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A Comparative Assessment Of Continuous Production Techniques To Generate Sub‐micron Size PLGA Particles

M. C. Operti, David Fecher, E. V. van Dinther, Silko Grimm, R. Jaber, C. Figdor, O. Tagit
Published 2018 · Materials Science, Medicine

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Graphical abstract Figure. No Caption available. Abstract The clinical and commercial development of polymeric sub‐micron size formulations based on poly(lactic‐co‐glycolic acid) (PLGA) particles is hampered by the challenges related to their good manufacturing practice (GMP)‐compliant, scale‐up production without affecting the formulation specifications. Continuous process technologies enable large‐scale production without changing the process or formulation parameters by increasing the operation time. Here, we explore three well‐established process technologies regarding continuity for the large‐scale production of sub‐micron size PLGA particles developed at the lab scale using a batch method. We demonstrate optimization of critical process and formulation parameters for high‐shear mixing, high‐pressure homogenization and microfluidics technologies to obtain PLGA particles with a mean diameter of 150–250 nm and a small polydispersity index (PDI, ≤0.2). The most influential parameters on the particle size distribution are discussed for each technique with a critical evaluation of their suitability for GMP production. Although each technique can provide particles in the desired size range, high‐shear mixing is found to be particularly promising due to the availability of GMP‐ready equipment and large throughput of production. Overall, our results will be of great guidance for establishing continuous process technologies for the GMP‐compliant, large‐scale production of sub‐micron size PLGA particles, facilitating their commercial and clinical development.
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