Design Space and Control Strategy for the Manufacturing of Wet Media Milled Drug Nanocrystal Suspensions by Adopting Mechanistic Process Modeling

Wet media milling is a fully industrialized technology for the manufacturing of drug nanocrystal suspensions. This work describes the development of an advanced control strategy and an associated design space for a manufacturing process at a commercial scale. Full-scale experiments and mechanistic p...

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Bibliographic Details
Published in:Pharmaceutics 2024-02, Vol.16 (3), p.328
Main Authors: Bitterlich, André, Mihorko, Andrej, Juhnke, Michael
Format: Article
Language:English
Subjects:
Case studies
control strategy
Cooling
Design of experiments
design space
Manufacturing
mechanistic
modeling
Nanocrystals
Particle size
Pharmaceutical industry
Process controls
Product quality
Production processes
Quality control
quality-by-design
Risk assessment
Statistical analysis
Surfactants
Temperature
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Summary:Wet media milling is a fully industrialized technology for the manufacturing of drug nanocrystal suspensions. This work describes the development of an advanced control strategy and an associated design space for a manufacturing process at a commercial scale. Full-scale experiments and mechanistic process modeling have been used to establish a physically reasonable control strategy of factors relevant to the quality attributes of the nanocrystal suspension. The design space has been developed based on a mature mechanistic process model of the wet media milling procedure. It presents the process-product attribute relationship between a multidimensional range of measured process parameters and a range of the product-quality attribute mean particle sizes. The control strategy allows for simple, robust, and sound scientific process control as well as the operational flexibility of the suspension batch size. This is an industrial case study of control strategy and design-space definition with the crucial contribution of mechanistic process modeling for an intended commercial manufacturing process.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics16030328