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Role of n-methyl pyrrolidone in the enhancement of aqueous phase transdermal transport.

The role of n-methyl pyrrolidone (NMP) as an enhancer for permeants delivered from an aqueous phase was investigated in the transdermal delivery of the local anesthetics lidocaine free base, lidocaine-hydrochloride (HCl), and prilocaine-HCl. Lidocaine free-base flux increased from H2O/NMP binary systems containing over 50% (v/v) NMP with significant flux enhancement observed above 80% NMP. In this range, drug flux was found to correlate with NMP flux. The addition of oleic acid (1% w/v) further enhanced lidocaine flux sixfold, in these formulations. The H2O/NMP (50% v/v) system enhanced the transport of water-soluble hydrochloride salt derivatives of lidocaine and prilocaine by factors of 4.3 and 2.6, respectively, indicating that NMP was capable of enhancing hydrophilic and hydrophobic drugs from an aqueous phase. These findings were consistent with the model that NMP flux across the stratum corneum improves the transport of formulation solutes.