Pembrolizumab microgravity crystallization experimentation
| Autor: | Denarra Simmons, Giovanna Scapin, Chakravarthy Nachu Narasimhan, Paul Reichert, Corey Strickland, Ray Polniak, Erika Walsh, Xiaoyu Yang, Winifred W. Prosise, Wendy Benjamin, Thierry O. Fischmann, Johnathan Welch, Daya Patel, April Spinale |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Materials science
Physics and Astronomy (miscellaneous) Materials Science (miscellaneous) lcsh:Biotechnology Medicine (miscellaneous) 02 engineering and technology Biochemistry Genetics and Molecular Biology (miscellaneous) Biochemistry lcsh:Physiology Article law.invention 03 medical and health sciences Viscosity Rheology law lcsh:TP248.13-248.65 Biophysical chemistry Crystallization 030304 developmental biology 0303 health sciences lcsh:QP1-981 Sedimentation 021001 nanoscience & nanotechnology Agricultural and Biological Sciences (miscellaneous) Chemical engineering Space and Planetary Science Homogeneous Drug delivery Particle-size distribution 0210 nano-technology National laboratory |
| Zdroj: | NPJ Microgravity npj Microgravity, Vol 5, Iss 1, Pp 1-8 (2019) |
| ISSN: | 2373-8065 |
| Popis: | Crystallization processes have been widely used in the pharmaceutical industry for the manufacture, storage, and delivery of small-molecule and small protein therapeutics. However, the identification of crystallization processes for biologics, particularly monoclonal antibodies, has been prohibitive due to the size and the flexibility of their overall structure. There remains a challenge and an opportunity to utilize the benefits of crystallization of biologics. The research laboratories of Merck Sharp & Dome Corp. (MSD) in collaboration with the International Space Station (ISS) National Laboratory performed crystallization experiments with pembrolizumab (Keytruda®) on the SpaceX-Commercial Resupply Services-10 mission to the ISS. By leveraging microgravity effects such as reduced sedimentation and minimal convection currents, conditions producing crystalline suspensions of homogeneous monomodal particle size distribution (39 μm) in high yield were identified. In contrast, the control ground experiments produced crystalline suspensions with a heterogeneous bimodal distribution of 13 and 102 μm particles. In addition, the flight crystalline suspensions were less viscous and sedimented more uniformly than the comparable ground-based crystalline suspensions. These results have been applied to the production of crystalline suspensions on earth, using rotational mixers to reduce sedimentation and temperature gradients to induce and control crystallization. Using these techniques, we have been able to produce uniform crystalline suspensions (1–5 μm) with acceptable viscosity ( |
| Databáze: | OpenAIRE |
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