Feasibility of measuring the bioavailability of topical ibuprofen in commercial formulations using drug content in epidermis and a methyl nicotinate skin inflammation assay.
A method has been developed which simultaneously compares the inhibition of an inflammation induced by a methyl nicotinate assay with the concentration of drug in the human epidermis determined in vitro following topical application of two 10% ibuprofen formulations. The bioavailability of drug from commercial gel and emulsion was assessed after the application of various doses (3, 6 and 12 mg/cm2) and an application time of 0.5 h at two time points: 0.5 and 24 h (only with the 12 mg/cm2 dose) after the removal of the non-steroidal anti-inflammatory drug (NSAID) from the skin. In parallel, we assessed the epidermal concentration of the drug in vitro and evaluated the anti-inflammatory effect of the topicals in vivo. A correlation (r = 0.9603, p < 0.001) between the amount of drug in the epidermis expressed as micrograms per milligram of epidermal protein and the corresponding inhibition of the inflammation was observed. Increasing the amount of drug in the epidermis correlated with an increased inhibition of the inflammation. The gel formulation released more drug to the skin and produced a greater anti-inflammatory effect. Topical NSAID concentration in treated skin can therefore be determined and correlates well with the resulting pharmacodynamic activity. This approach will likely have utility in optimizing topical NSAIDs.
Treffel
P
P
Department of Biopharmacy, Spirig AG, Egerkingen, Switzerland.
Gabard
B
B
D000287:Administration, Topical; D000328:Adult; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D003872:Dermatitis / Q000188:drug therapy* / Q000378:metabolism; D004817:Epidermis / Q000737:chemistry; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D009539:Nicotinic Acids / Q000032:analysis / Q000494:pharmacology; D011506:Proteins / Q000032:analysis; D012869:Skin Absorption
D009539:Nicotinic Acids; D011506:Proteins; C008473:methyl nicotinate; D007052:Ibuprofen