a Pharmaceutical Research Center , Pharmaceutical Technology Institute, Mashhad University of Medical Sciences , Mashhad , Iran.
b Department of Pharmaceutics , School of Pharmacy, Mashhad University of Medical Sciences , Mashhad , Iran.
Pharm Dev Technol. 2019 Jul;24(6):720-728. doi: 10.1080/10837450.2019.1584632. Epub 2019 Mar 26.
Slow dissolution is a major drawback for poorly water-soluble drugs when they are extruded-spheronized with microcrystalline cellulose (MCC). Therefore, the aim of the current study was to explore excipients to enhance the dissolution of simvastatin without compromising the extrudability and sphericity of pellets. Pellets containing simvastatin, MCC and polyethylene glycols (PEGs) or superdisintegrants were prepared by extrusion-spheronization and their micromeritics and mechanical properties, drug release and solid state of simvastatin were studied. All formulations produced pellets with reasonable size and sphericity. Generally, the inclusion of PEG and superdisintegrants decreased crushing strength and elastic modulus of pellets and increased the dissolution rate of simvastatin. A substantial increase in dissolution rate was observed when a combination of PEG and superdisintegrant was used due to the formation of more porous matrix, faster disintegration and remarkable reduction in drug crystallinity. It was interesting to note that the use of PEG and superdisintegrant had a synergistic effect on the dissolution enhancement of simvastatin in pellet formulation. The results of this study confirmed that a simple method of extrusion-spheronization can be employed to enhance the dissolution of simvastatin in multi particulates dosage form which can also be employed for other poorly water-soluble drugs.
当将难溶性药物与微晶纤维素 (MCC) 挤出-滚圆时，缓慢溶解是一个主要缺点。因此，本研究旨在探索赋形剂，在不影响微丸挤出性和圆整度的情况下提高辛伐他汀的溶出度。通过挤出-滚圆法制备含有辛伐他汀、MCC 和聚乙二醇 (PEGs) 或超级崩解剂的微丸，并研究了微丸的微观特性和机械性能、药物释放和辛伐他汀的固体状态。所有配方均制得粒径和圆整度合理的微丸。通常，PEG 和超级崩解剂的加入会降低微丸的抗压强度和弹性模量，增加辛伐他汀的溶出度。由于形成了更多的多孔基质、更快的崩解和显著降低了药物结晶度，因此使用 PEG 和超级崩解剂的组合可以观察到溶出率的大幅提高。有趣的是，PEG 和超级崩解剂的使用对辛伐他汀在微丸制剂中的溶出增强具有协同作用。本研究结果证实，挤出-滚圆法是一种简单的方法，可以提高多颗粒剂型中辛伐他汀的溶出度，也可用于其他难溶性药物。
