Characterization of a cyclosporine solid dispersion for inhalation.
For lung transplant patients, a respirable, inulin-based solid dispersion containing cyclosporine A (CsA) has been developed. The solid dispersions were prepared by spray freeze-drying. The solid dispersion was characterized by water vapor uptake, specific surface area analysis, and particle size analysis. Furthermore, the mode of inclusion of CsA in the dispersion was investigated with Fourier transform infrared spectroscopy. Finally, the dissolution behavior was determined and the aerosol that was formed by the powder was characterized. The powder had large specific surface areas (~ 160 m(2)). The water vapor uptake was dependant linearly on the drug load. The type of solid dispersion was a combination of a solid solution and solid suspension. At a 10% drug load, 55% of the CsA in the powder was in the form of a solid solution and 45% as solid suspension. At 50% drug load, the powder contained 90% of CsA as solid suspension. The powder showed excellent dispersion characteristics as shown by the high emitted fraction (95%), respirable fraction (75%), and fine-particle fraction (50%). The solid dispersions consisted of relatively large (x(50) approximately 7 mum), but low-density particles (rho approximately 0.2 g/cm(3)). The solid dispersions dissolved faster than the physical mixture, and inulin dissolved faster than CsA. The spray freeze-drying with inulin increased the specific surface area and wettability of CsA. In conclusion, the developed powder seems suitable for inhalation in the local treatment of lung transplant patients.
Zijlstra
Gerrit S
GS
Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands. G.S.Zijlstra@rug.nl
Rijkeboer
Michiel
M
Jan van Drooge
Dirk
D
Sutter
Marc
M
Jiskoot
Wim
W
van de Weert
Marco
M
Hinrichs
Wouter L J
WL
Frijlink
Henderik W
HW
D000280:Administration, Inhalation; D000336:Aerosols; D016572:Cyclosporine / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding; D005612:Freeze Drying; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use; D007444:Inulin / Q000737:chemistry; D016040:Lung Transplantation; D010316:Particle Size; D011208:Powders; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D017155:Wettability
D000336:Aerosols; D004337:Drug Carriers; D007166:Immunosuppressive Agents; D011208:Powders; D016572:Cyclosporine; D007444:Inulin