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. 2007 Jun 15;9(2):E190–E199. doi: 10.1208/aapsj0902021

Characterization of a cyclosporine solid dispersion for inhalation

Gerrit S Zijlstra 1,✉, Michiel Rijkeboer 1, Dirk Jan van Drooge 1, Marc Sutter 3, Wim Jiskoot 2,3, Marco van de Weert 4, Wouter L J Hinrichs 1, Henderik W Frijlink 1
PMCID: PMC2751408  PMID: 17614361

Abstract

For lung transplant patients, a respirable, inulin-based solid dispersion containing cyclosporine A (CsA) has been developed. The solid dispersions were prepared by spray freezedrying. 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 m2). The water vapor uptake was dependent 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 (x50≈7 μm), but low-density particles (ρ≈0.2 g/cm3). 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.

Keywords: DPI, Cyclosporine A, solid dispersion, FTIR, aerosol, large porous particles

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