Stability of Dexamethasone during Hot-Melt Extrusion of Filaments based on Eudragit® RS, Ethyl Cellulose and Polyethylene Oxide

Hot-melt extrusion (HME) potentially coupled with 3D printing is a promising technique for the manufacturing of dosage forms such as drug-eluting implants which might even be individually adapted to patient-specific anatomy. However, these manufacturing methods involve the risk of thermal degradatio...

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Main Authors: Vanessa Domsta, Tessa Boralewski, Martin Ulbricht, Philipp Schick, Julius Krause, Anne Seidlitz
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:International Journal of Pharmaceutics: X
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2590156724000355
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author Vanessa Domsta
Tessa Boralewski
Martin Ulbricht
Philipp Schick
Julius Krause
Anne Seidlitz
author_facet Vanessa Domsta
Tessa Boralewski
Martin Ulbricht
Philipp Schick
Julius Krause
Anne Seidlitz
author_sort Vanessa Domsta
collection DOAJ
description Hot-melt extrusion (HME) potentially coupled with 3D printing is a promising technique for the manufacturing of dosage forms such as drug-eluting implants which might even be individually adapted to patient-specific anatomy. However, these manufacturing methods involve the risk of thermal degradation of incorporated drugs during processing. In this work, the stability of the anti-inflammatory drug dexamethasone (DEX) was studied during HME using the polymers Eudragit® RS, ethyl cellulose and polyethylene oxide. The extrusion process was performed at different temperatures. Furthermore, the influence of accelerated screw speed, the addition of the plasticizers triethyl citrate and polyethylene glycol 6000 or the addition of the antioxidants butylated hydroxytoluene and tocopherol in two concentrations were studied. The DEX recovery was analyzed by a high performance liquid chromatography method suitable for the detection of thermal degradation products. The strongest impact on the drug stability was found for the processing temperature, which was found to reduce the DEX recovery to <20% for certain processing conditions. In addition, differences between tested polymers were observed, whereas the use of additives did not result in remarkable changes in drug stability. In conclusion, suitable extrusion parameters were identified for the processing of DEX with high drug recovery rates for the tested polymers. Moreover, the importance of a suitable analysis method for drug stability during HME that is influenced by several parameters was highlighted.
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institution Kabale University
issn 2590-1567
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publishDate 2024-12-01
publisher Elsevier
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series International Journal of Pharmaceutics: X
spelling doaj-art-38eac8f9968b43e7a427b672c7a615b32024-12-17T05:00:33ZengElsevierInternational Journal of Pharmaceutics: X2590-15672024-12-018100263Stability of Dexamethasone during Hot-Melt Extrusion of Filaments based on Eudragit® RS, Ethyl Cellulose and Polyethylene OxideVanessa Domsta0Tessa Boralewski1Martin Ulbricht2Philipp Schick3Julius Krause4Anne Seidlitz5University of Greifswald, Institute of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, Felix-Hausdorff-Str. 3, 17489 Greifswald, GermanyUniversity of Greifswald, Institute of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, Felix-Hausdorff-Str. 3, 17489 Greifswald, Germany; Heinrich Heine University Düsseldorf, Faculty of Mathematics and Natural Sciences, Institute of Pharmaceutics and Biopharmaceutics, Universitätsstr. 1, 40225 Düsseldorf, GermanyUniversity of Greifswald, Institute of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, Felix-Hausdorff-Str. 3, 17489 Greifswald, GermanyUniversity of Greifswald, Institute of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, Felix-Hausdorff-Str. 3, 17489 Greifswald, GermanyUniversity of Greifswald, Institute of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, Felix-Hausdorff-Str. 3, 17489 Greifswald, GermanyUniversity of Greifswald, Institute of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, Felix-Hausdorff-Str. 3, 17489 Greifswald, Germany; Heinrich Heine University Düsseldorf, Faculty of Mathematics and Natural Sciences, Institute of Pharmaceutics and Biopharmaceutics, Universitätsstr. 1, 40225 Düsseldorf, Germany; Corresponding author.Hot-melt extrusion (HME) potentially coupled with 3D printing is a promising technique for the manufacturing of dosage forms such as drug-eluting implants which might even be individually adapted to patient-specific anatomy. However, these manufacturing methods involve the risk of thermal degradation of incorporated drugs during processing. In this work, the stability of the anti-inflammatory drug dexamethasone (DEX) was studied during HME using the polymers Eudragit® RS, ethyl cellulose and polyethylene oxide. The extrusion process was performed at different temperatures. Furthermore, the influence of accelerated screw speed, the addition of the plasticizers triethyl citrate and polyethylene glycol 6000 or the addition of the antioxidants butylated hydroxytoluene and tocopherol in two concentrations were studied. The DEX recovery was analyzed by a high performance liquid chromatography method suitable for the detection of thermal degradation products. The strongest impact on the drug stability was found for the processing temperature, which was found to reduce the DEX recovery to <20% for certain processing conditions. In addition, differences between tested polymers were observed, whereas the use of additives did not result in remarkable changes in drug stability. In conclusion, suitable extrusion parameters were identified for the processing of DEX with high drug recovery rates for the tested polymers. Moreover, the importance of a suitable analysis method for drug stability during HME that is influenced by several parameters was highlighted.http://www.sciencedirect.com/science/article/pii/S2590156724000355Hot-melt extrusionEudragit® RSEthyl cellulosePolyethylene oxideDexamethasoneDegradation
spellingShingle Vanessa Domsta
Tessa Boralewski
Martin Ulbricht
Philipp Schick
Julius Krause
Anne Seidlitz
Stability of Dexamethasone during Hot-Melt Extrusion of Filaments based on Eudragit® RS, Ethyl Cellulose and Polyethylene Oxide
International Journal of Pharmaceutics: X
Hot-melt extrusion
Eudragit® RS
Ethyl cellulose
Polyethylene oxide
Dexamethasone
Degradation
title Stability of Dexamethasone during Hot-Melt Extrusion of Filaments based on Eudragit® RS, Ethyl Cellulose and Polyethylene Oxide
title_full Stability of Dexamethasone during Hot-Melt Extrusion of Filaments based on Eudragit® RS, Ethyl Cellulose and Polyethylene Oxide
title_fullStr Stability of Dexamethasone during Hot-Melt Extrusion of Filaments based on Eudragit® RS, Ethyl Cellulose and Polyethylene Oxide
title_full_unstemmed Stability of Dexamethasone during Hot-Melt Extrusion of Filaments based on Eudragit® RS, Ethyl Cellulose and Polyethylene Oxide
title_short Stability of Dexamethasone during Hot-Melt Extrusion of Filaments based on Eudragit® RS, Ethyl Cellulose and Polyethylene Oxide
title_sort stability of dexamethasone during hot melt extrusion of filaments based on eudragit r rs ethyl cellulose and polyethylene oxide
topic Hot-melt extrusion
Eudragit® RS
Ethyl cellulose
Polyethylene oxide
Dexamethasone
Degradation
url http://www.sciencedirect.com/science/article/pii/S2590156724000355
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