Surface Composition and Aerosolization Stability of an Inhalable Combinational Powder Formulation Spray Dried Using a Three-Fluid Nozzle



This study aims to understand the impact of spray drying nozzles on particle surface composition and aerosol stability.


The combination formulations of colistin and azithromycin were formulated by 2-fluid nozzle (2 N) or 3-fluid (3 N) spray drying in a molar ratio of 1:1. A 3-factor, 2-level (23) factorial design was selected to investigate effects of flow rate, inlet temperature and feed concentration on yield of spray drying and the performance of the spray dried formulations for the 3 N.


FPF values for the 2 N formulation (72.9 ± 1.9% for azithromycin & 73.4 ± 0.8% for colistin) were higher than those for the 3 N formulation (56.5 ± 3.8% for azithromycin & 55.1 ± 1.6% for colistin) when stored at 20% RH for 1 day, which could be attributed to smaller physical size for the 2 N. There was no change in FPF for both drugs in the 2 N formulation after storage at 75% RH for 90 days; however, there was a slight increase in FPF for colistin in the 3 N formulation at the same storage conditions. Surface enrichment of hydrophobic azithromycin was measured by X-ray photoelectron spectroscopy for both 2 N and 3 N formulations and interactions were studied using FTIR.


The 3-fluid nozzle provides flexibility in choosing different solvents and has the capability to spray dry at higher feed solid concentrations. This study highlights the impact of hydrophobic azithromycin enrichment on particle surface irrespective of the nozzle type, on the prevention of moisture-induced deterioration of FPF for hygroscopic colistin.

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Fig. 1
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Fig. 6


2 N:

Two-fluid nozzle

3 N:

Three-fluid nozzle

ColAz (1-1):

Co-spray dried colistin and azithromycin at a molar ratio of 1:1


Design of experiments


Dry powder inhaler


Dynamic vapor sorption


Emitted dose


Fine particle fraction


Fourier-transform infrared spectroscopy


Geometric standard deviation


Median mass aerodynamic diameter


Next generation Impactor


Powder X-ray diffractometer


Relative humidity


Spray drying


Scanning electron microscopy


X-ray photoelectron spectroscopy


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Correspondence to Qi (Tony) Zhou.

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Shetty, N., Zhang, Y., Park, H. et al. Surface Composition and Aerosolization Stability of an Inhalable Combinational Powder Formulation Spray Dried Using a Three-Fluid Nozzle. Pharm Res 37, 219 (2020).

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Key words

  • aerosol performance
  • dry powder inhaler
  • spray drying
  • surface composition
  • three-fluid nozzle