Exploring pharmaceutical powder behavior in commercial-scale bin blending: A DEM simulation study.

Bin blending is one of the main steps in pharmaceutical production processes. Commercial-scale production of expensive products typically does not allow to perform a large number of experiments in order to optimize the process. Alternatively, Discrete Element Method (DEM) simulations can be used to evaluate the powder behavior (flow and blending pattern) during blending, identify the risks (e.

Development of a high-fidelity digital twin using the discrete element method for a continuous direct compression process. Part 2. Validation of calibration workflow.

This paper is the second in a series of two that describes the application of discrete element method (DEM) and reduced order modeling to predict the effect of disturbances in the concentration of drug substance at the inlet of a continuous powder mixer on the concentration of the drug substance at the outlet of the mixer. In the companion publication, small-scale material characterization tests, a careful DEM parameter calibration and DEM simulations of the manufacturing process were used to develop a reliable RTD models. In the current work, the same calibration workflow was employed to evaluate the predictive ability of the resulting reduced-order model for an extended design space.

Development of a high-fidelity digital twin using the discrete element method for a continuous direct compression process. Part 1. Calibration workflow.

In this work, a high-fidelity digital twin was developed to support the design and testing of control strategies for drug product manufacturing via direct compression. The high-fidelity digital twin platform was based on typical pharmaceutical equipment, materials, and direct compression continuous processes. The paper describes in detail the material characterization, the Discrete Element Method (DEM) model and the DEM model parameter calibration approach and provides a comparison of the system's response to the experimental results for stepwise changes in the API concentration at the mixer inlet.

Steady-state modeling of a new continuous API dryer: Reduced-order model and investigation of dryer performance.

In the present study, a reduced-order model is proposed to analyze a novel continuous dryer with an application in the pharmaceutical industry. The model was validated using process data from ibuprofen drying test runs, and the results were in good agreement with the experimental data. The test substance was an ibuprofen paste with an initial LOD of up to 30 w%.

Continuous mixing technology: Validation of a DEM model.

Continuous powder mixing is an important technology used in the development and manufacturing of solid oral dosage forms. Since critical quality attributes of the final product greatly depend on the performance of the mixing step, an analysis of such a process using the Discrete Element Method (DEM) is of crucial importance. On one hand, the number of expensive experimental runs can be reduced dramatically.