AAPS PharmSciTech

, Volume 10, Issue 1, pp 54–61 | Cite as

Temperature-Sensitive Microemulsion Gel: An Effective Topical Delivery System for Simultaneous Delivery of Vitamins C and E

  • Branka Rozman
  • Alenka Zvonar
  • Francoise Falson
  • Mirjana Gasperlin
Research Article


Microemulsions (ME)—nanostructured systems composed of water, oil, and surfactants—have frequently been used in attempts to increase cutaneous drug delivery. The primary objective addressed in this work has been the development of temperature-sensitive microemulsion gel (called gel-like ME), as an effective and safe delivery system suitable for simultaneous topical application of a hydrophilic vitamin C and a lipophilic vitamin E. By changing water content of liquid o/w ME (o/w ME), a gel-like ME with temperature-sensitive rheological properties was formed. The temperature-driven changes in its microstructure were confirmed by rotational rheometry, viscosity measurements, and droplet size determination. The release studies have shown that the vitamins’ release at skin temperature from gel-like ME were comparable to those from o/w ME and were much faster and more complete than from o/w ME conventionally thickened with polymer (o/w ME carbomer). According to effectiveness in skin delivery of both vitamins, o/w ME was found the most appropriate, followed by gel-like ME and by o/w ME carbomer, indicating that no simple correlation between vitamins release and skin absorption could be found. The cytotoxicity studies revealed good cell viability after exposure to ME and confirmed all tested microemulsions as nonirritant.

Key words

antioxidant microemulsion gel rheology skin permeation vitamin 



Authors would like to thank Prof. Hans E. Junginger for helpful discussion. We are grateful to assistant Karmen Teskač for her assistance with fluorescence microscope.


