Lysine as a multifunctional excipient for protein-based biopharmaceutical formulations
Jia-Yi Lv1, Shang-Yin Wu2, Tian-Yi Zhang3
1Institute of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Taizhou Institute of Zhejiang University, Taizhou 317000, China.
International Journal of Pharmaceutics
|July 16, 2026
Summary
Lysine, an essential amino acid, shows promise as a versatile excipient in biopharmaceutical formulations. Its unique properties stabilize therapeutic proteins, reduce viscosity, and protect against freezing and drying.
Area of Science:
- Biopharmaceutical Sciences
- Protein Formulation
- Amino Acid Chemistry
Background:
- Lysine (Lys) is an essential amino acid with a known safety profile.
- Its potential as a multifunctional excipient in protein-based biopharmaceutical formulation requires comprehensive review.
- Key physicochemical properties include a bifunctional amine structure, stable cationic charge, and low molecular weight.
Purpose of the Study:
- To comprehensively review lysine's potential as a multifunctional excipient for protein-based biopharmaceutical formulations.
- To discuss lysine's physicochemical properties in the context of protein formulation requirements.
- To explore lysine's protective mechanisms and applications throughout the biopharmaceutical manufacturing lifecycle.
Main Methods:
- Physicochemical characterization of lysine.
- Thermal characterization of lysine-based solids (frozen and dried).
- Stability assessment in liquid and freeze-dried protein systems (including monoclonal antibodies).
Main Results:
- Lysine's properties align with protein formulation needs, including anti-plasticization.
- Counter-ion selection significantly impacts the glass transition temperatures of lysine-based solids.
- Lysine demonstrated concentration-dependent aggregation suppression, viscosity reduction, and lyoprotection across various therapeutic proteins.
- Four FDA-approved biologics currently utilize lysine in their formulations.
- Observed protective mechanisms include ice nucleation inhibition, water replacement, vitrification, and beta-relaxation suppression.
Conclusions:
- Lysine is a promising multifunctional excipient for biopharmaceutical formulation due to its physicochemical properties and demonstrated stabilizing effects.
- Its utility extends across upstream (cell culture) and downstream (purification) manufacturing stages.
- Further research on counter-ion effects, mechanistic studies, and lysine derivatives is warranted for optimized formulation design.
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