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Pretreatment with a Water-Based Surfactant Formulation Affects Transdermal Iontophoretic Delivery of R-Apomorphine in Vitro

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Abstract

Purpose. To further increase the transdermal transport rate of R-apomorphine, a nonocclusive pretreatment with an aqueous surfactant formulation in combination with iontophoresis was explored in vitro.

Methods. The human stratum corneum was pretreated nonocclusively with formulations composed of laureth-3 oxyethylene ether (C12EO3), laureth-7 oxyethylene ether (C12EO7), and cholesterol sulfate (CSO4) prior to iontophoresis. The effect on the flux of the following parameters was examined: the composition, the charge, and the applied amount of surfactant formulations.

Results. The iontophoretic flux of R-apomorphine was appreciably increased by pretreatment with surfactant formulations. A formulation containing C12EO3/C12EO7/CSO4 at a molar ratio of 70:30:5 was very stable and increased the iontophoretic flux of R-apomorphine from 92.2 ± 13.9 nmol/cm2*h to 181.5 ± 22.6 nmol/cm2*h. When further increasing the negative charge of this formulation the iontophoretic transport rate was slightly inhibited. A dose of 40 μL/cm2 of the formulation with a total surfactant concentration of 5% (w/w) was sufficient for a maximum enhancing effect.

Conclusions. The results obviously show that nonocclusive pretreatment with the surfactant formulation enhances the iontophoretic transport of R-apomorphine, and is a promising approach to achieve therapeutic concentrations of R-apomorphine.

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REFERENCES

  1. C. Colosimo, M. Merello, and A. Albanese. Clinical usefulness of apomorphine in movement disorders. Clin. Neuropharmacol. 17:243-259 (1994).

    Google Scholar 

  2. D. Muguet, E. Broussolle, and G. Chazot. Apomorphine in patients with Parkinson's disease. Biomed. Pharmacother. 49:197-209 (1995).

    Google Scholar 

  3. H. Sage. Iontophoresis. In E. W. Smith and H. I. Maibach (eds.), Percutaneous Penetration Enhancers, CRS Press, Boca Raton, Florida, 1995 pp. 351-368.

    Google Scholar 

  4. V. Nair, O. Pillai, R. Poduri, and R. Panchagnula. Transdermal iontophoresis. Part I: Basic principles and considerations. Methods Find. Exp. Clin. Pharmacol. 21:139-151 (1999).

    Google Scholar 

  5. R. van der Geest, M. Danhof, and H. E. Boddé. Iontophoretic delivery of apomorphine I: In vitro optimization and validation. Pharm. Res. 14:1798-1803 (1997).

    Google Scholar 

  6. R. van der Geest, T. van Laar, J. Gubbens-Stibbe, H. E. Boddé, and M. Danhof. Iontophoretic delivery of apomorphine II: An in vivo study in patients with Parkinson's disease. Pharm. Res. 14:1804-1810 (1997).

    Google Scholar 

  7. S. Mitragotri. Synergistic effect of enhancers for transdermal drug delivery. Pharm. Res. 17:1354-1359 (2000).

    Google Scholar 

  8. E. H. Choi, S. H. Lee, S. K. Ahn, and S. M. Hwang. The pretreatment effect of chemical skin penetration enhancers in transdermal drug delivery using iontophoresis. Skin Pharmacol. Appl. Skin Physiol. 12:326-335 (1999).

    Google Scholar 

  9. S. Chesnoy, D. Durand, J. Doucet, and G. Couarraze. Structural parameters involved in the permeation of propranolol HCl by iontophoresis and enhancers. J. Control. Release 58:163-175 (1999).

    Google Scholar 

  10. K. Hirvonen, Kontturi L., Murtomäki P, Paronen, and A. Urtti. Transdermal iontophoresis of sotalol and salicylate; the effect of skin charge and penetration enhancers. J. Control. Release 26:109-117 (1993).

    Google Scholar 

  11. G. L. Li, R. van der Geest, L. Chanet, E. van Zanten, M. Danhof, and J. A. Bouwstra. In vitro iontophoresis of R-apomorphine across human stratum corneum: The structure/transport relationship of penetration enhancement. J. Control. Release.

  12. J. Baillie, A. T. Florence, L. R. Hume, G. T. Muirhead, and A. Rogerson. The preparation and properties of niosomes-nonionic surfactant vesicles. J. Pharm. Pharmacol. 37:863-868 (1985).

