No abstract

Objective: To determine the amount of drug which is absorbed during 1 day following topical application of three different preparations containing salicylic acid. Methods: Ten grams of the formulations, either (a) Kerasal™ 5% ointment, (b) salicylic acid 5% or (c) 10% in petrolatum, were administered consecutively to a 600-cm² area on alternating sides of the back of healthy volunteers (n = 9). Thirty minutes after application, a skin area of 2.54 cm² was stripped with D-Squame™ adhesive disks to determine the amount of salicylic acid in the stratum corneum. The entire application site was then covered by a thin gauze bandage and was not washed for the next 24 h. Urine was collected for 26 h following administration, hydrolyzed and assayed by HPLC analysis. Results: The absolute amounts absorbed and excreted were 52.6 ± 29.4 mg (mean ± SD), 127.1 ± 43.9 mg and 208.0 ± 81.7 mg, and the doses absorbed in relation to the doses applied (500 mg salicylic acid in case of formulations a and b and 1,000 mg for formulation c) were 9.3 ± 3.8, 25.1 ± 8.5 and 20.2 ± 7.7%, respectively. The amounts of salicylic acid in the skin 30 min after application were 36.3 ± 16.5, 18.2 ± 11.9 and 31.3 ± 15.4 μg/ cm² as determined by the tape stripping procedure. Conclusions: Significant differences in the doses absorbed were detected between the two formulations a and b (same concentration) with different vehicles (p value < 0.001) as well as between b and c (same vehicle) with different concentrations (p value = 0.018) using Student’s paired t test. These results demonstrate that salicylic acid is well absorbed by healthy skin.

No abstract

From the membrane permeation experiment it can be concluded, that the drug flux might be increased supra-proportionally with increasing donor concentration, drug (super-)saturation (proportional), beyond what would be anticipated based on ideal donor concentration and partition coefficient considerations only. These findings could not be confirmed in the in vivo investigation, probably due to additional vehicle effects (e.g., enhancement, irritation, drug binding) which have to be expected and could have altered the integrity of the stratum corneum and therewith topical bioavailability of the drug.