Date of Award

1977

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Pharmaceutical Sciences

First Advisor

Christopher T. Rhodes

Abstract

Salicylic acid was applied topically to the skin of rabbits and humans in order to study the pharmacokinetics of percutaneous absorption, and the effects of formulation and application variables on the rate and extent of absorption. Drug samples incorporated into hydrophilic ointment (USP}and hydrophilic ointment containing 10% urea, were applied to the shaved abdominal areas of female New Zealand rabbits for either four or eight hours. Drug samples used for the human studies were taken up in either hydrophilic ointment or in a polyethylene glycol/water solution. Blood samples were drawn from the rabbits over a twenty-four hour period and from humans over an eight-hour period. Absorption of salicylic acid was determined by fluorometric analysis. Pharmacokinetic analysis of (blood) data resulted from two treatments: the Wagner-Nelson methods; and a computerized, non-linear, least squares regression program NONLIN. The systemic absorption of salicylic acid from hydrophilic ointment was substantial in rabbits; however, incorporation of urea, 10% (w/w) effected no significant change. into the test ointment. The effect of ointment contact time on serum levels showed that the absorption process was essentially complete within six hours. The elimination curve for salicylic acid applied to animals fed during the test period exhibited an interesting and very substantial secondary peak not seen in fasted animals. The second peak may be due to biliary recycling. The systemic absorption of salicylic acid from polyethylene glycol/water solution applied to human skin was negligible, suggesting the formation of a salicylate-glycol complex. Plasma concentrations resulting from the application of salicylic acid in hydrophylic ointment to the intact skin of humans were less than 1 mg. However absorption from the same system was increased considerably by disrupting the stratum corneum at the site of ointment application.

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