AAPS PharmSciTech

, Volume 18, Issue 5, pp 1739–1749 | Cite as

Potential of Non-aqueous Microemulsions to Improve the Delivery of Lipophilic Drugs to the Skin

  • Vanessa F. Carvalho
  • Debora P. de Lemos
  • Camila S. Vieira
  • Amanda Migotto
  • Luciana B. Lopes
Research Article


In this study, non-aqueous microemulsions were developed because of the challenges associated with finding pharmaceutically acceptable solvents for topical delivery of drugs sparingly soluble in water. The formulation irritation potential and ability to modulate the penetration of lipophilic compounds (progesterone, α-tocopherol, and lycopene) of interest for topical treatment/prevention of skin disorders were evaluated and compared to solutions and aqueous microemulsions of similar composition. The microemulsions (ME) were developed with BRIJ, vitamin E-TPGS, and ethanol as surfactant-co-surfactant blend and tributyrin, isopropyl myristate, and oleic acid as oil phase. As polar phase, propylene glycol (MEPG) or water (MEW) was used (26% w/w). The microemulsions were isotropic and based on viscosity and conductivity assessment, bicontinuous. Compared to drug solutions in lipophilic vehicles, MEPG improved drug delivery into viable skin layers by 2.5–38-fold; the magnitude of penetration enhancement mediated by MEPG into viable skin increased with drug lipophilicity, even though the absolute amount of drug delivered decreased. Delivery of progesterone and tocopherol, but not lycopene (the most lipophilic compound), increased up to 2.5-fold with MEW, and higher amounts of these two drugs were released from MEW (2–2.5-fold). Both microemulsions were considered safe for topical application, but MEPG-mediated decrease in the viability of reconstructed epidermis was more pronounced, suggesting its higher potential for irritation. We conclude that MEPG is a safe and suitable nanocarrier to deliver a variety of lipophilic drugs into viable skin layers, but the use of MEW might be more advantageous for drugs in the lower range of lipophilicity.


lipophilic drugs microemulsion skin transdermal 



This study was supported by São Paulo Research Foundation (FAPESP grant#2013/16617-7) and PhRMA Foundation (Research Starter Grant in Pharmaceutics). Fellowships from CAPES (V. Carvalho) and FAPESP (D. de Lemos and A. Migotto) are greatly appreciated. We would like to thank Dr. A. Steiner for critical comments on the manuscript.


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Copyright information

© American Association of Pharmaceutical Scientists 2016

Authors and Affiliations

  • Vanessa F. Carvalho
    • 1
  • Debora P. de Lemos
    • 1
  • Camila S. Vieira
    • 1
  • Amanda Migotto
    • 1
  • Luciana B. Lopes
    • 1
    • 2
  1. 1.Department of Pharmacology, Institute of Biomedical SciencesUniversity of São PauloSão PauloBrazil
  2. 2.Albany College of Pharmacy and Health SciencesAlbanyUSA

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