EFFECT OF LIPOPHILIC MULTICOMPONENT SYSTEM ON THE SKIN PERMEATION OF KETOTIFEN FUMARATE

The effect of a lipophilic chemical enhancer system on the skin permea tion of ketotifen fumarate (KF) was investigated in vitro using excise d hairless rat skin. Organic acids, alcohols and oleaginous solvents w ere selected as fundamental components of the system. Among the severa l lipophilic systems, a ternary component vehicle consisting of L-lact ic acid, ethanol and isopropyl myristate (IPM) (3:10:87) exhibited a s ignificant skin penetration-enhancing effect. The rank order of the ef fect on KF skin permeation for oleaginous components containing ethano l or L-lactic acid/ethanol was IPM > ethyl oleate > diisobutyl adipate > oleic acid. This order was similar to that on ethanol flux. The KF permeation was thus enhanced and regulated by the ethanol permeation. The KF flux from various alcohol/IPM systems was increased, with an in crease in the solubility parameter of alcohols. L-Lactic acid in the a lcohol/IPM systems did not have a marked effect on the alcohol flux, w hereas it increased the KF flux. Addition of several organic acids int o the ethanol/IPM system (1:10:89) shortened the lag time of KF permea tion, and the effect may be related to these chain lengths and functio nal groups.