EP0491076A1 — Penetration enhancement with multi-component system of N-aliphatic pyrrolidones with lower alcohols

USPTO Abstract

Penetration-enhancing pharmaceutical compositions for topical transepidermal and percutaneous application are disclosed which are non-irritating to the skin. These compositions are made up of a safe and effective amount of an active pharmaceutical permeant, including hydrophilic salt forms, contained in a novel penetration-enhancing vehicle comprising, (1) 0.01 to 20% w. of an N-aliphatic pyrrolidone, wherein the aliphatic portion is a C₈ to C₂₂ alkyl or alkenyl chain which can be a straight or branched; (ii) 5-75% w. of a lower alkanol selected from the group consisting of ethanol, propanol and isopropanol and mixtures thereof; (iii) 5.0 to 94.99% w. an inert carrier such as water and (iv) 0 to 20% w. of a cell-envelope disordering compound, such as methyl laurate, glycerol monolaurate, oleic acid, oleyl alcohol, glycerol monooleate, glycerol dioleate, glycerol trioleate and mixtures thereof. Capryl, lauryl, myristoleyl and oleyl pyrrolidones are exemplary of the N-alkyl or alkenyl pyrrolidones which may be utilized. The compositions may be administered to humans or warm-blooded animals by being applied directly to the skin or, preferably, administered in the form of a sustained release device such as a patch.