Topical formulation studies with DEET (N, N-diethyl-3-methylbenzamide) and cyclodextrins

Stefan Proniuk, Bianca M. Liederer, Sarah E. Dixon, Judith A. Rein, Michael A. Kallen, James Blanchard

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


The purpose of this study was to investigate the utility of cyclodextrins as a safer alternative to the commonly used cosolvent ethanol in topical N, N-diethyl-3-methylbenzamide (DEET) formulations. Ethanol is a known penetration enhancer and would ideally not be used in a formulation containing DEET, a compound known for its potential toxicity. DEET formulations were prepared containing up to 20% w/w γ-cyclodextrin (GCD) or 30% w/w hydroxypropyl-β-cyclodextrin (HPBCD). These formulations were evaluated by determining the release rate of DEET from its vehicle through a synthetic membrane into a receiver medium with a high affinity for DEET using a fully automated Franz-diffusion cell system. DEET release was measured by ultraviolet spectrophotometry at 260 nm. Both the traditional Higuchi release model and an alternate repeated measures analysis of variance with nested factors were used to analyze the data. The influence of the cyclodextrins on the volatility of DEET was determined by solid-phase microextraction. Morphological characterization of the formulations was performed by light microscopy. Physical stability of the formulations was evaluated by rheology in an accelerated study performed at 50°C for 28 days. The cyclodextrins caused a decrease in the release of DEET from its vehicle compared with an ethanol-containing formulation. This effect became more pronounced as the amount of cyclodextrin in the formulation was increased. The addition of the cyclodextrins resulted in a cream-like product compared with the ethanol formulation, which was a lotion. The DEET formulations had the following rank order of volatility: ethanol < DEET = GCD < HPBCD. Examination of the formulations by light microscopy indicated that the CD-based formulations produced a smaller and more homogeneous droplet size distribution than the ethanol-based formulations. The accelerated physical stability study indicated that cyclodextrin-based formulations are both technically and commercially feasible. Cyclodextrins are a promising alternative to ethanol in DEET-containing formulations. The reduced release rate of DEET from these formulations suggests that the toxic potential of DEET may be decreased in these products, while its repellency and stability are maintained.

Original languageEnglish (US)
Pages (from-to)101-110
Number of pages10
JournalJournal of Pharmaceutical Sciences
Issue number1
StatePublished - Jan 1 2002


  • Cyclodextrin
  • DEET
  • In vitro release
  • Light microscopy
  • Viscosity
  • Volatility

ASJC Scopus subject areas

  • Pharmaceutical Science

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