Evolution characteristics of micromechanics provides insights into the microstructure of pharmaceutical tablets fabricated by bimodal mixtures.

This research focuses on the evolution of mechanical behavior of bimodal mixtures undergoing compaction and diametrical compression. The clusters were built and discrete element method (DEM) was used to investigate the densification process and micromechanics of bimodal mixtures. Additionally, a more comprehensive investigate of the respective breakage of the bimodal mixtures has been carried out. On this basis, qualitative and quantitative analysis of the compressive force, force chain, contact bonds and density field evolution characteristics of the clusters are investigated during the compression process. The entire loading process of the clusters is divided into three stages: rearrangement, breakage and elastic-plastic deformation. Additionally, there are differences in the evolution of micromechanics behavior of different particles in the bimodal mixture, with pregelatinized starch breakage and deformation occurring before microcrystalline cellulose. With the tablet deformation, the fragmentation process of the tablet started at the point of contact and extended toward the center, and the curvature of the force chain increased. This approach may potentially hold a valuable new information relevant to important transformation forms batch manufacturing to advanced manufacturing for the oral solid dosage form.

A new methodology of understanding the mechanism of high shear wet granulation based on experiment and molecular dynamics simulation.

In high shear wet granulation (HSWG), the interaction mechanism between binder and powder with different sugar content is still unclear. Herein, the law and mechanism of the interaction between binder and powder were studied on the molecular level by combining experiment analysis through the Kriging model and molecular dynamics (MD) simulation. For the sticky powder with high sugar content, the ethanol in the binder played a pivotal role in dispersing water into powders, and the amount of water determined the growth of granules. In the saturating stage, the reduction of sugar content facilitates the penetration of ethanol molecules. The concentration of ethanol determines whether the mixture is blended uniformly in the merging stage. The simulation results are consistent with the actual situation and explain the competition mechanism of interaction with binder and powder. Therefore, this research offers an efficient strategy for the in-depth understanding of the HSWG process where the powder is sticky, as well as providing guidelines for the practical application of preparation for Traditional Chinese Medicine (TCM) granules.

Investigation of mixing homogeneity of binary particle systems in high-shear wet granulator by DEM.

To provide a theoretical foundation and a good understanding for the real manufacturing granulation process, this paper investigates the effect of particle properties on the mixing process in the high-shear wet granulator, a common equipment in one of the key technologies in the growth of the pharmaceutical industry that has rarely been used to examine particle mixing-related problems in previous numerical simulations. The discrete element method (DEM) and the relative standard deviation (RSD) to explore binary particle systems with a range of sizes, densities, and volume fractions, and measure the mixing homogeneity of the particles. Results show that, for binary particle systems, particle size, density, and volume fraction all significantly affect mixing homogeneity, with good mixing occurring for a single size and a 1:1 volume fraction for the same density. Similar Brazil nut effect and Reverse-Brazil nut effect occurrences were discovered for many particle systems at various stages. There is a size threshold for a given binary particle system. Then, in a binary system, particles of a single size and density had nearly similar vertical driving forces, and these forces may vary by up to 10 times with changes in size or density. In the end, granular temperature rises with radial position and reaches its highest point at the pelletizer's wall and the top of the impeller. Density has less of an impact on granule velocity fluctuation than size.