Research

The mixing of granular materials is fundamental process operation in pharmaceutical industry and particle homogeneity is the key factor for the content uniformity.Thus, the mixing process of particulate materials plays an important role in achieving the desired quality for the finished pharmaceutical product. However, segregation of well mixed particles of drug and excipients takes place due to difference of density, size and morphology during mechanical vibration oftabletting or capsule filling.Conventional techniques can provide neither full-scale characterization of particles nor high-resolution visualization ofparticle distributions. Therefore, it is particularly of interest to develop new methodologies for visualizationand quantification of the homogeneity and mixing dynamics of granules.

A joint team directed by Professor ZHANG Jiwen and Professor XIAO Tiqiao from Shanghai Institute of Materia Medica and Shanghai Institute of Applied Physics, Chinese Academy of Sciences has pinned on the point using the synchrotron radiation X-ray computed microtomography (SR-μCT).Ms. LIU Ruihao and Mr. YIN Xianzhen investigated the three dimensional visualization and quantitative profiling of mixing and segregation of granules.All the microcrystalline cellulose granules and starch granules were characterized in an n-in-one manner, and the dynamic particle distributions for different levels of the powders were obtained. The particle distributions were quantitatively evaluated by the frequency distribution of granularsphericity.A mixing index based upon the standard deviation for the sphericity was developedso as to quantitatively evaluate the homogeneityof the samples. Influences of the time of rotations and the time of vibrationon the mixture homogeneity were studied with statistical evaluation.The results showed that homogeneity was improved with increasing rotation timeand segregation increased in line with the vibration time.

This researchis the first workof Shanghai Synchrotron Radiation Facility on the primary properties as mixing and segregation of pharmaceutical solid granular materials in three-dimensions combined with statistic method.The new methodology has great potential for clarifying relationships between physical characteristics of granules and prmaceutical operation processes.This work has been published online by nternational Journal of Pharmaceutics on February 22, 2013(http://dx.doi.org/10.1016/j.ijpharm.2013.02.010).

Visualization and quantitative profiling of mixing of granules using synchrotron radiation X-ray microtomography and three dimensional reconstruction(IMAGE BY SIMM)