Particle engineering using sonocrystallization: salbutamol sulphate for pulmonary delivery

Area of Science:

• Pharmaceutical Technology
• Materials Science
• Chemical Engineering

Background:

• Pulmonary drug delivery requires precise control over particle characteristics.
• Traditional methods for preparing salbutamol sulphate (SS) crystals can result in suboptimal aerodynamic properties.
• Improving the fine particle fraction (FPF) is crucial for efficient lung deposition.

Purpose of the Study:

• To produce fine, elongated salbutamol sulphate (SS) crystals using sonocrystallization.
• To evaluate the in vitro aerosolization behavior of sonocrystallized SS (SCSS) compared to micronized and spray-dried SS (SDSS).
• To assess the stability and aerodynamic performance of the prepared SS formulations.

Main Methods:

• Sonocrystallization was employed during anti-solvent crystallization of SS, optimizing parameters like sonication amplitude, time, concentration, and temperature.
• Sonocrystallized SS (SCSS) was spray-dried to obtain loose aggregates (SD-SCSS).
• In vitro aerosolization performance was assessed using a cascade impactor with a coarse lactose carrier.

Main Results:

• Sonocrystallization yielded fine, elongated SS crystals (SCSS), contrasting with irregular aggregates from conventional methods.
• The fine particle fraction (FPF) significantly increased from 16.66% (micronized SS) to 31.12% (SDSS) and 44.21% (SD-SCSS).
• SD-SCSS demonstrated excellent stability over 3 months, maintaining crystallinity and aerodynamic behavior, unlike amorphous SDSS which recrystallized.

Conclusions:

• Sonocrystallization is a rapid and effective technique for producing elongated SS crystals suitable for inhalation.
• The elongated crystal habit of SD-SCSS reduces cohesive/adhesive forces, enhancing aerodynamic performance and FPF.
• Sonocrystallization offers a promising approach for developing stable and efficient pulmonary drug delivery systems.