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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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/1/53 |
| _version_ | 1797437852354609152 |
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| author | Annalisa Bianchera Marino Nebuloni Nicola Colombo Davide Pirola Ruggero Bettini |
| author_facet | Annalisa Bianchera Marino Nebuloni Nicola Colombo Davide Pirola Ruggero Bettini |
| author_sort | Annalisa Bianchera |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T11:28:37Z |
| format | Article |
| id | doaj.art-937e5eec5508450fad6de07c017a2082 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T11:28:37Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-937e5eec5508450fad6de07c017a20822023-11-30T23:57:00ZengMDPI AGPharmaceutics1999-49232022-12-011515310.3390/pharmaceutics15010053Highly Polymorphic Materials and Dissolution Behaviour: The Peculiar Case of RifaximinAnnalisa Bianchera0Marino Nebuloni1Nicola Colombo2Davide Pirola3Ruggero Bettini4Food and Drug Department, University of Parma, 43121 Parma, ItalyRedox S.R.L., 20900 Monza, ItalyRedox S.R.L., 20900 Monza, ItalyRedox S.R.L., 20900 Monza, ItalyFood and Drug Department, University of Parma, 43121 Parma, ItalyRifaximin 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.https://www.mdpi.com/1999-4923/15/1/53rifaximindissolutionpseudopolymorphssupersaturationkinetic solubility |
| spellingShingle | Annalisa Bianchera Marino Nebuloni Nicola Colombo Davide Pirola Ruggero Bettini Highly Polymorphic Materials and Dissolution Behaviour: The Peculiar Case of Rifaximin Pharmaceutics rifaximin dissolution pseudopolymorphs supersaturation kinetic solubility |
| 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 | rifaximin dissolution pseudopolymorphs supersaturation kinetic solubility |
| url | https://www.mdpi.com/1999-4923/15/1/53 |
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