Analysis of Microstructure of Granules Prepared by Continuous Twin Screw Granulator Using X-Ray Micro-computed Tomography

摘要

Granules prepared by a continuous twin screw granulator (TSG) were analyzed by X-ray micro-computed tomography (X-ray μCT) and the relationships between porosity of granules and granule properties were investigated. A model formulation containing ibuprofen, lactose monohydrate, microcrystalline cellulose, and hydroxypropyl cellulose was used. The porosity of granules was measured by X-ray μCT and mercury porosimetry. The data sets obtained by both methods showed linear correlation despite different values, which were attributed to the resolution of X-ray μCT and a low-signal-to-noise ratio of the original cross-sectional images. The porosity of granules measured by X-ray μCT decreased from 11–14 to 6–7% as liquid-to-solid ratio ( L / S ) increased, while the standard deviation (S.D.) of the porosity of individual granules decreased from 4–5 to 2%. L / S affected the porosity of granules. By contrast, the effect of screw speed was not significant. Pressure transmission, G , which indicates the liquid dispersion in wet kneaded masses, increased as the porosity of granules and the S.D. decreased. The cross-sectional images showed that granules were densified as L / S increased. Based on these results, the effect of L / S on the porosity of granules can be explained by liquid dispersion and densification of the wet granules. The porosity of granules measured by X-ray μCT showed good linear correlation with friability and drug dissolution rate ( R sup2/sup?=?0.9107 and 0.8834, respectively). This study revealed that the drug dissolution rate was regulated by a disintegration step in which the porosity of granules plays an important role.