Abstract
Few data are available for excipients administered by inhalation route. This study evaluated the in vitro potential toxicity of three surfactants (Polysorbate 20, Polysorbate 80 and Poloxamer 188) by using an original air-liquid interface (ALI) method of exposure compared to liquid/liquid (L/L) model. Two cell toxicity tests were conducted on BEAS-2B cells, a human immortalized bronchial epithelial cell lines; measurement of Lactate Dehydrogenase activity and XTT cell proliferation assay. We found that Polysorbate 20 appeared to be more toxic than Polysorbate 80, Poloxamer 188. An increased toxicity of Polysorbate 20 in L/L system as shown in comparison to ALI exposure. A toxicity was also observed for polysorbate 80 but at higher concentrations and without difference between L/L and ALI exposure. No toxicity was observed for Poloxamer 188 at high concentrations. Poloxamer 188 seems to be the better candidate, out of the three tested, for galenic formulations designed to the inhalation route such as biotherapies. To evaluate the cytotoxicity of excipients for inhalation route the ALI exposure have to be used instead of L/L.
Highlights
The toxicity of excipients is often considered as secondary to that of active ingredients
The toxicity of Polysorbate 20 appears to be higher than Polysorbate 80 whereas the toxicity of Poloxamer was lowest in both the condition we L/L and air-liquid interface (ALI) exposures at high concentrations (5 and 10 v/v%)
We focused on the toxicity of surfactants in a BEAS-2B bronchial epithelial cell model, in order to assess a cytotoxic activity of these surfactants and to be able to determine the maximum threshold concentration acceptable in a galenic formulation for the inhalation route that will be tested in future experiments
Summary
The toxicity of excipients is often considered as secondary to that of active ingredients. There are recommendations for industrial use made by the Food and Drug Administration (FDA), the European Medicines Agency (EMA) and the International Pharmaceutical Excipients Council (IPEC) [1,2,3,4,5,6]. Even with these recommendations, the risk assessment for some excipients appears to be incomplete. The risk assessment for some excipients appears to be incomplete Surfactants, such as Polysorbates and benzalkonium chloride are commonly used in galenic formulations for the inhalation route, but data on their toxicity by inhalation pathway are not available
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
