Systemic Delivery of Parathyroid Hormone (1–34) Using Spray Freeze-Dried Inhalable Particles Publisher Pubmed



Poursina N¹ ; Vatanara A¹ ; Rouini MR¹ ; Gilani K¹ ; Rouholamini Najafabadi A¹ Show Affiliations
Source: Pharmaceutical Development and Technology Published:2017

Abstract

Pulmonary delivery of peptides remains an important, noninvasive route of administration that is attractive because it offers high bioavailability and patient compliance. Optimization of particle characteristics for deposition in the deep regions of the lung after inhalation and retention of peptide stability are key challenges to their delivery to the lungs. The present study investigated the use of spray freeze-drying to produce porous inhalable parathyroid hormone (1–34)-loaded microparticles suitable for pulmonary delivery. The influence of different excipients in the medium of water or citrate buffer on microparticles characteristics, peptide stability and its systemic delivery in rats were evaluated. Using leucine at 10% (w/w) and hydroxy propyl-β-cyclodextrin (HPβCD) at 0.04% (w/w) in water or citrate medium preserved parathyroid hormone (1–34) stability by spray freeze-drying. Aerosol performance showed that leucine was more effective than HPβCD in producing inhalable microparticles. Nevertheless, there was no statistical difference between bioavailabilities of HPβCD containing formulations and leucine-containing formulations in the presence of citrate buffer; and even in the presence of water, HPβCD resulted in higher bioavailability compared to leucine. The high absolute bioavailability (up to 47.25%) of formulations could facilitate replacement of injected form of parathyroid hormone (1–34) by dry powder inhaler form. © 2015 Informa UK Limited, trading as Taylor & Francis Group.