Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Eur J Pharm Sci. 2012 Aug 15;46(5):492-9. doi: 10.1016/j.ejps.2012.03.015. Epub 2012 Apr 3.
The present study was undertaken to develop a solid self-emulsifying drug delivery system of coenzyme Q(10) (CoQ(10)/s-SEDDS) with high photostability and oral bioavailability. The CoQ(10)/s-SEDDS was prepared by spray-drying an emulsion preconcentrate containing CoQ(10), medium-chain triglyceride, sucrose ester of fatty acid, and hydroxypropyl cellulose, and its physicochemical, photochemical, and pharmacokinetic properties were evaluated. The CoQ(10)/s-SEDDS powder with a diameter of ca. 15 μm was obtained by spray-drying, in which the CoQ(10) was mostly amorphized. The CoQ(10)/s-SEDDS exhibited immediate self-emulsification when introduced to aqueous media under gentle agitation, forming uniform fine droplets with a mean diameter of ca. 280 nm. There was marked generation of reactive oxygen species, in particular superoxide, from CoQ(10) exposed to simulated sunlight (250W/m(2)), suggesting potent photoreactivity. Nano-emulsified solution of CoQ(10) under light exposure underwent photodegradation with 22-fold higher degradation kinetics than crystalline CoQ(10), although the CoQ(10)/s-SEDDS was less photoreactive. After the oral administration of CoQ(10)/s-SEDDS (100 mg-CoQ(10)/kg) in rats, enhanced exposure of CoQ(10) was observed with increases in both C(max) and AUC of ca. 5-fold in comparison with those of orally administered crystalline CoQ(10). From the improved physicochemical and pharmacokinetic data, the s-SEDDS approach upon spray-drying might be a suitable dosage option for enhancing nutraceutical and pharmaceutical values of CoQ(10).
本研究旨在开发一种辅酶 Q(10)（CoQ(10)/s-SEDDS）的固态自乳化药物递送系统，以提高其光稳定性和口服生物利用度。采用喷雾干燥法制备 CoQ(10)/s-SEDDS，其处方组成为 CoQ(10)、中链甘油三酯、脂肪酸蔗糖酯和羟丙基纤维素。对 CoQ(10)/s-SEDDS 的理化性质、光化学稳定性和药代动力学性质进行了评价。喷雾干燥得到的 CoQ(10)/s-SEDDS 粉末粒径约为 15 μm，其中 CoQ(10)主要呈无定形态。该粉末在温和搅拌下引入水相时可立即自乳化，形成平均粒径约为 280nm 的均匀小微滴。CoQ(10)在模拟太阳光（250W/m(2)）下暴露时会产生大量的活性氧，特别是超氧自由基，表明其具有很强的光反应性。与结晶型 CoQ(10)相比，纳米乳化 CoQ(10)溶液在光照下的光降解速度快 22 倍，尽管 CoQ(10)/s-SEDDS 的光反应性较低。与口服给予结晶型 CoQ(10)相比，大鼠口服给予 CoQ(10)/s-SEDDS（100mg-CoQ(10)/kg）后，CoQ(10)的暴露量增加，C(max)和 AUC 分别增加约 5 倍。从改善的理化性质和药代动力学数据来看，喷雾干燥法制备 s-SEDDS 可能是提高 CoQ(10)的营养和药物价值的一种合适的剂型选择。
