The pharmaceutical industry is encountering a decline in productivity, and outdated “tried-and-true” batch processes are at the root of the problem.
The batch-based systems currently in place are inefficient due to segmented steps involving multiple facilities and requiring start-and-stop of the batch, site-to-site transfer and warehouse storage. Performed through sampling and in post-production, quality assessment of the product is also cumbersome, causing long lead times and waste.
Continuous manufacturing, a non-stop end-to-end manufacturing process, could modernize the industry and solve its productivity crisis. Before continuous manufacturing can become main-stream, potentially suitable candidate processes must be identified and designed, and risks must be analyzed and mitigated. This will help manage regulatory compliance and make a business case for implementation.
Multi-physics Computational Fluid Dynamics (CFD), a numerical method for predicting the coupled behavior of fluid, gas and particulate flows including heat and mass transport, offers a solution for the enhanced understanding and design of these novel processes.
Case study:
Direct element modeling (DEM) for pill coating
Figure 1. DEM simulation with STAR-CCM+ showing tablet velocity magnitude as they tumble in a coating pan
Figure 2. DEM simulation for tablet coating with STAR-CCM+ showing pill coating thickness in a fluidized bed
DEM simulates the motion of a large number of interacting particles and tracks them in a numerically efficient manner, modeling contact forces and energy transfer due to collision and heat transfer between particles. DEM will be particularly important in the design and optimization of continuous coating processes to help identify the important factors for equipment design (e.g. number of spray guns) and to determine optimal equipment operation conditions (e.g. inlet temperature).
Figures 1 and 2 show STAR-CCM+ generated solutions for two types of equipment currently used for real-world tablet coating: coating pan (rotating drum) and fluidized bed. In these simulations, DEM is used to analyze the random movement of the particles as layers of coating are applied. Parameters such as particle velocities, residence time and coating thickness are tracked to assess and improve tablet coating uniformity. In addition to tablet coating, DEM can also be used to simulate other steps in manufacturing such as filling, filtering and conveyer processes.
In today’s competitive climate, manufacturing must become leaner with a focus on building quality into the process.
Continuous manufacturing for the pharmaceutical industry will change the way drugs are made and multi-physics CFD simulations offer a cost-effective way to perform rapid prototyping for design of new equipment and processes.
In particular, design optimization tools and powerful multiphase models such as DEM and EMP will play an important role, and the pharmaceutical industry should fully leverage these state-to-the-art technologies for the design and implementation of continuous manufacturing processes.
