COMPARISON OF TOPICAL VEHICLES 309 Table VII Twenty-One Day Cumulative Irritancy Grade* Test Material Total Mean + S.D. p Value Caprylic/Capric Triglyceride 4.0 0.16 + 0.47 Propylene Glycol 72.0 2.88 + 7.31 0.0077 * 25 Subjects. no statistically significant differences between the effects of different vehicles on the bioactivity of the steroids at either the eight-hour or the 24-hour evaluations. Caprylic/capric triglyceride demonstrated a minimal potential compared to propylene glycol for causing irritation. When applied under occlusion for 21 days in 25 volunteers, caprylic/capric triglyceride elicited a total cumulative irritation score of 4, whereas propylene glycol had a total cumulative score of 72 (Table VII). This difference was statistically significant (p 0.01). Bioactivity of a topical dosage form can be optimized by using the minimum amount of solvent necessary to completely dissolve the drug. For several hydrophobic steroids, this requires high concentrations of propylene glycol. However, propylene glycol has been reported to be an irritant and/or sensitizer at high concentrations (10% or more). The in vitro and in vivo data show that caprylic/capric triglyceride is an acceptable vehicle for topical formulations, exhibiting an efficacy equal to that achieved with propylene glycol. Further, since caprylic/capric triglyceride is not an irritant and/or sensitizer, it can be safely used in place of propylene glycol in optimized formulations requiring high solvent concentration. CONCLUSIONS 1. The in vitro steady-state penetration flux of difiorasone diacetate from the caprylic/ capric triglyceride vehicle was higher than that from the propylene glycol vehicle. For the other steroids used in this study, no differences were observed in the in vitro penetration from the two vehicles. 2. There are no statistically significant differences between the vehicles in the in vivo vasoconstriction assay of selected corticosteroids. 3. Caprylic/capric triglyceride has significantly less potential for causing irritation (p 0.01) than propylene glycol. 4. Caprylic/capric triglyceride is a suitable vehicle for topical formulations and, due to lack of irritancy, is preferred over propylene glycol in optimized formulations requiring high solvent concentrations. ACKNOWLEDGEMENT The 21-Day Cumulative Irritancy Assay was performed by Derma Test Labs, Inc., Long Island, New York.

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