Lindner Sera, Ricci Fabrizio, Sandmeier Matthias, Holm René, Michalowski Cecilia Bohns, Washburn Nathaniel, Sun Dajun, Di Pretoro Giustino, Bernkop-Schnürch Andreas
Thiomatrix Forschungs- und Beratungs GmbH, Trientlgasse 65, 6020, Innsbruck, Austria.
Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230, Odense, Denmark.
Drug Deliv Transl Res. 2025 Jan 16. doi: 10.1007/s13346-024-01787-4.
It was the aim of this study to compare two different dry reverse micelle (RM) preparation methods for the incorporation of hydrophilic drugs into oral self-emulsifying drug delivery systems (SEDDS).
Cationic ethacridine lactate, anionic fluorescein sodium salt and the antibiotic peptide bacitracin were solubilized in RM containing sodium docusate, soy phosphatidylcholine and sorbitan monooleate in highly lipophilic oils such as squalane. In the dry addition (DA) method, drugs were directly added to empty RM in their powder form. In the organic solvent-aided (OS) method, drugs were pre-dissolved in ethanol or 2-propanol, which were then evaporated to form loaded dry RM.
RM with sorbitan monooleate prepared via the DA method yielded up to 2.7-fold higher solubility only for bacitracin compared to the OS method. In contrast, OS-RM with sodium docusate and soy phosphatidylcholine exhibited significantly higher drug solubilities, achieving up to 109-fold, 44-fold and 97-fold increase for ethacridine, fluorescein and bacitracin, respectively. For all model drugs, the logD was highest for RM comprising sorbitan monooleate, with a slight increase for OS-RM. This was consistent with the release profiles from SEDDS, showing an enhanced retention when loaded with OS-RM. While DA-RM showed no significant difference in cellular uptake, it was 1.6-fold higher in OS-RM loaded squalane-based SEDDS.
The DA method is an easier approach for incorporating hydrophilic drugs into dry RM. However, the OS method presents a more promising alternative as it significantly enhanced the solubility and retention of these drugs in highly lipophilic formulations.
本研究旨在比较两种不同的干反胶束（RM）制备方法，用于将亲水性药物掺入口服自乳化药物递送系统（SEDDS）中。
将阳离子乳酸依沙吖啶、阴离子荧光素钠盐和抗生素肽杆菌肽溶解在含有多库酯钠、大豆磷脂酰胆碱和脱水山梨醇单油酸酯的RM中，该RM存在于如角鲨烷等高亲脂性油中。在干加法（DA）中，药物以粉末形式直接添加到空的RM中。在有机溶剂辅助（OS）法中，药物预先溶解在乙醇或异丙醇中，然后蒸发以形成负载的干RM。
与OS法相比，通过DA法制备的含脱水山梨醇单油酸酯的RM仅对杆菌肽的溶解度提高了2.7倍。相比之下，含多库酯钠和大豆磷脂酰胆碱的OS-RM表现出显著更高的药物溶解度，依沙吖啶、荧光素和杆菌肽的溶解度分别提高了109倍、44倍和97倍。对于所有模型药物，含脱水山梨醇单油酸酯的RM的logD最高，OS-RM略有增加。这与SEDDS的释放曲线一致，表明负载OS-RM时保留增强。虽然DA-RM在细胞摄取方面没有显著差异，但在基于角鲨烷的负载OS-RM的SEDDS中，其细胞摄取高1.6倍。
DA法是将亲水性药物掺入干RM的一种更简便的方法。然而，OS法是一种更有前景的替代方法，因为它显著提高了这些药物在高亲脂性制剂中的溶解度和保留率。
