Pharmaceutical Research

, Volume 16, Issue 2, pp 249–254

Protein Inhalation Powders: Spray Drying vs Spray Freeze Drying


    • Pharmaceutical Research and DevelopmentGenentech, Inc.
  • Phuong-Anh Nguyen
    • Pharmaceutical Research and DevelopmentGenentech, Inc.
  • Theresa Sweeney
    • Pharmaceutical Research and DevelopmentGenentech, Inc.
  • Steven J. Shire
    • Pharmaceutical Research and DevelopmentGenentech, Inc.
  • Chung C. Hsu
    • Pharmaceutical Research and DevelopmentGenentech, Inc.

DOI: 10.1023/A:1018828425184

Cite this article as:
Maa, Y., Nguyen, P., Sweeney, T. et al. Pharm Res (1999) 16: 249. doi:10.1023/A:1018828425184


Purpose. To develop a new technique, spray freeze drying, for preparing protein aerosol powders. Also, to compare the spray freeze-dried powders with spray-dried powders in terms of physical properties and aerosol performance.

Methods. Protein powders were characterized using particle size analysis, thermogravimetric analysis, scanning electron microscopy, X-ray powder diffractometry, and specific surface area measurement. Aerosol performance of the powders was evaluated after blending with lactose carriers using a multi-stage liquid impinger or an Anderson cascade impactor. Two recombinant therapeutic proteins currently used for treating respiratory tract-related diseases, deoxyribonuclase (rhDNase) and anti-IgE monoclonal antibody (anti-IgE MAb), were employed and formulated with different carbohydrate excipients.

Results. Through the same atomization but the different drying process, spray drying (SD) produced small (∼3 μm), dense particles, but SFD resulted in large (∼8−10 μm), porous particles. The fine particle fraction (FPF) of the spray freeze-dried powder was significantly better than that of the spray-dried powder, attributed to better aerodynamic properties. Powders collected from different stages of the cascade impactor were characterized, which confirmed the concept of aerodynamic particle size. Protein formulation played a major role in affecting the powder's aerosol performance, especially for the carbohydrate excipient of a high crystallization tendency.

Conclusions. Spray freeze drying, as opposed to spray drying, produced protein particles with light and porous characteristics, which offered powders with superior aerosol performance due to favorable aerodynamic properties.

spray freeze dryingspray dryingdispersibilityfine particle fractionliquid impingementcascade impactionaerodynamic particle size

Copyright information

© Plenum Publishing Corporation 1999