Arginine (L-arginine), as another amino acid widely used in biologics, has seen significantly increased applications in pharmaceutical preparations in recent years, particularly in high-concentration protein preparations for subcutaneous administration.
As of 2021, among approved protein-based biologics, 11 antibody products contain arginine, with 10 formulated for subcutaneous use and 1 as a lyophilized powder for intravenous injection. The arginine concentration ranges from 0.028 M to 0.24 M. Some approved biologics containing arginine are listed in the table below.
Table 2 Examples of Approved Biologics Containing Arginine
| Product | Dosage Form/Route of Administration | Antibody Concentration (mg/mL) | Arginine Concentration (mg/mL) |
| Entyvio | Lyophilized powder/Intravenous injection | 300 mg/dose | 130 mg/dose |
| Actemra | Solution/Subcutaneous injection | 180 | 21 |
| Benlysta | Solution/Subcutaneous injection | 200 |
5 |
| Dupixent | Solution/Subcutaneous injection | 150/175 | 5/10 |
| EnspryngTM | Solution/Subcutaneous injection | 120 | 26 |
| Hemlibra | Solution/Subcutaneous injection | 150 | 26 |
| Kevzara | Solution/Subcutaneous injection | 150/200 | 8 |
| Xolair | Solution/Subcutaneous injection | 150 | 42 |
Arginine comprises an α-carboxyl group (pKa 2.2), an α-amino group (pKa 9.0), and a guanidinium group (pKa 12.5) (Figure 4).
Unlike histidine, arginine exhibits insufficient buffering capacity within the typical pH range for biologics (5-8) due to its high pKa and therefore must be used synergistically with other buffering agents. Beyond pH regulation with other buffers, arginine also functions as a stabilizer, viscosity reducer and solubilizer in biologics. For example, adding arginine to etanercept can significantly reduce its viscosity.
In antibody drugs, arginine primarily reduces hydrophobic interactions between protein molecules via charge shielding, thereby inhibiting aggregation. In high-concentration antibody preparations (e.g., SPEVIGO), arginine may markedly decrease the solution viscosity and shorten the injection time.
Although amino acids are indispensable in protein-based biologics, combining them with other excipients—such as sugars, polyols, and surfactants—can further enhance stabilization for biologics.
With advancing research, amino acids are emerging in gene therapy and cell therapy. In gene therapy, they may participate in vector construction/modification to enhance efficiency and stability. In cell therapy, they optimize culture conditions to promote cell growth, proliferation, and differentiation, unlocking new possibilities for next-generation biologics. Future ration...
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