Abstract
FourN-adamantyln-alkanamides were prepared by amide, condensation reaction between amantadine and n-alkanoic acid. Their enhancing activity on the penetration of ibuprofen through rabbit skin from petrolatum ointment was evaluated in in-vivo experiment. The experiments showed that the compounds have a strong transdermal penetration-enhancing activity, and their activities were comparable with that of Azone. The measurements of the fluorescence polarization of DPH-labelled DPPC liposomes showed that these compounds considerablly decreased the phase transition temperature of the liposomes. The mechanism of the transdermal penetration-enhancing activity of the compounds was ascribed to the reduction of the resisitance to drug flux of the stratum corneum lipid layers due to the loose packing of the layers when the bulk head group of the enhancers inserts into the layers.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References Cited
Aoyagi, T., Yamamura, M., Matsui, K. and Nogase, Y., Preparation of cyclic sulfoxide and their evaluation as transdermal penetration enhancers.Chem. Pharm. Bull., 40, 1961–1963 (1991).
Barry, B. W.,Dermatological Formulations, Marcel Dekker, New York, p. 160 (1983).
Barry, B. W.,Drug Delivery Systems, Ellis Horwood, Chichester (England), p.200 (1987).
Bisset, D. L.,Transdermal Delivery of Drugs, Vol. 1, CRC Press, Boca Raton FL, p.29 (1987).
Chien, Y. W.,Transdermal Controlled Systemic Medication, Chien Y. W., Ed., Marcel Dekker, New York, p.1 (1987).
Han, S. K., Park Y. H., and Kim, C. K., Preparation of N-adamantyl n-alkanamides and evaluation of their transdermal penetration in the rabbit,Int. J. Pharm., 126, 35–40 (1995).
Hori, F., Saton, S., Maibach H. I., and Guy, R. H., Enhancement of propranolol hydrochloride and diazepam skin absorptionin vitro; Effect of enhancer lipophilicity.J. Pharm. Sci., 80, 32–35 (1991).
Horslay, M. D. and Stanley, K. K.Dynamics of Biological Membranes. John Wiley and Sons, New York, p.74 (1982).
Irwin, W. J., Sanderson, F. D., and Po, A. L. W., Percutaneous absorption of ibuprofen and naproxen; Effect of amide enhancers on transport through rat skin.Int. J. Pharm., 66, 243–252 (1990).
Jones, G. R., and Cossins, A. R., Physical methods of study.Liposomes, Oxford University Press, Oxford, 199, p.207.
Kydonieys, A. F.,Transdermal Delivery of Drugs, Vol. 1, Kydonieus, A. F. and Brener, Eds., CRC Press, Boca Raton, FS, p.81 (1987).
Li, V. H. K., and Robinson, J. R.,Controlled Drug Delivery, Marcel Dekker, New York, p.53 (1987).
Perron, Y. G., Minor, W. F., Holdrege, C. T., Goltstein, W. J., Godfrey, J. C., Crast, L. B., Babel, R. B., and Cheney, L. C., Dervatives of 6-aminopenicillanic acid. I. Partially synthetic penicillins prepared from α-aryloxyalkcnoic acids.J. Am. Chem. Soc., 82, 3934–3938 (1960).
Quan, D., Higychi, H. I., Takayama, K., Higashiyama, K., and Nagai, T., Promoting effect of 2-n-alkyl-cyclohexahone on the percutaneous absorption of indomethacin.Drug Res. Delivery, 5, 149–157 (1989a).
Quan, D., Takayama, K., Mitsuzono, T., Isowa, K., and Nagfgi, T., Influence of novel percutaneous absorption enhancers, cyclohexanone and piperidone derivatives on histology of rat skin.Int. J. Pharm., 68 139–253 (1991).
Quan, D., Takayama, K., and Nagagi, R., Effect of cyclohexane derivatives onin vitro percutaneous absorption of indomethacin.Drug Res. Delivery, 4, 323–330 (1989b).
Sasaki, H., Kojima, M., Mori, Y., Nakamura, J., and Shibasaki, J., Enhancing effect of pyrrolidone derivatives on transdermal penetration of 5-fluorouracil, triamcinolone acetonide, indomethacin and flurbiprofen.J. Pharm. Sci., 80, 533–538 (1991).
Scheuplein, R. J., and Dugard, P. H., Effects of ionic surfactants on the permeability of human epidermis: an eletrometric study.J. Invest. Dermatol., 60, 263–268 (1973).
Shen, W., Danti, A. G., and Bruscato, F. N., Effect of nonionic urfactants on percutaneous absorption of salicylic acid and sodium salicylate in the presence of dimethylsulfoxide.J. Pharm. Sci., 65, 263–268 (1976).
Stoughton, R. B., Enhanced percutaneous penetration with 1-dodecylazacycloheptane-2-one.Arch. Dermatol., 118, 474–477 (1982).
Wong, O., Huntington, J., Konishi, R., Rytting, J. H., and Higuchi, T., Unsaturated cyclic ureas as nontoxic biodegradable transdermal penetration enhancers, I. Synthesis.J. Pharm., Sci., 77, 967–971 (1988).
Wong, O., Tsuzuki, N., Ngheim, B., Kuenhoff, J., Iton, T., Masaki, N., Hntington, J., Konishi, R., Rytting, J. H., and Higuchi, T., Unsaturated cyclic ureas as non-toxic biodegradable transdermal penetration enhancers. II. Evaluation study.Int. J. Pharm., 52, 191–202 (1989).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Han, S.K., Park, Y.H., Ko, Y.I. et al. Transdermal permeation-enhancing activivity ofN-adamantyln-alkanamides for ibuprofen in the rabbit. Arch. Pharm. Res. 19, 95–99 (1996). https://doi.org/10.1007/BF02976841
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02976841