Nihei Takuya, Suzuki Hiroki, Aoki Asako, Yuminoki Kayo, Hashimoto Naofumi, Sato Hideyuki, Seto Yoshiki, Onoue Satomi
Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Department of Pharmaceutical Physicochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan.
Int J Pharm. 2016 Sep 10;511(1):455-461. doi: 10.1016/j.ijpharm.2016.07.038. Epub 2016 Jul 19.
The present study aimed to develop a nanoparticle (NP) formulation of thymoquinone (TQ), a potent anti-oxidant chemical, with use of a cold wet-milling (CWM) system to improve its dissolution behavior and pharmacokinetic properties. The NP formulation of TQ (TQ/CWM) was prepared by CWM system, and its physicochemical properties were characterized in terms of particle size distribution, morphology, crystallinity, and dissolution. The photochemical properties of TQ were also examined upon UV/VIS absorption, reactive oxygen species (ROS) generation, and photostability. Pharmacokinetic studies were carried out in rats. Application of the CWM system to TQ led to successful development of nano-sized TQ. The mean diameter of TQ in TQ/CWM was calculated to be 143nm, and TQ particles in TQ/CWM were found to be amorphous. There was a marked improvement in dissolution rate compared with TQ. TQ showed significant generation of singlet oxygen and superoxide upon exposure to simulated sunlight, suggesting its high photoreactivity, and solid samples such as TQ and TQ/CWM exhibited higher photostability than TQ solution. In comparison with TQ, enhanced TQ exposure was observed with a ca. 6-fold increase of oral bioavailability, and the Tmax was shown to be a quarter. From these findings, the NP approach employing the CWM system might be a promising dosage option for improving the nutraceutical values of TQ.
本研究旨在利用冷湿磨（CWM）系统开发一种有效的抗氧化化学物质百里醌（TQ）的纳米颗粒（NP）制剂，以改善其溶解行为和药代动力学性质。通过CWM系统制备了TQ的NP制剂（TQ/CWM），并从粒径分布、形态、结晶度和溶解性等方面对其理化性质进行了表征。还通过紫外/可见吸收、活性氧（ROS）生成和光稳定性研究了TQ的光化学性质。在大鼠身上进行了药代动力学研究。将CWM系统应用于TQ成功开发出了纳米级TQ。TQ/CWM中TQ的平均直径经计算为143nm，且TQ/CWM中的TQ颗粒为无定形。与TQ相比，溶解速率有显著提高。TQ在模拟阳光下照射时显示出单线态氧和超氧阴离子的大量生成，表明其高光反应性，并且TQ和TQ/CWM等固体样品比TQ溶液表现出更高的光稳定性。与TQ相比，观察到TQ的暴露增强，口服生物利用度提高了约6倍，且达峰时间缩短为四分之一。基于这些发现，采用CWM系统的NP方法可能是提高TQ营养保健价值的一种有前景的给药选择。
