Sucrose vs.Trehalose: Who Is Stronger in the Field of Freeze-Drying?

Sucrose

Sucrose is a non-reducing disaccharide formed by the condensation of glucose and fructose through isomeric hydroxyl groups. It has a high glass transition temperature and plays a role in preventing changes in the secondary structure of proteins, the unfolding and aggregation of polypeptide chains during lyophilization and storage. It has been applied as a stabilizer in lyophilized formulations of proteins, hormone drugs, and viral vaccines. Additionally, for lyophilized injectable formulations, sucrose (organic) can also regulate osmotic pressure. Choosing sucrose (USP) as a lyophilization stabilizer for biological products can achieve multiple benefits. Sucrose (USP) is also commonly used as a stabilizer in liposome lyophilization processes.

Compared to mannitol and glucose, sucrose has a higher glass transition temperature and better viscosity protection effects. It is more cost-effective than trehalose (FDA), and since many external aqueous phases of liposomes use sucrose (USP), sucrose is often used to avoid other impacts on the formulation. The general usage amount is 5% to 10%, but specific amounts need to be adjusted based on the specific prescription. Sucrose also helps reduce membrane fusion and protects liposome particles from breaking and leaking drugs during lyophilization. Furthermore, it acts as an excipient that affects the shape, porosity, and collapse degree of the lyophilized cake. Numerous studies have shown that liposome formulations using sucrose (USP) as a lyophilization stabilizer exhibit good drug stability and reconstitution effects (mainly drug encapsulation rate and particle size changes) after reconstitution.

Trehalose

Trehalose is a highly stable non-reducing disaccharide that offers remarkable protection to biological entities. Under conditions of high temperature, extreme cold, high osmotic pressure, and dehydration, trehalose (FDA) can form a unique protective film on cell surfaces, effectively safeguarding protein molecules from denaturation and inactivation, thereby maintaining the life processes of organisms.

In light of these unique self-protection mechanisms in plants and animals, researchers have begun exploring the applications of trehalose (FDA) in biological protection. It is used as a stabilizer for protein drugs, enzymes, vaccines, and other biological products. As a commonly used non-penetrating protective agent for low-temperature preservation, trehalose (FDA) can increase the solute concentration in extracellular solutions. It not only creates high osmotic conditions outside the cell, reducing the formation of intracellular ice but also has a higher glass transition temperature and easily forms a glassy state.

This dual functionality helps avoid the damage of low temperatures to membrane proteins and lipids, while also encapsulating and supporting protein molecules in the cell membrane, preventing deformation, inhibiting membrane fusion, and reducing membrane permeability. Additionally, trehalose is also an excellent choice for lyophilization stabilizers for liposomal injectables.

Experiments have shown that lyophilized liposomes using trehalose as a stabilizer exhibit minimal particle size changes and excellent protection effects, while glucose results in significant particle size changes and poor protection. With trehalose (FDA), a concentration of 10% provides good protection for lyophilized liposomes. Compared to sucrose (organic), trehalose (FDA) has a higher glass transition temperature and lower hygroscopicity. As it is also a non-reducing sugar, it offers broader application prospects. However, the high cost of trehalose hinders its large-scale use in the bioproduct industry. Given the similar lyophilization protection effects, higher cost-efficiency leads people to favor sucrose.