetry studies. Therefore, it seems likely enhanced permeabilities and lipid mobility within the stratum corneum are correlated. However, these macroscopic studies are unable to provide more specific information concerning the molecular origins of the thermal transitions. The studies provide even less information concerning possible irreversible alterations of the keratinized protein components of the stratum corneum. 

Figure 15.1 through Figure 15.6 show skin permeability coefficient measurements from hairless mouse, hairless rat, rat, shed snake, and the lesser-studied animals (guinea pig, marmoset, rabbit, pig, dog, mouse, nude rat) plotted as a function of log In Figure 15.1 to Figure 15.4 and Figure 15.6, compounds that were more than 90% ionized are identified by the form of the dominant ionic species (that is, cation, anion, or zwitterion) and labeled as excluded. Ionized species with undetermined log are plotted to the left of the dashed vertical line located at log = -6.0. Cations are plotted at log = -6.5, anions at log = -7.0, and zwitterions at log = -7.5. A few permeability coefficient measurements that are... 

Behl et al. studied the effect of prolonged contact of hairless mouse skin with water on permeability coefficients. The authors showed that permeability coefficients increase after extended periods of hydration. Because other permeability coefficients in the database we have assembled were measured on previously unhydrated skins or skins that were hydrated for short periods, the permeability coefficients with the shortest hydration time (0.3 to 0.8 h) from Table 1 were selected for the validated database. Permeability coefficients were determined with either water or ethanol as a copenetrant. The concentrations were dilute (alcohol concentrations less than 10 M) and probably were not damaging. Six reported measurements were averaged for methanol, two for ethanol, and two for butanol, and permeability coefficients were reported singly for hexanol, heptanol, and octanol. Although this article did not specify the diffusion cell temperature, subsequent articles by the same authors describing similar data indicated that the temperature was 37°C (e.g., Behl and Barrett, 1981 Behl, El-Sayed, et al., 1983 Behl, Linn, et al., 1983). It seems hkely that the temperature was also 37°C in the experiments described in this article. 

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