Novel solid self-emulsifying drug delivery system of coenzyme Q(10) with improved photochemical and pharmacokinetic behaviors

作者：Onoue Satomi^*; Uchida Atushi; Kuriyama Kazuki; Nakamura Tatsuya; Seto Yoshiki; Kato Masashi; Hatanaka Junya; Tanaka Toshiyuki; Miyoshi Hiroyuki; Yamada Shizuo

来源：European Journal of Pharmaceutical Sciences, 2012, 46(5): 492-499.

DOI：10.1016/j.ejps.2012.03.015

• Coenzyme Q(10)
• Solid self-emulsifying drug delivery system
• Dissolution
• Bioavailability
• Photostability

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 mu m 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 (250 W/m2), suggesting potent photo-reactivity. 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 photo-reactive. 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.

• 出版日期2012-8-15