DOI QR코드

DOI QR Code

Iontophoretic Delivery of Vitamine C-2-phosphate from Carbopol Hydrogel

하이드로겔을 이용한 비타민 C-인산염의 이온토포레시스 피부투과

  • 오승열 (숙명여자대학교 약학대학)
  • Published : 2007.06.21

Abstract

In order to develop an optimum formulation for iontophoretic delivery of vitamine C-2-phosphate (VCP) from Carbopol hydrogel, we have investigated various factors which can affect the iontophoretic flux through skin. Such factors as drug concentration, current density, current profile, current duration, ionic strength, pH and percutaneous enhancers (ethanol, glycerine, propylene glycerol, sorbitol, urea) were studied. Compared to the flux by passive or anodal delivery, the flux by cathodal delivery increased markedly, and thus, only cathodal delivery was used in the rest of the flux experiments. Flux increased linearly as the drug concentration and current density increased. As the duration of current application increased from 30 min to 120 min, flux increased linearly, however the AUC was not directly proportional to the applied amount of current. Flux also increased as the pH increased, possibly due to the increase in ionization of phosphate group. As the ionic strength increased, flux decreased. No significant increase in flux was observed after enhancer application, indicating that the effect of current on flux is dominating over the effect of percutaneous enhancers (P>0.05). These results provide important informations that are needed for optimal formulation of iontophortic delivery for VCP.

