title: Physicochemical characterization and aerosol dispersion performance of organic solution advanced spray-dried cyclosporine A multifunctional particles for dry powder inhalation aerosol delivery.
abstract: In this systematic and comprehensive study, inhalation powders of the polypeptide immunosuppressant drug - cyclosporine A - for lung delivery as dry powder inhalers (DPIs) were successfully designed, developed, and optimized. Several spray drying pump rates were rationally chosen. Comprehensive physicochemical characterization and imaging was carried out using scanning electron microscopy, hot-stage microscopy, differential scanning calorimetry, powder X-ray diffraction, Karl Fischer titration, laser size diffraction, and gravimetric vapor sorption. Aerosol dispersion performance was conducted using a next generation impactor with a Food and Drug Administration-approved DPI device. These DPIs displayed excellent aerosol dispersion performance with high values in emitted dose, respirable fraction, and fine particle fraction. In addition, novel multifunctional inhalation aerosol powder formulations of cyclosporine A with lung surfactant-mimic phospholipids were also successfully designed and developed by advanced organic solution cospray drying in closed mode. The lung surfactantmimic phospholipids were 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-snglycero- 3-(phosphor-rac-1-glycerol). These cyclosporine A lung surfactant-mimic aerosol powder formulations were comprehensively characterized. Powder X-ray diffraction and differential scanning calorimetry confirmed that the phospholipid bilayer structure in the solid state was preserved following advanced organic solution spray drying in closed mode. These novel multifunctional inhalation powders were optimized for DPI delivery with excellent aerosol dispersion performance and high aerosol performance parameters.
authors.affiliation: Department of Pharmaceutical Sciences - Drug Development Division, University of Kentucky, Lexington, KY 40536-0596 , USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wu
authors.forename: Weifen
authors.initials: W
authors.lastname: Zhang
authors.forename: Don
authors.initials: D
authors.lastname: Hayes
authors.forename: Heidi M
authors.initials: HM
authors.lastname: Mansour
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000280:Administration, Inhalation; D000336:Aerosols / Q000008:administration & dosage / Q000737:chemistry*; D000704:Analysis of Variance; D002942:Circular Dichroism; D016572:Cyclosporine / Q000008:administration & dosage / Q000737:chemistry*; D058995:Dry Powder Inhalers; D006813:Humidity; D000432:Methanol / Q000737:chemistry; D010316:Particle Size; D010715:Phosphatidylglycerols / Q000737:chemistry; D011663:Pulmonary Surfactants / Q000737:chemistry*; D013696:Temperature; D014867:Water; D014961:X-Ray Diffraction
chemical_list: D000336:Aerosols; D010715:Phosphatidylglycerols; D011663:Pulmonary Surfactants; D014867:Water; D015060:1,2-Dipalmitoylphosphatidylcholine; D016572:Cyclosporine; C030345:1,2-dipalmitoylphosphatidylglycerol; D000432:Methanol
keywords: calcineurin inhibitor; dipalmitoylphosphatidylcholine (DPPC); dipalmitoylphosphatidylglycerol (DPPG); dry powder inhaler (DPI); lung immunosuppression; lung surfactant; polypeptide drug; targeted lung immunosuppression