Inhalation powder development without carrier: How to engineer ultra-flying microparticles?
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 behaviour.
Hydroxypropyl-β-cyclodextrin (Kleptose HPB—molar substitution = 0.63), Pea Maltodextrin helicoïdal DE17 (Kleptose linecaps 17), Maltodextrin 19 (Glucidex 19) were kindly provided by Roquette (Lestrem, France). Raffinose pentahydrate was obtained from Acros organics (Thermo Fisher Scientific, Geel, Belgium). L-leucine was obtained from Sigma-Aldrich (Merck), Darmstadt, Germany.
Budesonide Ph. Eur. 8.3 micronized (BUD) was obtained from Crystal Pharma (Valladolid, Spain) and Formoterol Fumarate
Anna Lechanteur, Eva Gresse, Luisa Orozco, Erwan Plougonven, Angélique Léonard, Nicolas Vandewalle, Geoffroy Lumay, Brigitte Evrard, Inhalation powder development without carrier: How to engineer ultra-flying microparticles?, European Journal of Pharmaceutics and Biopharmaceutics, Volume 191, 2023, Pages 26-35, ISSN 0939-6411,