A computational-based approach to fabricate Ceritinib co-amorphous system using a novel co-former Rutin for bioavailability enhancement
Copyright © 2023 Elsevier B.V. All rights reserved..
In this study, we used molecular simulations to design Ceritinib (CRT) co-amorphous materials (CAMs) with concurrent improvement in solubility and bioavailability. Computational modeling enabled us to select the co-former by estimating the binding energy and intermolecular interactions. Rutin (RTH) was selected as a co-former for CRT CAMs using the solvent evaporation method to anticipate simultaneous improvement of solubility and bioavailability. The solid state characterization using DSC, XRPD, FT-IR, and a significant shift in Gordon Taylor experimental Tg values of co-amorphous materials revealed single amorphous phase formation and intermolecular interactions between CRT and RTH. The co-amorphous materials exhibited physical stability for up to 4 months under dry conditions (40 °C). Further, co-amorphous materials maintained the supersaturation for 24 hrs and improved solubility as well as dissolution of CRT. CRT:RTH 1:1 CAMs improved the permeability of CRT by 2 fold, estimated by employing the everted gut sac method. The solubility advantage of CAMs was also reflected in pharmacokinetic parameters, with a 3.1-fold and 2-fold improvement of CRT:RTH 2:1 in CRT exposure (AUC 0-t) and plasma concentration (Cmax) compared to the physical mixture, respectively.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:190 |
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| Enthalten in: |
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V - 190(2023) vom: 13. Sept., Seite 220-230 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yarlagadda, Dani Lakshman [VerfasserIn] |
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| Links: |
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| Themen: |
5G06TVY3R7 |
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| Anmerkungen: |
Date Completed 28.08.2023 Date Revised 28.08.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejpb.2023.07.019 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM360240410 |
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| 520 | |a Copyright © 2023 Elsevier B.V. All rights reserved. | ||
| 520 | |a In this study, we used molecular simulations to design Ceritinib (CRT) co-amorphous materials (CAMs) with concurrent improvement in solubility and bioavailability. Computational modeling enabled us to select the co-former by estimating the binding energy and intermolecular interactions. Rutin (RTH) was selected as a co-former for CRT CAMs using the solvent evaporation method to anticipate simultaneous improvement of solubility and bioavailability. The solid state characterization using DSC, XRPD, FT-IR, and a significant shift in Gordon Taylor experimental Tg values of co-amorphous materials revealed single amorphous phase formation and intermolecular interactions between CRT and RTH. The co-amorphous materials exhibited physical stability for up to 4 months under dry conditions (40 °C). Further, co-amorphous materials maintained the supersaturation for 24 hrs and improved solubility as well as dissolution of CRT. CRT:RTH 1:1 CAMs improved the permeability of CRT by 2 fold, estimated by employing the everted gut sac method. The solubility advantage of CAMs was also reflected in pharmacokinetic parameters, with a 3.1-fold and 2-fold improvement of CRT:RTH 2:1 in CRT exposure (AUC 0-t) and plasma concentration (Cmax) compared to the physical mixture, respectively | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Bioavailability | |
| 650 | 4 | |a Ceritinib | |
| 650 | 4 | |a Co-amorphous system | |
| 650 | 4 | |a Permeability | |
| 650 | 4 | |a Rutin | |
| 650 | 4 | |a Solubility | |
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| 650 | 7 | |a ceritinib |2 NLM | |
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| 650 | 7 | |a Sulfones |2 NLM | |
| 700 | 1 | |a Anand, Vullendula Sai Krishna |e verfasserin |4 aut | |
| 700 | 1 | |a Nair, Athira R |e verfasserin |4 aut | |
| 700 | 1 | |a Dengale, Swapnil J |e verfasserin |4 aut | |
| 700 | 1 | |a Pandiyan, Sudharsan |e verfasserin |4 aut | |
| 700 | 1 | |a Mehta, Chetan H |e verfasserin |4 aut | |
| 700 | 1 | |a Manandhar, Suman |e verfasserin |4 aut | |
| 700 | 1 | |a Nayak, Usha Y |e verfasserin |4 aut | |
| 700 | 1 | |a Bhat, Krishnamurthy |e verfasserin |4 aut | |
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