Transkarbams: Transdermal penetration-enhancing carbamates

Transkarbams (TRANSdermal penetration-enhancing CARBAMates) are a structurally unusual class of compounds that facilitate drug delivery through the skin. These two-chain amphiphiles containing an ammonium carbamate polar head are formed by the reaction of ω-amino acid derivatives (in particular, 6-aminohexanoates) with carbon dioxide. Transkarbams, e.g., 6-dodecyloxy-6-oxohexylammonium 6-dodecyloxy-6-oxohexylcarbamate (transkarbam 12 or T12), are up to an order of magnitude more active than Azone® (N-dodecylazepan-2-one or laurocapram) in enhancing the percutaneous penetration of a broad spectrum of drugs. Transkarbams act by a dual mechanism: first, the parent carbamate salt decomposes in the stratum corneum, which increases skin permeability, and second, the released protonated amino acid ester continues acting as an enhancer. The advantage of this dual effect is that the “daughter” enhancer, despite being less active, broadens the scope of action of the parent carbamate because it also enhances the permeation of hydrophilic drugs. Transkarbams are then degraded by esterases, which account for their low toxicity and low skin irritation. Due to these favorable properties, transkarbams meet the requirements for an ideal enhancer for transdermal or dermal drug delivery.