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Jennifer Markarian is manufacturing editor of Pharmaceutical Technology.
A presentation at the Leistritz Pharmaceutical-Nutraceutical Extrusion Seminar explained how simulation tools benefit the development process.
Twin-screw extruders (TSE) are used in multiple pharmaceutical manufacturing processes, including the extrusion of drug-loaded implants and hot-melt extrusion (HME) of amorphous solid-dispersions for improving bioavailability of oral solid-dosage formulations. The Leistritz Pharmaceutical-Nutraceutical Extrusion Seminar (June 12–13, 2019) offered demonstrations of operating equipment and presentations on best practices from extrusion experts. Philippe David, general manager at Sciences Computers Consultants, spoke about using computer simulation to model the extruder, which enables initial evaluation without using samples. Simulation is being used in HME development today, notes David, pointing to a research paper to be published in the August 2019 issue of the European Journal of Pharmaceutics and Biopharmaceutics titled “Holistic QbD Approach for Hot-Melt Extrusion Process Design Space Evaluation: Linking Materials Science, Experimentation and Process Modeling” (1). Pharmaceutical Technology spoke with David about the benefits and limitations of simulation in pharmaceutical extrusion.
PharmTech: What are the benefits of using numerical simulation in pharmaceutical twin-screw extrusion?
David (SC Consultants): Simulation is a powerful tool to schedule the best trials to perform. Even at an early stage of the processability evaluation (without any real samples), it is worth trying to see what could happen in term of the quality-by-design (QbD) operational domain. The bad news is that, in general, the physics of the HME process is by far too complex to be fully modelled. The good news is that even with raw or approximate data, it is worth running virtual trials to evaluate the trends. These trends obviously need to be confirmed by real tests [with material], but the required quantity of material needed has dramatically been reduced.
PharmTech: What do pharma developers need to understand about TSE simulation?
David (SC Consultants): Mechanistic [extrusion experts] understand the relation between torque, flow rate, RPM, residence time, shear rate, etc. These relations are generic and valid in the polymer world as well as in the pharma world. Pharmaceutical process people are specialists in degradability, solubility, etc. These two cultures need to share and fill the gap to design the mechanical-to-pharma bridge and understand the root causes.
PharmTech: How does your software for pharma extrusion differ from your original software for polymer extrusion?
David (SC Consultants): Ludovic software, designed as a general-purpose TSE simulation, is valid for plastic as well as pharma, but the Ludovic Pharma Edition (introduced in 2018) incorporates pharma-specific considerations. These include material characteristics defined as a function of temperature (rather than a constant value), a specific design of experiment adjusted to the QbD style, and several temperature-related outputs meaningful for pharma.
1. R.C. Evans et al., Eur. J. Pharmaceutics and Biopharmaceutics online DOI:10.1016/j.ejpb.2019.05.021 (Aug. 2019).