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The Pharmaceutical Society of Korea (대한약학회)
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Effect of Vehicles and Enhancers on the In Vitro Permeation of Melatonin through Hairless Mouse Skin

  • Gwak, Hye-Sun (Laboratory of Pharmaceutics, College of Pharmacy, Dongduk Women′s University) ;
  • Kim, Seung-Ung (Laboratory of Pharmaceutics, College of Pharmacy, Dongduk Women′s University) ;
  • Chun, In-Koo (Laboratory of Pharmaceutics, College of Pharmacy, Dongduk Women′s University)
  • Published : 2002.06.01
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Abstract

The effects of vehicles and penetration enhancers on the in vitro permeation of melatonin through dorsal hairless mouse skin were investigated. Propylene glycol laurate (PGL), isopropyl myristate (IPM), propylene glycol monolaurate (PGML) and propylene glycol monocaprylate (PGMC) showed high permeation fluxes and PGL, PGML and PGMC decreased lag time significantly. In both of the binary co-solvents of diethylene glycol monoethyl ether (DGME)-PGL and DGME-IPM, the highest fluxes were achieved at 20% of DGME, which were $10.5{\pm}1.5$ and $9.1{\pm}2.4{\;}{\mu\textrm{g}}/cm^2/h$, respectively. Among fatty acids used as a permeation enhancer, capric acid and oleic acid in DGME-PGL (80:20 v/v) showed relatively high enhancing effects. Capric acid also shortened the lag time of melatonin from $2.4{\pm}0.7{\;}to{\;}1.3{\pm}0.2{\;}h$. Oleic acid, however, failed to shorten the lag time. Therefore, for effective solution formulations in terms of permeation flux and lag time, capric acid-containing DGME-PGL (80 : 20 v/v) could be used to enhance the skin permeation of melatonin.

Keywords

References

  1. Barry, B.W, Mode of action of penetration enhancers in human skin. J. Controlled Rel., 6, 85-97 (1987) https://doi.org/10.1016/0168-3659(87)90066-6
  2. Benes, L., Claustrat, B., Horriere, F, Geoffriau, M., Konsil, J., Parrott, K., DeGrande, G., McQuinn, R. L. and Ayres, J. W, Transmucosal, oral controlled-release, and transdermal drug administration in human subjects: a crossover study with melatonin. J. Pharm. Sci., 86,1115-1119 (1997) https://doi.org/10.1021/js970011z
  3. Brzezinski, A., Mechanisms of disease: melatonin in humans. N. Eng. J. Med., 336,186-195 (1997) https://doi.org/10.1056/NEJM199701163360306
  4. Cho, Y. J. and Choi, H. K., Enhancement of percutaneous absorption of ketoprofen: effect of vehicles and adhesive matrix. Int. J. Pharm., 169,95-104 (1998) https://doi.org/10.1016/S0378-5173(98)00115-X
  5. Cooper, E.R, Merritt, E.W. and Smith, R.L., Effect of fatty acids and alcohols on the penetration of acyclovir across human skin in vitro. J. Pharm. Sci., 74, 688-689 (1985) https://doi.org/10.1002/jps.2600740623
  6. Cordero, J. A., Alarcon, L., Escribano, E., Obach, R. and Domenech, J., A comparative study of the transdermal penetration of a series of nonsteroidal anti-inflammatory drugs. J. Pharm. Sci., 86, 503-508 (1997) https://doi.org/10.1021/js950346l
  7. Fung, B. K., 1987. Transducin: structure, function, and role in phototransduction. In: Osborn NN, Chader GJ, eds. Progress in retinal research, Vol. 6.; Pergamon Press: Oxford, England, pp. 151-177
  8. Golden, G.M., McKie, J.E. and Potts, R.O., Role of stratum corneum lipid fluidity in transdermal drug flux. J. Pharm. Sci., 76,25-28 (1987) https://doi.org/10.1002/jps.2600760108
  9. Gwak, H. S. and Chun, I. K., Effect of vehicles and penetration enhancers on the in vitro percutaneous absorption of tenoxicam through hairless mouse skin. Int. J. Pharm., 236, 57-64(2002) https://doi.org/10.1016/S0378-5173(02)00009-1
  10. Kitagawa, S., Endo, J. and Kametani, F., Effects of long-chain cis-unsaturated fatty acids and their alcohol analogues on aggregation of bovine platelets and their relation with membrane fluidity change. Biochem. Biophys. Acta, 818, 391-397 (1985) https://doi.org/10.1016/0005-2736(85)90014-8
  11. Lee, B., Parrott, K. A., Ayres, J. W. and Sack, R L., Preliminary evaluation of transdermal delivery of melatonin in human subjects. Res. Commun. Mol. Path. Pharmacol., 85, 337-346(1994)
  12. Lerner, A. B., Case, J. D., Takahashi, Y, Lee, T. H. and Mori, W., Isolation of melatonin, the pineal gland factor that lightens melanocytes. J. Am. Chem. Soc., 80, 2587 (1958)
  13. Lieberman, H. R., Waldhauser, F., Garfield, G., Lynch, H. J. and Wurtman, R. J., Effects of melatonin on human mood and performance. Brain Res., 323, 201-207 (1984) https://doi.org/10.1016/0006-8993(84)90290-7
  14. Lynch, H. J., Wurtman, R. J., Moskowitz, M. A, Archer, M. A. and Ho, M. H., Daily rhythm in human urinary melatonin. Science, 187, 169-171 (1975) https://doi.org/10.1126/science.1167425
  15. Mollgaard, B. and Hoelgaard, A., Vehicle effects in topical drug delivery I. influence of glycols and drug concentration on skin transport. Acta. Pharm. Suec., 20, 433-442 (1983)
  16. Oh, H. J., Oh, Y. K. and Kim, C. K., Effects of vehicles and enhancers on transdermal delivery of melatonin. Int. J. Pharm., 212, 63-71 (2001) https://doi.org/10.1016/S0378-5173(00)00598-6
  17. Pangerl, B., Pangerl, A. and Reiter, R.J., Circadian variations of adrenergic receptors in the mammalian pineal gland: a review. J. Neural. Transm. Gen. Sect., 81,17-29 (1990) https://doi.org/10.1007/BF01245442
  18. Roy, S.D. and Flynn, G.L., Solubility and related physicochemical properties of narcotic analgesics. Pharm. Res., 5, 580-586 (1988) https://doi.org/10.1023/A:1015994030251
  19. Vollrath, L., Semm, P. and Gammel, G., Sleep induction by intranasal application of melatonin. Adv. Biosci., 29, 327-329(1981)
  20. Waldhauser, F, Waldhauser, M., Lieberman, H. R, Deng, M. H., Lynch, H. J. and Wurtman, R. J., Bioavailability of oral melatonin in humans. Neuroendocrinology, 39, 307-313(1984) https://doi.org/10.1159/000123997
  21. Yamada, M., Uda, Y. and Tanigawara, Y, Mechanism of enhancement of percutaneous absorption of molsidomine by oleic acid. Chem. Pharm. Bull., 35, 3399-3406 (1987) https://doi.org/10.1248/cpb.35.3399