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

Abstract

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 2 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.

Investigating the Effects of Mixing Dynamics on Twin-Screw Granule Quality Attributes via the Development of a Physics-Based Process Map

“…A granule microstructure encompasses several properties such as porosity, surface morphology, component content uniformity, pore size distribution, open-to-closed pore ratio, etc. All these factors together affect the flow, strength, content uniformity, and stability of the granules [ 3 , 11 , 12 , 13 ] and also affect the critical quality attributes of downstream final dosage forms like tablets and capsules [ 7 , 14 , 15 , 16 ]. Studies have shown that variance in the porosity of the granules significantly affects the strength and dissolution of tablets [ 8 , 15 , 17 , 18 , 19 ].…”

In situ wet pharmaceutical granulation captured using synchrotron radiation based dynamic micro-CT

“…Previous wet-granulation studies have been more focused on external structures and formation mechanisms (Emady et al, 2011(Emady et al, , 2013Gao et al, 2018Gao et al, , 2020Iveson et al, 2001;Li et al, 2019Li et al, , 2021. There have been lab-based micro-CT studies on granule internal structures, but these have focused on the final granule product and not on in situ granulation (Crean et al, 2010;Davis et al, 2017;Farber et al, 2003;Matsui et al, 2019). The X-ray flux from lab-based scanners is not sufficient to capture in situ wet granulation (Li et al, 2019).…”