Dual functional pullulan-based spray-dried microparticles for controlled pulmonary drug delivery

Two main challenges are associated with current spray-dried microparticles for inhalation, including the enhancement of aerosolization performance of microparticles and the creation of sustained drug release for continuous treatment on-site. For achieving these purposes, pullulan was explored as a novel excipient to prepare spray-dried inhalable microparticles (with salbutamol sulphate, SS, as a model drug), which were further modified by additives of leucine (Leu), ammonium bicarbonate (AB), ethanol and acetone. It was demonstrated that all pullulan-based spray-dried microparticles had improved flowability and enhanced aerosolization behavior, with the fine particle (<4.46 mu m) fraction of 42.0-68.7% w/w, much higher than 11.4% w/w of lactose-SS. Moreover, all modified microparticles showed augmented emitted fractions of 88.0-96.9% w/w, over 86.5% w/w of pullulan-SS. The pullulan-Leu-SS and pullulan-(AB)-SS microparticles demonstrated further increased fine particle (<1.66 mu m) doses of 54.7 mu g and 53.3 mu g respectively, surpassing that (49.6 mu g) of pullulan-SS, suggesting an additionally increased drug deposition in the deep lungs. Furthermore, pullulan-based microparticles revealed sustained drug release profiles with elongated time (60mins) over the control (2mins). Clearly, pullulan has a great potential to construct dual functional microparticles for inhalation with improved pulmonary delivery efficiency and sustained drug release on-site.

Automated summary

The challenges of current spray-dried microparticles for inhalation are improving aerosolization performance and creating sustained drug release. In this study, pullulan was used as an excipient to prepare inhalable microparticles, and different additives were used for modification. The pullulan-based microparticles showed improved flowability, enhanced aerosolization behavior, and a higher fine particle fraction compared to lactose-based microparticles. The modified microparticles also exhibited increased emitted fractions and fine particle doses, suggesting improved deep lung drug deposition. Additionally, pullulan-based microparticles demonstrated sustained drug release profiles with longer release time.