Purpose
A novel concept is presented for the formation of stable suspensions composed of low density flocs of high aspect ratio drug
particles in hydrofluoroalkane (HFA) propellants, and for subdividing (templating) the flocs with aerosolized HFA droplets
to achieve high fine particle fractions with a pressurized metered dose inhaler.
Methods
Bovine serum albumin (BSA) nanorods, produced by thin film freezing (TFF), were added to HFA to form a suspension. Particle
properties were analyzed with an Anderson cascade impactor (ACI), static and dynamic light scattering and optical microscopy.
Results
The space filling flocs in HFA were stable against settling for one year. The pMDI produced high fine particle fractions (38–47%)
with an emitted dose of 0.7 mg/actuation. The atomized HFA droplets break apart, that is template, the highly open flocs.
Upon evaporation of HFA, capillary forces shrink the templated flocs to produce porous particles with optimal aerodynamic
diameters for deep lung delivery.
Conclusions
Open flocs composed of nanorods, stable against settling, may be templated during actuation with a pMDI to produce optimal
aerodynamic diameters and high fine particle fractions. This concept is applicable to a wide variety of drugs without the
need for surfactants or cosolvents to stabilize the primary particles.
KEY WORDS bovine serum albumin - floc - nanorod - pressurized metered dose inhaler - suspension stability