The influence of liquid crystalline phases on drug percutaneous absorption. I. Development of a vehicle.

A phase diagram approach has been used to formulate topically applied vehicles containing liquid crystalline phases. The current paper describes the construction of a major portion of the polyoxyethylene(20)cetyl ether:dodecanol:water phase diagram. Known mixtures of the three components were equilibrated and centrifuged to separate the resultant conjugate phases. These were identified and analyzed quantitatively to determine phase boundaries in relevant portions of the phase diagram. Two isotropic liquid phases, several two- and three-phase regions, a solid surfactant phase, and at least three distinct liquid crystalline phases were identified. The determination of tie lines was undertaken in a two-phase region containing an aqueous isotropic micellar solution and a liquid crystalline gel. This information will be used to prepare a number of vehicles of known phase composition and concentration for a systematic evaluation of the effect of liquid crystalline phases on transdermal drug delivery.