A Platform for Preparing Homogeneous Proteinaceous Subvisible Particles With Distinct Morphologies.
| Autor: | Schack MM; Department of Pharmacy, Section of Pharmaceutical Design and Drug Delivery, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk A/S, Måløv, Denmark., Møller EH; Novo Nordisk A/S, Måløv, Denmark., Carpenter JF; Department of Pharmaceutical Sciences, University of Colorado-Denver, Aurora, Colorado 80045., Rades T; Department of Pharmacy, Section of Pharmaceutical Design and Drug Delivery, University of Copenhagen, Copenhagen, Denmark., Groenning M; Novo Nordisk A/S, Måløv, Denmark. Electronic address: mgqj@novonordisk.com. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of pharmaceutical sciences [J Pharm Sci] 2018 Jul; Vol. 107 (7), pp. 1842-1851. Date of Electronic Publication: 2018 Mar 21. |
| DOI: | 10.1016/j.xphs.2018.03.014 |
| Abstrakt: | Regulatory authorities and scientific communities are increasingly attentive to the known and universal presence of small particulates in biological drug products. The underlying concern is that these particulates may cause unwanted formation of antidrug antibodies in patients. Pharmacological studies, however, have to date not succeeded in unambiguously identifying risk-prone particle properties. This lack of success may be partly due to a lack of available, well-defined, homogenous particle material. Protein particles arising from stress of protein drug products are by nature often highly heterogeneous in size, morphology, and structure of the constituent protein in the particles. Here, we present simple and pharmaceutically relevant stress conditions to produce 8 different highly homogenous micrometer-sized protein particles from human insulin, representing very different morphologies and conformation of the constituent protein molecules in the particles generated. Insulin's self-association patterns were varied by formulation approaches to create diverse starting materials. The resulting collection of homogenous particles underlines that the particle formation is not necessarily a random process but a consequence of formulation and specific stress condition. Owing to the inherent homogenicity of these populations, the particle materials can act as a standard platform for further studies on insulin subvisible particles in drug products. (Copyright © 2018 American Pharmacists Association®. All rights reserved.) |
| Databáze: | MEDLINE |
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