Ha Eun-Sol, Choi Du Hyung, Baek In-Hwan, Park Heejun, Kim Min-Soo
College of Pharmacy, Pusan National University, 63 Busandaehak-ro, Geumjeong-gu, Busan 46241, Korea.
Department of Pharmaceutical Engineering, Inje University, Gyeongnam 50834, Korea.
Antioxidants (Basel). 2021 Jan 11;10(1):90. doi: 10.3390/antiox10010090.
In this study, we designed amorphous solid dispersions based on Eudragit E/HCl (neutralized Eudragit E using hydrochloric acid) to maximize the dissolution of -resveratrol. Solid-state characterization of amorphous solid dispersions of -resveratrol was performed using powder X-ray diffraction, scanning electron microscopy, and particle size measurements. In addition, an in vitro dissolution study and an in vivo pharmacokinetic study in rats were carried out. Among the tested polymers, Eudragit E/HCl was the most effective solid dispersion for the solubilization of -resveratrol. Eudragit E/HCl significantly inhibited the precipitation of -resveratrol in a pH 1.2 dissolution medium in a dose-dependent manner. The amorphous Eudragit E/HCl solid dispersion at a -resveratrol/polymer ratio of 10/90 exhibited a high degree of supersaturation without -resveratrol precipitation for at least 48 h by the formation of Eudragit E/HCl micelles. In rats, the absolute oral bioavailability (F%) of -resveratrol from Eudragit E/HCl solid dispersion (10/90) was estimated to be 40%. Therefore, -resveratrol-loaded Eudragit E/HCl solid dispersions prepared by spray drying offer a promising formulation strategy with high oral bioavailability for developing high-quality health supplements, nutraceutical, and pharmaceutical products.
在本研究中,我们设计了基于Eudragit E/盐酸(用盐酸中和Eudragit E)的无定形固体分散体,以最大化白藜芦醇的溶出度。采用粉末X射线衍射、扫描电子显微镜和粒度测量等方法对白藜芦醇无定形固体分散体进行了固态表征。此外,还进行了大鼠体外溶出度研究和体内药代动力学研究。在所测试的聚合物中,Eudragit E/盐酸是增溶白藜芦醇最有效的固体分散体。Eudragit E/盐酸在pH 1.2溶出介质中以剂量依赖性方式显著抑制白藜芦醇的沉淀。白藜芦醇/聚合物比例为10/90的无定形Eudragit E/盐酸固体分散体通过形成Eudragit E/盐酸胶束,在至少48小时内呈现出高度过饱和状态且无白藜芦醇沉淀。在大鼠中,Eudragit E/盐酸固体分散体(10/90)中白藜芦醇的绝对口服生物利用度(F%)估计为40%。因此,通过喷雾干燥制备的载白藜芦醇Eudragit E/盐酸固体分散体为开发高质量的健康补充剂、营养保健品和药品提供了一种具有高口服生物利用度的有前景的制剂策略。