Archives of Pharmacal Research

, 30:1155 | Cite as

Effects of vehicles and enhancers on transdermal delivery of clebopride

  • Yun-Seok Rhee
  • Jai-Yong Huh
  • Chun-Woong Park
  • Tae-Young Nam
  • Koog-Ryul Yoon
  • Sang-Cheol Chi
  • Eun-Seok Park
Article Drug development


The effects of vehicles and penetration enhancers on the skin permeation of clebopride were evaluated using Franz type diffusion cells fitted with excised rat dorsal skins. The binary vehicle system, diethylene glycol monoethyl ether/isopropyl myristate (40/60, w/w), significantly enhanced the skin permeation rate of clebopride. The skin permeation enhancers, oleic acid and ethanol when used in the binary vehicle system, resulted in relatively high clebopride skin permeation rates. A gel formulation consisting of 1.5% (w/w) clebopride, 5% (w/w) oleic acid, and 7% (w/w) gelling agent with the binary vehicle system resulted in a permeation rate of 28.90 μg/cm2/h. Overall, these results highlight the potential of clebopride formulation for the transdermal route.

Key words

Clebopride Skin permeation Vehicle Enhancer Binary vehicle system 


  1. Aboofazeli, R., Zia, H., and Needham, T. E., Transdermal delivery of nicardipine: an approach to in vitro permeation enhancement.Drug Deliv., 9, 239–247 (2002).PubMedCrossRefGoogle Scholar
  2. Aungst, B. J., Rogers, 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).CrossRefGoogle Scholar
  3. Barry, B. W.,Dermatological Formulations, Marcel Dekker Inc., New York, pp. 49–94 (1983).Google Scholar
  4. Barry, B. W., Yamane, M. A., and Williams, A. C., Effects of terpenes and oleic acid as skin penetration enhancers towards 5-fluorouracil as assessed with time; permeation, partitioning and differential scanning calorimetry.Int. J. Pharm., 116, 237–251 (1995).CrossRefGoogle Scholar
  5. Calpena, A. C., Blanes, C., Moreno, J., Obach, R., and Domenech, J., A comparative in vitro study of transdermal absorption of antiemetics.J. Pharm. Sci., 83, 29–33 (1994).PubMedCrossRefGoogle Scholar
  6. Cha, B. J., Lee, E. D., Kim, W. B., Chung, S. J., Lee, M. H., and Shim, C. K., Enhanced skin permeation of a new capsaicin derivative (DA-5018) from a binary vehicle system composed of isopropyl myristate and ethoxydiglycol.Arch. Pharm. Res., 24(3), 224–228 (2001).PubMedCrossRefGoogle Scholar
  7. Chi, S. C., Park, E. S., and Kim, H., Effect of penetration enhancers on flurbiprofen permeation through rat skin.Int. J. Pharm., 126, 267–274 (1995).CrossRefGoogle Scholar
  8. Cleary, G. W., Transdermal Controlled Release Systems. Langer, R. S. and Wise, D. L. (Eds.),Medical applications of controlled release, CRC Press, Boca Raton, pp. 203–251 (1984).Google Scholar
  9. Cooper, E. R., Increased skin permeability for lipophilic molecules.J. Pharm. Sci., 73, 1153–1156 (1984).PubMedCrossRefGoogle Scholar
  10. Cooper, E. R. and Patel, D. C., Practical considerations for topical drug formulations with and without enhancers. Osborne, D. W. and Amann, A. H. (Eds.),Topical drug delivery formulations, Marcel Dekker, Inc., New York, pp.1–12 (1990).Google Scholar
  11. Gorukanti, S. R., Li, L., and Kim, K. H., Transdermal delivery of antiparkinsonian agent, benztropine. I. Effect of vehicles on skin permeation.Int. J. Pharm., 192, 159–172 (1999).PubMedCrossRefGoogle Scholar
  12. Goto, S., Uchida, T., Lee, C. K., Yasutake, T., and Zhang, J. B., Effect of various vehicles on ketoprofen permeation across excised hairless mouse skin.J. Pharm. Sci., 82, 1155–1159 (1993).PubMedCrossRefGoogle Scholar
