3D-Printed, Liquid-Filled Capsules of Concentrated and Stabilized Polyphenol Epigallocatechin Gallate, Developed in a Clinical Trial
In vitro studies have shown that epigallocatechin gallate (EGCG), the most potent antioxidant of the green tea polyphenol catechins, is able to effectively prevent the formation of amyloid plaques and induce their clearance. However, its high chemical reactivity promotes high chemical instability, w...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/2/424 |
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| author | Philippe-Henri Secretan Victoire Vieillard Olivier Thirion Maxime Annereau Hassane Sadou Yayé Alain Astier Muriel Paul Thibaud Damy Bernard Do |
| author_facet | Philippe-Henri Secretan Victoire Vieillard Olivier Thirion Maxime Annereau Hassane Sadou Yayé Alain Astier Muriel Paul Thibaud Damy Bernard Do |
| author_sort | Philippe-Henri Secretan |
| collection | DOAJ |
| description | In vitro studies have shown that epigallocatechin gallate (EGCG), the most potent antioxidant of the green tea polyphenol catechins, is able to effectively prevent the formation of amyloid plaques and induce their clearance. However, its high chemical reactivity promotes high chemical instability, which represents a major obstacle for the development of pharmaceutical forms containing solubilized EGCG, an essential condition for a better systemic passage via the oral route. After discovering that EGCG forms a deep eutectic with choline chloride, we exploited this property to formulate and patent liquid-filled capsules containing 200–800 mg of soluble EGCG in easy-to-administer sizes. The gelatin envelopes used are of the conventional type and their filling has been achieved using 3D printing technology. Not only did the EGCG-choline complex allow the formulation of hydrophilic solutions with a high concentration of active substance but it also contributed significantly to its chemical stability, since after at least 18 months of storage at 25 °C/60% RH and one year at 40 °C/75% RH, the capsules show unchanged hardness, chromatographic profiles and antioxidant activity compared to T0. Preclinical studies in monkeys showed that bioavailability was increased by a factor of 10 compared to marketed capsules comprising EGCG powder. This pharmaceutical development was conducted in the context of upcoming clinical trials to evaluate EGCG alone or in combination when treating transthyretin and light-chain cardiac amyloidosis. |
| first_indexed | 2024-03-11T09:14:01Z |
| format | Article |
| id | doaj.art-666c1f6220f941cb85f56b4679579456 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-11T09:14:01Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-666c1f6220f941cb85f56b46795794562023-11-16T18:48:00ZengMDPI AGAntioxidants2076-39212023-02-0112242410.3390/antiox120204243D-Printed, Liquid-Filled Capsules of Concentrated and Stabilized Polyphenol Epigallocatechin Gallate, Developed in a Clinical TrialPhilippe-Henri Secretan0Victoire Vieillard1Olivier Thirion2Maxime Annereau3Hassane Sadou Yayé4Alain Astier5Muriel Paul6Thibaud Damy7Bernard Do8Matériaux et Santé, Université Paris-Saclay, 91400 Orsay, FranceDepartment of Pharmacy, Henri Mondor Hospital, AP-HP, 94000 Créteil, FranceDepartment of Pharmacy, Henri Mondor Hospital, AP-HP, 94000 Créteil, FranceMatériaux et Santé, Université Paris-Saclay, 91400 Orsay, FranceDepartment of Pharmacy, Hôpitaux Universitaires Pitié-Salpêtrière, AP-HP, 75013 Paris, FranceDepartment of Pharmacy, Henri Mondor Hospital, AP-HP, 94000 Créteil, FranceDepartment of Pharmacy, Henri Mondor Hospital, AP-HP, 94000 Créteil, FranceDepartment of Cardiology, Henri Mondor Hospital, AP-HP, 94000 Créteil, FranceMatériaux et Santé, Université Paris-Saclay, 91400 Orsay, FranceIn vitro studies have shown that epigallocatechin gallate (EGCG), the most potent antioxidant of the green tea polyphenol catechins, is able to effectively prevent the formation of amyloid plaques and induce their clearance. However, its high chemical reactivity promotes high chemical instability, which represents a major obstacle for the development of pharmaceutical forms containing solubilized EGCG, an essential condition for a better systemic passage via the oral route. After discovering that EGCG forms a deep eutectic with choline chloride, we exploited this property to formulate and patent liquid-filled capsules containing 200–800 mg of soluble EGCG in easy-to-administer sizes. The gelatin envelopes used are of the conventional type and their filling has been achieved using 3D printing technology. Not only did the EGCG-choline complex allow the formulation of hydrophilic solutions with a high concentration of active substance but it also contributed significantly to its chemical stability, since after at least 18 months of storage at 25 °C/60% RH and one year at 40 °C/75% RH, the capsules show unchanged hardness, chromatographic profiles and antioxidant activity compared to T0. Preclinical studies in monkeys showed that bioavailability was increased by a factor of 10 compared to marketed capsules comprising EGCG powder. This pharmaceutical development was conducted in the context of upcoming clinical trials to evaluate EGCG alone or in combination when treating transthyretin and light-chain cardiac amyloidosis.https://www.mdpi.com/2076-3921/12/2/424epigallocatechin gallateformulationeutectic solutionstabilitybioavailabilityoral solution |
| spellingShingle | Philippe-Henri Secretan Victoire Vieillard Olivier Thirion Maxime Annereau Hassane Sadou Yayé Alain Astier Muriel Paul Thibaud Damy Bernard Do 3D-Printed, Liquid-Filled Capsules of Concentrated and Stabilized Polyphenol Epigallocatechin Gallate, Developed in a Clinical Trial Antioxidants epigallocatechin gallate formulation eutectic solution stability bioavailability oral solution |
| title | 3D-Printed, Liquid-Filled Capsules of Concentrated and Stabilized Polyphenol Epigallocatechin Gallate, Developed in a Clinical Trial |
| title_full | 3D-Printed, Liquid-Filled Capsules of Concentrated and Stabilized Polyphenol Epigallocatechin Gallate, Developed in a Clinical Trial |
| title_fullStr | 3D-Printed, Liquid-Filled Capsules of Concentrated and Stabilized Polyphenol Epigallocatechin Gallate, Developed in a Clinical Trial |
| title_full_unstemmed | 3D-Printed, Liquid-Filled Capsules of Concentrated and Stabilized Polyphenol Epigallocatechin Gallate, Developed in a Clinical Trial |
| title_short | 3D-Printed, Liquid-Filled Capsules of Concentrated and Stabilized Polyphenol Epigallocatechin Gallate, Developed in a Clinical Trial |
| title_sort | 3d printed liquid filled capsules of concentrated and stabilized polyphenol epigallocatechin gallate developed in a clinical trial |
| topic | epigallocatechin gallate formulation eutectic solution stability bioavailability oral solution |
| url | https://www.mdpi.com/2076-3921/12/2/424 |
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