Salicylic acid percutaneous absorption

Wester RC, Melendres J, SedikL, et al. 1998. Percutaneous absorption of salicylic acid, theophylline, 2,4-dimethylamine, diethyl hexyl phthalic acid, and />-aminobenzoic acid in the isolated perfused porcine skin flap compared to man in vivo. Toxicol Appl Pharmacol 151 159-165. 

Schwarb, F., B. Gabard, G. lost, Th. Rufli, and C. Surber, Percutaneous absorption of salicylic acid in man following topical administration of different formulations. Dermatology, 1997, 195 129. 

Taylor, J.R. and K.M. Halprin, Percutaneous absorption of salicylic acid. Arch. Dermatol., 1975, 111 740-3. 

Roberts, M.S. and E. Horlock (1978). Effect of repeated application on percutaneous absorption of salicylic acid, J. Pharm. ScL, 67, 1685-1687. 

Many reports have described salicyhsm, intoxication due to percutaneous absorption of sahcylates, such as methyl salicylate (2). The first symptoms of sahcylism are pallor, fatigue and drowsiness, and altered respiration, which becomes more frequent and at the same time deeper, and which can be heard from a distance. Other early signs of intoxication with salicylic acid are nausea, vomiting, changes in the abihty to hear, and mental confusion. Several deaths have been recorded, mainly in children. 

Smith WO, Lyons D. Metabolic acidosis associated with percutaneous absorption of salicylic acid. J Okla State Med Assoc 1980 73(l) 7-8. 

The mass balance approach was used to develop an in vivo animal model for skin penetration of topically applied dmgs in hairless rats (Simonsen et al., 2002). Two dmgs, C-sahcylic acid and C-butyl salicylate were topically applied for the assessment of the model. Rapid and differentiated percutaneous absorption of both compounds was indicated by urinary excretion data. Total mass balance on the applied radioactivity was performed, and 90% recovery was achieved. Carver and Riviere (1989) conducted an extensive mass balance study with " C-labeled xeno-biotics after topical and intravenous administration to pigs. These authors reported that dermal absorption of C-benzoic acid, caffeine, malathion, parathion, progesterone, and testosterone was 25.7, 11.8, 5.2, 6.7, 16.2, and 8.8%, respectively, following topical administration to pigs. 

Its topical use lies mainly in the treatment of psoriasis, as a keratolytic agent to descale plaques (1-20% ointment). Salicylism is the term used to describe the toxicological state that occurs following percutaneous absorption of salicylic acid (Von Weis and Lever 1964). Intoxication depends largely on the total body area over which the salicylic acid is applied (Brubacher and Hoffman 1996). Formerly, salicylic acid also had a reputation as an anti-mycotic (3% in Whitfield ointment). Contact allergy was reported (Goh and Ng 1986). 

Poloxamers have also been incorporated into white petrolatum USP ointment bases in the presence of dimethylsulphoxide to modify the absorption of drugs presented in the base [252]. Percutaneous absorption of salicylic acid was increased significantly by poloxamers 231 and 182 and absorption of sodium salicylate by poloxamer 182. 

Figure 7.33(a) Effect of sorbitan and polysorbate surfactants on percutaneous absorption of salicylic acid in the presence of dimethyl sulphoxide. A, 10 % sorbitan monolaurate plus 10% dimethyl sulphoxide plus 10% salicylic acid V, 10% sorbitan monopalmitate plus 10% dimethyl sulphoxide plus 10% salicylic acid , 10% sorbitan trioleate plus 10% dimethyl sulphoxide plus 10% salicylic acid , 10% polysorbate 20 plus 10% dimethyl sulphoxide plus 10 % salicylic acid A, 10 % polysorbate 40 plus 10 % dimethyl sulphoxide plus 10% salicylic acid , 10% polysorbate 60 plus 10% dimethyl sulphoxide plus 10% salicylic acid O, 10% dimethyl sulphoxide plus 10% salicylic acid and , 10% salicylic acid. 

Topical applications in the form of spray also have been reported as vehicles for enhanced frawi-dermal delivery of drugs such as testosterone, estradiol, progesterone, and norethindrone acetate. More effective drug penetration was reported with enhancers padimate and octyl salicylate and compared with laurocapram and oleic acid (38). Other methods reported for enhanced percutaneous drug absorption include iontophoresis (39), ultrasound or sonophoresis (40), and electroporation (41). 

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