Discovery of compounds with viscosity-reducing effects on biopharmaceutical formulations with monoclonal antibodies
For the development of concentrated monoclonal antibody formulations for subcutaneous administration, the main challenge is the high viscosity of the solutions. To compensate for this, viscosity reducing agents are commonly used as excipients. Here, we applied two computational chemistry approaches...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Computational and Structural Biotechnology Journal |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037022004408 |
| _version_ | 1797978166818504704 |
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| author | Matic Proj Mitja Zidar Blaž Lebar Nika Strašek Goran Miličić Aleš Žula Stanislav Gobec |
| author_facet | Matic Proj Mitja Zidar Blaž Lebar Nika Strašek Goran Miličić Aleš Žula Stanislav Gobec |
| author_sort | Matic Proj |
| collection | DOAJ |
| description | For the development of concentrated monoclonal antibody formulations for subcutaneous administration, the main challenge is the high viscosity of the solutions. To compensate for this, viscosity reducing agents are commonly used as excipients. Here, we applied two computational chemistry approaches to discover new viscosity-reducing agents: fingerprint similarity searching, and physicochemical property filtering. In total, 94 compounds were selected and experimentally evaluated on two model monoclonal antibodies, which led to the discovery of 44 new viscosity-reducing agents. Analysis of the results showed that using a simple filter that selects only compounds with three or more charge groups is a good ‘rule of thumb’ for selecting potential viscosity-reducing agents for two model monoclonal antibody formulations. |
| first_indexed | 2024-04-11T05:18:38Z |
| format | Article |
| id | doaj.art-a635c0e9d2914fa29fff68bb75575823 |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-04-11T05:18:38Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-a635c0e9d2914fa29fff68bb755758232022-12-24T04:54:36ZengElsevierComputational and Structural Biotechnology Journal2001-03702022-01-012054205429Discovery of compounds with viscosity-reducing effects on biopharmaceutical formulations with monoclonal antibodiesMatic Proj0Mitja Zidar1Blaž Lebar2Nika Strašek3Goran Miličić4Aleš Žula5Stanislav Gobec6University of Ljubljana, Faculty of Pharmacy, Chair of Pharmaceutical Chemistry, Ljubljana, SloveniaBiologics Drug Product, Technical Research and Development, Global Drug Development, Novartis, Lek d.d., SloveniaUniversity of Ljubljana, Faculty of Pharmacy, Chair of Pharmaceutical Chemistry, Ljubljana, SloveniaUniversity of Ljubljana, Faculty of Pharmacy, Chair of Pharmaceutical Chemistry, Ljubljana, SloveniaBiologics Drug Product, Technical Research and Development, Global Drug Development, Novartis, Lek d.d., SloveniaBiologics Drug Product, Technical Research and Development, Global Drug Development, Novartis, Lek d.d., Slovenia; Corresponding authors.University of Ljubljana, Faculty of Pharmacy, Chair of Pharmaceutical Chemistry, Ljubljana, Slovenia; Corresponding authors.For the development of concentrated monoclonal antibody formulations for subcutaneous administration, the main challenge is the high viscosity of the solutions. To compensate for this, viscosity reducing agents are commonly used as excipients. Here, we applied two computational chemistry approaches to discover new viscosity-reducing agents: fingerprint similarity searching, and physicochemical property filtering. In total, 94 compounds were selected and experimentally evaluated on two model monoclonal antibodies, which led to the discovery of 44 new viscosity-reducing agents. Analysis of the results showed that using a simple filter that selects only compounds with three or more charge groups is a good ‘rule of thumb’ for selecting potential viscosity-reducing agents for two model monoclonal antibody formulations.http://www.sciencedirect.com/science/article/pii/S2001037022004408ViscosityProtein formulationsBiopharmaceuticalsViscosity-reducing agentsComputational screening |
| spellingShingle | Matic Proj Mitja Zidar Blaž Lebar Nika Strašek Goran Miličić Aleš Žula Stanislav Gobec Discovery of compounds with viscosity-reducing effects on biopharmaceutical formulations with monoclonal antibodies Computational and Structural Biotechnology Journal Viscosity Protein formulations Biopharmaceuticals Viscosity-reducing agents Computational screening |
| title | Discovery of compounds with viscosity-reducing effects on biopharmaceutical formulations with monoclonal antibodies |
| title_full | Discovery of compounds with viscosity-reducing effects on biopharmaceutical formulations with monoclonal antibodies |
| title_fullStr | Discovery of compounds with viscosity-reducing effects on biopharmaceutical formulations with monoclonal antibodies |
| title_full_unstemmed | Discovery of compounds with viscosity-reducing effects on biopharmaceutical formulations with monoclonal antibodies |
| title_short | Discovery of compounds with viscosity-reducing effects on biopharmaceutical formulations with monoclonal antibodies |
| title_sort | discovery of compounds with viscosity reducing effects on biopharmaceutical formulations with monoclonal antibodies |
| topic | Viscosity Protein formulations Biopharmaceuticals Viscosity-reducing agents Computational screening |
| url | http://www.sciencedirect.com/science/article/pii/S2001037022004408 |
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