Engineered spray-dried nanosuspension of budesonide with enhanced fine particle fraction and dissolution rate

Authors: , ,

Background. The interest in nanoparticles for pharmaceutical purposes as well as their importance in pulmonary drug delivery is rising. By producing drug nanoparticles, for instance by wet media milling, the dissolution rate can be enhanced, which is especially valuable for poorly water-soluble drugs. Spray drying enables embedding of nanoparticles into microparticles, which improves the nanoparticles’ stability and application. A particle engineering approach to the spray drying process allows the production of particles with superior properties by better understanding of the particle formation mechanism.

Methods. A stabilised nanosuspension of budesonide was produced by wet media milling. Subsequently, the nanosuspension was spray‑dried using the particle engineering approach to tune the particles’ aerodynamic properties and to increase the nanosuspension’s stability. The particles were co-sprayed using additives such as mannitol, leucine, and glycine. The resulting powders were characterised in terms of geometric and aerodynamic particle size, morphology, and shape. Furthermore, the dissolution rate of aerodynamically classified particles was measured.

Results. The samples containing leucine showed the most favourable aerodynamic and dissolution behaviour. With leucine we achieved the highest fine particle fraction (70.2%), which was ~ 40 % more compared to raw budesonide. Such formulation dissolved approximately two times faster than pure budesonide.

Conclusions. In this work, we present powders with enhanced aerodynamic properties and dissolution rate, and high fine particle fraction compared to raw budesonide. The particle engineering proved as a valuable tool for production of nanoparticle-containing microparticles with improved properties relevant for pulmonary drug delivery.