Abstract: 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.