DOE; DPI; inhalation; particle engineering; spray drying; Biotechnology; Pharmaceutical Science; General Medicine
Abstract :
[en] Particle engineering technologies have led to the commercialization of new inhaled powders like PulmoSolTM or PulmoSphereTM. Such platforms are produced by spray drying, a well-known process popular for its versatility, thanks to wide-ranging working parameters. Whereas these powders contain a high drug-loading, we have studied a low-dose case, in optimizing the production of powders with two anti-asthmatic drugs, budesonide and formoterol. Using a Design of Experiments approach, 27 powders were produced, with varying excipient mixes (cyclodextrins, raffinose and maltodextrins), solution concentrations, and spray drying parameters in order to maximize deep lung deposition, measured through fine particle fraction (next generation impactor). Based on statistical analysis, two powders made of hydropropyl-β-cyclodextrin alone or mixed with raffinose and L-leucine were selected. Indeed, the two powders demonstrated very high fine particle fraction (>55%), considerably better than commercially available products. Deep lung deposition has been correlated to very fine particle size and lower microparticles interactions shown by laser diffraction assays at different working pressures, and particle morphometry. Moreover, the two drugs would be predicted to deposit homogeneously into the lung according to impaction studies. Uniform delivery is fundamental to control symptoms of asthma. In this study, we develop carrier-free inhalation powders promoting very efficient lung deposition and demonstrate the high impact of inter-particular interactions intensity on their aerosolization behavior.
Disciplines :
Pharmacy, pharmacology & toxicology Chemical engineering
Author, co-author :
Lechanteur, Anna ; Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique
Gresse, Eva ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)
Orozco, Luisa ; GRASP, CESAM Research Unit Institute of Physics B5a, University of Liège, Liège (4000), Belgium
Plougonven, Erwan ; Université de Liège - ULiège > Department of Chemical Engineering > PEPs - Products, Environment, and Processes
Léonard, Angélique ; Université de Liège - ULiège > Department of Chemical Engineering > PEPs - Products, Environment, and Processes
Vandewalle, Nicolas ; Université de Liège - ULiège > Département de physique > Physique statistique
Lumay, Geoffroy ; Université de Liège - ULiège > Département de physique > Physique expérimentale de la matière molle et des systèmes complexes
Evrard, Brigitte ; Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique
Language :
English
Title :
Inhalation powder development without carrier: how to engineer ultra-flying microparticles?
Publication date :
16 August 2023
Journal title :
European Journal of Pharmaceutics and Biopharmaceutics
The authors thank the Walloon Region, SPW-EER, ProgramWin2Wal 2018/1 Convention n◦1810103 for funding. Authors want to also thank Pharmalex for statistical support and in particular Pierre Lebrun and Lan Tran. The authors thank Aquilon Pharma for their industrial support.
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