Spray-dried voriconazole-cyclodextrin complexes: Solubility, dissolution rate and chemical stability
Abstract
The present work investigates the effect of complexation with hydroxypropyl-beta-cyclodextrin (HPBCD) and 2-O-methyl-beta-cyclodextrin (2-O-MBCD), on voriconazole solubility, dissolution rate and chemical stability. Drug-cyclodextrin complexes were prepared as aqueous solutions, which were spray-dried, and their properties were compared to wet ground samples and physical mixtures. DSC analysis revealed absence of crystalline voriconazole from spray-dried complexes. FTIR spectroscopy indicated changes in the H-bonding network of the hydroxyl groups of cyclodextrin following drug inclusion. Dissolution rate of voriconazole was significantly higher from spray-dried complexes with either cyclodextrin in comparison with free drug, physical mixtures, or wet ground mixtures. However, two degradation impurities were found in aged samples, with slightly higher impurity level with HPBCD. Performed solubility studies suggested that 2-O-MBCD is more efficient solubilizer. Molecular docking simulat...ions showed a difference in the 1:1 binding affinities and sites, with HPBCD surprisingly forming complexes of much lower energy, thus suggesting a multiple rather than a 1:1 complexation.
Keywords:
Voriconazole / Cyclodextrins / Solubility / Dissolution / Stability / Molecular dockingSource:
Carbohydrate Polymers, 2013, 98, 1, 122-131Publisher:
- Elsevier Sci Ltd, Oxford
Funding / projects:
DOI: 10.1016/j.carbpol.2013.05.084
ISSN: 0144-8617
PubMed: 23987325
WoS: 000325835600016
Scopus: 2-s2.0-84879493192
Collections
Institution/Community
PharmacyTY - JOUR AU - Miletić, Tijana AU - Kyriakos, Kachrimanis AU - Graovac, Adrijana AU - Ibrić, Svetlana PY - 2013 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1841 AB - The present work investigates the effect of complexation with hydroxypropyl-beta-cyclodextrin (HPBCD) and 2-O-methyl-beta-cyclodextrin (2-O-MBCD), on voriconazole solubility, dissolution rate and chemical stability. Drug-cyclodextrin complexes were prepared as aqueous solutions, which were spray-dried, and their properties were compared to wet ground samples and physical mixtures. DSC analysis revealed absence of crystalline voriconazole from spray-dried complexes. FTIR spectroscopy indicated changes in the H-bonding network of the hydroxyl groups of cyclodextrin following drug inclusion. Dissolution rate of voriconazole was significantly higher from spray-dried complexes with either cyclodextrin in comparison with free drug, physical mixtures, or wet ground mixtures. However, two degradation impurities were found in aged samples, with slightly higher impurity level with HPBCD. Performed solubility studies suggested that 2-O-MBCD is more efficient solubilizer. Molecular docking simulations showed a difference in the 1:1 binding affinities and sites, with HPBCD surprisingly forming complexes of much lower energy, thus suggesting a multiple rather than a 1:1 complexation. PB - Elsevier Sci Ltd, Oxford T2 - Carbohydrate Polymers T1 - Spray-dried voriconazole-cyclodextrin complexes: Solubility, dissolution rate and chemical stability VL - 98 IS - 1 SP - 122 EP - 131 DO - 10.1016/j.carbpol.2013.05.084 ER -
@article{ author = "Miletić, Tijana and Kyriakos, Kachrimanis and Graovac, Adrijana and Ibrić, Svetlana", year = "2013", abstract = "The present work investigates the effect of complexation with hydroxypropyl-beta-cyclodextrin (HPBCD) and 2-O-methyl-beta-cyclodextrin (2-O-MBCD), on voriconazole solubility, dissolution rate and chemical stability. Drug-cyclodextrin complexes were prepared as aqueous solutions, which were spray-dried, and their properties were compared to wet ground samples and physical mixtures. DSC analysis revealed absence of crystalline voriconazole from spray-dried complexes. FTIR spectroscopy indicated changes in the H-bonding network of the hydroxyl groups of cyclodextrin following drug inclusion. Dissolution rate of voriconazole was significantly higher from spray-dried complexes with either cyclodextrin in comparison with free drug, physical mixtures, or wet ground mixtures. However, two degradation impurities were found in aged samples, with slightly higher impurity level with HPBCD. Performed solubility studies suggested that 2-O-MBCD is more efficient solubilizer. Molecular docking simulations showed a difference in the 1:1 binding affinities and sites, with HPBCD surprisingly forming complexes of much lower energy, thus suggesting a multiple rather than a 1:1 complexation.", publisher = "Elsevier Sci Ltd, Oxford", journal = "Carbohydrate Polymers", title = "Spray-dried voriconazole-cyclodextrin complexes: Solubility, dissolution rate and chemical stability", volume = "98", number = "1", pages = "122-131", doi = "10.1016/j.carbpol.2013.05.084" }
Miletić, T., Kyriakos, K., Graovac, A.,& Ibrić, S.. (2013). Spray-dried voriconazole-cyclodextrin complexes: Solubility, dissolution rate and chemical stability. in Carbohydrate Polymers Elsevier Sci Ltd, Oxford., 98(1), 122-131. https://doi.org/10.1016/j.carbpol.2013.05.084
Miletić T, Kyriakos K, Graovac A, Ibrić S. Spray-dried voriconazole-cyclodextrin complexes: Solubility, dissolution rate and chemical stability. in Carbohydrate Polymers. 2013;98(1):122-131. doi:10.1016/j.carbpol.2013.05.084 .
Miletić, Tijana, Kyriakos, Kachrimanis, Graovac, Adrijana, Ibrić, Svetlana, "Spray-dried voriconazole-cyclodextrin complexes: Solubility, dissolution rate and chemical stability" in Carbohydrate Polymers, 98, no. 1 (2013):122-131, https://doi.org/10.1016/j.carbpol.2013.05.084 . .