1: J Control Release. 2004 Oct 19;99(3):357-67. 

Aerosolization properties, surface composition and physical state of spray-dried
protein powders.

Bosquillon C, Rouxhet PG, Ahimou F, Simon D, Culot C, Preat V, Vanbever R.

Department of Pharmaceutical Technology, School of Pharmacy, Universite
catholique de Louvain, UCL 73.20 avenue E. Mounier, 73, 1200 Brussels, Belgium.

Powder aerosols made of albumin, dipalmitoylphosphatidylcholine (DPPC) and a
protein stabilizer (lactose, trehalose or mannitol) were prepared by
spray-drying and analyzed for aerodynamic behavior, surface composition and
physical state. The powders exited a Spinhaler trade mark inhaler as particle
aggregates, the size of which depending on composition, spray-drying parameters
and airflow rate. However, due to low bulk powder tap density (<0.15 g/cm(3)),
the aerodynamic size of a large fraction of aggregates remained respirable (<5
microm). Fine particle fractions ranged between 21% and 41% in an Andersen
cascade impactor operated at 28.3 l/min, with mannitol and lactose providing the
most cohesive and free-flowing powders, respectively. Particle surface analysis
by X-ray photoelectron spectroscopy (XPS) revealed a surface enrichment with
DPPC relative to albumin for powders prepared under certain spray-drying
conditions. DPPC self-organized in a gel phase in the particle and no sugar or
mannitol crystals were detected by X-ray diffraction. Water sorption isotherms
showed that albumin protected lactose from moisture-induced crystallization. In
conclusion, a proper combination of composition and spray-drying parameters
allowed to obtain dry powders with elevated fine particle fractions (FPFs) and a
physical environment favorable to protein stability.

PMID: 15451594 [PubMed - in process]