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Cyclodextrins Allow the Combination of Incompatible Vancomycin and Ceftazidime into an Ophthalmic Formulation for the Treatment of Bacterial Keratitis

Ceftazidime (CZ) and vancomycin (VA) are two antibiotics used to treat bacterial keratitis. Due to their physical incompatibility (formation of a precipitate), it is not currently possible to associate both molecules in a single container for ophthalmic administration. We firstly characterized the i...

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Autores principales: Bouattour, Yassine, Neflot-Bissuel, Florent, Traïkia, Mounir, Biesse-Martin, Anne-Sophie, Frederic, Robin, Yessaad, Mouloud, Jouannet, Mireille, Wasiak, Mathieu, Chennell, Philip, Sautou, Valerie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508691/
https://www.ncbi.nlm.nih.gov/pubmed/34638878
http://dx.doi.org/10.3390/ijms221910538
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author Bouattour, Yassine
Neflot-Bissuel, Florent
Traïkia, Mounir
Biesse-Martin, Anne-Sophie
Frederic, Robin
Yessaad, Mouloud
Jouannet, Mireille
Wasiak, Mathieu
Chennell, Philip
Sautou, Valerie
author_facet Bouattour, Yassine
Neflot-Bissuel, Florent
Traïkia, Mounir
Biesse-Martin, Anne-Sophie
Frederic, Robin
Yessaad, Mouloud
Jouannet, Mireille
Wasiak, Mathieu
Chennell, Philip
Sautou, Valerie
author_sort Bouattour, Yassine
collection PubMed
description Ceftazidime (CZ) and vancomycin (VA) are two antibiotics used to treat bacterial keratitis. Due to their physical incompatibility (formation of a precipitate), it is not currently possible to associate both molecules in a single container for ophthalmic administration. We firstly characterized the incompatibility then investigated if 2-hydroxypropyl-beta (HPβCD) and 2-hydroxypropyl-gamma cyclodextrins (HPγCD) could prevent this incompatibility. The impact of pH on the precipitation phenomena was investigated by analysing the supernatant solution of the mixture using high performance liquid chromatography. A characterization of the inclusion of CZ with HPγCD using (1)H nuclear magnetic resonance (NMR), and VA with HPβCD using (1)H-NMR and a solubility diagram was performed. A design of experiment was built to determine the optimal conditions to obtain a formulation that had the lowest turbidity and particle count. Our results showed that VA and CZ form an equimolar precipitate below pH 7.3. The best formulation obtained underwent an in-vitro evaluation of its antibacterial activity. The impact of HPCDs on incompatibility has been demonstrated through the inclusion of antibiotics and especially VA. The formulation has been shown to be able to inhibit the incompatibility for pH higher than 7.3 and to possess unaltered antibacterial activity.
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spelling pubmed-85086912021-10-13 Cyclodextrins Allow the Combination of Incompatible Vancomycin and Ceftazidime into an Ophthalmic Formulation for the Treatment of Bacterial Keratitis Bouattour, Yassine Neflot-Bissuel, Florent Traïkia, Mounir Biesse-Martin, Anne-Sophie Frederic, Robin Yessaad, Mouloud Jouannet, Mireille Wasiak, Mathieu Chennell, Philip Sautou, Valerie Int J Mol Sci Article Ceftazidime (CZ) and vancomycin (VA) are two antibiotics used to treat bacterial keratitis. Due to their physical incompatibility (formation of a precipitate), it is not currently possible to associate both molecules in a single container for ophthalmic administration. We firstly characterized the incompatibility then investigated if 2-hydroxypropyl-beta (HPβCD) and 2-hydroxypropyl-gamma cyclodextrins (HPγCD) could prevent this incompatibility. The impact of pH on the precipitation phenomena was investigated by analysing the supernatant solution of the mixture using high performance liquid chromatography. A characterization of the inclusion of CZ with HPγCD using (1)H nuclear magnetic resonance (NMR), and VA with HPβCD using (1)H-NMR and a solubility diagram was performed. A design of experiment was built to determine the optimal conditions to obtain a formulation that had the lowest turbidity and particle count. Our results showed that VA and CZ form an equimolar precipitate below pH 7.3. The best formulation obtained underwent an in-vitro evaluation of its antibacterial activity. The impact of HPCDs on incompatibility has been demonstrated through the inclusion of antibiotics and especially VA. The formulation has been shown to be able to inhibit the incompatibility for pH higher than 7.3 and to possess unaltered antibacterial activity. MDPI 2021-09-29 /pmc/articles/PMC8508691/ /pubmed/34638878 http://dx.doi.org/10.3390/ijms221910538 Text en © 2021 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
Bouattour, Yassine
Neflot-Bissuel, Florent
Traïkia, Mounir
Biesse-Martin, Anne-Sophie
Frederic, Robin
Yessaad, Mouloud
Jouannet, Mireille
Wasiak, Mathieu
Chennell, Philip
Sautou, Valerie
Cyclodextrins Allow the Combination of Incompatible Vancomycin and Ceftazidime into an Ophthalmic Formulation for the Treatment of Bacterial Keratitis
title Cyclodextrins Allow the Combination of Incompatible Vancomycin and Ceftazidime into an Ophthalmic Formulation for the Treatment of Bacterial Keratitis
title_full Cyclodextrins Allow the Combination of Incompatible Vancomycin and Ceftazidime into an Ophthalmic Formulation for the Treatment of Bacterial Keratitis
title_fullStr Cyclodextrins Allow the Combination of Incompatible Vancomycin and Ceftazidime into an Ophthalmic Formulation for the Treatment of Bacterial Keratitis
title_full_unstemmed Cyclodextrins Allow the Combination of Incompatible Vancomycin and Ceftazidime into an Ophthalmic Formulation for the Treatment of Bacterial Keratitis
title_short Cyclodextrins Allow the Combination of Incompatible Vancomycin and Ceftazidime into an Ophthalmic Formulation for the Treatment of Bacterial Keratitis
title_sort cyclodextrins allow the combination of incompatible vancomycin and ceftazidime into an ophthalmic formulation for the treatment of bacterial keratitis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508691/
https://www.ncbi.nlm.nih.gov/pubmed/34638878
http://dx.doi.org/10.3390/ijms221910538
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