Local anesthesia in the skin occurs approximately 1 h after application of a commercial topical formulation of lidocaine and prilocaine prepared as a eutectic mixture. A number of lidocaine salts was screened and lidocaine-ibuprofen was found to form a room-temperature ionic liquid. When applied to the skin of rats, local anesthesia of skin was achieved within 10-20 min in the rats' paws and tails with no apparent adverse effects to the skin as determined by histological analysis. We believe that the lidocaine-ibuprofen ionic liquid increased lidocaine absorption into the skin due to the high lidocaine concentration in the ionic liquid and due to possible interactions between the ionic liquid and the skin to increase skin permeability. These findings suggest that lidocaine-ibuprofen ionic liquid may provide a more rapid method of drug delivery to the skin for local anesthesia. (c) 2015 American Institute of Chemical Engineers AIChE J, 61: 2732-2738, 2015