College of Pharmacy, Chosun University, 375 Seosuk-dong, Dong-Gu, Gwangju, 501-759, Korea.
Arch Pharm Res. 2015 Jul;38(7):1336-44. doi: 10.1007/s12272-014-0547-6. Epub 2015 Jan 8.
Cilostazol is practically insoluble in water and thus results in poor bioavailability. Only a few approaches have been reported for improving the bioavailability of cilostazol. Solid dispersion technique via solvent evaporation method was applied to improve the solubility and dissolution of cilostazol. Various polymers, mixture of polymer and surfactant, and mixture of polymers were screened as a carrier for the solid dispersion. Solubility of cilostazol was improved significantly when Eudragit(®) L100 was used as a carrier. However, addition of surfactant to Eudragit(®) L100 decreased the solubility slightly. Whereas, the mixture of Eudragit(®) L100 and Eudragit(®) S100 as a carrier system further increased the solubility. Based on the highest solubility obtained among the carriers screened, 1:1 ratio of Eudragit(®) L100 and Eudragit(®) S100 was selected as a carrier, and drug to carrier ratio was optimized to 1:5. Differential scanning calorimetry and X-ray diffraction studies showed that the characteristic peak of cilostazol disappeared in the solid dispersion, indicating that cilostazol existed in amorphous form in this formulation. Spray drying method was superior to vacuum drying method in terms of dissolution rate. Meanwhile, it was observed that the disintegration rate and the concentration of polymer had some effect on the crystallization of cilostazol in dissolution medium. Tablet formulation containing spray dried solid dispersion showed significant improvement in dissolution as compared to the commercial tablet.
西洛他唑在水中几乎不溶，因此生物利用度较差。只有少数几种方法被报道用于提高西洛他唑的生物利用度。通过溶剂蒸发法的固体分散技术被应用于提高西洛他唑的溶解度和溶解速率。各种聚合物、聚合物和表面活性剂的混合物以及聚合物的混合物被筛选作为固体分散体的载体。当使用 Eudragit(®) L100 作为载体时，西洛他唑的溶解度显著提高。然而，向 Eudragit(®) L100 中添加表面活性剂会略微降低其溶解度。而 Eudragit(®) L100 和 Eudragit(®) S100 的混合物作为载体系统进一步增加了溶解度。基于筛选出的载体中获得的最高溶解度，选择 1:1 的 Eudragit(®) L100 和 Eudragit(®) S100 作为载体，并且优化了药物与载体的比例为 1:5。差示扫描量热法和 X 射线衍射研究表明，西洛他唑的特征峰在固体分散体中消失，表明西洛他唑在该制剂中以无定形形式存在。喷雾干燥法在溶解速率方面优于真空干燥法。同时，观察到崩解速率和聚合物浓度对西洛他唑在溶解介质中的结晶有一定影响。与市售片剂相比，含有喷雾干燥固体分散体的片剂配方在溶解方面有显著改善。
