Porous mannitol carrier for pulmonary delivery of cyclosporine A nanoparticles

Sharon Shui Yee Leung, Jennifer Wong, Heloisa Victorino Guerra, Kevin Samnick, Robert K. Prud’homme, Hak Kim Chan

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


This study employed the ultrasonic spray-freeze-drying technique to prepare porous mannitol carriers that incorporated hydrophobic cyclosporine A (CsA) nanoparticles (NPs) for pulmonary delivery. Two nanosuspension stabilization systems, (1) a combination of lecithin and lactose system and (2) a d-α-tocopheryl polyethylene glycol succinate (TPGS) system, were investigated. The ability of the lecithin and TPGS in anchoring the hydrophobic CsA NPs to the porous hydrophilic mannitol structure was first reported. Formulations stabilized by TPGS provided a much better dose uniformity, suggesting that TPGS is a better anchoring agent compared with lecithin. The effects of mannitol carrier density and CsA loading (4.9–27%) on aerosol performance and dissolution profiles were assessed. The fine particle fraction (FPF) increased from 44 to 63% as the mannitol concentration decreased from 1 to 5%. All formulations achieved full dissolution within an hour without significant influence from the mannitol content and CsA loading. The initial dissolution rates of the present formulations were almost double than that of the spray-dried counterpart, with 90% of the drug dissolved in 10 min. Overall, the CsA NPs were successfully incorporated into the porous mannitol which demonstrated good aerosol performance and enhanced dissolution profiles. These spray-freeze-drying (SFD) powders were stable after 2-year storage under desiccation at 20 ± 3°C.

Original languageEnglish (US)
Pages (from-to)578-586
Number of pages9
JournalAAPS Journal
Issue number2
StatePublished - Mar 1 2017

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science


  • aerosol
  • cyclosporin
  • inhalation
  • nanosuspension
  • spray freeze drying


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