    Google Scholar 

  13. P. M. Frederik, P. H. H. Bomans, and M. C. A. Stuart. The ultrastructure of cryo-sections and intact vitrified cells the effect of cryoprotectanta and acceleration voltage on beam induced bubbling. Scanning Microsc. Suppl. 5:S43-S52 (1991).

    Google Scholar 

  14. J. Aungst. Structure/effect studies of fatty acid isomers as skin penetration enhancers and skin irritants. Pharm. Res. 6:244-247 (1989).

    Google Scholar 

  15. S. K. Gupta, S. Kumar, S. Bolton, C. R. Behl, and A. W. Malick. Effect of chemical enhancers and conducting gels on iontophoretic transdermal delivery of cromolyn sodium. J. Control. Release 31:229-236 (1994).

    Google Scholar 

  16. K. D. Peck, J. Hsu, S. K. Li, A. H. Ghanem, and W. I. Higuchi. Flux enhancement effects of ionic surfactants upon passive and elecroosmotic transdermal transport. J. Pharm. Sci. 87:1161-1169 (1998).

    Google Scholar 

  17. W. Hoss and C. Smiley. Binding and immobilization of catecholamines by liposomes. J. Neuroscience Res. 3:249-256 (1977).

    Google Scholar 

  18. V. Smith, R. B. Velagapudi, A. M. McLean, and R. E. Wilcox. Interactions of apomorphine with serum and tissue proteins. J. Med. Chem. Res. 28:613-620 (1985).

    Google Scholar 

  19. G. Cevc. Transfersomes, liposomes and other lipid suspensions on the skin: Permeation enhancement, vesicle penetration, and transdermal drug delivery [review]. Crit. Rev. Ther. Drug Carrier Syst. 13:257-388 (1996).

    Google Scholar 

  20. H. E. J. Hofland. Vesicles as transdermal drug delivery systems. Ph.D. Thesis, Leiden University, The Netherlands, 1992, pp. 93-132.

    Google Scholar 

  21. S. J. Jiang, S. M. Hwang, E. H. Choi, P. M. Elias, S. K. Ahn, and S. H. Lee. Structural and functional effects of oleic acid and iontophoresis on hairless mouse stratum corneum. J. Invest. Dermatol. 114:64-70 (2000).

    Google Scholar 

  22. K. S. Bhatia and J. Singh. Effect of linolenic acid/ ethanol or limonene/ethanol and iontophoresis on the in vitro percutaneous absorption of LHH and ultrastructure of human epidermis. Int. J. Pharm. 180:235-250 (1999).

    Google Scholar 

  23. K. S. Bhatia, S. Gao, T. P. Freeman, and J. Singh. Effect of penetration enhancers and iontophoresis on the ultrastructure and cholecystokinin-8 permeability though porcine skin. J. Pharm. Sci. 86:1011-1015 (1997).

    Google Scholar 

  24. N. Kalia and R. H. Guy. Interaction between penetration enhancers and iontophoresis: Effect on human skin impedance in vivo. J. Control. Release 44:33-42 (1997).

    Google Scholar 

  25. H. E. J. Hofland, J. A. Bouwstra, J. C. Verhoef, G. Buckton, B. Z. Chowdry, M. Ponec, and H. E. Junginger. Safety aspects of non-ionic surfactant vesicles: a toxicity study related to the physicochemical characteristics of non-ionic surfactants. J. Pharm. Pharmacol. 44:287-294 (1992).

    Google Scholar 

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Authors and Affiliations

  1. Department of Pharmaceutical Technology, Leiden Amsterdam Centre for Drug Research, University of Leiden, P.O. Box 9502, 2300 RA, Leiden, The Netherlands

    Gai Ling Li & Joke A. Bouwstra

  2. Department of Pharmacology, Leiden Amsterdam Centre for Drug Research, University of Leiden, P.O. Box 9502, 2300 RA, Leiden, The Netherlands

    Meindert Danhof

  3. Department of Pathology, University of Limburg, P.O. Box 616, 6200 MD, Maastricht, The Netherlands

    Peter M. Frederik

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  1. Gai Ling Li
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  2. Meindert Danhof
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  3. Peter M. Frederik
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  4. Joke A. Bouwstra
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Correspondence to Joke A. Bouwstra.

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Li, G.L., Danhof, M., Frederik, P.M. et al. Pretreatment with a Water-Based Surfactant Formulation Affects Transdermal Iontophoretic Delivery of R-Apomorphine in Vitro . Pharm Res 20, 653–659 (2003). https://doi.org/10.1023/A:1023211219118

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