Methods for the determination of the substantivity of topical formulations

Abstract

Skin diseases are usually treated using topical formulations. Frequently, multiple applications per day are necessary, as up to 90% of the formulation (and thus of the active) are withdrawn from the skin by contact with the environment. During the development of topical formulations ex vivo permeation and penetration experiments are deployed to characterize the formulations. Still, these tests do not take into account the removal of formulations during the application period. To date, only few methods exist to probe the substantivity of dermal formulations. The aim of this investigation was to develop methods that simulate skin-to-skin or clothing-to-skin contact and enable the determination of the amount of formulation that is removed from the skin due to the contact. Three different types of formulations were used to validate the systems: a conventional semisolid cream, an oil-in-oil-emulsion, and a film forming formulation. The results showed that the substantivity decreased in the order: film forming formulation > semisolid cream > oil-in-oil-emulsion. A similar trend could be determined with both methods although the total amounts of withdrawn formulation differed. The developed methods can add to the knowledge about the formulation and can be used to develop formulations that exhibit higher substantivity.

Keywords:

• Film forming formulation
• formulation characterization
• nonivamide
• pig ear skin
• semisolids
• substantivity

Acknowledgements

The authors would like to thank PD Dr. Martin Schenk from the Department of Experimental Medicine at the University Hospital of Tuebingen for the supply with pig ears. Evonik Industries are thanked for the donation of Eudragit® polymers, Grace GmbH & Co. KG for the donation of Syloid and Dow Corning GmbH for the kind donation of silicone oils and surfactants.

Declaration of interest

This project was supported by the European Social Fund and by the Ministry of Science, Research and the Arts Baden-Wuerttemberg.