The Effect of Vehicles and Pressure Sensitive Adhesives on the Percutaneous Absorption of Quercetin through the Hairless Mouse Skin

  • Kim, Hye-Won (College of Pharmacy, Dongduk Women′s University) ;
  • Gwak, Hye-Sun (College of Pharmacy, Chosun University) ;
  • Chun, In-Koo (College of Pharmacy, Dongduk Women′s University)
  • Published : 2004.07.01

Abstract

To investigate the feasibility of developing a new quercetin transdermal system, a preformulation study was carried out. Therefore, the effects of vehicles and pressure-sensitive adhesives (PSA) on the in vitro permeation of quercetin across dorsal hairless mouse skin were studied. Among vehicles used, propylene glycol monocaprylate (PGMC) and propylene glycol mono-laurate were found to have relatively high permeation flux from solution formulation (i.e., the permeation fluxes were 17.25$\pm$1.96 and 9.60$\pm$3.87 $\mu\textrm{g}$/$\textrm{cm}^2$/h, respectively). The release rate from PSA formulations followed a matrix-controlled diffusion model and was mainly affected by the amount of PSA and drug loaded. The overall permeation fluxes from PSA formulations were less than 0.30 $\mu\textrm{g}$/$\textrm{cm}^2$/h, which were significantly lower compared to those obtained from solution formulations. The lower permeation fluxes may be due to the decrease of solubility and diffusivity of quercetin in the PSA layer, considering the fact that the highest flux of 0.26 $\mu\textrm{g}$/$\textrm{cm}^2$/h was obtained with the addition of 0.2% butylated hydroxyanisole in PGMC-diethyl-ene glycol monoethyl ether co-solvents (80-85 : 15-20, v/v). Taken together, these observations indicate that improvement in the solubility and diffusivity of quercetin is necessary to realize fully the clinically applicable transdermal delivery system for the drug.

Keywords

References

  1. Arora, A., Nair, M. G., and Strasburg, G. M., Structure-activity relationship for antioxidant activities of a series of flavonoids in a liposomal system. Free Radic. Biol. Med., 24, 1355-1363 (1998) https://doi.org/10.1016/S0891-5849(97)00458-9
  2. Aungst, B. J., Rgers, N. J., and Shefter, E, Enhancement of naloxone penetration through human skin in vitro using fatty acids, fatty alcohols, surfactants, sulfoxides and amides. Int. J. Pharm., 33, 225-234 (1986) https://doi.org/10.1016/0378-5173(86)90057-8
  3. Barry, B. W., Percutaneous absorption. In Dermatological Formulations; Barry, B. W. Eds.; Marcel Dekker, Inc.; New York, 49-94, (1983)
  4. Barry, B. W., Mode of action of penetration enhancers in human skin. J. Contr. Res., 6, 85-97 (1987) https://doi.org/10.1016/0168-3659(87)90066-6
  5. Chien, Y. W., and Lambert, H. J., Controlled drug release from polymeric delivery devices II: differentiation between partition-eontrolled and matrix-controlleddrug release mechanism. J. Pharm. Sci., 63, 515-519 (1974) https://doi.org/10.1002/jps.2600630405
  6. 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
  7. Chun, I. K., and Suh, E H., Solubilization of quercetin, and permeability study of quercetin and rutin to rabbit duodenal mucosa. Yakhak Hoeji, 42, 59-69 (1998)
  8. Cooper, E. R., Increased skin permeability for lipophilic molecules. J. Pharm. Sci., 73, 153-1156 (1984) https://doi.org/10.1002/jps.2600730204
  9. 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
  10. Formica, J. V. and Regelson, W., Review of the biology of quercetin and related bioflavonoids. Food Chem. Toxicol., 33, 1061-1080 (1995) https://doi.org/10.1016/0278-6915(95)00077-1
  11. Gordon, M. H. and Roedig-Penman, A, Antioxidant activity of quercetin and myricetin in liposomes. Chem. Phys. Lipids, 97, 79-85 (1998) https://doi.org/10.1016/S0009-3084(98)00098-X
  12. Green, P. G., Guy, R. H., and Hadgraft, J., In vitro and in vivo enhancement of skin permeation with oleic acid and lauric acids. Int. J. Pharm., 48, 103-111 (1988). https://doi.org/10.1016/0378-5173(88)90252-9
  13. 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
  14. Gwak, H. S., Kim, H. W., and Chun, I. K., Solubility and physicochemical stability of quercetin in various vehicles. J. Kor. Pharm. Sci., 34, 29-34 (2004)
  15. Gwak, H. S., Kim, S. U., and Chun, I. K., Effect of vehicles and enhancers on the in vitro permeation of melatonin through hairless mouse skin. Arch. Pharm. Res., 25, 392-396 (2002) https://doi.org/10.1007/BF02976645
  16. Hertog, M. G. L., Feskens, E. J. M., Hollman, P. C. H., Katan, M. B., and Kromhout, D., Dietary antioxidant flavonoids and risk of coronary heart disease. The Zutphen Elderly Study Lancet., 342, 1007-1111 (1993) https://doi.org/10.1016/0140-6736(93)92876-U
  17. Hollman, K. B., and Katan, M. B., Absorption, metabolism and health effects of dietary flavonoids in man. Biomed. Pharmacother., 51, 305-310 (1997) https://doi.org/10.1016/S0753-3322(97)88045-6
  18. Lamson, D. W. and Brignall, M. S., Antioxidants and cancer III: quercetin. Altern. Med. Rev., 5, 196-208 (2000)
  19. Nokhodchi, A, Shokri, J., Dashbolaghi, A, Hassan-Zadeh, D., Ghafourian, T., and Barzegar-Jalali, M., The enhancement effect of surfactants on the penetration of lorazepam through rat skin. Int. J. Pharm., 250, 359-369 (2003) https://doi.org/10.1016/S0378-5173(02)00554-9
  20. Silva, M. M., Santos, M. R., Caroco, G., Rocha, R., Justino, G., and Mira, L., Structure-antioxidant relationship of flavonoids: a re-examination. Free Radic. Res., 36, 1219-1227 (2002) https://doi.org/10.1080/198-1071576021000016472
  21. Skibola, C. F. and Smith, M. T., Potential health impacts of excessive flavonoid intake. Free Radic. Biol. Med., 29, 375-383 (2000) https://doi.org/10.1016/S0891-5849(00)00304-X
  22. Stavric, B., Quercetin in our diet: from potent mutagen to probable anticarcinogen. Clin. Biochem., 27, 2456-2458 (1994)
  23. 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