Protein inhalation powders: spray drying vs spray freeze drying.
OBJECTIVE
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 (approximately 3 microns), dense particles, but SFD resulted in large (approximately 8-10 microns), 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.
Maa
Y F
YF
Genentech, Inc., South San Francisco, California 94080, USA. yuh-fun_maa@powderject.com
Nguyen
P A
PA
Sweeney
T
T
Shire
S J
SJ
Hsu
C C
CC
D000280:Administration, Inhalation; D000336:Aerosols / Q000737:chemistry; D000888:Antibodies, Anti-Idiotypic / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003851:Deoxyribonucleases / Q000737:chemistry*; D005612:Freeze Drying / Q000379:methods*; D010316:Particle Size; D011208:Powders / Q000737:chemistry
D000336:Aerosols; D000888:Antibodies, Anti-Idiotypic; D011208:Powders; C026408:anti-IgE antibodies; D003851:Deoxyribonucleases