Multiphase chemical reactors with characteristic multiscale structures are intrinsically discrete at the elemental scale. However, due to the lack of multiscale models and the limitation of computational capability, such reactors are traditionally treated as continua through straightforward averaging in engineering simulations or as completely discrete systems in theoretical studies. The continuum approach is advantageous in terms of the scale and speed of computation but does not always give good predictions, which is, in many cases, the strength of the discrete approach. On the other hand, however, the discrete approach is too computationally expensive for engineering applications. Developments in computing science and technologies and encouraging progress in multiscale modeling have enabled discrete simulations to be extended to engineering systems and represent a promising approach to virtual process engineering (VPE, or virtual reality in process engineering). In this review, we analyze this emerging trend and emphasize that multiscale discrete simulations (MSDS), that is, considering multiscale structures in discrete simulation through rational coarse-graining and coupling between discrete and continuum methods with the effect of mesoscale structures accounted in both cases, is an effective way forward, which can be complementary to the continuum approach that is being improved by multiscale modeling also. For this purpose, our review is not meant to be a complete summary to the literature on discrete simulation, but rather a demonstration of its feasibility for engineering applications. We therefore discuss the enabling methods and technologies for MSDS, taking granular and particle-fluid flows as typical examples in chemical engineering. We cover the spectrum of modeling, numerical methods, algorithms, software implementation and even hardware-software codesign. The structural consistency among these aspects is shown to be the pivot for the success of MSDS. We conclude that with these developments, MSDS could soon become, among others, a mainstream simulation approach in chemical engineering which enables VPE.

Discrete simulation of granular and particle-fluid flows: from fundamental study to engineering application

The pharmaceutical industry has found new applications for the use of continuous processing for the manufacture of new therapies currently in development. The transformation has been encouraged by regulatory bodies as well as driven by cost reduction, decreased development cycles, access to new chemistries not practical in batch, improved safety, flexible manufacturing platforms, and improved product quality assurance. The transformation from batch to continuous manufacturing processing is the focus of this review. The review is limited to small, chemically synthesized organic molecules and encompasses the manufacture of both active pharmaceutical ingredients (APIs) and the subsequent drug product. Continuous drug product is currently used in approved processes. A few examples of production of APIs under current good manufacturing practice conditions using continuous processing steps have been published in the past five years, but they are lagging behind continuous drug product with respect to regulatory filings.

Continuous Manufacturing in Pharmaceutical Process Development and Manufacturing.

Process analysis and optimization of continuous pharmaceutical manufacturing using flowsheet models

https://biblio.ugent.be/publication/8556932/file/8556933.pdf

Development and validation of an in-line NIR spectroscopic method for continuous blend potency determination in the feed frame of a tablet press

A dynamic model of a continuous direct compression process for pharmaceutical tablets is presented. The objective is to assess the impact of the variability from the feeder system on the concentration of drug in the powder in the feed frame of a tablet press. The model is based on principles of dispersed flow from the reaction engineering field. An estimability analysis was performed to understand the impact of the available measurements on the estimated parameters and suggest better ways to approach the parametrization. Predictions are successfully contrasted with experimental data. The model is used to produce residence time distributions at different process conditions and a graphical representation of the allowable range of disturbances in the feeders that can be mitigated by the process. The model was used in support of the method development for an online near infrared sensor. © 2017 American Institute of Chemical Engineers AIChE J, 64: 511–525, 2018

Daniel Mateo-Ortiz

Papers

Particle size segregation promoted by powder flow in confined space: The die filling process case

Analysis of powder phenomena inside a Fette 3090 feed frame using in-line NIR spectroscopy.

Relationship between residence time distribution and forces applied by paddles on powder attrition during the die filling process

Microdynamic analysis of particle flow in a confined space using DEM: The feed frame case

Motivating K-12 students to study pharmaceutical engineering using guided hands-on visits