306 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS 80- J 70- 60 50 40- 30- 20- 10- FREEZING TIME (days) Figure 4. Permeation freezing profile in the nude rat. Legend ß METHANOL [] ETHANOL ß BUTANOL ¸ HEXANOL A OCTANOL SUMMARY AND CONCLUSION The skin permeability profile and lipid partitioning sensitivity (m-value) of the nude rat appear mechanistically similar to those of human and hairless mouse skins. Therefore, it can be concluded that the nude rat is a suitable model for laboratory skin permeation studies and it should provide permeability data which are correlatable with human data. From a functional point of view, this animal is desirable because of its availability, size, and sparse hair distribution. Its size permits both in vitro and in situ/in vivo experimen- tation. Its abdominal hair distribution is sparse enough to eliminate hair clipping which could damage the skin. Furthermore, the data indicate that the skin may be frozen for up to one month without significantly altering its permeability. The ability to use frozen skin in the laboratory is more efficient. Experimental setup is rapid when

NUDE RAT SKIN PERMEABILITY 307 skin preparation immediately prior to use is eliminated. Skin variables, such as animal age and gender, are better controlled. Additionally, the use of frozen skin can be more economical than using freshly excised skin because of reduced housing and procurement COSTS. REFERENCES (i) (2) (3) (4) (5) (6) (7) (8) (9) (lO) (11) (12) R. J. Scheuplien and I. H. Blank, Permeability of the skin, Physiol. Rev., 59, 702-747 (1971). C. R. Behl, N. H. Bellantone, and G. L. Flynn, "Influence of Age on Percutaneous Absorption of Drug Substances," in Percutaneous Absorption, R. L. Bronauch and H. I. Maibach, Eds. (Marcel Dekker, Inc., New York, 1985), Ch. 14. B. Garcia, J. p. Marty, and J. Wepierre, Etude des facteurs conditionnant l'absorption percutanee des alcools incorpores dans des melanges eau-monooleate de sorbitanne polyoxyethylene-myristate d'iso- propyle, Int. J. Pharm., 4, 205-217 (1980). C. R. Behl and N. H. Bellantone, Influence of alkyl chain length on the in situ permeation of n-alkanols through fuzzy rat skins and comparisons with the in vitro data. Comparisons of the fuzzy rat and hairless mouse skin results, Presented at the 31 't Annual Meeting of the Academy of Pharmaceutical Sciences, Miami Beach, FL, 1983, Abstract #38. C. R. Behl, N. H. Bellantone, and J. Pei, Effects of alkyl chain length and anatomical site on the alkanol permeability through fuzzy rat skins, Presented at the I30 th Annum Meeting of the American Pharmaceutical Association, New Orleans, LA, 1983, Abstract #32. C. R. Behl, G. L. Flynn, and M. Barrett, Skin permeability profile of n-alkanols and water through Swiss (furry) mouse skin, In preparation. C. R. Behl, A. A. E1-Sayed, and G. L. Flynn, Influence of hydration on n-alkanol permeation through rat skin. Comparison with hairless and Swiss mice, J. Pharm. Sci. 72(1), 79-82 (1983). C. R. Behl and G. L. Flynn, Permeation profile of n-alkanols and water using Silastic © as a mem- brane, In preparation. C. R. Behl, R. Meyer, and G. L. Flynn, Percutaneous absorption by the living mouse--Uptake of water and n-alkanols across normal and stripped skin, Presented at the 128 th Annual Meeting of the American Pharmaceutical Association, St. Louis, MO, 1981, Abstract #22. C. R. Behl, N. H. Bellantone, J. Pei, A. W. Malick, and S. DelTerzo, Skin permeation studies of n-alkanols using fuzzy rat. In vitro/in situ correlations and comparisons with hairless mouse data, Submitted to Dr•g Dev. Ind. Pharm. (1986). S. M. Harrison, B. W. Barry, and P. H. Dugard, Effects of freezing on human skin permeability,J. Pharm. Pharmacol., 36, 261-262 (1985). J. Swarbrick, G. Lee, and J Brom, Drug permeation through the skin: I. Effect of storage condition of the skin, J. Invest. Derre. 78, 63-66 (1982).