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A Way to Increase the Bioaccesibility and Photostability of Roflumilast, a COPD Treatment, by Cyclodextrin Monomers
Roflumilast is an orally available inhibitor of phosphodiesterase (PDE) type 4, which is widely used in chronic obstructive pulmonary diseases. However, it has low solubility and adverse effects include diarrhea and nausea. Since its solubilization may improve treatment and, dismissing any adverse e...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571910/ https://www.ncbi.nlm.nih.gov/pubmed/31060253 http://dx.doi.org/10.3390/polym11050801 |
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author | Matencio, Adrián Hernández-García, Samanta García-Carmona, Francisco López-Nicolás, José Manuel |
author_facet | Matencio, Adrián Hernández-García, Samanta García-Carmona, Francisco López-Nicolás, José Manuel |
author_sort | Matencio, Adrián |
collection | PubMed |
description | Roflumilast is an orally available inhibitor of phosphodiesterase (PDE) type 4, which is widely used in chronic obstructive pulmonary diseases. However, it has low solubility and adverse effects include diarrhea and nausea. Since its solubilization may improve treatment and, dismissing any adverse effects, its interaction with cyclodextrins (CDs) was studied. The Higuchi-Connors method was used to determine the complexation constant with different CDs, pH values and temperatures. Molecular docking was used to predict interaction between the complexes. An in vitro digestion experiment was carried out to test roflumilast protection. Finally, the photostability of the complex was evaluated. The complex formed with β-CD had the highest K(11) value (646 ± 34 M(−1)), although this value decreased with increasing temperature. Similarly, K(11) decreased as the pH increased. In vitro digestion showed that CDs protect the drug during digestion and even improve its bioaccessibility. Finally, CDs reduced the drug’s extreme photosensitivity, originating a fluorescence signal, which is described for first time. The kinetic parameters of the reaction were obtained. This study not only completes the complexation study of roflumilast-CD, but also points to the need to protect roflumilast from light, suggesting that tablets containing the drug might be reformulated. |
format | Online Article Text |
id | pubmed-6571910 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-65719102019-06-18 A Way to Increase the Bioaccesibility and Photostability of Roflumilast, a COPD Treatment, by Cyclodextrin Monomers Matencio, Adrián Hernández-García, Samanta García-Carmona, Francisco López-Nicolás, José Manuel Polymers (Basel) Article Roflumilast is an orally available inhibitor of phosphodiesterase (PDE) type 4, which is widely used in chronic obstructive pulmonary diseases. However, it has low solubility and adverse effects include diarrhea and nausea. Since its solubilization may improve treatment and, dismissing any adverse effects, its interaction with cyclodextrins (CDs) was studied. The Higuchi-Connors method was used to determine the complexation constant with different CDs, pH values and temperatures. Molecular docking was used to predict interaction between the complexes. An in vitro digestion experiment was carried out to test roflumilast protection. Finally, the photostability of the complex was evaluated. The complex formed with β-CD had the highest K(11) value (646 ± 34 M(−1)), although this value decreased with increasing temperature. Similarly, K(11) decreased as the pH increased. In vitro digestion showed that CDs protect the drug during digestion and even improve its bioaccessibility. Finally, CDs reduced the drug’s extreme photosensitivity, originating a fluorescence signal, which is described for first time. The kinetic parameters of the reaction were obtained. This study not only completes the complexation study of roflumilast-CD, but also points to the need to protect roflumilast from light, suggesting that tablets containing the drug might be reformulated. MDPI 2019-05-04 /pmc/articles/PMC6571910/ /pubmed/31060253 http://dx.doi.org/10.3390/polym11050801 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Matencio, Adrián Hernández-García, Samanta García-Carmona, Francisco López-Nicolás, José Manuel A Way to Increase the Bioaccesibility and Photostability of Roflumilast, a COPD Treatment, by Cyclodextrin Monomers |
title | A Way to Increase the Bioaccesibility and Photostability of Roflumilast, a COPD Treatment, by Cyclodextrin Monomers |
title_full | A Way to Increase the Bioaccesibility and Photostability of Roflumilast, a COPD Treatment, by Cyclodextrin Monomers |
title_fullStr | A Way to Increase the Bioaccesibility and Photostability of Roflumilast, a COPD Treatment, by Cyclodextrin Monomers |
title_full_unstemmed | A Way to Increase the Bioaccesibility and Photostability of Roflumilast, a COPD Treatment, by Cyclodextrin Monomers |
title_short | A Way to Increase the Bioaccesibility and Photostability of Roflumilast, a COPD Treatment, by Cyclodextrin Monomers |
title_sort | way to increase the bioaccesibility and photostability of roflumilast, a copd treatment, by cyclodextrin monomers |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571910/ https://www.ncbi.nlm.nih.gov/pubmed/31060253 http://dx.doi.org/10.3390/polym11050801 |
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