Targeting intermolecular interactions to reduce viscosity in monoclonal antibody formulations : a review

Prašnikar, Monika (author), Bjelošević Žiberna, Maja (author), Ahlin Grabnar, Pegi (author)

Monoclonal antibodies (mAb) have transformed modern medicine, offering targeted therapies for cancer, autoimmune disorders, and infectious diseases. To enhance patient convenience, subcutaneous administration is increasingly prioritized, requiring highly concentrated formulations. However, high viscosity of these formulations hinders manufacturability, injectability, and stability. Viscosity-reducing additives are a promising solution, disrupting protein-protein interactions and thereby reducing the viscosity of mAb formulations. Most promising additives are small organic electrolytes, where key properties influencing their efficacy include charge, size, and salt form. Relatively small molecules with three or more charges are most efficient, while the counter-ion provides opportunity for increased solubility and additional interactions. Our data analysis further highlights topological polar surface area and heteroatoms as significant predictors of viscosity reduction, while the role of aromatic moieties remains questionable. Another promising strategy is combining viscosity-reducing additives, which can achieve synergistic viscosity reduction while enhancing stability. Polyelectrolytes also demonstrate promising efficacy via complex formation with mAbs. Conversely, other common excipients of mAb formulations, such as sugars and surfactants, often increase viscosity of the formulation. This review provides a foundation for advancing viscosity-reducing strategies and offers actionable insights to guide future research and development of effective, patient-oriented mAb formulations.

• Language: English
• Keywords: monoclonal antibody, protein-protein interactions, biopharmaceuticals, highly concentrated mAb formulations, viscosity-reducing additives, subcutaneous administration
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: Str. 1-14
• Numbering: Vol. 327, part 2
• PID: 20.500.12556/RUL-175082
• UDC: 616-097
• ISSN on article: 0141-8130
• DOI: 10.1016/j.ijbiomac.2025.147515
• COBISS.SI-ID: 248572419
• Publication date in RUL: 15.10.2025

Record is a part of a journal

• Title: International journal of biological macromolecules
• Shortened title: Int. j. biol. macromol.
• Publisher: Butterworth Scientific Ltd, Elsevier
• ISSN: 0141-8130
• COBISS.SI-ID: 25637888

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: monoklonska protitelesa, interakcije beljakovin-beljakovin, biofarmacevtski izdelki, visoko koncentrirane formulacije monoklonskih protiteles, dodatki za zmanjšanje viskoznosti, subkutana uporaba, farmacevtska kemija

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P1-0189
• Name: Farmacevtska tehnologija: od dostavnih sistemov učinkovin do terapijskih izidov zdravil pri otrocih in starostnikih

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: L1-3160
• Name: Razvoj visokokoncentriranih proteinskih formulacij in vrednotenje kinetike absorpcije po subkutani aplikaciji