Abstract：
Cannabidiol (CBD) is a highly lipophilic compound with poor oral bioavailability, due to poor aqueous solubility and extensive pre-systemic metabolism. The aim of this study was to explore the potential of employing Hot Melt Extrusion (HME) technology for the continuous production of Self Emulsifying Drug Delivery Systems (SEDDS) to improve the solubility and in vitro dissolution performance of CBD. Accordingly, different placebos were processed through HME in order to obtain a lead CBD loaded solid SEDDS. Two SEDDS were prepared with sesame oil, Poloxamer 188, Gelucire®59/14, PEO N80 and Soluplus®. Moreover, Vitamin E was added as an antioxidant. The SEDDS formulations demonstrated emulsification times of 9.19 and 9.30 min for F1 and F2 respectively. The formed emulsions showed smaller droplet size ranging from 150-400 nm that could improve lymphatic uptake of CBD and reduce first pass metabolism. Both formulations showed significantly faster in vitro dissolution rate (90% for F1 and 83% for F2) compared to 14% for the pure CBD within the first hour, giving an enhanced release profile. The formulations were tested for stability over a 60-day time period at 4°C, 25°C, and 40°C. Formulation F1 was stable over the 60-day time-period at 4°C. Therefore, the continuous HME technology could replace conventional methods for processing SEDDS and improve the oral delivery of CBD for better therapeutic outcomes.
摘要：
大麻二酚（CBD）是一种高度亲脂性的化合物，口服生物利用度较差，由于水溶性差和广泛的系统前代谢。这项研究的目的是探索采用热熔挤出（HME）技术连续生产自乳化药物递送系统（SEDDS）的潜力，以提高CBD的溶解度和体外溶出性能。因此，通过HME处理不同的安慰剂，以获得负载铅CBD的固体SEDDS。用芝麻油制备了两个SEDDS，泊洛沙姆188、Gelucire®59/14、PEON80和Soluplus®。此外，添加维生素E作为抗氧化剂。SEDDS制剂证明F1和F2的乳化时间分别为9.19和9.30分钟。所形成的乳液显示出150-400nm范围内的较小液滴尺寸,其可以改善CBD的淋巴摄取并减少首过代谢。两种制剂在第一小时内显示出明显更快的体外溶出速率（F1为90％，F2为83％），而纯CBD为14％。提供增强的释放配置文件。在4°C下，在60天的时间段内测试制剂的稳定性。25°C,和40°C。制剂F1在4°C下在60天的时间段内是稳定的。因此,连续HME技术可以替代处理SEDDS的常规方法,并改善CBD的口服给药,从而获得更好的治疗效果.
