1: J Pharm Sci.  2004 May;93(5):1241-52.  

Impact of formulation and methods of pulmonary delivery on absorption of
parathyroid hormone (1-34) from rat lungs.

Codrons V, Vanderbist F, Ucakar B, 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 optimize the absorption of parathyroid hormone 1-34
(PTH) from the lungs by determining factors favoring its transport from the air
spaces into the bloodstream. We simultaneously conducted pharmacokinetic and
regional lung deposition studies in vivo in the rat following intratracheal
administration of PTH in solution or dry powder form. Dry powders of PTH or
albumin were prepared by spray-drying using lactose and
dipalmitoylphosphatidylcholine (DPPC). Deposition in the trachea, peripheral,
and central lobe sections was assessed after tissue grinding using albumin as a
marker. The method of intratracheal instillation had a significant impact on PTH
absorption from the lungs, and the deeper the deposition within the respiratory
tract, the higher the absorption. Inhalation of the PTH powder resulted in high
systemic bioavailability despite deposition of the formulation principally in
upper airways. We demonstrated that the increased absorption resulted from DPPC
that had permeation enhancer properties even though it was abundantly present
locally in pulmonary surfactant. Optimization of PTH absorption from the lungs
could be attained by targeting the peripheral lungs as well as codelivering
DPPC. Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association J
Pharm Sci 93:1241-1252, 2004

PMID: 15067700 [PubMed - in process]