Large porous estradiol particles were formulated by spray drying estradiol
in combination with various U.S. Food and Drug Administration (FDA)-approve
d or endogenous excipients. The powders were characterized in terms of thei
r geometrical size, mass density, and aerosolization properties. Small nonp
orous particles were also prepared using the same excipients and were physi
cally characterized to insure that they possessed a similar mean aerodynami
c size as the large porous particles. The two powders were aerosolized into
the lungs of rats via an endotracheal tube or subcutaneously injected as a
control to assess relative bioavailability. Two different large porous par
ticle formulations were found to produce elevated systemic estradiol concen
trations upon inhalation for approximately 5 days, with relative bioavailab
ilities of 59.7% and 86.0%. Systemic estradiol concentrations following inh
alation of two different small nonporous particle powders remained elevated
for only approximately 1 day, with relative bioavailabilities of 18.3% and
38.7%. Bronchoalveolar lavage was performed up to 96 hours after inhalatio
n of porous and nonporous estradiol powders. Small changes in neutrophil an
d macrophage populations were observed following inhalation of both the por
ous and nonporous powders.