Characterization of a cyclosporine solid dispersion for inhalation

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, 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.

Development of Budesonide Microparticles Using Spray-Drying Technology for Pulmonary Administration: Design, Characterization, In Vitro Evaluation, and In Vivo Efficacy Study

“…Spray drying is a one-step process that converts liquid feed (solution, coarse suspension, colloidal dispersion) to a dried particulate form. Principal advantages of spray drying with respect to pulmonary drug delivery are ability to manipulate and control particle size and size distribution, particle shape, and density in addition to macroscopic powder properties such as bulk density, flowability, and dispersibility (44). Various process parameters were optimized by 3 2 factorial design.…”

Physicochemical characterization and aerosol dispersion performance of organic solution advanced spray-dried cyclosporine A multifunctional particles for dry powder inhalation aerosol delivery

“…12 A metered-dose inhaler of CsA has been aerosolized in asthmatic patients. 8 A nebulized liquid aerosol of CsA encapsulated in liposomes composed of nonionic surfactants and phospholipids, 13 inhaled CsA dry powders produced by wet-milling, 14 and inhaled CsA inulin-based dry powders produced by spray freeze drying from a tert-butyl alcohol/water cosolvent system 15 have been reported. Recently, CsA nanosuspensions containing mannitol (ie, a water-soluble sugar) produced by antisolvent precipitation followed by aqueous solution spray drying (SD) generated inhalable CsA mannitol powders.…”

Preparation and In Vitro Evaluation of Budesonide Spray Dried Microparticles for Pulmonary Delivery

“…Spray-drying is a one-step process that converts liquid feed (solution, coarse suspension, colloidal dispersion) to a dried particulate form. Principle advantages of spray drying with respect to pulmonary drug delivery are ability to manipulate and control particle size and size distribution, particle shape and density in addition to macroscopic powder properties such as bulk density, flowability and dispersibility [47]. Various process parameters were optimized by 2 2 factorial design.…”