Generation of Gelatin Aerosol Particles from Nebulized Solutions as Model Drug Carrier Systems

Abstract

Purpose. Aerodynamically stable, nebulized aerosols are desirable to achieve optimum asthma therapy. Stabilizing droplet size using gel-forming polymers may assist in achieving this goal. Semisolid particles may be generated through aerosolization of a polymer solution. Gelatin was employed as a model polymer in a process optimization study using the marker, disodium fluorescein, and the drug, budesonide delivered from two commercially available air-jet nebulizers.

Methods. The aerosol delivery system consisted of either of the air-jet nebulizers attached to a 30 cm drying column. The nebulizers employed were the Aerotech II and Salter SL8900. Two gelatin solutions (0.1 and 0.7%w/v) were evaluated following initial density and viscosity measurements. Particle characterization was conducted by scanning electron microscopy, eight-stage cascade impaction (CI), and phase-Doppler analysis. Disodium fluorescein (NaF, 5 and 7%w/v) and budesonide (B, 0.05%w/v) were added to the gelatin solutions in a 2⁴-factorial design study and the follow-up drug formulation study, respectively. The factorial design experiment evaluated the influence of device, operating pressure, marker, and gelatin concentrations on mass median aerodynamic diameter (MMAD) and fine particle fraction (FPF). Spectrophotometry of the CI samples was performed at wavelengths of 486 (NaF) and 254 (B) nm.

Results. The factorial design experiment utilizing NaF showed that MMADs were not influenced significantly by the device, operating pressure, marker, or gelatin concentrations (p>0.05). However, FPFs were significantly influenced by marker concentration and device (p<0.05). In the presence of budesonide, the MMADs and FPFs for Aerotech and Salter, respectively, were: MMAD=1.39±0.30 μm and 1.75±0.63 μm, FPF=93.5±4% and 68.5±5%, (n=3). These values were consistent with those predicted in the designed experiment.

Conclusions. A range of semisolid particle sizes were produced (1.3<MMAD<1.8 μm) for the 0.7%w/v gelatin formulation using different nebulizers. The budesonide formulation produced FPFs of 69–93%.

Keywords:

• Aerosol
• Budesonide
• Experimental designs
• Gelatin
• Nebulizers
• Particles