Pulmonary delivery of growth hormone using dry powders
and visualization of its local fate in rats
Cynthia Bosquillon, Ve´ronique Pre´at, Rita Vanbever*
Department of Pharmaceutical Technology, Universite´ catholique
de Louvain, School of Pharmacy, Avenue E. Mounier,
73 UCL 73.20, 1200 Brussels, Belgium
Received 3 September 2003; accepted 15 January 2004
Abstract
A dry powder aerosol formed of human growth hormone (hGH), lactose and
dipalmitoylphosphatidylcholine was assessed
for systemic delivery of the hormone in rats. The fate of the protein
locally in the deep lung was examined post-delivery. The
powder was prepared by spray-drying and presented a primary particle
diameter of 4.4 Am and a tap density of 0.069 g/cm3. The
mass median aerodynamic diameter was 4.4 Am in the multi-stage liquid
impinger at 60 l/min using a Spinhalerk device. The
emitted dose and fine particle fraction were 89% and 58%, respectively.
Varying the airflow rate from 30 to 90 l/min had limited
impact on aerosolization properties in vitro. No hGH dimers or
glycation adducts were produced during formulation of the
powder. hGH absorbed into the bloodstream with a time to peak of 23 and
52 min and with an absolute bioavailability of 23%
and 8% following intratracheal insufflation of the dry powder and
intratracheal spray-instillation of a solution of the hormone,
respectively. Confocal imaging of rat lung revealed an intense uptake
of fluorescein isothiocyanate (FITC)-hGH by alveolar
macrophages as early as 1 h post-delivery. A dry powder aerosol made of
selected GRAS excipients improved absorption of
hGH from the lung over a simple solution.
D 2004 Elsevier B.V. All rights reserved.
Keywords: Inhalation dry powders; Human growth hormone; Pulmonary
absorption; Dipalmitoylphosphatidylcholine; Alveolar macrophages