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Ternary Eutectic Ezetimibe–Simvastatin–Fenofibrate System and the Physical Stability of Its Amorphous Form

[Image: see text] In this study, the phase diagram of the ternary system of ezetimibe–simvastatin–fenofibrate was established. It has been proven that the ternary composition recommended for the treatment of mixed hyperlipidemia forms a eutectic system. Since eutectic mixtures are characterized by g...

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Autores principales: Knapik-Kowalczuk, Justyna, Kramarczyk, Daniel, Jurkiewicz, Karolina, Chmiel, Krzysztof, Paluch, Marian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424683/
https://www.ncbi.nlm.nih.gov/pubmed/34420300
http://dx.doi.org/10.1021/acs.molpharmaceut.1c00485
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author Knapik-Kowalczuk, Justyna
Kramarczyk, Daniel
Jurkiewicz, Karolina
Chmiel, Krzysztof
Paluch, Marian
author_facet Knapik-Kowalczuk, Justyna
Kramarczyk, Daniel
Jurkiewicz, Karolina
Chmiel, Krzysztof
Paluch, Marian
author_sort Knapik-Kowalczuk, Justyna
collection PubMed
description [Image: see text] In this study, the phase diagram of the ternary system of ezetimibe–simvastatin–fenofibrate was established. It has been proven that the ternary composition recommended for the treatment of mixed hyperlipidemia forms a eutectic system. Since eutectic mixtures are characterized by greater solubility and dissolution rate, the obtained result can explain the marvelous medical effectiveness of combined therapy. Considering that another well-known method for improving the aqueous solubility is amorphization, the ternary system with eutectic concentration was converted into an amorphous form. Thermal properties, molecular dynamics, and physical stability of the obtained amorphous system were thoroughly investigated through various experimental techniques compared to both: neat amorphous active pharmaceutical ingredients (considered separately) and other representative concentrations of ternary mixture. The obtained results open up a new way of selecting the therapeutic concentrations for combined therapies, a path that considers one additional variable: eutecticity.
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spelling pubmed-84246832021-09-08 Ternary Eutectic Ezetimibe–Simvastatin–Fenofibrate System and the Physical Stability of Its Amorphous Form Knapik-Kowalczuk, Justyna Kramarczyk, Daniel Jurkiewicz, Karolina Chmiel, Krzysztof Paluch, Marian Mol Pharm [Image: see text] In this study, the phase diagram of the ternary system of ezetimibe–simvastatin–fenofibrate was established. It has been proven that the ternary composition recommended for the treatment of mixed hyperlipidemia forms a eutectic system. Since eutectic mixtures are characterized by greater solubility and dissolution rate, the obtained result can explain the marvelous medical effectiveness of combined therapy. Considering that another well-known method for improving the aqueous solubility is amorphization, the ternary system with eutectic concentration was converted into an amorphous form. Thermal properties, molecular dynamics, and physical stability of the obtained amorphous system were thoroughly investigated through various experimental techniques compared to both: neat amorphous active pharmaceutical ingredients (considered separately) and other representative concentrations of ternary mixture. The obtained results open up a new way of selecting the therapeutic concentrations for combined therapies, a path that considers one additional variable: eutecticity. American Chemical Society 2021-08-22 2021-09-06 /pmc/articles/PMC8424683/ /pubmed/34420300 http://dx.doi.org/10.1021/acs.molpharmaceut.1c00485 Text en © 2021 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Knapik-Kowalczuk, Justyna
Kramarczyk, Daniel
Jurkiewicz, Karolina
Chmiel, Krzysztof
Paluch, Marian
Ternary Eutectic Ezetimibe–Simvastatin–Fenofibrate System and the Physical Stability of Its Amorphous Form
title Ternary Eutectic Ezetimibe–Simvastatin–Fenofibrate System and the Physical Stability of Its Amorphous Form
title_full Ternary Eutectic Ezetimibe–Simvastatin–Fenofibrate System and the Physical Stability of Its Amorphous Form
title_fullStr Ternary Eutectic Ezetimibe–Simvastatin–Fenofibrate System and the Physical Stability of Its Amorphous Form
title_full_unstemmed Ternary Eutectic Ezetimibe–Simvastatin–Fenofibrate System and the Physical Stability of Its Amorphous Form
title_short Ternary Eutectic Ezetimibe–Simvastatin–Fenofibrate System and the Physical Stability of Its Amorphous Form
title_sort ternary eutectic ezetimibe–simvastatin–fenofibrate system and the physical stability of its amorphous form
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424683/
https://www.ncbi.nlm.nih.gov/pubmed/34420300
http://dx.doi.org/10.1021/acs.molpharmaceut.1c00485
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