College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Ansan, 426-791, Sangnok-gu, South Korea.
College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan, 712-749, South Korea.
Carbohydr Polym. 2015 Oct 5;130:26-31. doi: 10.1016/j.carbpol.2015.04.071. Epub 2015 May 12.
The purpose of this research was to evaluate the effect of the HPC (hydroxypropylcellulose) and Tween 80 on the physicochemical properties and oral bioavailability of ezetimibe-loaded solid dispersions. The binary solid dispersions were prepared with drug and various amounts of HPC. Likewise, ternary solid dispersions were prepared with different ratios of drug, HPC and Tween 80. Both types of solid dispersions were prepared using the solvent evaporation method. Their aqueous solubility, physicochemical properties, dissolution and oral bioavailability were investigated in comparison with the drug powder. All the solid dispersions significantly improved the drug solubility and dissolution. As the amount of HPC increased in the binary solid dispersions to 10-fold, the drug solubility and dissolution were increased accordingly. However, further increase in HPC did not result in significant differences among them. Similarly, up to 0.1-fold, Tween 80 increased the drug solubility in the ternary solid dispersions followed by no significant change. However, Tween 80 hardly affected the drug dissolution. The physicochemical analysis proved that the drug in binary and ternary solid dispersion was existed in the amorphous form. The particle-size measurements of these formulations were also not significantly different from each other, which showed that Tween 80 had no impact on physicochemical properties. The ezetimibe-loaded binary and ternary solid dispersions gave 1.6- and 1.8-fold increased oral bioavailability in rats, respectively, as compared to the drug powder; however, these values were not significantly different from each other. Thus, HPC greatly affected the solubility, dissolution and oral bioavailability of drug, but Tween 80 hardly did. Furthermore, this ezetimibe-loaded binary solid dispersion prepared only with HPC would be suggested as a potential formulation for oral administration of ezetimibe.
本研究旨在评估 HPC（羟丙纤维素）和 Tween 80 对载有依泽替米贝的固体分散体的物理化学性质和口服生物利用度的影响。二元固体分散体是由药物和不同量的 HPC 制备的。同样，也用不同比例的药物、HPC 和 Tween 80 制备了三元固体分散体。这两种类型的固体分散体都是通过溶剂蒸发法制备的。与原料药相比，研究了它们的水溶解度、物理化学性质、溶解和口服生物利用度。所有固体分散体都显著提高了药物的溶解度和溶解速率。随着二元固体分散体中 HPC 用量增加到 10 倍，药物的溶解度和溶解速率也随之增加。然而，进一步增加 HPC 并没有导致它们之间的显著差异。同样，在三元固体分散体中，Tween 80 增加药物溶解度的量高达 0.1 倍，随后没有明显变化。然而，Tween 80 几乎不影响药物的溶解。物理化学分析证明，二元和三元固体分散体中的药物以无定形形式存在。这些配方的粒径测量结果彼此之间也没有显著差异，这表明 Tween 80 对物理化学性质没有影响。与原料药相比，载有依泽替米贝的二元和三元固体分散体在大鼠体内的口服生物利用度分别提高了 1.6 倍和 1.8 倍；然而，这些值彼此之间没有显著差异。因此，HPC 极大地影响了药物的溶解度、溶解速率和口服生物利用度，但 Tween 80 几乎没有影响。此外，仅用 HPC 制备的载有依泽替米贝的二元固体分散体可被推荐为依泽替米贝口服给药的潜在制剂。
