Journal of Pharmaceutical Investigation

The Korean Society of Pharmaceutical Sciences and Technology (한국약제학회)
권호 표지
DOI QR코드

DOI QR Code

Electrotransport of Levodopa through Skin: Permeation at Low pH

전류를 이용한 Levodopa의 경피전달: 낮은 pH에서의 투과

  • Jo, Jung-Eun (College of Pharmacy, Sookmyung Women's University) ;
  • Oh, Seaung-Youl (College of Pharmacy, Sookmyung Women's University)
  • 조정은 (숙명여자대학교 약학대학) ;
  • 오승열 (숙명여자대학교 약학대학)
  • Published : 2010.02.20
Download PDF
⟨ Previous Next ⟩

Abstract

In our previous work on levodopa delivery at pH 2.5 using iontophoresis, we found that cathodal delivery showed higher permeation than anodal delivery and electroosmosis plays more dominant role than electrorepulsion. In this work, we studied the transdermal transport of levodopa at very low pH (pH=1.0) where all levodopa molecules are cations, and evaluated some factors which affect the transdermal transport. The transport study at pH 2.5 was also conducted for comparison. The contribution of electrorepulsion and electroosmosis on flux was also evaluated. Using stable aqueous solution, the effect of electrode polarity, current density, current type and drug concentration on transport through skin were studied and the results were compared. We also investigated the iontophoretic flux from hydroxypropyl cellulose (HPC) hydrogel containing levodopa. In vitro flux study was performed at $33^{\circ}C$, using side-by-side diffusion cell. Full thickness hairless mouse skin were used. Current densities applied were 0.2, 0.4 or $0.6\;mA/cm^2$. Contrary to the pH 2.5 result, anodal delivery showed higher flux, indicating that electrorepulsion is the dominant force for the transport, overcoming the electroosmotic flow which is acting against the direction of electrorepulsion. Cumulative amount of levodopa transported was increased as the current density or drug concentration was increased. When amount of current dose was constant, continuous current was more beneficial than pulsed current in promoting levodopa permeation. Similar transport results were obtained when hydrogel was used as the donor phase. These results indicate that iontophoretic delivery of zwitterion such as levodopa is much complicated than that can be expected from small ionic molecules. The results also indicate that, only at very low pH like pH 1.0, electrorepulsion can be the dominant force over the electroosmosis in the levodopa transport.

