Budesonide dry powder for inhalation: effects of leucine and mannitol on the efficiency of delivery

Abstract

Objective: The aim of this study was to develop a budesonide dry powder for inhalation using l-leucine and l-leucine - sieved mannitol as a carrier.

Materials and methods: Budesonide and l-leucine were co-spray dried at a mass ratio of 1:50 then blended with various mass ratios of sieved mannitol in the range of 20-80. A 2(3) factorial study was applied to investigate the effects of the spray drying variables; feed rate, aspirator setting and airflow rate on the powder characteristics. The prepared dry powders were characterized using fourier transform-infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and ultracentrifugation. Drug contents and aerosolization properties were evaluated using high performance liquid chromatography (HPLC) and the Andersen cascade impactor (ACI), respectively.

Results and discussion: There was no interaction between budesonide and l-leucine after co-spraying. The budesonide dry powders had a mass median aerodynamic diameter (MMAD) in the range of 1.9-2.2 µm at a flow rate of 60 L/min that was suitable for pulmonary delivery. Sieved mannitol as a coarse carrier decreased the interparticulate forces between fine particles of the co-spray dried budesonide-l-leucine and resulted in a high fine particle fraction (FPF) in the range of 64-68% while the co-spray dried powder of budesonide-l-leucine had an FPF of ∼49%.

Conclusions: Blending of the co-spray dried powder with sieved mannitol significantly improved the delivery efficiency of the micronized budesonide better than the co-spray dried with l-leucine alone.

Keywords: Adhesion force; aerosolization; anti-inflammatory; carrier; spray dried powder.