Dextran Mass Ratio Controls Particle Drying Dynamics in a Thermally Stable Dry Powder Vaccine for Pulmonary Delivery

Area of Science:

• Pharmaceutical Sciences
• Biotechnology
• Vaccine Delivery

Background:

• Pulmonary delivery of vaccines offers a promising alternative to injection, particularly for respiratory diseases.
• Spray drying is a viable method for producing thermally stable vaccines, but requires careful excipient selection to protect labile biologics.
• Adenoviral vectors (AdHu5) are potent vaccine candidates but are susceptible to deactivation during formulation and drying.

Purpose of the Study:

• To investigate the impact of dextran mass ratio and molecular weight on the activity retention, thermal stability, and aerosol behavior of spray-dried adenoviral vector (AdHu5) formulations.
• To determine optimal excipient compositions for inhalable AdHu5 vaccines.
• To evaluate the role of mannitol-dextran blends in protecting AdHu5 during spray drying and storage.

Main Methods:

• Spray drying of AdHu5 with mannitol-dextran blends at varying mass ratios (1:3 and 3:1) and dextran molecular weights (40 kDa and 500 kDa).
• In vitro quantification of viral activity losses and assessment of powder flowability.
• Evaluation of thermal stability under accelerated aging conditions.
• Measurement of moisture absorption, agglomeration, mass median aerodynamic diameter, and emitted dose for aerosol performance.

Main Results:

• A mannitol to dextran ratio of 1:3, particularly with 500 kDa dextran, significantly reduced viral titre losses (<0.5 log) and demonstrated robust thermal stability.
• Dextran-rich formulations exhibited higher moisture absorption and agglomeration, but the 1:3 ratio with 500 kDa dextran yielded optimal aerosol performance (4.4 µm MMAD, 84% emitted dose) under low humidity.
• Increased dextran molecular weight improved activity retention at the 1:3 ratio, but the ratio itself was a more critical parameter.

Conclusions:

• Dextran-rich formulations enhance viscosity during spray drying, hindering viral partitioning to particle surfaces and improving activity retention.
• Reducing mannitol content minimizes AdHu5 exclusion from crystalline regions, preventing deactivation at air-solid interfaces.
• Optimized spray-dried formulations with improved encapsulation efficiency enable higher potency inhalable vaccines with enhanced delivery efficiency.