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.

Low-volume regimen without additional liquids or adjunctive agents versus standard bowel preparation in non-constipated patients: a propensity score matching analysis.

AIMS: Split-dose, 4-L polyethylene glycol (PEG, HSD) is currently the first-line choice for unselected or difficult colon preparations. Almost all low-volume bowel preparations (BPs) include a large volume of additional liquid and adjunctive agents to improve cleansing efficiency. However, neither HSD nor additional liquids or adjunctive agents of low-volume regimens may be necessary for low-risk patients. The aim of this study was to compare the cleansing efficiency between split-dose, low-volume (2-L) PEG without additional liquids or adjunctive agents (LSD) and HSD in non-constipated patients. METHODS: A retrospective study was performed from January 2013 to December 2015. Consecutive non-constipated patients who received LSD or HSD BPs were enrolled into LSD and HSD groups. Propensity score matching (PSM) was used to reduce selection bias and potential confounders. The primary outcome was bowel cleansing quality, as evaluated by the Boston Bowel Preparation Scale (BBPS). The adenoma detection rate (ADR), the most important secondary outcome, was also recorded. Follow-up was conducted in 2016. RESULTS: After excluding those participants who meet exclusion criteria or lost follow-up, 1656 non-constipated patients underwent LSD (n = 999) or HSD (n = 657) BP. Most patients had a BBPS score ≥6 (LSD vs. HSD, 93.6 vs. 92.9%, p = .166). The segmental BBPS scores were ≥2 in 92 and 91.9% in the LSD and HSD groups, respectively. The overall ADR was 16.7% in the LSD group and 17.5% in the HSD group (p = .334). CONCLUSION: For non-constipated patients, LSD is not inferior to HSD in cleansing efficiency, while more willing to repeat the same BP.