AVT (Shanghai) Pharmaceutical Tech Co., Ltd.

Application Advantage of Sucrose as Lyophilized Protectant

We all know that in the freeze-drying and storage process of food, medicine and organisms, many factors can affect the stability of the active components, and even lead to inactivation. Most pharmaceuticals and biological products require the addition of suitable freeze-drying protectants and additives to be prepared into a mixture for effective freeze-drying and storage. 

Sucrose is One of The Commonly Used Freeze-drying Protectants

Before discussing the advantages of sucrose as a lyophilized protective agent, let's explain why sucrose can be used as a lyophilized protective agent for biological products.  

In order to protect the quality and activity of the protein and other active substances in biological products, sugar protectants are usually added to drug formulations for lyophilization. There are two hypotheses about the protection mechanism of lyophilization: the vitreous hypothesis and the water substitution hypothesis.  

The first hypothesis is the glassy hypothesis  

The viscous protective agent surrounded the protein molecules, forming a carbohydrate vitreous body similar to the glass ice in structure, which blocked the chain forging movement of macromolecular substances, prevented the extension and precipitation of proteins, and maintained the stability of the three-dimensional structure of protein molecules, thus playing a protective role.  

The second hypothesis is the water substitution hypothesis  

When the protein loses moisture during freeze-drying, the hydroxyl group of the protective agent can replace the hydroxyl group of the water on the protein surface, so that a putative hydration film is formed on the protein surface, which can protect the bonding position of the hydrogen bond from direct exposure to the surrounding environment and prevent the denaturation of the protein due to freeze-drying.  

The theoretical basis of the above two hypotheses is to achieve partial or total vitrification freezing of the liquid medicine, so the appropriate lyophilization protectants need to have the following four characteristics: high vitrification transition temperature, low hygroscopicity, low crystallization rate, and no reduction group.  

Monosaccharides Can't Protect The Freeze-drying Process of Proteins

because monosaccharides can only provide weak stability during freezing, making proteins irreversible denaturation before dehydration and drying.  

Disaccharide is a very suitable protective agent, which can not only increase the free energy of protein in the freezing process to prevent protein denaturation but also replace the hydrogen bond between protein and water molecules to stabilize the protein in the drying process. Moreover, it does not contain a reductive group and will not cause the protein browning reaction of biological products to degenerate and inactivate.  

The protective effect of sugar is related to the type of protein, so the protective agent suitable for drugs needs to be determined through a comparison of experimental data. At present, sucrose and trehalose in disaccharides are widely studied and recognized as effective protective agents for biological products.  

Sucrose is a non-reductive disaccharide formed from glucose and fructose through condensation of the isomer hydroxyl group. It has a high vitrification transition temperature and plays an obvious role in preventing the change of secondary structure of protein and the extension and aggregation of protein polypeptide chain during freeze-drying and storage. It has been used as a protective agent in protein, Ji SU drug lyophilized preparation, and virus vaccine.