Discovery of compounds with viscosity-reducing effects on biopharmaceutical formulations with monoclonal antibodies.
Comput Struct Biotechnol J
; 20: 5420-5429, 2022.
Article
in En
| MEDLINE
| ID: mdl-36212536
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.
Biopharmaceuticals; Computational screening; GRAS, Generally Recognized as Safe; HIC, hydrophobic interaction chromatography; MW, molecular weight; PSA, polar surface area; Protein formulations; SASA, solvent accessible surface area; SlogP, partition coefficient; VRAs, viscosity-reducing agents; Viscosity; Viscosity-reducing agents; mAbs, monoclonal antibodies
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Comput Struct Biotechnol J
Year:
2022
Document type:
Article
Affiliation country:
Slovenia
Country of publication:
Netherlands