基于同步辐射显微CT技术研究冻干口腔崩解片的精细结构

Investigation of microstructures of freeze-dried orally disintegrating tablets by synchrotron radiation X-ray computed microtomography

采用低温冰颗粒直压冻干法制备口腔崩解片,与模制冻干法相比较,以同步辐射显微CT技术(SR-μCT)观测片剂内部的精细结构,得到显示内部结构差异的切片图,构建三维模型,确定灰度阈值后,提取片剂子结构,定量分析子结构,同时测定片剂的崩解性质和脆碎特征,研究片剂内部精细结构与其药剂学性质的关系。SR-μCT观测结果显示,不同制备工艺、处方所得的口腔崩解片的精细结构存在显著的差异,模制冻干法得到一体化致密网状结构,而低温冰颗粒直压冻干法得到松散聚集状态颗粒结构,这些结构特征合理地解释了低温冰颗粒直压法所得冻干口腔崩解片崩解迅速的机制,其微观子结构决定了片剂结构力学的宏观性质。结果显示,SR-μCT表征制剂内部精细结构的研究对阐明速释制剂的崩解特征有重要意义。

Freeze-dried orally disintegrating tablets prepared by direct compression of the freezing powders under low-temperature were shown of different properties compared with molded freeze-dried orally disintegrating tablets. The aim of this study were to scan the interior microstructures of orally disintegrating tablets by synchrotron radiation X-ray computed microtomography（SR-μCT）and to reconstruct and characterize the three-dimensional structural models shown in the slice of the central section within tablets. By setting the threshold of gray value, the sub-structures of the orally disintegrating tablets were extracted and quantitatively analyzed by Image pro Analyzer 3D software. Disintegration time and frangibility of tablets were determined and compared to study the correlation between pharmaceutical properties and internal microstructures. The results indicated that internal microstructures of orally disintegrating tablets with different preparation processes and formulations varied markedly. Molded freeze-dried tablets had an integral net structure, while tablets made by direct compression had a loose clusters grainy one. The difference in the internal microstructures could well explain why freeze-dried orally disintegrating tablets made by direct compression would disintegrate fast in less than 5s. Different preparation processes and formulation could led to a variety of sub-structure sections, such as reticulation structure, compact enclosure, fragments and small particles, which was responsible for the macroscopic structural mechanical properties. In conclusion, the research showed that SR-μCT was powerful in providing insight into the internal microstructures, and the pharmaceutical properties of freeze-dried orally disintegrating tablets were directly related to the internal microstructures.