Objective: The aim of the current study was to develop stable submicronized formulation of
budesonide (BUD) for pulmonary delivery to treat chronic inflammation associated with asthma.
Method: Submicronized formulation was prepared by antisolvent nanoprecipitation method and freeze
dried using mixture of cryoprotectants. The optimized DPI formulation contains 200 μg labelled dose of
budesonide, 0.5% w/v of leutro F68 as a stabilizer, mannitol (2% w/v) in combination with sorbitol
(0.5% w/v) and lactose (1.5% w/v) as cryoprotectant. Z-average diameter (433.93 ± 8.32 nm) and polydispersity
index (0.204) of submicron particles suggested narrow size distribution and particle size uniformity.
The solid state characterization revealed loss of crystallinity of BUD in the submicronized formulation.
The submicronized particles exhibited a burst effect over the first few minutes followed by
72-90% release in 2-3 hrs, significantly higher (p < 0.01) compared to conventional micronized formulation
and pure budesonide. The device removal efficiency and aerosolization efficiency of BUD were
estimated for 10 mg samples (~200 μg BUD) of the submicronized DPI formulation, conventional micronized
formulation and stock drug using the Twin-stage impinger (TSI). Total emitted dose (84.5%)
for submicronized DPI formulation showed fairly good device BUD removal and aerosolization efficiency,
regardless of the loaded BUD dose in the lactose blends. The physical stability study was performed
at 25°C/60% RH (controlled) for 12 month and at 40°C/75% RH (accelerated) for 6 month.
Result: At controlled condition, the formulation was found stable and no any significant change was observed
in drug content, particle size, Fine Particle Dose (FPD) and emitted dose.
Conclusion: The results suggest that developed submicronized formulation of BUD can be used for
pulmonary drug delivery with successful landing of drug from mouth to lungs.