  13. 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).PubMedCrossRefGoogle Scholar
  14. Hadgraft, J., Pugh, J. W., and Wolff, H. M., Transdermal delivery of some anti-emetics.Int. J. Pharm., 123, 285–289 (1995).CrossRefGoogle Scholar
  15. Higuchi, T., Physical chemical analysis of percutaneous absorption process from creams and ointments.J. Soc. Cosmet. Chem., 11, 85–97 (1960).Google Scholar
  16. Hori, M., Satoh, S., Maibach, H. I., and Guy, R. H., Enhancement of propranolol hydrochloride and diazepam skin absorption in vitro; Effect of enhancer lipophilicity.J. Pharm. Sci., 80, 32–35 (1991).PubMedCrossRefGoogle Scholar
  17. Jeans, C. W. and Heard, C. M., A therapeutic dose of primaquine can be delivered across excised human skin from simple transdermal patches.Int. J. Pharm., 189, 1–6 (1999).PubMedCrossRefGoogle Scholar
  18. Kaiho, F., Nomura, H., Makabe, E., and Kato, Y., Percutaneous absorption of indomethacin from mixtures of fatty alcohol and propylene glycol (FAPG bases) through rat skin: Effects of fatty acid added to FAPG base.Chem. Pharm. Bull., 35, 2928–2934 (1987).PubMedGoogle Scholar
  19. Kandimalla, K. K., Kanikkannan, N., and Singh, M., Optimization of a vehicle mixture for the transdermal delivery of melatonin using artificial neural networks and response surface method.J. Control. Release, 61(1–2), 71–82 (1999).PubMedCrossRefGoogle Scholar
  20. Karande, P., Jain, A., and Mitragotri, S., Insights into synergistic interactions in binary mixtures of chemical permeation enhancers for transdermal drug delivery.J. Control. Release, 115(1), 85–93 (2006).PubMedCrossRefGoogle Scholar
  21. Krishnaiah, Y. S., Satyanarayana, V., and Karthikeyan, R. S., Effect of the solvent system on the in vitro permeability of nicardipine hydrochloride through excised rat epidermis.J. Pharm. Pharm. Sci., 5, 123–130 (2002).PubMedGoogle Scholar
  22. Lee, C. K., Uchida, T., Noguchi, E., Kim, N.S., and Goto, S., Skin permeation enhancement of tegafur by ethanol/panasate 800 or ethanol/water binary vehicle and combined effect of fatty acids and fatty alcohols.J. Pharm. Sci., 82, 1155–1159 (1993).PubMedCrossRefGoogle Scholar
  23. Lee, C. K., Uchida, T., Kitagawa, K., Yagi, A., Kim, N. S., and Goto, S., Skin permeability of various drugs with different lipophilicity.J. Pharm. Sci., 83(4), 562–565 (1994).PubMedCrossRefGoogle Scholar
  24. Lenz, H. J., Hicking, W., Robinson, P. R., and Ehninger, G., Disposition of clebopride after intravenous administration.Drug Invest, 4, 47–50 (1992).Google Scholar
  25. Leopold, C. S. and Lippold, B. C., Enhancing effects of lipophilic vehicles on skin penetration of methyl nicotinate in vivo.J. Pharm. Sci., 84, 195–198 (1995).PubMedCrossRefGoogle Scholar
  26. Mayorga, P., Puisieux, F., and Couarraze, G., Formulation study of a transdermal delivery system of primaquine.Int. J. Pharm., 132, 71–79 (1996).CrossRefGoogle Scholar
  27. Murillo C. E. and Sanchez Romero, J. A., Double blind crossover study comparing clebopride and placebo in the prevention of nausea and vomiting in patients undergoing cancer chemotherapy.Curr. Ther. Res. Clin. Exp., 31, S61- S68 (1982).Google Scholar
  28. 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).PubMedCrossRefGoogle Scholar
  29. Okamoto, H., Muta, K., Hashida, M., and Sezaki, H., Percutaneous penetration of acyclovir through excised hairless mouse and rat skin: Effect of vehicle and percutaneous penetration enhancer.Pharm. Res., 7, 64–68 (1990).PubMedCrossRefGoogle Scholar
