The influence of surface active agents on methylisothiazolinone bioavailability

1. The influence of surface active agents on methylisothiazolinone bioavailability Jacek Arct1, Katarzyna Pytkowska1, Justyna Pijewska2 1Academy of Cosmetics and Health Care, Warsaw, Poland, 2Warsaw University of Technology, Faculty of Chemistry, Poland Correspondingauthor: Jacek Arct j.arct@wszkipz.pl

2. Preservativesin cosmetics • Preservatives used in cosmetics meet a great number of requirements, most importantly they must be safe and effective • There is no research on the skinpenetration of preservatives and the existing data is often inadequate totheactual application in thecosmetic form • One of the factors which are important for the direct biological effect after topical application is vehiculumcomposition, especially the presence of surfactants considered as permeation enhancers • One of the most controversial preservatives widely used in shampoos and cleansing preparationsismethylisothiazolinone (MI), INCI:Methylisothiazolinone, a potential irritant and sensitizer

3. Methylisothiazolinone (MI) • SCCNFP reports and literature data do not settle the matter of MI bioavailability after topical application, especially in the presence of surfactants. • It is considered that the use of MI in cleansing formulations containing a high content of surfactants is related to the increase of bioavailability up to 100% • The presence of surfactants increases the risk of adverse skin reactions to MI Fig. 1. Methylisothiazolinone

4. Preliminaryresults Materials and methods Results Under the conditions of the experiment (LogP = -0.09) MI readily penetrates the liquid-crystal membrane Contrary to expectations, the presence of common anionic surfactants inhibited the penetration of MI This is probably because of the reduction of thermodynamic activity of MI in the donor solution, through formation of molecular complexes or micellar systems • We have analyzed the effect of the presence of various surfactants, particularly anionic, on the rate of MI penetration through the epidermal barrier • As the test system were used side by side Flynn cells with liquid crystal lipid membrane modelling stratum corneum, the donor and receptor medium was phosphate buffer pH=7.4 • Permeation rate of MI was evaluated by determination and comparison of diffusion coefficients Kp in the investigated system

5. The influence of a surfactantconcentration on MI Kp • Below the CMC the presence of surfactant does not affect the MI penetration • Increasing the concentration of SLES-3 results in a stronger inhibition of diffusion than for SLES-2 • SLS strongly inhibits the penetration of MI. The degree of inhibition virtually no depends on the concentration. • Nonionic surfactants strongly inhibit the permeation of MI • The results contradict the thesis ofthemicellarmechanism of permeation inhibition

6. The influence of surfactantmixturecomposition on MI Kp • The results clearly indicate the inhibitory effect of the commonly used surfactants, on the bioavailability of MI • Regardless of the composition of the mixture of surfactants and their concentrations, the diffusion is inhibited approximately 50% • This is probably the result of setting the equilibrium of the solution, determining the concentration of free MI • Afterapplication of toiletries and shampoos on the healthy intact skin, the risk of MI penetration and thus irritation and or allergy is low.