TI: Influence of formulation excipients and physical
characteristics of inhalation dry powders on their aerosolization performance.
AU: Bosquillon,-C; Lombry,-C; Preat,-V; Vanbever,-R
AD: Universite catholique de Louvain, School of Pharmacy, Department
of Pharmaceutical Technology, UCL 73.20 avenue, E. Mounier 73, 1200 Brussels,
Belgium.
SO: J-Control-Release. 2001 Feb 23; 70(3): 329-39
JN: Journal-of-controlled-release
PY: 2001
AB: The objective of this study was to determine the effects
of formulation excipients and physical characteristics of inhalation particles
on their in vitro aerosolization performance, and thereby to maximize their
respirable fraction. Dry powders were produced by spray-drying using excipients
that are FDA-approved for inhalation as lactose, materials that are endogenous
to the lungs as albumin and dipalmitoylphosphatidylcholine (DPPC); and/or
protein stabilizers as trehalose or mannitol. Dry powders suitable for
deep lung deposition, i.e. with an aerodynamic diameter of individual particles
<3 microm, were prepared. They presented 0.04--0.25 g/cm(3) bulk tap
densities, 3--5 microm geometric particle sizes, up to 90% emitted doses
and 50% respirable fractions in the Andersen cascade impactor using a Spinhaler
inhaler device. The incorporation of lactose, albumin and DPPC in the formulation
all improved the aerosolization properties, in contrast to trehalose and
the mannitol which decreased powder flowability. The relative proportion
of the excipients affected aerosol performance as well. The lower the bulk
powder tap density, the higher the respirable fraction. Optimization of
in vitro aerosolization properties of inhalation dry powders can be achieved
by appropriately selecting composition and physical characteristics of
the particles.