Tabboon Peera, Pongjanyakul Thaned, Limpongsa Ekapol, Jaipakdee Napaphak
Division of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand.
Center for Research and Development of Herbal Health Products, Khon Kaen University, Khon Kaen 40002, Thailand.
Pharmaceutics. 2022 Aug 13;14(8):1687. doi: 10.3390/pharmaceutics14081687.
In this study, the mucosal permeation and deposition of cannabidiol (CBD) with neat and binary vehicles were investigated. Permeation experiments were performed using static diffusion cells coupled with fresh porcine esophageal mucosa. The CBD-vehicle solutions were applied at a fixed dose (~5 mg/cm), and the corresponding permeation parameters were calculated. In neat vehicles, the permeation flux () ranged from 0.89 ± 0.15 to 179.81 ± 23.46 µg·cm·h, while the CBD deposition ranged from 11.5 ± 1.8 to 538.3 ± 105.3 μg·cm. Propylene glycol (PG) and diethylene glycol monoethyl ether (DEGEE) yielded the highest permeability () and CBD deposition, while medium-chain triglycerides (MCT) yielded the lowest and deposition. This was due to the difference in apparent partition coefficient (), which is related to the solubility of CBD in the vehicle. The PG:DEGEE binary vehicle boosted (1.5-1.6 fold) and deposition (2.0-2.7 folds) significantly, compared to neat DEGEE. The combination of DEGEE with MCT dramatically enhanced (11-44 fold) and deposition (1.6-4.7 fold). The addition of lipophilic enhancers, laurocapram, and oleic acid, to PG:DEGEE and DEGEE:MCT vehicles significantly reduced (0.3-0.7 fold) and deposition (0.4-0.8 fold) while nerolidol had no effect. These permeation reductions were found to be related to modification of the and/or diffusivity values. This study provides useful basic information for the development of CBD formulations intended for transmucosal delivery.
在本研究中，研究了大麻二酚（CBD）在纯溶剂和二元溶剂中的黏膜渗透及沉积情况。使用与新鲜猪食管黏膜耦合的静态扩散池进行渗透实验。以固定剂量（约5 mg/cm）施加CBD-溶剂溶液，并计算相应的渗透参数。在纯溶剂中，渗透通量（）范围为0.89±0.15至179.81±23.46 μg·cm·h，而CBD沉积范围为11.5±1.8至538.3±105.3 μg·cm。丙二醇（PG）和二甘醇单乙醚（DEGEE）产生的渗透率（）和CBD沉积最高，而中链甘油三酯（MCT）产生的渗透率和沉积最低。这是由于表观分配系数（）的差异，其与CBD在溶剂中的溶解度有关。与纯DEGEE相比，PG:DEGEE二元溶剂显著提高了渗透率（1.5 - 1.6倍）和沉积（2.0 - 2.7倍）。DEGEE与MCT的组合显著提高了渗透率（11 - 44倍）和沉积（1.6 - 4.7倍）。向PG:DEGEE和DEGEE:MCT溶剂中添加亲脂性增强剂月桂氮卓酮和油酸显著降低了渗透率（0.3 - 0.7倍）和沉积（0.4 - 0.8倍），而橙花叔醇没有影响。发现这些渗透率的降低与分配系数和/或扩散率值的改变有关。本研究为开发用于经黏膜给药的CBD制剂提供了有用的基础信息。
