Transdermal delivery of anxiolytics: in vitro skin permeation of midazolam maleate and diazepam

The skin permeation profiles of midazolam maleate and diazepam from various solvent systems were investigated. Results were computed using a program designed to manipulate skin permeation data. It was shown that the permeation rates of diazepam and midazolam maleate may be affected by using aqueous mixtures of polar organic solvents. The effect of 1% and 5% Azone on the permeation of diazepam and midazolam maleate was studied. It was found that Azone increases the permeation fluxes of both drugs, the hydrophobic diazepam and the salt midazolam maleate. In the presence of 5% Azone in a solvent system of propylene glycol (PG-ETH-H₂O) the fluxes were increased 43 times for diazepam and 86 times for midazolam maleate. The performance of a novel hydrophilic transdermal matrix containing 50 mg midazolam maleate was tested in vitro. The steady-state flux obtained was used for a coarse estimation of the feasibility of transdermal administration of midazolam maleate.