  1. 1.
    M. Kreilgaard. Influence of microemulsions on cutaneous drug delivery. Adv. Drug Del. Rev. 54 Suppl 1:S77–S98 (2002).CrossRefGoogle Scholar
  2. 2.
    K. Welin-Berger, J. Neelissen, and B. Bergenstahl. In vitro permeation profile of a local anaesthetic compound from topical formulations with different rheological behaviour-verified by in vivo efficacy data. Eur. J. Pharm. Sci. 14:229–236 (2001).PubMedCrossRefGoogle Scholar
  3. 3.
    D. Libster, A. Aserin, and N. Garti. A novel dispersion method comprising a nucleating agent solubilized in a microemulsion, in polymeric matrix I. Dispersion method and polymer characterization. J. Colloid Interface Sci. 299:172–181 (2006).PubMedCrossRefGoogle Scholar
  4. 4.
    G. M. Eccleston. Microemulsions. In J. Swarbirck, and J. C. Boylan (eds.), Encyclopedia of Pharmaceutical Technology, Dekker, New York, 1994, pp. 411–412.Google Scholar
  5. 5.
    P. Spiclin, M. Homar, A. Zupancic-Valant, and M. Gasperlin. Sodium ascorbyl phosphate in topical microemulsions. Int. J. Pharm. 256:65–73 (2003).PubMedCrossRefGoogle Scholar
  6. 6.
    V. M. Adhami, D. N. Syed, N. Khan, and F. Afaq. Phytochemicals for prevention of solar ultraviolet radiation-induced damages. Photochem. Photobiol. 84:489–500 (2008).PubMedCrossRefGoogle Scholar
  7. 7.
    A. Svobodova, D. Walterova, and J. Vostalova. Ultraviolet light induced alteration to the skin. Biomed. Pap. Med. Fac. Palacky Univ. Olomouc Czech Repub. 150:25–38 (2006).Google Scholar
  8. 8.
    K. E. Burke. Interaction of vitamins C and E as better cosmeceuticals. Dermatol. Ther. 20:314–321 (2007).PubMedGoogle Scholar
  9. 9.
    M. P. Lupo. Antioxidants and vitamins in cosmetics. Clin. Dermatol. 19:467–473 (2001).PubMedCrossRefGoogle Scholar
  10. 10.
    J. Y. Lin, M. A. Selim, C. R. Shea, J. M. Grichnik, M. M. Omar, N. A. Monteiro-Riviere, and S. R. Pinnell. UV photoprotection by combination topical antioxidants vitamin C and vitamin E. J. Am. Acad. Dermatol. 48:866–874 (2003).PubMedCrossRefGoogle Scholar
  11. 11.
    E. Niki, N. Noguchi, H. Tsuchihashi, and N. Gotoh. Interaction among vitamin C, vitamin E, and beta-carotene. Am. J. Clin. Nutr. 62:1322S–1326S (1995).PubMedGoogle Scholar
  12. 12.
    A. Spernath, and A. Aserin. Microemulsions as carriers for drugs and nutraceuticals. Adv. Colloid Interface Sci. 128–130:47–64 (2006).PubMedCrossRefGoogle Scholar
  13. 13.
    I. P. Kaur, M. Kapila, and R. Agrawal. Role of novel delivery systems in developing topical antioxidants as therapeutics to combat photoageing. Ageing Res. Rev. 6:271–288 (2007).PubMedCrossRefGoogle Scholar
  14. 14.
    G. Bonacucina, M. Cespi, M. Misici-Falzi, and G. F. Palmieri. Colloidal soft matter as drug delivery system. J. Pharm. Sci. 981:1–42 (2008).CrossRefGoogle Scholar
  15. 15.
    J. Kristl, K. Teskac, M. Milek, and I. Mlinaric-Rascan. Surface active stabilizer Tyloxapol in colloidal dispersions exerts cytostatic effects and apoptotic dismissal of cells. Toxicol. Appl. Pharmacol. 2322:218–225 (2008).PubMedCrossRefGoogle Scholar
  16. 16.
    M. Tomsic, F. Podlogar, M. Gasperlin, M. Bester-Rogac, and A. Jamnik. Water-Tween 40/Imwitor 308-isopropyl myristate microemulsions as delivery systems for ketoprofen: small-angle X-ray scattering study. Int. J. Pharm. 327:170–177 (2006).PubMedCrossRefGoogle Scholar
  17. 17.
    F. Podlogar, M. Bester Rogac, and M. Gasperlin. The effect of internal structure of selected water-Tween 40-Imwitor 308-IPM microemulsions on ketoprofene release. Int. J. Pharm. 302:68–77 (2005).PubMedCrossRefGoogle Scholar
  18. 18.
    J. J. Koleng, J. W. McGinity, and W. R. Wilber. Carbomer. In R. C. Rowe, P. J. Sheskey, and P. J. Weller (eds.), Handbook of Pharmaceutical Excipients, Pharmaceutical, London, 2003, pp. 89–91.Google Scholar
  19. 19.
    A. R. Lee, and K. Tojo. An experimental approach to study the binding properties of vitamin E (alpha-tocopherol) during hairless mouse skin permeation. Chem. Pharm. Bull. 49:659–663 (2001).PubMedCrossRefGoogle Scholar
  20. 20.
    H. Guo, Z. Liu, J. Li, S. Nie, and W. Pan. Effects of isopropyl palmitate on the skin permeation of drugs. Biol. Pharm. Bull. 29:2324–2326 (2006).PubMedCrossRefGoogle Scholar
  21. 21.
    C. Caddeo, K. Teskac, C. Sinico, and J. Kristl. Effect of resveratrol incorporated in liposomes on proliferation and UV-B protection of cells. Int. J. Pharm. 3631–2:183–191 (2008).PubMedCrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2009

Authors and Affiliations

  • Branka Rozman
    • 1
  • Alenka Zvonar
    • 1
  • Francoise Falson
    • 2
  • Mirjana Gasperlin
    • 1
  1. 1.Department of Pharmaceutical Technology, Faculty of PharmacyUniversity of LjubljanaLjubljanaSlovenia
  2. 2.Laboratoire de Recherche et Development de Pharmacie Gallenique Industrielle, EA4169, Faculty of PharmacyUniversity of LyonLyonFrance

Personalised recommendations