Balakrishnan Prabagar, Lee Beom-Jin, Oh Dong Hoon, Kim Jong Oh, Lee Young-Im, Kim Dae-Duk, Jee Jun-Pil, Lee Yong-Bok, Woo Jong Soo, Yong Chul Soon, Choi Han-Gon
College of Pharmacy, Yeungnam University, 214-1 Dae-Dong, Gyongsan, South Korea.
Int J Pharm. 2009 Jun 5;374(1-2):66-72. doi: 10.1016/j.ijpharm.2009.03.008. Epub 2009 Mar 19.
To enhance the solubility and bioavailability of poorly water-soluble Coenzyme Q(10) (CoQ(10)), self-emulsifying drug delivery system (SEDDS) composed of oil, surfactant and cosurfactant for oral administration of CoQ(10) was formulated. The solubility of CoQ(10) was determined in various oils and surfactants. The formulations were prepared using two oils (Labrafil M 1944 and Labrafil M 2125), surfactant (Labrasol) and cosurfactant (Lauroglycol FCC and Capryol 90). In all the formulations, the level of CoQ(10) was fixed at 6% (w/v) of the vehicle. These formulations were characterized by solubility of the drug in the vehicle, particle size of the dispersed emulsion, zeta potential and drug release profile. Ternary phase diagrams were used to evaluate the emulsification domain. The self-emulsification time following introduction into an aqueous medium under gentle agitation was evaluated. The optimized SEDDS formulation consist of 65% (v/v) Labrasol, 25% (v/v) Labrafil M 1944 CS and 10% (v/v) Capryol 90 of each excipient showed minimum mean droplet size (about 240 nm) and optimal drug release profile in water. The pharmacokinetic study in rats for the optimized formulation was performed and compared to powder formulation. SEDDS have significantly increased the C(max) and area under the curve (AUC) of CoQ(10) compared to powder (P<0.05). Thus, this self-micro emulsifying drug delivery system should be an effective oral dosage form for improving oral bioavailability of lipophilic drug, CoQ(10).
为提高难溶性辅酶Q10(CoQ10)的溶解度和生物利用度,制备了由油、表面活性剂和助表面活性剂组成的用于口服CoQ10的自乳化给药系统(SEDDS)。测定了CoQ10在各种油和表面活性剂中的溶解度。使用两种油(Labrafil M 1944和Labrafil M 2125)、表面活性剂(Labrasol)和助表面活性剂(月桂二醇FCC和辛酸癸酸甘油酯90)制备制剂。在所有制剂中,CoQ10的含量固定为载体的6%(w/v)。这些制剂通过药物在载体中的溶解度、分散乳液的粒径、ζ电位和药物释放曲线进行表征。使用三元相图评估乳化区域。评估了在温和搅拌下引入水性介质后的自乳化时间。优化后的SEDDS制剂由65%(v/v)Labrasol、25%(v/v)Labrafil M 1944 CS和10%(v/v)辛酸癸酸甘油酯90组成,每个辅料均显示出最小平均液滴尺寸(约240nm)和在水中的最佳药物释放曲线。对优化后的制剂进行了大鼠体内药代动力学研究,并与粉末制剂进行了比较。与粉末制剂相比,SEDDS显著提高了CoQ10的Cmax和曲线下面积(AUC)(P<0.05)。因此,这种自微乳化给药系统应该是一种有效的口服剂型,可提高亲脂性药物CoQ10的口服生物利用度。