Benefits

• High purity grade
• Low bioburden, low endotoxin
• Q3D statement for inhalation and parenteral applications
• Conforms to Ph. Eur., USP-NF, JP, and ChP
• Listed in FDA inactive ingredient database for inhalation and parenteral applications
• Usage for stabilization and protectant in temperature sensitive production processes

Applications:

• DPI formulations
• Parenteral/Injectables
• (Thin-film) freeze-drying and spray-drying (high dose formulations and sensitive APIs)

Lactose is listed in the FDA Inactive Ingredient Database (IID) for parenteral and ophthalmic applications

Excipients which are suitable to stabilize products during freezedrying (lyophilization) and spray-drying, and which are approved by regulatory agencies for parenteral formulations are highly limited. The FDA regulatory requirements for parenteral formulations are quite strict: they must be proven safe, non-toxic, sterile, pyrogen-free and particle-free. Notably, lactose is listed in the FDA Inactive Ingredient Database (IID) for parenteral and ophthalmic applications. β-Lactoglobulin (BLG) is monitored as marker allergen/milk protein, levels are below LOQ (0.010 ppm).

Sugars for protection during drying and as bulking agent. Understanding Cryo- and Lyoprotectants/Stabilizers

Cryo- and Lyoprotectants/Stabilizers are substances that show a molecular protection for sensitive ingredients which would ratherly suffer damages caused by freeze- or spray-drying.

Role of Disaccharides in Vitrification

Disaccharides like lactose, sucrose and trehalose are well known to form a glassy or amorphous matrix surrounding the biomolecules, which helps stabilizing them by reducing mobility and preventing crystallization and aggregation. This effect is called Vitrification. Moreover, lactose can replace water molecules through hydrogen bonds to the biological material, which reduces stress during drying and minimizes structural damage and denaturation of proteins and nucleic acids.

Protective Properties of Lactose

Zimmermann et. al (2022, Spray drying siRNA-lipid nanoparticles for dry powder pulmonary delivery) showed the protective properties of lactose. RNA-loaded lipid nanoparticle systems suspended in a 5 % lactose solution were spray dried at highest possible temperatures (up to 100°C inlet temperature) while retaining the lipid nanoparticles structure and remaining the RNA bioactivity.

Advantages of Lactose in Dry Powder Inhalers

The administration of RNA drugs via dry powder inhalers offers many advantages related to physical, chemical and microbial stability of RNA and nanosuspensions. The high solubility of lactose, as well as the lower costs of this material show advantages by using lactose instead of trehalose. Another benefit of lactose is the well established use for inhalation products.

Formulation Considerations and Additives

The glass transition temperature of amorphous lactose is lower than the one for trehalose, but higher than the one for sucrose. Additives like leucine might be beneficial to further improve performance and stability.