Inhalable Protein Powder Prepared by Spray-Freeze-Drying Using Hydroxypropyl-β-Cyclodextrin as Excipient

Area of Science:

• Pharmaceutical Technology
• Biologics Delivery
• Materials Science

Background:

• Inhaled biologics offer advantages for pulmonary drug delivery.
• Producing inhalable dry powders requires careful control of aerosol performance and protein stability.
• Spray-freeze-drying (SFD) is a promising technique for generating lung-depositable microparticles.

Purpose of the Study:

• To evaluate SFD conditions and formulation composition for inhalable biologics.
• To investigate the impact of formulation variables on aerosol performance and protein stability using bovine serum albumin (BSA) and 2-hydroxypropyl-beta-cyclodextrin (HPβCD).

Main Methods:

• Utilized spray-freeze-drying (SFD) with bovine serum albumin (BSA) as a model protein and 2-hydroxypropyl-beta-cyclodextrin (HPβCD) as a stabilizer.
• Employed a factorial design to analyze the effects of BSA content, solute concentration, and atomization gas flow rate.
• Assessed aerosol performance (emitted fraction, fine particle fraction), particle size, and protein aggregation.

Main Results:

• Atomization gas flow rate significantly influenced aerosol performance and protein aggregation.
• High atomization gas flow rates led to increased protein aggregation, necessitating further optimization.
• All formulations demonstrated excellent dispersibility and no BSA fragmentation, confirming SFD feasibility.

Conclusions:

• SFD is a viable method for producing inhalable dry powders of biologics.
• HPβCD shows potential as an effective excipient for stabilizing proteins during SFD.
• Further optimization of SFD parameters is needed to mitigate protein aggregation while maintaining aerosol performance.