Structural changes of polymer-coated microgranules and excipients on tableting investigated by microtomography using synchrotron X-ray radiation.
Structural changes of polymer-coated microgranules and excipients on tableting investigated by microtomography using synchrotron X-ray radiation.
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DOI：
10.1016/j.ijpharm.2015.02.007
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发表时间：
2015-03
影响因子：
5.8
通讯作者：
Ryusuke Kajihara;Shuji Noguchi;Y. Iwao;Yoshio Suzuki;Y. Terada;K. Uesugi;S. Itai
中科院分区：
文献类型：
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作者：
Ryusuke Kajihara;Shuji Noguchi;Y. Iwao;Yoshio Suzuki;Y. Terada;K. Uesugi;S. Itai
由聚合物包膜微颗粒和赋形剂组成的多单位片剂具有许多有利的药物特性。聚合物包被微颗粒通常会因压片对聚合物包被造成损伤而失去其功能，目前对聚合物包被损伤的机理以及赋形剂在压片时的结构变化进行了研究，但尚未进行原位可视化和定量分析。为了阐明包衣损伤的机理，采用同步加速器x射线计算机微断层扫描技术对多片包衣的内部结构进行了研究。亚微米空间分辨率的片剂的横截面图像清楚地显示，在含有纤维素和乳糖组成的片剂（Cellactose®80）的片剂中，压缩的赋形剂颗粒周围仍然存在空隙，而在含有山梨糖醇（Parteck®SI 150）的片剂中，仍然存在更小的空隙。考察了孔洞与片剂硬度、崩解等物理性质的关系。两类片剂中高分子包被微颗粒主要在直接接触处出现聚合物包被的破坏，这可能是由于赋形颗粒和高分子包被微颗粒芯部硬度的差异造成的。
Multiple-unit tablets consisting of polymer-coated microgranules and excipients have a number of advantageous pharmaceutical properties. Polymer-coated microgranules are known to often lose their functionality because of damage to the polymer coating caused by tableting, and the mechanism of polymer coating damage as well as the structural changes of excipients upon tableting had been investigated but without in-situ visualization and quantitative analysis. To elucidate the mechanism of coating damage, the internal structures of multiple-unit tablets were investigated by X-ray computed microtomography using synchrotron X-rays. Cross sectional images of the tablets with sub-micron spatial resolution clearly revealed that void spaces remained around the compressed excipient particles in the tablets containing an excipient composed of cellulose and lactose (Cellactose®80), whereas much smaller void spaces remained in the tablets containing an excipient made of sorbitol (Parteck®SI 150). The relationships between the void spaces and the physical properties of the tablets such as hardness and disintegration were investigated. Damage to the polymer coating in tablets was found mainly where polymer-coated microgranules were in direct contact with each other in both types of tablets, which could be attributed to the difference in hardness of excipient particles and the core of the polymer-coated microgranules.