Effect of surfactants or a water soluble polymer on the crystal transition of clarithromycin during a wet granulation process
Effect of surfactants or a water soluble polymer on the crystal transition of clarithromycin during a wet granulation process
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湿法制粒过程中表面活性剂或水溶性聚合物对克拉霉素晶型转变的影响
DOI：
10.1016/j.ijpharm.2015.08.080
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发表时间：
2015
影响因子：
5.8
通讯作者：
S
中科院分区：
文献类型：
--
作者：
Nozawa;K.;Iwao;Y.;Noguchi;S.;Itai;S
为了生成含有稳定形式的克拉霉素（CAM）（II型）的产品，无论CAM的初始晶型或制粒溶剂的类型如何，测定了五种表面活性剂或水溶性聚合物（聚乙二醇400）对CAM晶型转变的影响。在加入表面活性剂或水溶性聚合物后，将亚稳形式（形式I）与水捏合。在加入相同的添加剂后，还将形式II与乙醇捏合。通过粉末X射线衍射分析所得样品。通过使用带有聚氧乙烯链的添加剂如聚山梨醇酯80（PS80）、聚氧乙烯40硬脂酸酯或聚乙二醇400的水进行湿法制粒，将I型完全转化为II型。使用乙醇和这些添加剂对II型进行造粒不会导致晶型转变为I型。此外，CAM片剂使用颗粒与PS80，这些晶型和溶出行为进行了研究。结果，CAM与PS80的湿法制粒得到仅含II型的CAM片剂，并且PS80对片剂特性没有任何不利影响。因此，这些数据表明，CAM的晶型可以使用带有聚氧乙烯链的添加剂的湿法制粒工艺控制为II型，而与CAM的初始晶型或制粒溶剂的类型无关。
To generate products containing a stable form of clarithromycin (CAM) (form II) regardless of the initial crystal form of CAM or type of granulation solvent, the effects of five surfactants, or a water-soluble polymer (macrogol 400) were determined on the crystal transition of CAM. The metastable form (form I) was kneaded with water, after adding surfactants, or a water-soluble polymer. Form II was also kneaded with ethanol, after adding the same additives. The resulting samples were analyzed by powder X-ray diffraction. Form I was completely converted to form II by a wet granulation using water with additives bearing polyoxyethylene chains such as polysorbate 80 (PS80), polyoxyl 40 stearate or macrogol 400. The granulation of the form II using ethanol with these additives did not result in a crystal transition to form I. Furthermore, CAM tablets were manufactured using granules with PS80, and these crystal forms and dissolution behaviors were investigated. As a result, the wet granulation of CAM with PS80 gave CAM tablets containing only form II and PS80 did not have any adverse effects on tablet characteristics. Therefore, these data suggests that the crystal form of CAM can be controlled to be form II using a wet granulation process with additives bearing polyoxyethylene chains regardless of the initial crystal form of CAM or type of granulation solvent.