Abstract
Clinically available pressurized metered-dose inhalers (pMDIs) mainly directly use
micronized drugs as inhalable microparticles. Although technology for preparing pMDIs
has proven to obtain clinically appropriate aerosol performance, the fine particle
fraction and delivered dose content uniformity (DDCU) of pMDIs still need to be improved.
DDCU problem is usually exacerbated by patients' handling errors prior to taking a
dose. In this study, novel phospholipid microparticle inhalation pMDIs were prepared
by a spray-freeze-drying process using mometasone furoate and formoterol fumarate
dihydrate as model drugs and distearoylphosphatidylcholine as an excipient. Combined
with the material composition, the atomization and freeze-drying processes were also
studied. Our data showed that both atomization parameters of gas–liquid ratio and
freeze-drying curve settings met the requirements of drug design. According to aerodynamic
performance in vitro and DDCU evaluation, the performance of the phospholipid microparticle inhalation
pMDI was better than that of the micronized drug microparticle pMDI. In conclusion,
preparing pMDIs with particle engineering has the potential to ensure accuracy of
quantification and to improve the efficiency of drug deposition in lungs in clinical
practice.
Keywords
spray-freeze-drying - inhalable microparticles - pMDIs - phospholipids
