Effect of spray drying and subsequent processing conditions on residual moisture content and physical/biochemical stability of protein inhalation powders.
OBJECTIVE
To understand the effect of spray drying and powder processing environments on the residual moisture content and aerosol performance of inhalation protein powders. Also, the long-term effect of storage conditions on the powder's physical and biochemical stability was presented.


METHODS
Excipient-free as well as mannitol-formulated powders of a humanized monoclonal antibody (anti-IgE) and recombinant human deoxyribonuclease (rhDNase) were prepared using a Buchi 190 model spray dryer. Residual moisture content and moisture uptake behavior of the powder were measured using thermal gravimetric analysis and gravimetric moisture sorption isotherm, respectively. Protein aggregation, the primary degradation product observed upon storage, was determined by size-exclusion HPLC. Aerosol performance of the dry powders was evaluated after blending with lactose carriers using a multi-stage liquid impinger (MSLI).


RESULTS
Spray-dried powders with a moisture level (approximately 3%) equivalent to the freeze-dried materials could only be achieved using high-temperature spray-drying conditions, which were not favorable to large-male manufacturing, or subsequent vacuum drying. These dry powders would equilibrate with the subsequent processing and storage environments regardless of the manufacturing condition. As long as the relative humidity of air during processing and storage was lower than 50%, powders maintained their aerosol performance (fine particle fraction). However, powders stored under drier conditions exhibited better long-term protein biochemical stability.


CONCLUSIONS
Manufacturing, powder processing, and storage environments affected powder's residual moisture level in a reversible fashion. Therefore, the storage condition determined powder's overall stability, but residual moisture had a greater impact on protein chemical stability than on powder physical stability.
Maa
Y F
YF
Pharmaceutical Research and Development, Genentech, Inc., South San Francisco, California 94080, USA. maa.yuh-fun@gene.com
Nguyen
P A
PA
Andya
J D
JD
Dasovich
N
N
Sweeney
T D
TD
Shire
S J
SJ
Hsu
C C
CC
D000280:Administration, Inhalation; D000336:Aerosols / Q000737:chemistry*; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003851:Deoxyribonucleases / Q000737:chemistry*; D004355:Drug Stability; D006813:Humidity; D010316:Particle Size; D011208:Powders / Q000737:chemistry*; D014618:Vacuum
D000336:Aerosols; D000911:Antibodies, Monoclonal; D011208:Powders; D003851:Deoxyribonucleases