Building competence to develop better biological medicine formulations

Biologics are medicines containing proteins and other components extracted from living systems. They are sensitive to external physical conditions and contamination, which is why the medicines must be formulated in a way that supports the stability of the biological components.

Altering the protein formula can help maintain the quality of the medicine, but the process poses complex challenges to researchers.

If biologics, like insulin, would be available in powder form, they would be much easier to transport to disaster areas, where many people depend on them.

Ekaterina Bogdanova

“Many proteins don’t have very good stability in a liquid state; that’s why scientists do solidification to create a powder-like formulation, which can then be transported, stored and used easily. The process affects different proteins in different ways and increases the risk of destabilisation, which is an issue because if the native properties change, the medicine will not work,” says Ekaterina Bogdanova, who has recently defended her dissertation on the subject.

“My project focused on how we can produce this powder-like formulation by freeze-drying and using different excipients, such as sucrose and maltodextrin. These filler substances are commonly used in medicines. The aim was to find out if this synthetic formula could help preserve the properties of the protein. By using lysozyme, a protein found in eggs, we studied how heat affects the protein and how much energy it takes for it to denature.”

One major challenge is that the powder formulation, a so-called glassy state, is unstable because it tends to crystallise. If this happens, the medicine cannot be used.

The dissertation project contributes to a larger, cross-institutional study on biological medicine formulations. Medicines that are only available in liquid form do not just pose challenges to scientists and pharmaceutical suppliers but also to users.

“Tablet is generally the best and most user-friendly form of medicine; it affects the daily life of the user less than having to take injections and it is easy to carry along when travelling. But things get more complicated here because even if we could preserve the native state of the protein in a tablet, it goes through the digestive system, where the body might use it as nutrition. When injected, it goes directly into the blood stream,” Bogdanova says.

While making more medicines available as tablets or capsules is a great ambition for the researchers, the study is more likely to help solve storing and transportation problems, she believes.

“Storing medicines in refrigerators is not always possible, but dry powder can be kept at room temperature and mixed with water before use. If biologics, like insulin, would be available in powder form, they would be much easier to transport to disaster areas, where many people depend on them.”

Text: Anna Jaakonaho