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, specifi c 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 specifi c 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 fi ne-particle fraction (50%). The solid dispersions consisted of relatively large (x 50 ≈ 7 m m), but low-density particles ( r ≈ 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 specifi c surface area and wettability of CsA. In conclusion, the developed powder seems suitable for inhalation in the local treatment of lung transplant patients.
A formulation and process development study was performed to formulate recombinant human deoxyribonuclease I as a powder for inhalation. First, excipient compatibility (with bovine DNase as a model substance) was examined with a stability study at stressed conditions (60 and 85 degrees C) while monitoring for occurrence of the Maillard reaction. Next, powders for inhalation were prepared by spray drying and spray freeze drying. We found that spray drying with inulin as stabilizer resulted in the best powder for inhalation. Finally, an ex-vivo test with the spray dried rhDNase I/inulin powder significantly decreased elastic and viscous moduli of sputum from five cystic fibrosis patients.
A new analysis of moving interfaces between ferrite and austenite at high temperatures using in-situ EBSD.• In contrast to the well-known classical Johnson-Mehl-Avrami-Kolmogorov (JMAK) equation it has been demonstrated that the interphase boundaries move in a jerky-type fashion. • A linear dependence between the average velocity and the driving force turns out to be a far too simple and a nonlinear description is offered. • The mean interphase boundary velocity did not critically depend on the crystal (mis)orientations.
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