Making Concentrated Antibody Formulations Accessible for Vibrating-Mesh Nebulization.

Area of Science:

• Biopharmaceutical formulation
• Drug delivery technologies
• Respiratory medicine

Background:

• Therapeutic antibodies are of significant interest for treating airway diseases.
• Nebulizing concentrated antibody formulations presents a challenge due to high viscosity.
• Existing studies have not addressed the nebulization of viscous antibody formulations.

Purpose of the Study:

• To determine the maximum viscosity for vibrating-mesh nebulization of antibody formulations.
• To identify excipients that reduce viscosity while maintaining antibody stability.
• To enable nebulization of concentrated antibody formulations for airway disease treatment.

Main Methods:

• Determined the viscosity threshold for the eFlow®rapid vibrating-mesh nebulizer using sucrose as a viscosity enhancer.
• Supplemented a concentrated model antibody formulation (125 mg/mL) with lysine and arginine to reduce viscosity.
• Evaluated aerosol output rate and droplet diameter post-nebulization.
• Assessed the stability of the antibody formulation after nebulization.

Main Results:

• The viscosity threshold for the eFlow®rapid device was approximately 6 mPa*s.
• Supplementation with lysine (≥50 mM) and arginine (≥20 mM) reduced viscosity to below 5.5 mPa*s.
• The previously non-nebulizable formulation achieved an output rate of up to ~0.5 g/min with a droplet diameter <5 μm.
• Antibody formulation stability was not compromised by nebulization with lysine and arginine.

Conclusions:

• Concentrated antibody formulations can be nebulized using vibrating-mesh technology by managing viscosity.
• Lysine and arginine are effective excipients for reducing viscosity in antibody formulations for nebulization.
• This research provides a foundation for aerosolizing concentrated protein formulations via vibrating-mesh technology, potentially improving airway disease treatments.