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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...

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Autores principales: Matencio, Adrián, Hernández-García, Samanta, García-Carmona, Francisco, López-Nicolás, José Manuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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