Deng Li, Wang Yu, Gong Tao, Sun Xun, Zhang Zhi-Rong
a Key Laboratory of Drug Targeting and Delivery Systems , Sichuan University , Chengdu , China.
Drug Dev Ind Pharm. 2017 Nov;43(11):1817-1826. doi: 10.1080/03639045.2017.1349783. Epub 2017 Jul 11.
Alpha (α)-asarone (1-propenyl-2,4,5-methoxybenzol) (ARE) has been extensively used to treat chronic obstructive pulmonary diseases (COPD), bronchial asthma, pneumonia, and epilepsy. Due to its poor solubility and bioavailability, ARE was clinically administered via intravenous injection. However, severe allergies were often reported due to the presence of solublizers in the injection formulation. In our study, we sought to explore the biopharmaceutical classification of ARE, elucidate the mechanisms behind ARE absorption, and to develop a viable formulation to improve the oral bioavailability of ARE. ARE was not a P-glycoprotein substrate, which was absorbed in the passive mode without site specificity in the gastrointestinal tract. Solid dispersions prepared using hydrophilic matrix materials such as Pluronic F68, and polyethylene glycol (PEG) of varying molecular weights (PEG4K, PEG10K, and PEG20K) were proven to significantly improve the dissolution of ARE in vitro and the oral bioavailability of ARE in rats, which represent a promising strategy for the oral administration of ARE and other BCS II compounds.
α-细辛脑（1-丙烯基-2,4,5-三甲氧基苯）（ARE）已被广泛用于治疗慢性阻塞性肺疾病（COPD）、支气管哮喘、肺炎和癫痫。由于其溶解度和生物利用度较差，ARE在临床上通过静脉注射给药。然而，由于注射制剂中存在增溶剂，经常报告有严重过敏反应。在我们的研究中，我们试图探索ARE的生物药剂学分类，阐明ARE吸收背后的机制，并开发一种可行的制剂以提高ARE的口服生物利用度。ARE不是P-糖蛋白底物，它以被动模式吸收，在胃肠道中没有位点特异性。使用亲水性基质材料如普朗尼克F68和不同分子量的聚乙二醇（PEG）（PEG4K、PEG10K和PEG20K）制备的固体分散体被证明能显著提高ARE的体外溶出度和在大鼠体内的口服生物利用度，这代表了一种用于ARE和其他BCS II类化合物口服给药的有前景的策略。
