Enhanced dissolution of inhalable cyclosporine nano-matrix particles with mannitol as matrix former

Keishi Yamasaki, Philip Chi Lip Kwok, Kaori Fukushige, Robert K. Prud'Homme, Hak Kim Chan

Research output: Contribution to journalArticlepeer-review

70 Scopus citations


This study aims to improve the dissolution of inhalable cyclosporine A nanoparticles by formulating the drug with mannitol as a hydrophilic nano-matrix former. The effect of mannitol content on the aerosol performance of the nano-matrix particles was also examined. Cyclosporine A nanosuspensions were produced by anti-solvent precipitation using a multi-inlet vortex mixer. Various amounts of mannitol were dissolved into the suspensions before spray drying to obtain micron-sized aggregates (nano-matrix powders). Dissolution properties of the powders in an aqueous medium, with the drug content, aggregate size distribution, surface roughness, physicochemical properties and aerosol performance were determined. The powders contained amorphous cyclosporine A and α-crystalline mannitol, with drug content being very close to the theoretical doses. Inclusion of mannitol enhanced the dissolution rate of the drug, without significantly affecting the aggregate size distribution, surface roughness and aerosol performance. This formulation approach may be applicable to improving the dissolution rate and bioavailability of hydrophobic drugs.

Original languageEnglish (US)
Pages (from-to)34-42
Number of pages9
JournalInternational Journal of Pharmaceutics
Issue number1
StatePublished - Nov 25 2011

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science


  • Cyclosporine A
  • Dissolution
  • Dry powder aerosol
  • Mannitol
  • Nanoparticles
  • Pulmonary drug delivery


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