Co-amorphous systems consisting of indomethacin and the chiral co-former tryptophan : Solid-state properties and molecular mobilities
Copyright © 2023 Elsevier B.V. All rights reserved..
In this study the influence of an enantiomeric co-former and the preparation method on the solid-state properties and physical stability of co-amorphous systems were investigated. Co-amorphous systems consisting of indomethacin (IND) and chiral tryptophan (TRP) as co-former in its two enantiomeric forms, as racemate, and as conglomerate (equimolar mixture of D- and L-TRP) were prepared. Co-amorphization was achieved by ball milling (BM) and spray drying (SD). The effects of chirality and preparation method on the solid-state properties and physical stabilities of the systems were investigated by XRPD, FTIR and mDSC. Differences in the BM process were caused by the enantiomeric properties of the co-former: The IND/TRP conglomerate (IND/TRPc) turned co-amorphous after 60 min. In contrast, co-amorphization of IND/L-TRP and IND/D-TRP required 80 min of ball milling, respectively, and the co-amorphous IND/TRP racemate (IND/TRPr) was obtained only after 90 min of ball milling. Although the intermolecular interactions of the co-amorphous systems prepared by BM and SD were similar (determined by FTIR), the Tg values differed (∼87 °C for the ball milled and ∼62 °C for the spray dried systems). The physical stabilities of the ball milled co-amorphous systems varied between 3 and 11 months if stored at elevated temperature and dry conditions, with the highest stability for the IND/TRPc system and the lowest stability for the IND/TRPr system, and these differences correlated with the calculated relaxation times. In contrast, all spray dried systems were stable only for 1 month and their relaxation times were similar. It could be shown that the chirality of a co-former and the preparation method influence the solid-state properties, thermal properties and physical stability of IND/TRP systems.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:636 |
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| Enthalten in: |
International journal of pharmaceutics - 636(2023) vom: 05. Apr., Seite 122840 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Holzapfel, Katharina [VerfasserIn] |
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| Links: |
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| Themen: |
8DUH1N11BX |
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| Anmerkungen: |
Date Completed 04.04.2023 Date Revised 04.04.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijpharm.2023.122840 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM354272748 |
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| 245 | 1 | 0 | |a Co-amorphous systems consisting of indomethacin and the chiral co-former tryptophan |b Solid-state properties and molecular mobilities |
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| 500 | |a Date Revised 04.04.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Elsevier B.V. All rights reserved. | ||
| 520 | |a In this study the influence of an enantiomeric co-former and the preparation method on the solid-state properties and physical stability of co-amorphous systems were investigated. Co-amorphous systems consisting of indomethacin (IND) and chiral tryptophan (TRP) as co-former in its two enantiomeric forms, as racemate, and as conglomerate (equimolar mixture of D- and L-TRP) were prepared. Co-amorphization was achieved by ball milling (BM) and spray drying (SD). The effects of chirality and preparation method on the solid-state properties and physical stabilities of the systems were investigated by XRPD, FTIR and mDSC. Differences in the BM process were caused by the enantiomeric properties of the co-former: The IND/TRP conglomerate (IND/TRPc) turned co-amorphous after 60 min. In contrast, co-amorphization of IND/L-TRP and IND/D-TRP required 80 min of ball milling, respectively, and the co-amorphous IND/TRP racemate (IND/TRPr) was obtained only after 90 min of ball milling. Although the intermolecular interactions of the co-amorphous systems prepared by BM and SD were similar (determined by FTIR), the Tg values differed (∼87 °C for the ball milled and ∼62 °C for the spray dried systems). The physical stabilities of the ball milled co-amorphous systems varied between 3 and 11 months if stored at elevated temperature and dry conditions, with the highest stability for the IND/TRPc system and the lowest stability for the IND/TRPr system, and these differences correlated with the calculated relaxation times. In contrast, all spray dried systems were stable only for 1 month and their relaxation times were similar. It could be shown that the chirality of a co-former and the preparation method influence the solid-state properties, thermal properties and physical stability of IND/TRP systems | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Chirality | |
| 650 | 4 | |a Co-amorphous | |
| 650 | 4 | |a Glass transition temperature | |
| 650 | 4 | |a Intermolecular interactions | |
| 650 | 4 | |a Molecular mobility | |
| 650 | 4 | |a Physical stability | |
| 650 | 7 | |a Indomethacin |2 NLM | |
| 650 | 7 | |a XXE1CET956 |2 NLM | |
| 650 | 7 | |a Tryptophan |2 NLM | |
| 650 | 7 | |a 8DUH1N11BX |2 NLM | |
| 700 | 1 | |a Rades, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Leopold, Claudia S |e verfasserin |4 aut | |
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