Methods to simulate rubbing of topical formulation for in vitro skin permeation studies

Rubbing a topical formulation on skin is generally assumed to enhance drug penetration. The aim of this study was to demonstrate different techniques such as using glass rod, rheometer, and gloved finger for rubbing a 2% salicylic acid gel on skin and investigate their effect on in vitro permeation of salicylic acid through dermatomed porcine ear skin. The studies included evaluation of the gel's rheological properties, gel distribution on skin surface, in vitro permeability, drug distribution in skin, skin extraction recovery, and mass balance. Rubbing with a gloved finger resulted in a uniform gel layer with a thickness of 49.61 +/- 15.33 mu m on the skin surface. No significant difference between the different test groups was observed in terms of the cumulative amount of drug that permeated in 24h (p > 0.05). Drug levels in stratum corneum, epidermis, and dermis were also analyzed. Rubbing with gloved finger delivered significantly higher amount of drug into the skin layers as compared to other test groups (p < 0.05). Amount of drug extracted from skin was reliably correlated to the actual drug levels in skin (R-2= 0.99). Considering drug amounts in different compartments, mass balance ranged from 75.86 +/- 2.90% to 80.44 +/- 2.99%. (C) 2017 Elsevier B.V. All rights reserved.