IRRITATION POTENTIAL OF A NEW TOPICAL TRETINOIN FORMULATION AND A COMMERCIALLY-AVAILABLE TRETINOIN FORMULATION AS MEASURED BY PATCH TESTINGIN HUMAN-SUBJECTS

Background: A novel tretinoin preparation uses polyolprepolymer-2, a c ompound designed to reduce skin irritation by helping retain drugs on and in the surface layers of the skin. Objective: We used patch testin g to measure the effect of polyolprepolymer-2 on tretinoin-associated irritation. Methods: Two patch test studies were conducted. The first assessed the effect of polyolprepolymer-2 by comparing commercially-av ailable tretinoin formulations with respective polyolprepolymer-contai ning formulations of 0.025% tretinoin gel and 0.025%, 0.05%, and 0.1% tretinoin creams. The second assessed the effect of the polyolprepolym er-2 concentration on the potential decrease in irritation by comparin g: (1) a commercially-available tretinoin cream with prototype tretino in creams containing 20% polyolprepolymer-2 at three different concent rations of tretinoin (0.025%, 0.05%, and 0.1%); and (2) the effect of three different polyolprepolymer-2 concentrations (10%, 15%, and 20%) in prototype tretinoin creams on cumulative irritation. Patch agents w ere assigned to subjects according to a randomization schedule, and du ring a period of 5 days each subject received three 24-hour exposures to the test materials. Twenty-four hours elapsed between old patch rem oval and new patch application. Results: In the first study, the treti noin gel and cream containing polyolprepolymer-2 caused significantly less irritation than all equivalent formulations of the commercially-a vailable tretinoin gel and creams except the 0.025% cream formulation. Irritation scores were not significantly different in terms of irrita tion in the 0.025% creams although scores did indicate a trend towards lower irritation with 0.025% tretinoin cream containing polyolprepoly mer-2. In the second study, the tretinoin gel containing polyolprepoly mer-2 and the three tretinoin prototype creams also containing polyolp repolymer-2 caused significantly less irritation than comparable conce ntrations of the commercially-available tretinoin. In addition, the 0. 025% tretinoin gel formulation containing polyolprepolymer-2 was no mo re irritating than the commercially-available 0.025% tretinoin cream. Conclusion: Tretinoin formulations containing polyolprepolymer-2 are, in general, less irritating than the currently marketed tretinoin form ulations.