1: J Pharm Sci. 2003 May;92(5):938-50.  

Systemic delivery of parathyroid hormone (1-34) using inhalation dry powders in
rats.

Codrons V, Vanderbist F, Verbeeck RK, Arras M, Lison D, Preat V, Vanbever R.

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

The aim of this work was to prepare and characterize inhalation dry powders of
human parathyroid hormone (PTH), as well as to assess their efficacy for
systemic delivery of the peptide and safety in rats. The powders were prepared
by spray-drying using PTH, sugars, dipalmitoylphosphatidylcholine, and/or
albumin. They presented an average primary particle diameter of 4.5 microm and
tap density of 0.06 g/cm(3), a mass median aerodynamic diameter between 3.9 and
5.9 microm, and reached up to 98% emitted dose and up to 61% fine particle
fraction in the multi-stage liquid impinger using a Spinhaler inhaler device.
Varying the airflow rate from 30 to 100 L/min had limited influence on the
aerodynamic behavior of the aerosols. The absolute PTH bioavailability was 21%
after intratracheal administration of the powder formed of
PTH/albumin/lactose/dipalmitoylphosphatidylcholine and 18% after subcutaneous
injection in rats. Equilibrium dialysis revealed a 78% binding of PTH to albumin
and the withdrawal of albumin from the powder increased absolute bioavailability
after inhalation from 21 to 34%. No acute inflammation appeared in the lung up
to 48 h after a single inhalation. The increased bioavailability of the
optimized powder aerosol of PTH makes it a promising alternative to subcutaneous
injection. Copyright 2003 Wiley-Liss, Inc. and the American Pharmaceutical
Association J Pharm Sci 92:938-950, 2003

PMID: 12712413 [PubMed - in process]