Inhalable Submicronized Formulation of Budesonide by Antisolvent Nanoprecipitation: Process Optimization and in vitro Characterization

Author(s): Abdul Rauf*, Aseem Bhatnagar, S.S. Sisodia, Md. Akhlaquer Rahman, Roop K. Khar, Farhan J. Ahmad.

Journal Name: Micro and Nanosystems

Volume 9 , Issue 2 , 2017

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Abstract:

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.

Keywords: Inflammation, asthma, submicronized particles, nanoprecipitation, aerosolization, chronic obstructive pulmonary disease.

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Article Details

VOLUME: 9
ISSUE: 2
Year: 2017
Page: [102 - 110]
Pages: 9
DOI: 10.2174/1876402910666180115113509
Price: $58

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