Self-emulsifying drug delivery systems (SEDDS) of coenzyme Q10:: formulation development and bioavailability assessment
Self-emulsifying drug delivery systems (SEDDS) of coenzyme Q10:: formulation development and bioavailability assessment
复制标题
DOI：
10.1016/s0378-5173(00)00614-1
复制
发表时间：
2001-01-16
影响因子：
5.8
通讯作者：
Reddy, IK
中科院分区：
文献类型：
--
作者：
Kommuru, TR;Gurley, B;Reddy, IK
我们的研究目标是开发和表征辅酶Q(10)(辅酶Q(10))的自乳化给药系统(SEDDS)，以聚羟基甘油酯(PGG)为乳化剂，并评价其在犬体内的生物利用度。测定了辅酶Q(10)在各种油和表面活性剂中的溶解度。SEDDS由油、表面活性剂和助表面活性剂组成。用两种油(MyVacet 9-45和Captex-200)、两种乳化剂(Labrafac CM-10和Labrasol)和助表面活性剂(月桂二醇)制备了四种类型的自乳化制剂。在所有配方中，辅酶Q(10)的水平固定在车辆重量的5.66%。研究了这些制剂在温和搅拌条件下加入水后的体外自乳化性能和液滴大小分析。构建了假三元相图，确定了有效的自乳化区。从这些研究中，选择了一种优化的处方，并将其与粉剂在犬体内的生物利用度进行了比较。中链油和MyVacet 9-45的溶解度高于长链油。观察到含有Labrafac CM-10的体系比含有Labrasol的配方更有效且更好的自乳化过程。添加助表面活性剂提高了自乳化的自发性。从这些研究中，选择了由MyVacet 9-45(40%)、拉布拉索尔(50%)和月桂醇(10%)组成的优化处方进行生物利用度评估。与粉末制剂相比，自乳化系统的生物利用度增加了两倍。SEDDS显著提高了辅酶Q(10)的生物利用度。这些数据表明，SEDDS的潜在用途是提供一种有效的方法来改善脂类药物的口服吸收。(C)2001 Elsevier Science B.V.保留所有权利。
The goals of our investigations are to develop and characterize self-emulsifying drug delivery systems (SEDDS) of coenzyme Q(10) (CoQ(10)), using polyglycolyzed glycerides (PGG) as emulsifiers and to evaluate their bioavailability in dogs. Solubility of CoQ(10) was determined in various oils and surfactants. SEDDS consisted of oil, a surfactant and a cosurfactant. Four types of self-emulsifying formulations were prepared using two oils (Myvacet 9-45 and Captex-200), two emulsifiers (Labrafac CM-10 and Labrasol) and a cosurfactant (lauroglycol). In all the formulations, the level of CoQ(10) was fixed at 5.66% w/w of the vehicle. The in vitro self-emulsification properties and droplet size analysis of these formulations upon their addition to water under mild agitation conditions were studied. Pseudo-ternary phase diagrams were constructed identifying the efficient self-emulsification region. From these studies, an optimized formulation was selected and its bioavailability was compared with a powder formulation in dogs. Medium chain oils and Myvacet 9-45 provided higher solubility than long chain oils. Efficient and better self-emulsification processes were observed for the systems containing Labrafac CM-10 than formulations containing Labrasol. Addition of a cosurfactant improved the spontaneity of self-emulsification. From these studies, an optimized formulation consisting of Myvacet 9-45 (40%), Labrasol (50%) and lauroglycol (10%) was selected for its bioavailability assessment. A two-fold increase in the bioavailability was observed for the self-emulsifying system compared to a powder formulation. SEDDS have improved the bioavailability of CoQ(10) significantly. The data suggest the potential use of SEDDS to provide an efficient way of improving oral absorption of lipophilic drugs. (C) 2001 Elsevier Science B.V. All rights reserved.