The use of a new hydrophilic polymer, Kollicoat IR®, in the formulation of solid dispersions of Itraconazole
The use of a new hydrophilic polymer, Kollicoat IR®, in the formulation of solid dispersions of Itraconazole
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DOI：
10.1016/j.ejps.2006.11.015
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发表时间：
2007-03-01
影响因子：
4.6
通讯作者：
Van den Mooter, Guy
中科院分区：
文献类型：
--
作者：
Janssens, Sandrien;de Armas, Hector Nouoa;Van den Mooter, Guy
Kollicoat IR（R）是一种新的药用辅料，作为速释片剂的包衣聚合物，在伊曲康唑固体分散体中作为载体进行了评价。通过热阶段挤出制备固体分散体。采用调制式差示扫描量热法和X射线粉末衍射法对药物和载体的相容性进行了评价。通过在不含胃蛋白酶的模拟胃液（SGF（sp））中进行的溶出实验来评价药物性能。在X射线衍射图中，没有伊曲康唑峰可见;另一方面，聚合物似乎是半结晶的。此外，由于暴露于热和剪切力，其结晶度在挤出过程中增加。调温差示扫描量热法分析表明，药物和聚合物形成了一个两相系统。对于40%或更高的载药量，存在单独的玻璃状伊曲康唑簇，表明进一步的相分离。溶出度测量表明，与物理混合物相比，固体分散体的溶出速率显著增加。有趣的是，由玻璃态伊曲康唑和Kollicoat IR（R）（20/80，w/w）组成的物理混合物显示出的溶出速率和最大值远高于由结晶伊曲康唑组成的物理混合物和纯玻璃态伊曲康唑的溶出速率和最大值。本研究的结果表明，Kollicoat IR（R）是一种很有前途的赋形剂，可用于热阶段挤出法制备伊曲康唑固体分散体。(c)2006年Elsevier B. V.。All rights reserved.
Kollicoat IR (R), a new pharmaceutical excipient developed as a coating polymer for instant release tablets, was evaluated as a carrier in solid dispersions of Itraconazole. The solid dispersions were prepared by hot stage extrusion. Modulated temperature differential scanning calorimetry and X-ray powder diffraction were used to evaluate the miscibility of the drug and the carrier. The pharmaceutical performance was evaluated by dissolution experiments, performed in simulated gastric fluid without pepsin (SGF(sp)). In the X-ray diffractograms no ltraconazole peaks were visible; the polymer, on the other hand, appeared to be semi-crystalline. Moreover, its crystallinity increased during the extrusion process due to exposure to heat and shear forces. Modulated temperature differential scanning calorimetry analysis showed that the drug and the polymer formed a two-phase system. Separate clusters of glassy Itraconazole were present for drug loads of 40% or higher, indicating further phase separation. Dissolution measurements demonstrated a significantly increased dissolution rate for the solid dispersions compared to physical mixtures. Interestingly, the physical mixture made up of glassy Itraconazole and Kollicoat IR (R) (20/80, w/w) showed a dissolution rate and maximum that was much higher than that of the physical mixture made up of crystalline Itraconazole and that of pure glassy Itraconazole. The results of this study show that Kollicoat IR (R) is a promising excipient for the formulation of solid dispersions of Itraconazole prepared by hot stage extrusion. (c) 2006 Elsevier B.V.. All rights reserved.