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Highly Polymorphic Materials and Dissolution Behaviour: The Peculiar Case of Rifaximin

Rifaximin is a locally acting antibiotic practically insoluble in water. It presents several crystal phases characterized by different degrees of hydration. The aim of this work is to investigate the dissolution behaviour of rifaximin α, β, and amorphous forms in relation to their relative thermodyn...

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Detalles Bibliográficos
Autores principales: Bianchera, Annalisa, Nebuloni, Marino, Colombo, Nicola, Pirola, Davide, Bettini, Ruggero
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9865978/
https://www.ncbi.nlm.nih.gov/pubmed/36678682
http://dx.doi.org/10.3390/pharmaceutics15010053
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author Bianchera, Annalisa
Nebuloni, Marino
Colombo, Nicola
Pirola, Davide
Bettini, Ruggero
author_facet Bianchera, Annalisa
Nebuloni, Marino
Colombo, Nicola
Pirola, Davide
Bettini, Ruggero
author_sort Bianchera, Annalisa
collection PubMed
description Rifaximin is a locally acting antibiotic practically insoluble in water. It presents several crystal phases characterized by different degrees of hydration. The aim of this work is to investigate the dissolution behaviour of rifaximin α, β, and amorphous forms in relation to their relative thermodynamic stability to contribute to clarifying possible solvent- or humidity-mediated conversion patterns. Kinetic and intrinsic solubility were investigated along with particle size distribution, specific surface area, and external morphology. The solution and moisture mediated conversion from metastable α and amorphous forms to stable β form were elucidated by coupling intrinsic dissolution test with chemometric analysis as well as by dynamic vapour sorption measurements. The dissolution behaviour of the α form stems mainly from the transition to β form that occurs upon exposition to relative humidity higher than 40%. The α form converted more rapidly than the amorphous form due to the smaller supersaturation ratio. It can be concluded that, due to its marked tendency to transform into β form, the dissolution test for the α form, even if conducted according to compendial procedures, needs to be accompanied by a panel of further tests that allow to uniquely identify the solid phase under investigation.
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spelling pubmed-98659782023-01-22 Highly Polymorphic Materials and Dissolution Behaviour: The Peculiar Case of Rifaximin Bianchera, Annalisa Nebuloni, Marino Colombo, Nicola Pirola, Davide Bettini, Ruggero Pharmaceutics Article Rifaximin is a locally acting antibiotic practically insoluble in water. It presents several crystal phases characterized by different degrees of hydration. The aim of this work is to investigate the dissolution behaviour of rifaximin α, β, and amorphous forms in relation to their relative thermodynamic stability to contribute to clarifying possible solvent- or humidity-mediated conversion patterns. Kinetic and intrinsic solubility were investigated along with particle size distribution, specific surface area, and external morphology. The solution and moisture mediated conversion from metastable α and amorphous forms to stable β form were elucidated by coupling intrinsic dissolution test with chemometric analysis as well as by dynamic vapour sorption measurements. The dissolution behaviour of the α form stems mainly from the transition to β form that occurs upon exposition to relative humidity higher than 40%. The α form converted more rapidly than the amorphous form due to the smaller supersaturation ratio. It can be concluded that, due to its marked tendency to transform into β form, the dissolution test for the α form, even if conducted according to compendial procedures, needs to be accompanied by a panel of further tests that allow to uniquely identify the solid phase under investigation. MDPI 2022-12-24 /pmc/articles/PMC9865978/ /pubmed/36678682 http://dx.doi.org/10.3390/pharmaceutics15010053 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bianchera, Annalisa
Nebuloni, Marino
Colombo, Nicola
Pirola, Davide
Bettini, Ruggero
Highly Polymorphic Materials and Dissolution Behaviour: The Peculiar Case of Rifaximin
title Highly Polymorphic Materials and Dissolution Behaviour: The Peculiar Case of Rifaximin
title_full Highly Polymorphic Materials and Dissolution Behaviour: The Peculiar Case of Rifaximin
title_fullStr Highly Polymorphic Materials and Dissolution Behaviour: The Peculiar Case of Rifaximin
title_full_unstemmed Highly Polymorphic Materials and Dissolution Behaviour: The Peculiar Case of Rifaximin
title_short Highly Polymorphic Materials and Dissolution Behaviour: The Peculiar Case of Rifaximin
title_sort highly polymorphic materials and dissolution behaviour: the peculiar case of rifaximin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9865978/
https://www.ncbi.nlm.nih.gov/pubmed/36678682
http://dx.doi.org/10.3390/pharmaceutics15010053
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