Koch Nathan, Bourcy Quentin, Jennotte Olivier, Chiap Patrice, Lechanteur Anna, Cardot Jean-Michel, Evrard Brigitte
Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège, 4000 Liège, Belgium.
Department of Toxicology, Center for Interdisciplinary Research on Medicines (CIRM), Academic Hospital of Liège, 4000 Liège, Belgium.
Pharmaceutics. 2025 Jan 9;17(1):79. doi: 10.3390/pharmaceutics17010079.
Cannabidiol (CBD) shows interesting therapeutic properties but has yet to demonstrate its full potential in clinical trials partly due to its low solubility in physiologic media. Two different formulations of CBD (amorphous and lipid-based) have been optimized and enable an increase in bioavailability in piglets. In vivo studies are time-consuming, costly and life-threatening. Therefore, we need to develop in vitro tests that can predict what will happen in vivo. Comparisons in terms of dissolution were made especially by using different media (FaSSGF, FaSSIF, FeSSIF, HCl 0.1N with or without SLS, phosphate buffer pH 6.8 with or without SLS) and different conditions (sink or non-sink conditions). These in vitro results were confronted with in vivo results to select the most appropriate dissolution test conditions. The importance of the presence of surfactants to enable solubilization of CBD was demonstrated. Neutral media enabled a relatively good prediction of the extent of absorption observed in vivo, whereas the rate of absorption was more complicated to predict. FeSSIF media, and FaSSIF sink media to a lesser extent, were the only compositions enabling predictions of both extent and rate, indicating that emulsification is possibly a major contributor to the in vivo availability of the drug.
大麻二酚（CBD）具有有趣的治疗特性，但部分由于其在生理介质中的低溶解度，尚未在临床试验中充分展现其全部潜力。两种不同的CBD制剂（无定形和脂质基）已得到优化，并能提高仔猪的生物利用度。体内研究耗时、成本高且危及生命。因此，我们需要开发能够预测体内情况的体外试验。特别是通过使用不同介质（FaSSGF、FaSSIF、FeSSIF、含或不含十二烷基硫酸钠的0.1N盐酸、含或不含十二烷基硫酸钠的pH 6.8磷酸盐缓冲液）和不同条件（漏槽或非漏槽条件）进行溶出度比较。将这些体外结果与体内结果进行对比，以选择最合适的溶出度测试条件。已证明表面活性剂的存在对实现CBD增溶的重要性。中性介质能够相对较好地预测体内观察到的吸收程度，而吸收速率则更难预测。FeSSIF介质以及程度稍低的FaSSIF漏槽介质是仅有的能够同时预测吸收程度和速率的组合物，这表明乳化可能是药物体内可用性的主要影响因素。
