Novel solid self-emulsifying drug delivery system of coenzyme Q₁₀ with improved photochemical and pharmacokinetic behaviors.
Novel solid self-emulsifying drug delivery system of coenzyme Q₁₀ with improved photochemical and pharmacokinetic behaviors.
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DOI：
10.1016/j.ejps.2012.03.015
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发表时间：
2012-08
期刊：
影响因子：
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通讯作者：
S. Onoue;Atushi Uchida;K. Kuriyama;Tatsuya Nakamura;Yoshiki Seto;Masashi Kato;J. Hatanaka;Toshiyuki Tanaka;H. Miyoshi;S. Yamada
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文献类型：
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作者：
S. Onoue;Atushi Uchida;K. Kuriyama;Tatsuya Nakamura;Yoshiki Seto;Masashi Kato;J. Hatanaka;Toshiyuki Tanaka;H. Miyoshi;S. Yamada
本研究旨在制备一种具有良好光稳定性和口服生物利用度的辅酶Q10固体自乳化给药系统（CoQ 10/s-SEDDS）。采用喷雾干燥法制备了含辅酶Q10、中链甘油三酯、蔗糖脂肪酸酯和羟丙基纤维素的乳剂预浓缩物，并对其理化、光化学和药代动力学特性进行了评价。CoQ 10/s-SEDDS粉末直径约为100 μ m。喷雾干燥得到粒径为15μm的CoQ 10，其中CoQ 10大部分为非晶化。CoQ 10/s-SEDDS在温和搅拌下加入到水性介质中时，可立即自乳化，形成平均直径约为100 μ m的均匀细液滴。280纳米。模拟太阳光（250 W/m2）照射下，辅酶Q10产生了大量的活性氧，特别是超氧阴离子，表明辅酶Q10具有较强的光反应性。CoQ 10/s-SEDDS在光照下的光降解动力学比CoQ 10晶体高22倍，但CoQ 10/s-SEDDS的光反应性较低。大鼠口服CoQ 10/s-SEDDS（100 mg-CoQ 10/kg）后，CoQ 10的暴露量增加，Cmax和AUC均增加约10%。5-倍，与口服给药的结晶辅酶Q10相比。从改进的理化和药代动力学数据，喷雾干燥后的s-SEDDS方法可能是一个合适的剂量选择，以提高辅酶Q10的营养和药用价值。
The present study was undertaken to develop a solid self-emulsifying drug delivery system of coenzyme Q10(CoQ10/s-SEDDS) with high photostability and oral bioavailability. The CoQ10/s-SEDDS was prepared by spray-drying an emulsion preconcentrate containing CoQ10, medium-chain triglyceride, sucrose ester of fatty acid, and hydroxypropyl cellulose, and its physicochemical, photochemical, and pharmacokinetic properties were evaluated. The CoQ10/s-SEDDS powder with a diameter of ca. 15μm was obtained by spray-drying, in which the CoQ10was mostly amorphized. The CoQ10/s-SEDDS exhibited immediate self-emulsification when introduced to aqueous media under gentle agitation, forming uniform fine droplets with a mean diameter of ca. 280nm. There was marked generation of reactive oxygen species, in particular superoxide, from CoQ10exposed to simulated sunlight (250W/m2), suggesting potent photoreactivity. Nano-emulsified solution of CoQ10under light exposure underwent photodegradation with 22-fold higher degradation kinetics than crystalline CoQ10, although the CoQ10/s-SEDDS was less photoreactive. After the oral administration of CoQ10/s-SEDDS (100mg-CoQ10/kg) in rats, enhanced exposure of CoQ10was observed with increases in both Cmaxand AUC of ca. 5-fold in comparison with those of orally administered crystalline CoQ10. 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 CoQ10.