Cargando…
Aggregation versus inclusion complexes to solubilize drugs with cyclodextrins. A case study using sulphobutylether-β-cyclodextrins and remdesivir
The formation of small hybrid aggregates between excipient and drug molecules is one of the mechanisms that contributes to the solubilization of active principles in pharmaceutical formulations. The characterization of the formation, governing interactions and structure of such entities is not trivi...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Author(s). Published by Elsevier B.V.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447550/ https://www.ncbi.nlm.nih.gov/pubmed/34548723 http://dx.doi.org/10.1016/j.molliq.2021.117588 |
_version_ | 1784569039445557248 |
---|---|
author | Piñeiro, Ángel Pipkin, James Antle, Vince Garcia-Fandino, Rebeca |
author_facet | Piñeiro, Ángel Pipkin, James Antle, Vince Garcia-Fandino, Rebeca |
author_sort | Piñeiro, Ángel |
collection | PubMed |
description | The formation of small hybrid aggregates between excipient and drug molecules is one of the mechanisms that contributes to the solubilization of active principles in pharmaceutical formulations. The characterization of the formation, governing interactions and structure of such entities is not trivial since they are highly flexible and dynamic, quickly exchanging molecules from one to another. In the case of cyclodextrins, this mechanism and the formation of inclusion complexes synergistically cooperate to favour the bioavailability of drugs. In a previous study we reported a detailed characterization of the possible formation of inclusion complexes with 1:1 stoichiometry between remdesivir, the only antiviral medication currently approved by the United States Food and Drug Administration for treating COVID-19, and sulphobutylether-β-cyclodextrins. Here we extend our study to assess the role of the spontaneous aggregation in the solubilization of the same drug, by molecular dynamics simulations at different relative concentrations of both compounds. The number of sulphobutylether substitutions in the cyclodextrin structure and two different protonation states of the remdesivir molecule are considered. We aim to shed light in the solubilization mechanism of sulphobutylether-β-cyclodextrins, broadly used as an excipient in many pharmaceutical formulations, in particular in the case of remdesivir as an active compound. |
format | Online Article Text |
id | pubmed-8447550 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Author(s). Published by Elsevier B.V. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84475502021-09-17 Aggregation versus inclusion complexes to solubilize drugs with cyclodextrins. A case study using sulphobutylether-β-cyclodextrins and remdesivir Piñeiro, Ángel Pipkin, James Antle, Vince Garcia-Fandino, Rebeca J Mol Liq Article The formation of small hybrid aggregates between excipient and drug molecules is one of the mechanisms that contributes to the solubilization of active principles in pharmaceutical formulations. The characterization of the formation, governing interactions and structure of such entities is not trivial since they are highly flexible and dynamic, quickly exchanging molecules from one to another. In the case of cyclodextrins, this mechanism and the formation of inclusion complexes synergistically cooperate to favour the bioavailability of drugs. In a previous study we reported a detailed characterization of the possible formation of inclusion complexes with 1:1 stoichiometry between remdesivir, the only antiviral medication currently approved by the United States Food and Drug Administration for treating COVID-19, and sulphobutylether-β-cyclodextrins. Here we extend our study to assess the role of the spontaneous aggregation in the solubilization of the same drug, by molecular dynamics simulations at different relative concentrations of both compounds. The number of sulphobutylether substitutions in the cyclodextrin structure and two different protonation states of the remdesivir molecule are considered. We aim to shed light in the solubilization mechanism of sulphobutylether-β-cyclodextrins, broadly used as an excipient in many pharmaceutical formulations, in particular in the case of remdesivir as an active compound. The Author(s). Published by Elsevier B.V. 2021-12-01 2021-09-17 /pmc/articles/PMC8447550/ /pubmed/34548723 http://dx.doi.org/10.1016/j.molliq.2021.117588 Text en © 2021 The Author(s) Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Piñeiro, Ángel Pipkin, James Antle, Vince Garcia-Fandino, Rebeca Aggregation versus inclusion complexes to solubilize drugs with cyclodextrins. A case study using sulphobutylether-β-cyclodextrins and remdesivir |
title | Aggregation versus inclusion complexes to solubilize drugs with cyclodextrins. A case study using sulphobutylether-β-cyclodextrins and remdesivir |
title_full | Aggregation versus inclusion complexes to solubilize drugs with cyclodextrins. A case study using sulphobutylether-β-cyclodextrins and remdesivir |
title_fullStr | Aggregation versus inclusion complexes to solubilize drugs with cyclodextrins. A case study using sulphobutylether-β-cyclodextrins and remdesivir |
title_full_unstemmed | Aggregation versus inclusion complexes to solubilize drugs with cyclodextrins. A case study using sulphobutylether-β-cyclodextrins and remdesivir |
title_short | Aggregation versus inclusion complexes to solubilize drugs with cyclodextrins. A case study using sulphobutylether-β-cyclodextrins and remdesivir |
title_sort | aggregation versus inclusion complexes to solubilize drugs with cyclodextrins. a case study using sulphobutylether-β-cyclodextrins and remdesivir |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447550/ https://www.ncbi.nlm.nih.gov/pubmed/34548723 http://dx.doi.org/10.1016/j.molliq.2021.117588 |
work_keys_str_mv | AT pineiroangel aggregationversusinclusioncomplexestosolubilizedrugswithcyclodextrinsacasestudyusingsulphobutyletherbcyclodextrinsandremdesivir AT pipkinjames aggregationversusinclusioncomplexestosolubilizedrugswithcyclodextrinsacasestudyusingsulphobutyletherbcyclodextrinsandremdesivir AT antlevince aggregationversusinclusioncomplexestosolubilizedrugswithcyclodextrinsacasestudyusingsulphobutyletherbcyclodextrinsandremdesivir AT garciafandinorebeca aggregationversusinclusioncomplexestosolubilizedrugswithcyclodextrinsacasestudyusingsulphobutyletherbcyclodextrinsandremdesivir |