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dc.contributor.authorMetz, Julia K
dc.contributor.authorScharnowske, Lara
dc.contributor.authorHans, Fabian
dc.contributor.authorSchnur, Sabrina
dc.contributor.authorKnoth, Katharina
dc.contributor.authorZimmer, Horst
dc.contributor.authorLimberger, Markus
dc.contributor.authorGroß, Henrik
dc.contributor.authorLehr, Claus Michael
dc.contributor.authorHittinger, Marius
dc.date.accessioned2020-02-25T15:42:42Z
dc.date.available2020-02-25T15:42:42Z
dc.date.issued2020-01-29
dc.identifier.citationALTEX. 2020 Jan 29. doi: 10.14573/altex.1910231.en_US
dc.identifier.issn1868-596X
dc.identifier.pmid32052853
dc.identifier.doi10.14573/altex.1910231
dc.identifier.urihttp://hdl.handle.net/10033/622170
dc.description.abstractThe development of new orally inhaled drug products requires the demonstration of safety which must be proven in animal experiments. New in vitro methods may replace, or at least reduce, these animal experiments provided they are able to correctly predict the safety or eventual toxicity in humans. However, the challenge is to link human in vitro data to human in vivo data. We here present a new approach to the safety assessment of excipients (SAFE) for pulmonary drug delivery. The SAFE model is based on a dose response curve of 23 excipients tested on the human pulmonary epithelial cell lines A549 and Calu-3. The resulting in vitro IC50 values were correlated with the FDA-approved concentration in pharmaceutical products for either pulmonary (if available) or parenteral administration. Setting a threshold of 0.1% (1 mg/mL) for either value yielded four safety classes, allowed to link IC50 data as measured on human cell cultures in vitro with the concentrations of the same compounds in FDA-approved drug products. The necessary in vitro data for novel excipients can be easily generated while the SAFE approach allows putting them in the context for eventual use in human pulmonary drug products. Excipients, that are most likely not safe for use in humans, can be early excluded from further pharmaceutical development. The SAFE approach helps thus to avoid unnecessary animal experiments.en_US
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject3R principleen_US
dc.subjectaerosol medicineen_US
dc.subjectin vitro in vivo correlationen_US
dc.subjectlungsen_US
dc.subjectpulmonary drug developmenten_US
dc.titleSafety assessment of excipients (SAFE) for orally inhaled drug products.en_US
dc.typeArticleen_US
dc.contributor.departmentHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.en_US
dc.identifier.journalALTEXen_US
refterms.dateFOA2020-02-25T15:42:42Z
dc.source.journaltitleALTEX


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Attribution-NonCommercial-ShareAlike 4.0 International
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