Topical Formulation Studies with DEET (N,N‐Diethyl‐3‐methylbenzamide) and Cyclodextrins

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