COMPARISON OF TOPICAL VEHICLES 307 on the bioactivity of the steroids was evaluated in the modified version of the McKenzie- Stoughton vasoconstriction assay (32), using a total of 30 subjects. The steroid prep- arations were occluded on the volar aspect of each subject's forearm in a double-blind randomized manner for a period of six hours. At six hours the occlusive dressings were removed, the excess steroids were washed from the test sites using tepid water, and the arms were patted dry. The test sites were evaluated for blanching at eight hours and again at 24 hours postapplication. The degree of blanching was determined uti- lizing the following scale: 0 = no blanching 1 = mild blanching 2 = moderate blanching 3 = maximum blanching 2 •-r)av CUMU•.aT•VF• mR•TaNCY assay The irritation potentials of caprylic/capric triglyceride and propylene glycol were com- pared, employing a modified method summarized by Phillips eta/. (33) and using a total of 25 normal, healthy volunteers. The test materials were applied in a double- blind fashion to each subject's back on a Webril © (nonwoven absorbent cotton material) patch (Kendall Products, Orthopedics Div., Boston, MA) and occluded to the skin with Scanpor © (Norgesplaster A/S. Oslo, Norway) tape. The materials were removed daily, except on Saturdays and Sundays, at which times the patches were left in situ until Monday. The sites were examined and graded for irritation, and then the materials were reapplied to the same sites. This procedure was continued for 21 days. The following grading system was used to evaluate the test sites: 0--No dermatitis 0.5--An equivocal dermatitis not covering the test site 1--Erythema covering the test site 2--Erythema and induration covering the test site 3--Erythema, induration, and vesicles covering the test site 4--Erythema, induration, vehicles, and/or bulla(e) covering the test site Table IV Influence of the Vehicle on the Solubility and Steady-State Flux of Steroids Steroid Vehicle No. Saturation Concentration (mg/mL) Flux* (mg/hr) X 104 Hydrocortisone Hydrocortisone Hydrocortisone 17-butyrate Hydrocortisone 17-butyrate Desonide Desonide Difiorasone Diacetate Diflorasone Diacetate 1-Propylene glycol 2-Caprylic/Capric Triglyceride 1-Propylene glycol 2-Caprylic/Capric Triglyceride 1-Propylene glycol 2-Caprylic/Capric Triglyceride 1-Propylene glycol 2-Caprylic/Capric Triglyceride 1.39 0.81 0.45 O.9O O.4O 0.53 0.07 0.23 17.17 + 4.90 18.49 + 8.00 1.80 + 0.09 2.36 + 0.60 8.34 + 4.30 12.93 + 8.50 0.48 + 0.20 1.89 --- O.4O * Average of 3 determinations.

308 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Table V Vasoconstriction Scores at Eight Hours* Steroid None Mild Moderate Maximum Average Vehicle (0) (1) (2) (3) Score p Value Hydrocortisone 17-butyrate Desonide Diflorasone Diacetate 1-Propylene glycol 1 (3.3%) 5 (16.7%) 11 (36.7%) 13 (43.3%) 2.20 0.05 2-Caprylic/Capric 1 (3.3%) 1 (3.3%) 14 (46.7%) 14 (46.7%) 2.37 1-Propylene glycol 1 (3.3%) 8 (26.7%) 16 (53.3%) 5 (16.7%) 1.83 0.05 2-Caprylic/Capric Triglyceride 2 (6.7%) 10 (33.3%) 12 (40.0%) 6 (20.0%) 1.73 1-Propylene glycol 3 (10.0%) 11 (36.7%) 10 (33.3%) 6 (20.0%) 1.63 0.05 2-Caprylic/Capric 2 (6.7%) 11 (36.7%) 7 (23.3%) 10(33.3%) 1.83 * 30 Subjects. RESULTS AND DISCUSSION The flux of hydrocortisone, hydrocortisone 17-butyrate, and desonide from the caprylic/ capric triglyceride vehicle was found to be similar to that from propylene glycol vehicle (Table IV). The flux of diflorasone diacetate was higher from the caprylic/capric tri- glyceride vehicle. Theoretically, if there are no skin-solvent interactions, the steady- state penetration flux of a given steroid from different vehicles should be the same, regardless of the solvents used (1). The results suggest that there is little or no inter- action between the skin and the two vehicles used in this study. The results of the vasoconstriction assay are summarized in Tables V and VI. The vasoconstrictor scores were evaluated using Wilcoxoh's signed ranks test. There were Table VI Vasoconstriction Scores at Twenty-four Hours* None Mild Moderate Maximum Average Steroid Vehicle (0) (1) (2) (3) Score p Value Hydrocortisone 17-butyrate 1-Propylene glycol 18 (60.0%) 12 (40.0%) -- -- 0.40 2-Caprylic/Capric Triglyceride 16 (53.3%) 12 (40.0•) 2 (6.7%) -- 0.53 Desonide 1-Propylene glycol 17 (56.7%) 12 (40.0%) 1 (3.3%) -- 0.47 Diflorasone Diacetate 2-Caprylic/Capric Triglyceride 13 (43.3%) 14 (46.7%) 3 (10.0%) 1-Propylene glycol 16 (53.3%) 10 (33.3%) 4 (13.3%) -- 1-Caprylic/Capric Triglyceride 14 (46.7%) 14 (46.7%) 2 (6.7%) -- 0.67 0.60 0.60 0.05 0.05 * 30 Subjects.