  30. Panchagnula, R., Salve, P. S., Thomas, N.S., Jain, A. K., and Ramarao, P., Transdermal delivery of naloxone: effect of water, propylene glycol, ethanol and their binary combinations on permeation through rat skin.Int. J. Pharm., 219, 95- 105 (2001).PubMedCrossRefGoogle Scholar
  31. Panchagnula, R., Desu, H., Jain, A., and Khandavilli, S., Feasibility studies of dermal delivery of paclitaxel with binary combinations of ethanol and isopropyl myristate: role of solubility, partitioning and lipid bilayer perturbation.Farmaco, 60, 894–899 (2005).PubMedCrossRefGoogle Scholar
  32. Pfister, W. R. and Hsieh, D. S. T., Permeation enhancers compatible with transdermal drug delivery systems.Pharm. Technol., 14, 132–140 (1990).Google Scholar
  33. Rojas, J., Falson, F., Couarraze, G., Francis, A., and Puisieux, F., Optimization of binary and ternary solvent systems in the percutaneous absorption of morphine base.S.T.P Rharma Sci., 1, 70–75 (1991).Google Scholar
  34. Sato, K., Sugibayashi, K., Morimoto, Y., Omiya, H., and Enomoto, N., Prediction of the in-vitro human skin permeability of nicorandil from animal data.J. Pharm. Pharmacol., 41, 379- 383 (1989).PubMedGoogle Scholar
  35. Sato, K., Mitsui, N., Hasegawa, T., Sugibayashi, K., and Morimoto, Y., Potential usefulness of solubility index for prediction of the skin permeation rate of 5-ISMN from pressure-sensitive adhesive tape.J. Control. Release, 73, 269–277 (2001).PubMedCrossRefGoogle Scholar
  36. Sugibayashi, K., Nemoto, M., and Morimoto, Y., Effect of several penetration enhancers on the percutaneous absorption of indomethacin in hairless rats.Chem. Pharm. Bull., 36, 1519- 1528 (1988).PubMedGoogle Scholar
  37. Suwanpidokkul, N., Thongnopnua, P., and Umprayn, K., Transdermal delivery of zidovudine (AZT): the effects of vehicles, enhancers, and polymer membranes on permeation across cadaver pig skin.AAPS Pharm. Sci. Tech., 5, e48 (2004).CrossRefGoogle Scholar
  38. Takahashi, K., Tamagawa, S., Katagi, T., Yoshitomi, H., Kamada, A., Rytting, J. H., Nishihata, T., and Mizuno, N., In vitro transport of sodium diclofenac across rat abdominal skin: Effect of selection of oleaginous component and the addition of alcohols to the vehicle.Chem. Pharm. Bull., 39, 154–158 (1991).PubMedGoogle Scholar
  39. Thomas, N. S. and Panchagnula, R., Transdermal delivery of zidovudine: effect of vehicles on permeation across rat skin and their mechanism of action.Eur. J. Pharm. Sci., 18, 71–79 (2003).PubMedCrossRefGoogle Scholar
  40. Tonini, M., Cipollina, L., Poluzzi, E., Crema, F., Corazza, G. R., and De Ponti, F., Review article: clinical implications of enteric and central D2 receptor blockade by antidopaminergic gastrointestinal prokinetics.Aliment. Pharmacol. Ther., 19, 379–90 (2004).PubMedCrossRefGoogle Scholar
  41. Watkinson, A. C., Hadgraft, J., and Bye, A., Aspects of the transdermal delivery of prostaglandins.Int. J. Pharm., 74, 229–236 (1991).CrossRefGoogle Scholar
  42. Yazdanian, M. and Chen, E., The effect of diethylene glycol monoethyl ether as a vehicle for topical delivery of ivermectin.B.T. Gattefossé, 88, 69–70 (1995).Google Scholar

Copyright information

© The Pharmaceutical Society of Korea 2007

Authors and Affiliations

  • Yun-Seok Rhee
    • 1
  • Jai-Yong Huh
    • 1
  • Chun-Woong Park
    • 1
  • Tae-Young Nam
    • 1
  • Koog-Ryul Yoon
    • 1
  • Sang-Cheol Chi
    • 1
  • Eun-Seok Park
    • 1
  1. 1.College of PharmacySungkyunkwan UniversitySuwonKorea

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