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

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.