Formulation of topical insect repellent N, N-diethyl- m-toluamide (DEET): vehicle effects on DEET in vitro skin permeation

Abstract

The broad-spectrum topical insect repellent N, N-diethyl- m-toluamide (DEET) is highly skin permeable, and serious adverse effects associated with the use of commercial DEET products have occurred in users due to extensive DEET skin permeation. In an effort to develop topical DEET formulations with reduced DEET skin permeation and extended repellency, this study investigated the effects of vehicle on DEET in vitro skin permeation from topical DEET solution and gel emulsion formulations prepared with ethanol, polyethylene glycol 400 (PEG 400), stearic acid and polyacrylic acid polymers Carbopol 940NF and Pemulen TR-2. In vitro skin permeation of DEET was evaluated in Franz diffusion cells using freshly excised abdominal cotton rat skin at 32±1°C. The receiver phase samples were analyzed by HPLC with N, N-diethyl-2-phenylacetamide as reference standard. Relative to technical DEET, 40 and 50% (v/v) aqueous ethanol solutions increased DEET steady-state skin flux ( J ss) by 157 and 137%, respectively, while 75% (v/v) aqueous ethanol solution, neat ethanol and PEG 400 decreased the J ss by 67, 74 and 59%, respectively. The incorporation of skin humectants glycerol, dimethicone or mineral oil to DEET gel emulsions based on Carbopol 940NF and stearic acid at 15% (w/w) did not significantly reduce the J ss. Compared with a name-brand lotion of 7.125% (w/w) DEET, the use of 20% (w/w) PEG 400 and 1% (w/w) Tween 80, or 75% (v/v) aqueous ethanol in Carbopol 940NF and Pemulen TR-2 based formulations containing 7.5% (w/w) DEET resulted in 22.7, 18.2 and 9.1% reduction in the J ss, respectively. For safety concerns, the incorporation of ethanol in commercial DEET products needs to be reevaluated. The topical formulation vehicle based on PEG 400, Carbopol 940NF and Pemulen TR-2 was effective in reducing DEET skin permeation.