Application of biorelevant in vitro assays for the assessment and optimization of ASD-based formulations for pediatric patients.

Autor: Niessen J; Abbvie Deutschland GmbH & Co. KG, Small Molecule CMC Development, Knollstrasse, Ludwigshafen, Germany., López Mármol Á; Abbvie Deutschland GmbH & Co. KG, Small Molecule CMC Development, Knollstrasse, Ludwigshafen, Germany., Ismail R; Abbvie Deutschland GmbH & Co. KG, Small Molecule CMC Development, Knollstrasse, Ludwigshafen, Germany., Schiele JT; Abbvie Deutschland GmbH & Co. KG, Small Molecule CMC Development, Knollstrasse, Ludwigshafen, Germany., Rau K; Abbvie Deutschland GmbH & Co. KG, Small Molecule CMC Development, Knollstrasse, Ludwigshafen, Germany., Wahl A; Abbvie Deutschland GmbH & Co. KG, Small Molecule CMC Development, Knollstrasse, Ludwigshafen, Germany., Sauer K; Abbvie Deutschland GmbH & Co. KG, Small Molecule CMC Development, Knollstrasse, Ludwigshafen, Germany., Heinzerling O; Abbvie Deutschland GmbH & Co. KG, Small Molecule CMC Development, Knollstrasse, Ludwigshafen, Germany., Breitkreutz J; Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University Düsseldorf, Germany., Koziolek M; Abbvie Deutschland GmbH & Co. KG, Small Molecule CMC Development, Knollstrasse, Ludwigshafen, Germany. Electronic address: mirko.koziolek@abbvie.com.
Jazyk: angličtina
Zdroj: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V [Eur J Pharm Biopharm] 2023 Apr; Vol. 185, pp. 13-27. Date of Electronic Publication: 2023 Feb 20.
DOI: 10.1016/j.ejpb.2023.02.008
Abstrakt: Amorphous solid dispersions (ASD) have been a successful formulation strategy to overcome the poor aqueous solubility of many novel drugs, but the development of pediatric formulations presents a special challenge due to variable gastrointestinal conditions in children. It was the aim of this work to design and apply a staged biopharmaceutical test protocol for the in vitro assessment of ASD-based pediatric formulations. Ritonavir was used as a model drug with poor aqueous solubility. Based on the commercial ASD powder formulation, a mini-tablet and a conventional tablet formulation were prepared. Drug release from the three formulations was studied in different biorelevant in vitro assays (i.e. MicroDiss, two-stage, transfer model, tiny-TIM) to consider different aspects of human GI physiology. Data from the two-stage and transfer model tests indicated that by controlled disintegration and dissolution excessive primary precipitation can be prevented. However, this advantage of the mini-tablet and tablet formulation did not translate into better performance in tiny-TIM. Here, the in vitro bioaccessibility was comparable for all three formulations. In the future, the staged biopharmaceutical action plan established herein will support the development of ASD-based pediatric formulations by improving the mechanistic understanding so that formulations are developed for which drug release is robust against variable physiological conditions.
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 © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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