University of Liège, Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines (CIRM), Liège 4000, Belgium.
University of Liège, Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines (CIRM), Liège 4000, Belgium.
Int J Pharm. 2024 May 25;657:124173. doi: 10.1016/j.ijpharm.2024.124173. Epub 2024 Apr 27.
Cannabidiol (CBD) suffers from poor oral bioavailability due to poor aqueous solubility and high metabolism, and is generally administered in liquid lipid vehicles. Solid-state formulations of CBD have been developed, but their ability to increase the oral bioavailability has not yet been proven in vivo. Various approaches are investigated to increase this bioavailability. This study aimed to demonstrate the enhancement of the oral bioavailability of oral solid dosage forms of amorphous CBD and lipid-based CBD formulation compared to crystalline CBD. Six piglets received the three formulations, in a cross-over design. CBD and 7 - COOH - CBD, a secondary metabolite used as an indicator of hepatic degradation, were analyzed in plasma. A 10.9-fold and 6.8-fold increase in oral bioavailability was observed for the amorphous and lipid formulations, respectively. However, the lipid-based formulation allowed reducing the inter-variability when administered to fasted animals. An entero-hepatic cycle was confirmed for amorphous formulations. Finally, this study showed that the expected protective effect of lipids against hepatic degradation of the lipid-based formulation did not occur, since the ratio CBD/metabolite was higher than that of the amorphous one.
由于 CBD（大麻二酚）的水溶性差和代谢率高，其口服生物利用度较差，一般以液体脂质载体给药。已经开发出 CBD 的固态制剂，但它们在体内增加口服生物利用度的能力尚未得到证实。正在研究各种方法来提高这种生物利用度。本研究旨在证明与结晶 CBD 相比，无定形 CBD 和基于脂质的 CBD 制剂的口服固体剂型可提高口服生物利用度。6 头小猪以交叉设计的方式接受了这三种制剂。在血浆中分析了 CBD 和 7-COOH-CBD，这是一种用于指示肝降解的次级代谢物。无定形和脂质制剂的口服生物利用度分别提高了 10.9 倍和 6.8 倍。然而，当给予禁食动物时，基于脂质的制剂可以降低变异性。证实了无定形制剂的肠肝循环。最后，本研究表明，脂质对基于脂质制剂的肝降解的预期保护作用并未发生，因为 CBD/代谢物的比值高于无定形制剂。
