Abstract

Hygiene Risk of Unpreserved Semisolid Cutaneous Formulations

This study evaluates the hygiene risk of unpreserved creams while they are in use. In general, lipophilic creams are expected to have a much lower hygiene risk compared to hydrophilic creams. Usually the hygiene risk of cutaneous formulations is assessed by the criteria provided in the text on „Efficacy of antimicrobial preservation“ (Ph. Eur 5.1.3). Without addition of preservatives the test usually failed. However, it could be shown that the count of micro-organisms constantly decreased in unpreserved lipophilic creams when they were prepared with an aqueous phase which had been specifically contaminated with E. coli and Candida albicans as test organisms. When these micro-organisms were applied to the surface of lipophilic creams, they did not penetrate into the bulk. Therefore the hygiene risk of lipohilic creams seems to be marginal and the addition of an antimicrobial preservative seems not to be mandatory. Micro-organisms applied to the surface of hydrophilic dermal formulations were also frequently not able to penetrate bulk especially when the continuous aqueous phase comprises a dense gel network. Such a structure could be obtained from lamellar liquid crystals, or sufficiently high concentrations of hydrocolloids, e. g. 10 % hypromellose. Even unpreserved hydrogels behaved comparably, if the used gelling agent could not be enzymatically cleaved by micro-organisms. Therefore, the hygiene risk of hydrophilic formulations for cutaneous application has to be regarded in a more differentiated fashion and should not simply be judged by testing the efficacy of antimicrobial preservation. More detailed information on the individual hygiene risk of a formulation can be obtained using a test strategy which has been developed in this study. If this test reveals a low hygiene risk, it should be possible, without any risk to the customer, to avoid preservatives even in hydrophilic creams and hydrogels, if the concept for production and packaging was chosen properly.