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Voriconazole Eye Drops: Enhanced Solubility and Stability through Ternary Voriconazole/Sulfobutyl Ether β-Cyclodextrin/Polyvinyl Alcohol Complexes

Voriconazole (VCZ) is a broad-spectrum antifungal agent used to treat ocular fungal keratitis. However, VCZ has low aqueous solubility and chemical instability in aqueous solutions. This study aimed to develop VCZ eye drop formulations using cyclodextrin (CD) and water-soluble polymers, forming CD c...

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Autores principales: Soe, Hay Man Saung Hnin, Kerdpol, Khanittha, Rungrotmongkol, Thanyada, Pruksakorn, Patamaporn, Autthateinchai, Rinrapas, Wet-osot, Sirawit, Loftsson, Thorsteinn, Jansook, Phatsawee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917179/
https://www.ncbi.nlm.nih.gov/pubmed/36768671
http://dx.doi.org/10.3390/ijms24032343
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author Soe, Hay Man Saung Hnin
Kerdpol, Khanittha
Rungrotmongkol, Thanyada
Pruksakorn, Patamaporn
Autthateinchai, Rinrapas
Wet-osot, Sirawit
Loftsson, Thorsteinn
Jansook, Phatsawee
author_facet Soe, Hay Man Saung Hnin
Kerdpol, Khanittha
Rungrotmongkol, Thanyada
Pruksakorn, Patamaporn
Autthateinchai, Rinrapas
Wet-osot, Sirawit
Loftsson, Thorsteinn
Jansook, Phatsawee
author_sort Soe, Hay Man Saung Hnin
collection PubMed
description Voriconazole (VCZ) is a broad-spectrum antifungal agent used to treat ocular fungal keratitis. However, VCZ has low aqueous solubility and chemical instability in aqueous solutions. This study aimed to develop VCZ eye drop formulations using cyclodextrin (CD) and water-soluble polymers, forming CD complex aggregates to improve the aqueous solubility and chemical stability of VCZ. The VCZ solubility was greatly enhanced using sulfobutyl ether β-cyclodextrin (SBEβCD). The addition of polyvinyl alcohol (PVA) showed a synergistic effect on VCZ/SBEβCD solubilization and a stabilization effect on the VCZ/SBEβCD complex. The formation of binary VCZ/SBEβCD and ternary VCZ/SBEβCD/PVA complexes was confirmed by spectroscopic techniques and in silico studies. The 0.5% w/v VCZ eye drop formulations were developed consisting of 6% w/v SBEβCD and different types and concentrations of PVA. The VCZ/SBEβCD systems containing high-molecular-weight PVA prepared under freeze–thaw conditions (PVA-H hydrogel) provided high mucoadhesion, sustained release, good ex vivo permeability through the porcine cornea and no sign of irritation. Additionally, PVA-H hydrogel was effective against the filamentous fungi tested. The stability study revealed that our VCZ eye drops provide a shelf-life of more than 2.5 years at room temperature, while a shelf-life of only 3.5 months was observed for the extemporaneous Vfend(®) eye drops.
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spelling pubmed-99171792023-02-11 Voriconazole Eye Drops: Enhanced Solubility and Stability through Ternary Voriconazole/Sulfobutyl Ether β-Cyclodextrin/Polyvinyl Alcohol Complexes Soe, Hay Man Saung Hnin Kerdpol, Khanittha Rungrotmongkol, Thanyada Pruksakorn, Patamaporn Autthateinchai, Rinrapas Wet-osot, Sirawit Loftsson, Thorsteinn Jansook, Phatsawee Int J Mol Sci Article Voriconazole (VCZ) is a broad-spectrum antifungal agent used to treat ocular fungal keratitis. However, VCZ has low aqueous solubility and chemical instability in aqueous solutions. This study aimed to develop VCZ eye drop formulations using cyclodextrin (CD) and water-soluble polymers, forming CD complex aggregates to improve the aqueous solubility and chemical stability of VCZ. The VCZ solubility was greatly enhanced using sulfobutyl ether β-cyclodextrin (SBEβCD). The addition of polyvinyl alcohol (PVA) showed a synergistic effect on VCZ/SBEβCD solubilization and a stabilization effect on the VCZ/SBEβCD complex. The formation of binary VCZ/SBEβCD and ternary VCZ/SBEβCD/PVA complexes was confirmed by spectroscopic techniques and in silico studies. The 0.5% w/v VCZ eye drop formulations were developed consisting of 6% w/v SBEβCD and different types and concentrations of PVA. The VCZ/SBEβCD systems containing high-molecular-weight PVA prepared under freeze–thaw conditions (PVA-H hydrogel) provided high mucoadhesion, sustained release, good ex vivo permeability through the porcine cornea and no sign of irritation. Additionally, PVA-H hydrogel was effective against the filamentous fungi tested. The stability study revealed that our VCZ eye drops provide a shelf-life of more than 2.5 years at room temperature, while a shelf-life of only 3.5 months was observed for the extemporaneous Vfend(®) eye drops. MDPI 2023-01-25 /pmc/articles/PMC9917179/ /pubmed/36768671 http://dx.doi.org/10.3390/ijms24032343 Text en © 2023 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
Soe, Hay Man Saung Hnin
Kerdpol, Khanittha
Rungrotmongkol, Thanyada
Pruksakorn, Patamaporn
Autthateinchai, Rinrapas
Wet-osot, Sirawit
Loftsson, Thorsteinn
Jansook, Phatsawee
Voriconazole Eye Drops: Enhanced Solubility and Stability through Ternary Voriconazole/Sulfobutyl Ether β-Cyclodextrin/Polyvinyl Alcohol Complexes
title Voriconazole Eye Drops: Enhanced Solubility and Stability through Ternary Voriconazole/Sulfobutyl Ether β-Cyclodextrin/Polyvinyl Alcohol Complexes
title_full Voriconazole Eye Drops: Enhanced Solubility and Stability through Ternary Voriconazole/Sulfobutyl Ether β-Cyclodextrin/Polyvinyl Alcohol Complexes
title_fullStr Voriconazole Eye Drops: Enhanced Solubility and Stability through Ternary Voriconazole/Sulfobutyl Ether β-Cyclodextrin/Polyvinyl Alcohol Complexes
title_full_unstemmed Voriconazole Eye Drops: Enhanced Solubility and Stability through Ternary Voriconazole/Sulfobutyl Ether β-Cyclodextrin/Polyvinyl Alcohol Complexes
title_short Voriconazole Eye Drops: Enhanced Solubility and Stability through Ternary Voriconazole/Sulfobutyl Ether β-Cyclodextrin/Polyvinyl Alcohol Complexes
title_sort voriconazole eye drops: enhanced solubility and stability through ternary voriconazole/sulfobutyl ether β-cyclodextrin/polyvinyl alcohol complexes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917179/
https://www.ncbi.nlm.nih.gov/pubmed/36768671
http://dx.doi.org/10.3390/ijms24032343
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