The Increased Dissolution and Oral Absorption of Itraconazole by Nanocrystals with an Endogenous Small-Molecule Surfactant as a Stabilizer

Chang, Sheng; Yang, Qiang; Liu, Jiahuan; Yin, Li; Han, Jihong; Zong, Lanlan; Pu, Xiaohui

Abstract

The aim of this study was to develop cholic-acid-stabilized itraconazole nanosuspensions (ITZ-Nanos) with the objective of enhancing drug dissolution and oral absorption. A laboratory-scale microprecipitation–high-pressure homogenization method was employed for the preparation of the ITZ-Nanos, while dynamic light scattering, transmission electron microscope analysis, X-ray diffraction, differential scanning calorimetry, and high-performance liquid chromatography analysis were utilized to evaluate their physicochemical properties. The absorption and bioavailability of the ITZ-Nanos were assessed using Caco-2 cells and rats, with Sporanox® pellets as a comparison. Prior to lyophilization, the particle size of the ITZ-Nanos measured approximately 225.7 nm. Both X-ray diffraction and differential scanning calorimetry confirmed that the ITZ remained crystalline within the nanocrystals. Compared to the pellets, the ITZ-Nanos exhibited significantly higher levels of supersaturation dissolution and demonstrated enhanced drug uptake by the Caco-2 cells. The AUC(0–t) value for the ITZ-Nanos in rats was 1.33-fold higher than that observed for the pellets. These findings suggest that cholic acid holds promise as a stabilizer for ITZ nanocrystals, as well as potentially other nanocrystals.

Citation

Chang, S., Yang, Q., Liu, J., Yin, L., Han, J., Zong, L., & Pu, X. (in press). The Increased Dissolution and Oral Absorption of Itraconazole by Nanocrystals with an Endogenous Small-Molecule Surfactant as a Stabilizer. Molecules, 29(8), Article 1769. https://doi.org/10.3390/molecules29081769

• Journal Article Type: Article
• Acceptance Date: Apr 10, 2024
• Online Publication Date: Apr 13, 2024
• Deposit Date: Apr 29, 2024
• Journal: Molecules
• Electronic ISSN: 1420-3049
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 29
• Issue: 8
• Article Number: 1769
• DOI: https://doi.org/10.3390/molecules29081769
• Public URL: https://keele-repository.worktribe.com/output/799779