Injectable-Grade Sucrose Solutions: A Sustainable Innovation in Biopharmaceutical Excipients

Moving Glycoscience Forward

How does the Sucrose SG product’s manufacturing process fit into your company’s strong sustainability commitments?
Our proprietary manufacturing system operates in an environmentally responsible and resource-efficient way. All products in the Solbiote portfolio are manufactured using water throughout the process instead of ICH Q3C class 1, 2, or 3 solvents, which are used often during saccharide purification and recrystallization. Thus, our products are manufactured at high purity with low endotoxin levels for injectable applications without relying on organic solvents. Our manufacturing processes are optimized through strategic inventory management and meticulous planning to preserve water and minimize waste and CO2 emissions.

Our sustainability approach prioritizes environmental and social impacts along with maintenance of product quality. By offering sustainably manufactured, high-quality excipients to biopharmaceutical developers and manufacturers, we are helping to advance sustainability in the industry.

What is next for your company?
Since our founding, our advanced R&D capabilities in glycoscience have driven us to explore new possibilities for saccharides. For example, we are investigating applications of Solbiote solutions as processing aids during both upstream and downstream bioprocess development.

Our goal is to be an essential partner in the sustainable manufacture and equitable distribution of biopharmaceuticals. We are eager to continue developing saccharide excipients and providing thought-leadership in the glycoscience field.

A Breadth of Applications

How does sucrose stabilize antibody formulations? For which kinds of antibody products might it be effective as an excipient?
Sucrose is a disaccharide comprising glucose and fructose molecules linked by α-1,2 glycosidic bonds. Because of its structure, it is nonoxidizing, nonreducing, and highly water-soluble, presenting as colorless crystals.

Sucrose stabilizes antibody formulations by interacting with both water molecules and protein structures. Through hydrogen bonding with such molecules, sucrose helps to maintain native protein conformations, reducing risks for denaturation (2).

In freeze-dried formulations, sucrose replaces water molecules and inhibits protein unfolding during drying. It also prevents antibody aggregation and degradation during freezing by suppressing ice-crystal formation and reducing molecular motion. Furthermore, sucrose is known to minimize surface adsorption, reducing protein loss or denaturation caused by adsorption to final-container surfaces. Because of such properties, sucrose is particularly effective for antibody formulations in freeze-dried and highly concentrated solutions as well as for antibody–drug conjugates (ADCs).

In addition to its role as lyoprotectant, sucrose enhances protein stability in liquid formulations, making it an essential excipient for preserving antibodies under a breadth of long-term storage conditions.

Can sucrose also work for lipid nanoparticles (LNPs) containing nucleic acids?
It indeed stabilizes LNP formulations by preserving particles’ structural integrity during freezing and storage (1). Sucrose prevents LNP fusion and aggregation by reducing water activity, promoting formation of a “glassy” state that immobilizes the nanoparticles. Thus, sucrose effectively minimizes LNP damage during freezing by inhibiting ice-crystal formation. It also helps to maintain stable microenvironments within LNPs, preventing nucleic-acid degradation. Such properties make sucrose particularly effective for LNP formulations that require long-term stability, such as mRNA-based therapeutics and vaccines.

To validate general use of sucrose as a stabilizer for LNPs, our scientists performed experiments with LNP-preparation kits from Cayman Chemical. LNP compositions were prepared by replacing the sucrose used in Comirnaty vaccine formulations with other carbohydrates, such as our Maltose PH, Trehalose SG, and Sucrose SG products. Then, samples were subjected to freeze–thaw cycles, with storage at –20 °C for one hour followed by storage at room temperature for 30 minutes.

Addition of the Sucrose SG excipient resulted in the least change in particle size among the tested carbohydrates. Notably, our scientists observed a trend toward larger LNP sizes with the other tested molecules (Figure 1).

Addressing an Industry Need

Why did your company develop this saccharide product, and how is it manufactured?
We developed it to address the critical issue of stability in parenteral biopharmaceuticals. Manufactured and refined in Japan, the highly purified sucrose provides guaranteed safety and reliable quality.

Endotoxin removal is critical to the Sucrose SG saccharide’s manufacture. The purification process is controlled strictly by advanced refining technologies that our company has developed through decades of experience. We also conduct endotoxin analysis according to internationally standardized methods in major pharmacopoeias, including the United States Pharmacopeia–National Formulary (USP–NF), the European Pharmacopoeia (EP), and the Japanese Pharmacopoeia (JP). By complying with stringent global standards for parenteral dosage forms, our Sucrose SG excipient helps biopharmaceutical developers to ensure exceptional quality in their products.

Industry Background and Product Development

Sucrose has a long and successful history as a pharmaceutical excipient. As I learned from Toshio Ariyasu (senior scientist) and Kanso Iwaki (pharmaceutical business development advisor) of Nagase Viita, that saccharide has been used not only in oral formulations of small-molecule drugs, but also in biopharmaceuticals formulated for parenteral administration. They noted, “Sucrose serves as an excellent stabilizer for monoclonal antibody (mAb) products, peptide-based drugs, and traditional vaccines. It even has been used in mRNA-based vaccines against viral infections.” Indeed, Pfizer–BioNTech’s Comirnaty and Moderna’s Spikevax COVID-19 vaccines leveraged high concentrations of sucrose as a cryoprotectant — a nontrivial factor considering those products’ distinctive requirements for cold storage (1).

As biopharmaceutical products proliferate, industry demand for saccharide excipients will grow. Thus, biomanufacturers will benefit from an expanded array of tools for stabilizing the quality of drug products. Ariyasu and Iwaki explained to me that their company is leveraging 140 years of expertise in glycoscience and saccharide production to address such needs. Nagase Viita already has developed the Solbiote family of saccharide excipients — including high-purity, low-endotoxin Trehalose SG and Maltose PH products — to help biomanufacturers stabilize their drug products. In 2025, the company will expand the portfolio by introducing the injectable-grade Sucrose SG saccharide excipient.

During our discussion, Ariyasu and Iwaki explained how sucrose stabilizes biopharmaceutical quality and how addition of the Sucrose SG solution to the Solbiote portfolio “will increase the breadth of solutions available to the industry.” They also highlighted their company’s commitment to sustainable saccharide manufacturing.

References

1 Buschmann MD, et al. Nanomaterial Delivery Systems for mRNA Vaccines. Vaccines 9(1) 2021: 65–94;https://doi.org/10.3390/vaccines9010065.

2 Wood VE, et al. Investigation of the Solid-State Interactions in Lyophilized Human G-CSF Using Hydrogen−Deuterium Exchange Mass Spectrometry. Mol. Pharm. 21(4) 2024: 1965−1976; https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.3c01211.

Brian Gazaille, PhD, is managing editor of BioProcess International; [email protected]. Toshio Ariyasu, PhD, is a senior scientist, and Kanso Iwaki, DVM, PhD, is a pharmaceutical business development advisor, both at Nagase Viita; https://group.nagase.com/viita/en/products_solutions/pharmaceutical_ingredients.

Adapted from: “Expanding the Toolbox of Biopharmaceutical Excipients: Sustainably Manufactured, Injectable-Grade Sucrose Solutions” by Brian Gazaille, Toshio Ariyasu, and Kanso Iwaki, published on BioProcess International, March 7, 2025. Available here.