Keywords

References

  1. J. Uitto, M. J. Fazio and D. R. Olsen, Molecular mechanism of cutaneous aging, J. Am. Acad. Dermatol., 21, 614-622 (1989) https://doi.org/10.1016/S0190-9622(89)70228-0
  2. D. Darr, S. Combs, S. Dunston, T. Manning and S. Pinnell, Topical vitamin C protects porcine skin from ultraviolet radiationinduced damage, Br. J. Dermatol., 53, 127-247 (1992) https://doi.org/10.1111/j.1365-2133.1941.tb10539.x
  3. A. D. Harper, G. J. Handelman, J. M. Harris, C. A. Belmont and J. B. Blumberg, Protection by vitamin C of loss of vitamin E in cultured rat hepatocytes, Arch. Biochem. Biophys., 359, 305-309 (1998) https://doi.org/10.1006/abbi.1998.0914
  4. B. V. Nusgens, P. Humbert, A. Rougier, A. C. Colige, M. Haftek, C. A. Lambert, A. Richard, P. Creidi and C. M. Lapiere, Topically applied vitamin C enhances the mRNA level of collagen I and III their processing enzymes and tissue inhibitor of matrix metalloproteinase 1 in the human dermis, J. Invest. Dermatol., 116(6), 853-859 (2001) https://doi.org/10.1046/j.0022-202x.2001.01362.x
  5. K. Kameyama, C. Sakai, S. Kondoh, K. Yonemoto, S. Nishiyama, M. Tagawa, T. Murata, T. Ohnuma, J. Quigley, A. Dorsky, D. Bucks and K. Blanock, Inhibitory effect of magnesium L-ascorbyl-2-phosphate (VC-PMG) on melanogenesis in vitro and in vivo, J. Am. acad. Dermatol., 34(1), 29-33 (1996) https://doi.org/10.1016/S0190-9622(96)90830-0
  6. H. I. Roach, K. Hillier and J. R. Shearer, Stability of ascorbic acid and uptake of the vitamin by embryonic chick femurs during long-term culture, Biochim. Biophys. Acta, 842, 133-138 (1985) https://doi.org/10.1016/0304-4165(85)90194-1
  7. R. Austria, A. Semenzato and A. Bettero, Stability of vitamin c derivatives in solution and topical formulations, J. Pharm. Biomed. Anal., 15, 795-801 (1997) https://doi.org/10.1016/S0731-7085(96)01904-8
  8. S. Nayama, M. Takehana, M. Kanke, S. Itoh, E. Ogata and S. Kobayashi, Protective effects of sodium-L-ascorbyl-2 phosphate on the development of UVB-induced damage in cultured mouse skin, Biol. pharm. bul., 22(12), 1301-1305 (1999) https://doi.org/10.1248/bpb.22.1301
  9. S. Kobayashi, M. Takehana, S. Itoh and E. Ogata, Effect of magnesium-L-ascorbyl-2-phosphate on cutaneous damage induced by UVB irradiation, Photomed. Photobiol., 17, 39-40 (1995)
  10. D. C. Mahan, A. J. Lepine and K. Dabrowski, Efficacy of magnesium-L-ascorbyl-2-phosphate as a vitamin C source for weanling and growing-finishing swine, J. Animal Science, 72(9), 2354-2356 (1994) https://doi.org/10.2527/1994.7292354x
  11. T. Ueda, R. Soeda, H. Suzuki and K. Akao, Noninvasive detection of L-ascorbyl-2 -phosphate transported into skin by iontophoresis, J. Fragrance, 31(8), 120-125 (2003)
  12. A. R. Elmore, Final report of the safety assessment of LAscorbic Acid, Calcium Ascorbate, Magnesium Ascorbate, Magnesium Ascorbyl Phosphate, Sodium Ascorbate, and Sodium Ascorbyl Phosphate as used in cosmetics, Int. J. Toxicol., 24(Suppl 2), 51-111 (2005) https://doi.org/10.1080/10915810590936382
  13. D. Ross, S. Mendiratta, Z. C. Qu, C. E. Cobb and J. M. May, Ascorbate 6-palmitate protects human erythrocytes from oxidative damage, Free Rad. Biol. Med., 26, 81-89 (1999) https://doi.org/10.1016/S0891-5849(98)00198-1
  14. R. Panchagnula, O. Pillai, V. B. Nair and P. Ramarao, Transdermal iontophoresis revisited, Curr. Opin. Chem. Biol., 4(4), 468-473 (2000) https://doi.org/10.1016/S1367-5931(00)00111-3
  15. Y. Wang, R. Thakur, Q Fan and B. Michniak, Transdermal iontophoresis: combination strategies to improve transdermal iontophoretic drug delivery, Eur. J. Pharm. Biopharm., 60, 179-191 (2005) https://doi.org/10.1016/j.ejpb.2004.12.008
  16. V. Nair, O. Pillai, R. Poduri and R. Panchagnula, Transdermal iontophoresis. Part 1: basic principles and considerations, Methods Find Exp, Clin, Pharmacol., 21(2), 139-151 (1999) https://doi.org/10.1358/mf.1999.21.2.529241
  17. N. Kanikkannan, Iontophoresis-based transdermal delivery systems, BioDrugs, 16(5), 339-347 (2002) https://doi.org/10.2165/00063030-200216050-00003
  18. G. M. Khan and Z. Jaibai, Formulation and in vitro evaluation of Ibuprofen-Carbopol 974P-NF controlled release matrix tablets III influence of co-exepients on release rate of drug, J. Contr. Rel., 54, 185-190 (1998) https://doi.org/10.1016/S0168-3659(97)00225-3
  19. M. K. Chun, B. T. Kwak and H. K. Choi, Preparation of buccal patch composed of carbopol, poloxamer and hydroxypropyl methylcellulose, Archiv. Pharmacal Research, 26(11), 973-978 (2003) https://doi.org/10.1007/BF02980208
  20. S. Proniuk and J. Blanchard, Anhydrous Carbopol polymer gels for the topical delivery of oxygen/water sensitive compounds, Pharm. Develop. Tech., 7(2), 249-255 (2002) https://doi.org/10.1081/PDT-120003492
  21. A. Semenzato, R. Austria, C. Dall'Aglio and A. Bettero, High-performance liquid chromatographic determination of ionic compounds in cosmetic emulsions: application to magnesium ascorbyl phosphate, J. chrom. A., 705(2), 385-389 (1995) https://doi.org/10.1016/0021-9673(95)00149-H
  22. M. J. Pikal and S. Shah, Transport mechanisms in. iontophoresis. I. A theoretical model for the effect of. electroosmotic flow on flux enhancement in transdermal iontophoresis, Pharm Res., 7, 118-126 (1990) https://doi.org/10.1023/A:1015816532532
  23. M. J. Pikal and S. Shah, Transport mechanisms in iontophoresis. III. An experimental study of the contributions of electroosmotic flow and permeablity change in transport of low and high molecular weight solutes, Pharm. Res., 7, 222-229 (1990) https://doi.org/10.1023/A:1015809725688
  24. R. H. Guy, Y. N. Kalia, M. B. Delgado-Charro, V. Merino, A. Lopez and D. Marro, Iontophoresis: Electrorepulsion and electroosmosis, J. Contr. Rel., 64, 129-132 (2000) https://doi.org/10.1016/S0168-3659(99)00132-7
  25. 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)
  26. S. Y. Oh, Transdermal delivery of ketoprofen and the effect of electroosmosis, J. Kor. Pharm. Sci., 34(6), 491-497 (2004)
  27. C. Cullander and R. H. Guy, Sites of iontophoretic current flow into the skin: Identification and characterization with the vibrating probe electrode, J. Invest. Dermatol., 97, 55-64 (1991) https://doi.org/10.1111/1523-1747.ep12478060
  28. R. R. Burnette and B. Ongpipattanakul, Characterization of the pore transport properties and tissue alteration of excised human skin during iontophoresis, J. Pharm. Sci., 76, 765-773 (1987) https://doi.org/10.1002/jps.2600761003
  29. J. Hirvonen and R. H. Guy, Iontophoretic delivery across the skin: electroosmosis and its modulation by drug substances, Pharm. Res., 14(9), 1258-1263 (1997) https://doi.org/10.1023/A:1012127512251
  30. M. B. Delgado-Charro, A. M. Rodriguez-Bayon and R. H. Guy, Iontophoresis of nafarelin: effects of current density and concentration on electrotransport in vitro, J. Control. Rel., 35, 35-40 (1995) https://doi.org/10.1016/0168-3659(95)00015-Z
  31. A. Luzardo-Alvarez, M. B. Delgado-Charro and J. Blanco-Mendez, Iontophoretic delivery of ropinirole hydrochloride: effect of current density and vehicle formulation, Pharm. Res., 18, 1714-1720 (2001) https://doi.org/10.1023/A:1013322613436
  32. J. A. Kim and S. Y. Oh, Iontophoretic transport of letoprofen, J. Kor. Pharm. Sci., 34(4), 275-281 (2004)