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Effect of tretinoin inclusion in dimethyl-beta-cyclodextrins on release rate from a hydrogel formulation

  • Andreia Ascenso
  • Filipe Vultos
  • Diogo Ferrinho
  • Ana Salgado
  • Samuel Guerra Filho
  • Viviane Ferrari
  • Sandra Simões
  • Helena Cabral Marques
Short Communication

Abstract

The aim of this work was to study the release, permeation and skin retention profiles of 0.05% tretinoin hydrogel formulations in which tretinoin was in free form or complexed with dimethyl-beta-cyclodextrin in a stoichiometry of 1:4. Theoretically, this complexation will mainly allow to: overcome drug’s low water solubility and low stability; enhance the drug permeation by promoting skin absorption and alleviate drug inducing local irritation. In vitro release, permeation and skin retention tests were performed in both formulations in order to compare the main advantages of this complexation. The influence of the thermodynamic activity on the drug release profile was also investigated. This study proved that tretinoin inclusion complexes formulation with excess of cyclodextrins had better release profile than the free tretinoin formulation. It was concluded that in this study, thermodynamic activity was not the driving force for the release rate improvement observed with cyclodextrins. Probably, this improvement was due to the increased availability of tretinoin near the membrane surface. In fact, the percentage of total drug that had been retained in the skin was 0.41 ± 0.08% for complexed tretinoin gel and 0.17 ± 0.04% for the free tretinoin gel.

Keywords

Tretinoin Dimethyl-beta-cyclodextrin In vitro drug release/permeation and skin retention Thermodynamic activity 

Notes

Acknowledgments

We thank to Marta Machado from iMed for technical support; to Allergisa, S. Paulo, Campinas, Brazil for the performance of the active retention studies and to Dr. John Pugh from the University of Wales, College of Cardiff for the Modelling Enhancer Activity calculations.

References

  1. 1.
    Ascenso, A., Marques, H.: Cabral: acne in the adult. J. Med. Chem. 9, 1–10 (2009)Google Scholar
  2. 2.
    Zaenglein, A.: Topical retinoids in the treatment of Acne Vulgaris. Semin. Cutan. Med. Surg. 27, 177–182 (2008)CrossRefGoogle Scholar
  3. 3.
    Ascenso, A., Duarte, A., Silva, A., Salgado, A., Marques, H. Cabral: Formulation studies on a topical gel of tretinoin—dimethyl-beta-cyclodextrin complex. J. Incl. Phenom. Macrocycl. Chem. (2009). doi: 10.1007/s10847-010-9745-0
  4. 4.
  5. 5.
    Baumann, L.: Cosmetic Dermatology, McGraw-Hill Professional, New York, pp. 85–92 (2002)Google Scholar
  6. 6.
    Vuligonda, V., Lin, Y., Thacher, S., Standeven, A., Kochar, D., Chandraratna, R.: A new class of RAR subtype selective retinoids: correlation of pharmacological effects with receptor activity. Bioorg. Med. Chem. 7, 263–270 (1999)CrossRefGoogle Scholar
  7. 7.
    Caddeo, C., Manconi, M., Valenti, D., Pini, E., Sinico, C.: Photostability and solubility improvement of beta-cyclodextrin-included tretinoin. J. Incl. Phenom. Macrocycl. Chem. 59, 293–300 (2007)CrossRefGoogle Scholar
  8. 8.
    Montassier, P., Duchene, D., Poelman, M.-C.: Inclusion complexes of tretinoin with cyclodextrins. Int. J. Pharm. 153, 199–209 (1997)CrossRefGoogle Scholar
  9. 9.
    Szejtli, J.: Utilization of cyclodextrins in industrial products and processes. J. Mater. Chem. 7, 575–587 (1997)CrossRefGoogle Scholar
  10. 10.
    Masson, M., Loftsson, T., Másson, G., Stefánsson, E.: Cyclodextrins as permeation enhancers: some theoretical evaluations and in vitro testing. J. Control Release 59, 107–118 (1999)CrossRefGoogle Scholar
  11. 11.
    Challa, R., Ahuja, A., Ali, J., Khar, R.K.: Cyclodextrins in drug delivery: an updated review. AAPS Pharmscitech 6, E329–E357 (2005)CrossRefGoogle Scholar
  12. 12.
    Sigurdsson, H., Stefánsson, E., Gudmundsdóttir, E., Eysteinsson, T., Thorsteinsdottir, M., Loftsson, T.: Cyclodextrin formulation of dorzolamide and its distribution in the eye after topical administration. J. Control Release 10, 255–262 (2005)CrossRefGoogle Scholar
  13. 13.
    Melo, N., Grillo, R., Rosa, A., Fraceto, L.: Interaction between nitroheterocyclic compounds with β-cyclodextrins: phase solubility and HPLC studies. J. Pharm. Biomed. Anal. 47, 865–869 (2008)CrossRefGoogle Scholar
  14. 14.
    Hadgraft, J.: Skin, the final frontier. Int. J. Pharm. 224, 1–18 (2001)CrossRefGoogle Scholar
  15. 15.
    Tashtoush, B., Jacobson, E., Jacobson, M.: A rapid HPLC method for simultaneous determination of tretinoin and isotretinoin in dermatological formulations. J. Pharm. Biomed. Anal. 43, 859–864 (2007)CrossRefGoogle Scholar
  16. 16.
    Brown, C.K., Chokshi, H. P., Nickerson, B., Reed, R.A., Rohrs, B.R., Shah, P.A.: Acceptable analytical practices for dissolution testing of poorly soluble compounds. Pharm. Technol. 28, 56–65 (2004)Google Scholar
  17. 17.
    Jug, M., Becirevic-Lacan, M., Kwokal, A., Cetina-Cizmek, B.: Influence of cyclodextrin complextation on piroxicam gel formulations. Acta Pharm 55, 223–236 (2005)Google Scholar
  18. 18.
    Vyas, A., Saraf, S.: Cyclodextrin based novel drug delivery systems. J. Incl. Phenom. Macrocycl. Chem. 62, 23–42 (2008)CrossRefGoogle Scholar
  19. 19.
    Bettoni, C.C.: Avaliação da Penetração Cutânea de nanocápsulas de isotretinoína por tape stripping in vitro em pele humana e suína. Master Thesis, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (2009)Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Andreia Ascenso
    • 1
  • Filipe Vultos
    • 1
  • Diogo Ferrinho
    • 1
  • Ana Salgado
    • 1
  • Samuel Guerra Filho
    • 2
  • Viviane Ferrari
    • 2
  • Sandra Simões
    • 1
  • Helena Cabral Marques
    • 1
  1. 1.Faculdade de FarmáciaUniversidade de Lisboa, Av. Prof. Gama PintoLisbonPortugal
  2. 2.Grupo Investiga, Lasa Pesquisas Laboratoriais, Lda/AllergisaCampinasBrazil

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