Effects of Tubing Type, Operating Parameters, and Surfactants on Particle Formation During Peristaltic Filling Pump Processing of a mAb Formulation
| Autor: | John F. Carpenter, Swati Bandi, Renuka Thirumangalathu, Theodore W. Randolph, Krishna M.G. Mallela, Laura M. Tanenbaum, Yannick Elias, Cheng Her |
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| Rok vydání: | 2020 |
| Předmět: |
Materials science
Pharmaceutical Science Nanoparticle Nanoparticle tracking analysis 02 engineering and technology Pharmaceutical formulation 021001 nanoscience & nanotechnology 030226 pharmacology & pharmacy Surface-Active Agents 03 medical and health sciences Acceleration 0302 clinical medicine Chemical engineering Microscopy Nanoparticles Particle Thermal stability Particle Size Microparticle 0210 nano-technology |
| Zdroj: | Journal of Pharmaceutical Sciences. 109:1439-1448 |
| ISSN: | 0022-3549 |
| DOI: | 10.1016/j.xphs.2020.01.009 |
| Popis: | Filling pump operation is an important cause of particle formation in therapeutic protein formulations. The goals of the present study were to investigate the impacts of peristaltic filling pump tubing type, pump operating parameters (acceleration and velocity), and formulation on both nanoparticle and microparticle formation in water, placebo, and a 120 mg/mL mAb drug formulation. Microparticles were quantified using flow imaging microscopy and light obscuration, and nanoparticles were counted with nanoparticle tracking analysis. Pumping of all solutions through Pharmed® tubing resulted in much higher particle levels than processing with Accusil™ or Masterflex® tubing. Pump acceleration did not measurably affect particle levels in pumped solutions, but in some cases, a relatively high pumping velocity of 400 rpm enhanced nanoparticle formation. The presence of surfactants reduced pumping-induced particle formation in the mAb solution, and the effects of 4 different surfactants tested were similar. Biophysical properties (secondary and tertiary structure, and thermal stability) of the protein in solution were not altered by pumping. Overall, this study demonstrates that investigations of pumping parameters and formulations using both nanoparticle and microparticle measurement methods are important for understanding pumping-induced particle formation and developing effective control strategies. |
| Databáze: | OpenAIRE |
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