Enhancement of the solubility and oral bioavailability of altrenogest through complexation with hydroxypropyl-β-cyclodextrin

Chen, Wojun; Zheng, Xianwen; Lao, Wenxuan; Wang, Hongxin; Chen, Shengfeng; Liu, Canying; Chen, Zhisheng; Bai, Yinshan; Zhang, Hui; Zhan, Xiaoshu; Wang, Bingyun

doi:10.1016/j.ejps.2024.106691

Cited by 2 publications

(2 citation statements)

References 34 publications

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“…Phase solubility diagrams have been widely utilized to investigate the solubilizing effect produced by different cyclodextrins on drugs [18,19]. Two unique phase solubility diagrams emerged due to variations in drug properties and cyclodextrin interactions.…”

Section: Phase Solubility Studiesmentioning

confidence: 99%

“…β-CD is a go-to choice in CD S owing to its affordable price and easy availability. β-CD derivatives (such as M-β-CD and HP-β-CD) undergo chemical modification at β-CD's hydroxyl group, offering improved water solubility and reduced toxicity as key benefits [17,18]. For example, one study found that daidzein's solubility increased 1474-fold after forming an inclusion complex with HP-β-CD [17].…”

Section: Introductionmentioning

confidence: 99%

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Inclusion Complexes of Ethanamizuril with β- and Hydroxypropyl-β-Cyclodextrin in Aqueous Solution and in Solid State: A Comparison Study

Guo,

Zhang,

Wang

et al. 2024

Molecules

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Ethanamizuril (EZL) is a new anticoccidial drug developed by our Shanghai Veterinary Research Institute. Since EZL is almost insoluble in water, we conducted a study to improve the solubility of EZL by forming inclusion complexes with β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD). In this study, we performed molecular docking and then systematically compared the interactions of EZL with β-CD and HP-β-CD in both aqueous solution and the solid state, aiming to elucidate the solubilization effect and mechanism of cyclodextrins (CDs). The interactions were also examined in the solid state using DSC, PXRD, and FT-IR. The interactions of EZL with CDs in an aqueous solution were investigated using PSA, UV-vis spectroscopy, MS, 1H NMR, and 2D ROESY. The results of phase solubility experiments revealed that both β-CD and HP-β-CD formed inclusion complexes with EZL in a 1:1 molar ratio. Among them, HP-β-CD exhibited higher Kf (stability constant) and CE (complexation efficiency) values as well as a stronger solubilization effect. Furthermore, the two cyclodextrins were found to interact with EZL in a similar manner. The results of our FT-IR and 2D ROESY experiments are in agreement with the theoretical results derived from molecular simulations. These results indicated that intermolecular hydrogen bonds existing between the C=O group on the triazine ring of EZL and the O-H group of CDs, as well as the hydrophobic interactions between the hydrogen on the benzene ring of EZL and the hydrogen of CDs, played crucial roles in the formation of EZL/CD inclusion complexes. The results of this study can lay the foundation for the future development of high-concentration drinking water delivery formulations for EZL.

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Section: Phase Solubility Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inclusion Complexes of Ethanamizuril with β- and Hydroxypropyl-β-Cyclodextrin in Aqueous Solution and in Solid State: A Comparison Study

Guo,

Zhang,

Wang

et al. 2024

Molecules

View full text Add to dashboard Cite

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In Vitro Stability and Pharmacokinetic Study of Pedunculoside and Its Beta-CD Polymer Inclusion Complex

Wu,

Li,

Wang

et al. 2024

Pharmaceutics

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Pedunculoside, a triterpene saponin derived from various Ilex species, holds potential as a treatment for cardiovascular diseases. However, its clinical application is hindered by poor bioavailability, rapid elimination, and extensive intestinal metabolism to rotundic acid. To address these issues, a water-soluble inclusion complex of pedunculoside, namely, the beta-CD polymer inclusion complex of pedunculoside (pedunculoside–βCDP), was prepared in this study, and a comparative in vitro stability and pharmacokinetic behavior study was performed between pedunculoside and pedunculoside–βCDP. Both pedunculoside and pedunculoside–βCDP exhibited the highest stability in simulated gastric fluid and simulated intestinal fluid but were readily metabolized when co-incubated with Bifidobacterium adolescentis and Bifidobacterium breve. An LC-MS/MS analytical method for the simultaneous determination of pedunculoside and rotundic acid in rat plasma was successfully established, validated, and applied to investigate the pharmacokinetic behavior after rats were intravenously administered with pedunculoside or pedunculoside–βCDP. The results indicated that pedunculoside–βCDP could significantly improve the pharmacokinetic profile of pedunculoside by increasing plasma exposure, retarding elimination, and reducing intestinal metabolism. This study enhances our understanding of pedunculoside–βCDP’s metabolic fate and pharmacokinetic properties and potentially advances its further research, development, and clinical application.

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Enhancement of the solubility and oral bioavailability of altrenogest through complexation with hydroxypropyl-β-cyclodextrin

Cited by 2 publications

References 34 publications

Inclusion Complexes of Ethanamizuril with β- and Hydroxypropyl-β-Cyclodextrin in Aqueous Solution and in Solid State: A Comparison Study

Inclusion Complexes of Ethanamizuril with β- and Hydroxypropyl-β-Cyclodextrin in Aqueous Solution and in Solid State: A Comparison Study

In Vitro Stability and Pharmacokinetic Study of Pedunculoside and Its Beta-CD Polymer Inclusion Complex

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