Abstract
The effect of urea and urea derivatives on the percutaneous absorption of salicylic acid and sodium salicylate through the skin of rabbit from petrolatum ointment was investigated. It was found that addition of urea or urea derivatives to the ointment base significantly increased the percutaneous absorption of the drugs in proportion to the concentratoin of the additive. The percutaneous absorptoin-enhancing activities of these compounds were that urea derivatives with the more and longer alkyl substituents showed the stronger activities. These activities of urea and urea derivatives were ascribed to the binding of these compounds with the lipids and proteins of the stratum corneum of the skin and the swelling of the tissues, which leads to the reduction of the barrier property of the layer. The preliminary skin irritation test showed that urea and urea derivatives were quite non-irritating to the skin. These results suggest that urea derivatives have a strong possibility to be developed as a percutaneous absorption enhancer.
Similar content being viewed by others
Literature Cited
Kydonieus, A.F. and Berner, B.:Trandermal Delivery of Drugs, Vol. I,II and III, CRC Press, Boca Raton, Florida (1987).
Chien, Y.W.:Transdermal Controlled Systemic Medications, Marcel Dekker, New York (1987).
Tyle, P.:Drug Delivery Devices, Marcel Dekker, New York, p. 385 (1988).
Katz, M. and Poulsen, B.J.:Handbook of Experimental Pharmacology, Vol. 28, pt.1, Springer Verlag, New York, p. 103 (1971).
Barry, B.W.:Dermatological Formulatins, Marcel Dekker, New York, p. 160 (1983).
Stelzer, Jr. J.M., Colaizzi, J.L. and Wurdack, P.J.: Influence of dimethyl sulfoxide on the percutaneous absorption of salicylic acid and sodium salicylate from ointments,J. Pharm. Sci.,37, 1732 (1968).
Weiner, N.D., Lu, M.Y. and Rosoff, M.: Interactions of dimethyl sulfoxide with lipid and protein monolayers,J. Pharm. Sci.,61, 1098 (1972).
Bettlef, F.R.: The influence of detergents and surfactants on epidermal permeability,Br. J. Dermatol.,77, 98 (1965).
Scheuplein, R.J. and Ross, L.: Effect of surfactants and solvents on the permeability,J. Soc. Cosmet. Chem. 21, 853 (1970).
Scheuplein, R.J. and Dugard, P.H.: Effects of ionic surfactants on the permeability of human epidermis,J. Invest. Dermtol. 60 263 (1973).
Shen, W., Danti, A.G. and Bruscato, F.N.: Effect of nonionic surfactants on percutaneous absorption of salicylic acid and sodium salicylate in the presence of dimethyl sulfoxide,J. Pharm. Sci. 65, 1780 (1976).
Hwang, C. and Danti, A.G.: Percutaneous absorption of flufenamic acid in rabbits, Effect of dimethyl sulfoxide and various nonionic surface-active agents,J. Pharm. Sci. 72, 857 (1983).
Cooper, E.R.:Effect of Decylmethyl Sulfoxide on Skin Penetration, Mittal, K.L. and Fendler, E.J., Eds., Plenum Press, New York (1982).
Cooper, E.R.: Increased skin permeability for lipophilic molecules,J. Pharm. Sci. 73, 1153 (1984).
Cooper, E.R., Merritt, E.W. and Smith, R.L.: Effect of fatty acids and alcohols on the penetration of acyclovir across human skinin vitro.J. Pharm. Sci. 74, 688 (1985).
Feldman, R.J. and Maibach, H.I.:Arch. Dermatol. 109, 38 (1974).
Han, S.K., Lee, S.M. and Schott, H.: The effect of protein denaturants on the cloud point of a nonionic surfactant,J. Colloid Interface Sci. 126, 393 (1988).
Han, S.K., Lee, S.M. Kim, M. and Schott, H.: The effect of protein denaturants on the cloud point and Krafft point of a nonionic surfactant,J. Colloid Interface Sci.,132, 444 (1989).
Trinder, P.:Biochem. J.,57, 301 (1954).
Kauzmana, W.:Advan. Protein Chem,14, 1 (1959).
Feldman, S. and Gibaldi, M.: Effect of urea on solubility of salicylic acid,J. Pharm. Sci.,56, 370 (1967).
Bonner, O.D., Bednarelc, J.M. and Arisman, R.K.: Heat capacities of ureas and water in water and dimethylformamide,J. Am. Chem. Soc.,99, 2898 (1977).
Baglioni, P., Rivara-Minten, E., Dei, L. and Ferroni, E.: ESR study of sodium dodecyl sulfate and dodecyltrimethyl-ammonium bromide micellar solutions. Effect of ureas,J. Phys. Chem.,94, 8112 (1990).
Kuharski, R.A. and Rossky, P.J.: Solvation of hydrophobic species in aqueous urea solution. A molecular dynamic study,J. Am. Chem. Soc.,106, 5794 (1984).
Brown, Jr., J.F.: Inclusion compounds,Sci. Am.,207, 82 (1962).
Forman, B.J. and Grady, L.T.:J. Pharm. Sci.,58, 1262 (1969).
Herskovits, T.T. and Kelly, T.M.: Viscosity studies of aqueous solutions of alcohols, ureas and amides,J. Phys. Chem. 77, 381 (1973).
Schick, M.J.: Effect of electrolytes and urea on micellar formation,J. Phys. Chem. 68, 3585 (1964).
Herskovits, T.T., Jailet, H. and Gadegbeku, B.:J. Biol. Chem.,245, 4544 (1970).
Marongiu, B., Monaci, R., Caminilli, R. and Atzl, D.: Solute-solvent interactions in dilute aqueous solution of some alkylureas and diazolidin-2-one.J. Mol. Liquids,30, 139 (1985).
Kurihara, T.: Physicochemical study of the accelerant effect of DMSO on percutaneous absorption of an antiviral drug and other chemical prototype, Ph. D. Thesis, Univ. of Michigan, Ann Arbor (1983).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Han, S.K., Jun, Y.H., Rho, Y.J. et al. Percutaneous absorptoin-enhancing activity of urea derivatives. Arch. Pharm. Res. 14, 12–18 (1991). https://doi.org/10.1007/BF02857807
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02857807