Design and physicochemical characterization of advanced spray-dried tacrolimus multifunctional particles for inhalation

ign and physicochemical characterization of advanced spray-dried tacrolimus multifunctional particles for inhalation Original Research (1272) Total Article Views Authors: Wu X, Hayes D Jr, Zwischenberger JB, Kuhn RJ, Mansour HM Published Date February 2013 Volume 2013:7 Pages 59 - 72 DOI: http://dx.doi.org/10.2147/DDDT.S40166 Received: 10 November 2012 Accepted: 13 December 2012 Published: 05 February 2013 Xiao Wu,1 Don Hayes Jr,2,3 Joseph B Zwischenberger,4 Robert J Kuhn,5 Heidi M Mansour1,6 1University of Kentucky, College of Pharmacy, Department of Pharmaceutical Sciences-Drug Development Division, Lexington, KY, USA; 2The Ohio State University College of Medicine, Departments of Pediatrics and Internal Medicine, Lung and Heart-Lung Transplant Programs, Nationwide Children's Hospital, Columbus, OH, USA; 3The Ohio State University College of Medicine, The Davis Heart and Lung Research Institute, Columbus, OH, USA; 4University of Kentucky College of Medicine, Departments of Pediatrics, Biomedical Engineering, Diagnostic Radiology, and Surgery, Lexington, KY, USA; 5University of Kentucky, College of Pharmacy, Division of Pharmacy Practice and Science, Lexington, KY, USA; 6University of Kentucky, Center of Membrane Sciences, Lexington, KY, USA Abstract: The aim of this study was to design, develop, and optimize respirable tacrolimus microparticles and nanoparticles and multifunctional tacrolimus lung surfactant mimic particles for targeted dry powder inhalation delivery as a pulmonary nanomedicine. Particles were rationally designed and produced at different pump rates by advanced spray-drying particle engineering design from organic solution in closed mode. In addition, multifunctional tacrolimus lung surfactant mimic dry powder particles were prepared by co-dissolving tacrolimus and lung surfactant mimic phospholipids in methanol, followed by advanced co-spray-drying particle engineering design technology in closed mode. The lung surfactant mimic phospholipids were 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-sn-glycero-3-[phosphor-rac-1-glycerol]. Laser diffraction particle sizing indicated that the particle size distributions were suitable for pulmonary delivery, whereas scanning electron microscopy imaging indicated that these particles had both optimal particle morphology and surface morphology. Increasing the pump rate percent of tacrolimus solution resulted in a larger particle size. X-ray powder diffraction patterns and differential scanning calorimetry thermograms indicated that spray drying produced particles with higher amounts of amorphous phase. X-ray powder diffraction and differential scanning calorimetry also confirmed the preservation of the phospholipid bilayer structure in the solid state for all engineered respirable particles. Furthermore, it was observed in hot-stage micrographs that raw tacrolimus displayed a liquid crystal transition following the main phase transition, which is consistent with its inter