Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, Mississippi, 38677, USA.
Pharmaceutics and Pharmaceutical Technology Department, College of Pharmacy, Taibah University, Al Madinah AlMunawarah, 30001, Saudi Arabia.
AAPS PharmSciTech. 2024 Jun 11;25(5):136. doi: 10.1208/s12249-024-02857-z.
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, Gelucire59/14, 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.
大麻二酚(CBD)是一种高度亲脂性化合物,由于其水溶性差和广泛的前体系统代谢,口服生物利用度较差。本研究旨在探索采用热熔挤出(HME)技术连续生产自乳化药物传递系统(SEDDS)以提高 CBD 的溶解度和体外溶解性能的潜力。因此,通过 HME 对不同的赋形剂进行处理,以获得载有 CBD 的固体 SEDDS 作为先导。使用芝麻油、泊洛沙姆 188、Gelucire 59/14、PEO N80 和 Soluplus 制备了两种 SEDDS。此外,还添加了维生素 E 作为抗氧化剂。SEDDS 配方的乳化时间分别为 F1 和 F2 的 9.19 和 9.30 分钟。形成的乳液粒径较小,范围在 150-400nm 之间,可提高 CBD 的淋巴摄取并减少首过代谢。与纯 CBD 在第一小时内的 14%相比,两种配方均显示出明显更快的体外溶解速率(F1 为 90%,F2 为 83%),释放曲线得到改善。在 4°C、25°C 和 40°C 下,对制剂进行了 60 天的稳定性测试。在 4°C 下,制剂 F1 在 60 天的时间内稳定。因此,连续的 HME 技术可以替代传统的 SEDDS 加工方法,提高 CBD 的口服递送,以获得更好的治疗效果。
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