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1 From the Medical Research Division, Edgewood Arsenal, Maryland
1. A study of the cutaneous absorption of methyl salicylate was conducted, the ester being applied in pure form, in aqueous suspensions; in solution in certain oils and in alcohol; in ointment bases. The surfaces of both hands served as the area of application in the great majority of the experiments, the duration being one hour and the temperature of immersion baths 43° to 44°C. The quantity absorbed was measured by the excretion of salicyl in the urine expressed in milligrams of sodium salicylate.
2. The maximum absorption resulted from immersion in an aqueous suspension of the ester of 11.8 volume per cent; the next in order from immersion in a 50 per cent solution in ethyl alcohol; and the minimum from immersion in the pure ester. The three respective average quantities were 694, 488, and 95 mgm.
3. Immersion in an aqueous suspension of 11.8 volume per cent as compared with immersion in pure methyl salicylate resulted in a rise of 632 per cent. The effect of intermittent immersion in methyl salicylate with and without massage was contrasted with alternate immersion in hot water and the ester with and without massage with an increased absorption of 126 and 101 per cent respectively.
4. Immersion was conducted in a 50 per cent solution of methyl salicylate in the following vehicles in order to study their comparative influence on absorption. There was no essential difference between olive and lard oil. The absorption, however, from liquid petrolatum and anhydrous lanoline was 26 and 66 per cent higher respectively. The absorption results for these 50 per cent solutions exceeded in all instances that found with the pure ester: the increase varying from 29 per cent with lard oil to 117 per cent with anhydrous lanoline. The influence of alternate immersion in hot water and the ester solution with massage was compared with continuous immersion; the absorption from lard oil and liquid petrolatum being increased 158 and 30 per cent respectively with no essential difference for anhydrous lanoline.
5. The average result of absorption from a 50 per cent solution of methyl salicylate in ethyl alcohol was 414 per cent greater than that from the pure ester.
6. Massage increased materially the absorption in the tests with the pure ester varying from 34 to 158 per cent according to the experimental conditions.
7. Temperature proved to be an important factor; a rise from 26-28° to 43-44°C. in the immersion bath in the tests with aqueous suspensions resulting in an increase of absorption of salicyl of 190 and 237 per cent. When raised from 32-33° to 43-44° in tests with 50 per cent solutions in vehicles the rise was 143 per cent for anhydrous lanoline and 175 per cent for liquid petrolatum.
8. The effect of the vehicle on absorption was also studied with 8-gram portions of ointments of anhydrous lanoline, benzoinated lard and petrolatum containing 20 per cent of the ester applied to a sealed cutaneous area of approximately 46.5 square inches for twenty-four hours. The type of vehicle was found to have no differential effect on the quantity of salicyl absorbed. The combined average penetration with all three ointments was 355 mgm.
Submitted on May 24, 1933