Keywords

References

  1. T. Kankkunen, I. Huupponen, K. Lahtinen, M. Sundell, K. Ekman, K. Kontturi and J. Hirvonen, Improved stability and release control of levodopa and metaraminol using ionexchange fibers and transdermal iontophoresis, European Journal of Pharmaceutical Sciences, 16, 273-280 (2002). https://doi.org/10.1016/S0928-0987(02)00113-6
  2. A. Goodman Gilman, L.S. Goodman and A. Gilman, The Pharmacological Basis of Therapeutics, 6th Edition, Macmillan Publishing (1980).
  3. H.D. Kao, A. Traboulsi, S. Itoh and A. Hussain, Enhancement of the systemic and CNS specific delivery of L-dopa by the nasal administration of its water soluble prodrugs. Pharm. Res. 17, 978-984 (2000). https://doi.org/10.1023/A:1007583422634
  4. S.A. Jung, H.S. Gwak, I.K. Chun and S.Y. Oh, Levodopa transport through skin using iontophoresis: the role of electroosmosis and electrorepulsion, J. Kor. Pharm. Sci., 38(1), 31-38 (2008).
  5. R.H. Guy, Transdermal science and technology - an update, Drug Delivery System, 22(4) (2007).
  6. R. Burnette, Transdermal drug delivery : In J. Hadgratf, R.H. Guy (Eds.), Drug Delivery Reviews, Marcel Dekker, New York, pp. 247-292 (1988).
  7. J. Hirvonen, Y.N. Kalia and R.H. Guy, Transdermal delivery of peptides by iontophoresis, Nat. Biotech. 14, 1710-1713 (1996). https://doi.org/10.1038/nbt1296-1710
  8. J. Hirvonen and R.H. Guy, Iontophoretic delivery across the skin: Electroosmosis and its modulation by drug substances, Pharm. Res. 9, 1258-1263 (1997). https://doi.org/10.1023/A:1012127512251
  9. R.C. Scott, R.H. Guy and J. Hadgraft, Prediction of percutaneous penetration: Methods, Measurements and Modelling, IBC technical Services, London, UK, 19-33 (1990).
  10. G.L. Flynn, R.L. Bronaugh and H.I. Mailbach, Percutaneous absortion, Marcel Dekker, New York, U.S.A., 27-51 (1989).
  11. V. Merino, A. Lopez, Y.N. Kalia and R.H. Guy, Electrorepulsion versus electroosmosis : effect of pH on the iontophoresis flux of 5-fluorouracil, Pharm. Res., 16(5), 758-761 (1999). https://doi.org/10.1023/A:1018841111922
  12. J.P. Hsu and B.T. Liu, Transport of ions through elliptic ionselective membrane, J. Memb. Sci., 142(2), 245-255 (1998). https://doi.org/10.1016/S0376-7388(97)00335-9
  13. M.J. Pikal and S. Shah, Transport mechanisms in iontophoresis. III. An experimental the contributions of electroosmotic flow and permeablity change in transport of low high molecular weight solutes, Pharm. Res., 7, 222-229 (1990). https://doi.org/10.1023/A:1015809725688
  14. T. Kankkunen, I. Huuponen, K. Lahtinen, M. Sundell, K. Ekman, K. Kontturi and J. Hirvonen, Improved stability and release control of levodopa and metaraminol using ionexchange fibers and transdermal iontophoresis, Eur. J.Pharm. Sci., 16(4-5), 273-80 (2002). https://doi.org/10.1016/S0928-0987(02)00113-6
  15. D.J. Stennett, J.M. Christensen, J.L. Anderson and K.A. Parrott, Stability of levodopa in 5% dextrose injection at pH 5 or 6, Am. J. Hospital Pharm., 43(7), 1726-1728 (1986).
  16. Viquiry material safety data sheet, http://www.vinquiry.com.
  17. X. Chen, J. Xie, C. Li and Z. Hu, Investigation of the factors that induce analyte peak splitting in capillary electrophoresis. J. Sep. Sci., 27(12), 1005-1010 (2004). https://doi.org/10.1002/jssc.200401817
  18. R.H. Guy, Y.N. Kalia, M.B. Delgado-Charro, V. Merino, A. Lopez and D. Marro, Electrorepulsion and electroosmosis, J. Control. Rel., 64, 129-132 (1995). https://doi.org/10.1016/S0168-3659(99)00132-7
  19. B.D. Bath, H.S. White and E.R. Scott, Visualization and analysis of electroosmotic in hairless mouse skin, Pharm. Res., 17, 471-475 (2000). https://doi.org/10.1023/A:1007589306661
  20. D. Marro, R.H. Guy and M.B. Delgado-Charro, Characterization of the iontophoretic properties of human and pig skin, J. Control. Rel., 70, 213-217 (2001). https://doi.org/10.1016/S0168-3659(00)00350-3
  21. J.H. Lee and S.Y. Oh, Current pretreatment of skin and its effect on the permeability, J. Kor. Pharm. Sci., 35(2), 81-87 (2005).
  22. R.R. Burnette and T.M. Bagniefski, Influence of constant current iontophoresis on the impedance and passive Na+ permeability of excised mouse skin, J. Pharm. Sci., 77, 492-497 (1988). https://doi.org/10.1002/jps.2600770606
  23. S.Y. Oh and R.H. Guy, Effect of iontophoresis on the electrical properties of human skin in vivo, Int. J. Pharm., 124, 137-142 (1995). https://doi.org/10.1016/0378-5173(95)00180-Q
  24. B. Langer, New methods of drug delivery, Science, 249, 1527-1533 (1990). https://doi.org/10.1126/science.2218494
  25. A.M. Mathur, S.K. Moorjani and A.B. Scranton, Methods or synthesis of hydrogel networks: a review, Macromol. Chem. Physics, C36(2), 405-430 (1996). https://doi.org/10.1080/15321799608015226
  26. M.D. Blanco, O. Garcia, R. Olmo, J.M. Teijon and I. Katime, Release of 5-fluorouracil from poly (acrylamide-comonopropylitaconate) hydrogels, J. Chrom. B., 680, 243-253 (1996). https://doi.org/10.1016/0378-4347(95)00401-7

Cited by

  1. Modulation of Electroosmotic Flow through Skin: Effect of Poly(Amidoamine) Dendrimers vol.26, pp.2, 2018, https://doi.org/10.4062/biomolther.2017.203