Prediction of subcutaneous drug absorption - Development of novel simulated interstitial fluid media for predictive subcutaneous in vitro assays.

Autor: Torres-Terán I; University of Greifswald. Department of Pharmacy, Institute of Biopharmaceutics and Pharmaceutical Technology, Center of Drug Absorption and Transport, 3 Felix Hausdorff Street, 17489 Greifswald, Germany; Sanofi-Aventis Deutschland GmbH, R&D, Global CMC Development, Synthetics Platform. Industriepark Hoechst, H770, D-65926 Frankfurt am Main, Germany., Venczel M; University of Greifswald. Department of Pharmacy, Institute of Biopharmaceutics and Pharmaceutical Technology, Center of Drug Absorption and Transport, 3 Felix Hausdorff Street, 17489 Greifswald, Germany., Klein S; Sanofi-Aventis Deutschland GmbH, R&D, Global CMC Development, Synthetics Platform. Industriepark Hoechst, H770, D-65926 Frankfurt am Main, Germany. Electronic address: sandra.klein@uni-greifswald.de.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 Jun 10; Vol. 658, pp. 124227. Date of Electronic Publication: 2024 May 13.
DOI: 10.1016/j.ijpharm.2024.124227
Abstrakt: Media that mimic physiological fluids at the site of administration have proven to be valuable in vitro tools for predicting in vivo drug release, particularly for routes of administration where animal studies cannot accurately predict human performance. The objective of the present study was to develop simulated interstitial fluids (SISFs) that mimic the major components and physicochemical properties of subcutaneous interstitial fluids (ISFs) from preclinical species and humans, but that can be easily prepared in the laboratory and used in in vitro experiments to estimate in vivo drug release and absorption of subcutaneously administered formulations. Based on data from a previous characterization study of ISFs from different species, two media were developed: a simulated mouse-rat ISF and a simulated human-monkey ISF. The novel SISFs were used in initial in vitro diffusion studies with a commercial injectable preparation of liraglutide. Although the in vitro model used for this purpose still requires significant refinement, these two new media will undoubtedly contribute to a better understanding of the in vivo performance of subcutaneous injectables in different species and will help to reduce the number of unnecessary in vivo experiments in preclinical species by implementation in predictive in vitro models.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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