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

Wu X, Hayes D, Zwischenberger JB, Kuhn RJ, Mansour HM - Drug Des Devel Ther (2013)

Bottom Line: Increasing the pump rate percent of tacrolimus solution resulted in a larger particle size.Conclusively, advanced spray-drying particle engineering design from organic solution in closed mode was successfully used to design and optimize solid-state particles in the respirable size range necessary for targeted pulmonary delivery, particularly for the deep lung.These particles were dry, stable, and had optimal properties for dry powder inhalation as a novel pulmonary nanomedicine.

View Article: PubMed Central - PubMed

Affiliation: University of Kentucky, College of Pharmacy, Department of Pharmaceutical Sciences-Drug Development Division, Lexington, KY 40536-0596 , 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 interfacial properties. Water vapor uptake and lyotropic phase transitions in the solid state at varying levels of relative humidity were determined by gravimetric vapor sorption technique. Water content in the various powders was very low and well within the levels necessary for dry powder inhalation, as quantified by Karl Fisher coulometric titration. Conclusively, advanced spray-drying particle engineering design from organic solution in closed mode was successfully used to design and optimize solid-state particles in the respirable size range necessary for targeted pulmonary delivery, particularly for the deep lung. These particles were dry, stable, and had optimal properties for dry powder inhalation as a novel pulmonary nanomedicine.

Show MeSH

Related in: MedlinePlus

Differential scanning calorimetry thermograms at 5.00°C/minute heating scan rate of raw tacrolimus, pure dipalmitoylphosphatidylcholine (DPPC), pure sodium dipalmitoylphosphatidylglycerol (DPPG), and organic solution advanced co-spray-dried lung surfactant mimic inhalable particles (tacrolipo25 and tacrolipo75) for dry powder inhalation.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3569053&req=5

f5-dddt-7-059: Differential scanning calorimetry thermograms at 5.00°C/minute heating scan rate of raw tacrolimus, pure dipalmitoylphosphatidylcholine (DPPC), pure sodium dipalmitoylphosphatidylglycerol (DPPG), and organic solution advanced co-spray-dried lung surfactant mimic inhalable particles (tacrolipo25 and tacrolipo75) for dry powder inhalation.

Mentions: The thermograms of raw tacrolimus and organic solution advance co-spray-dried lung surfactant mimic powders are shown in Figure 5. DPPC powders exhibit two endothermic phase transitions at 66.9°C and 73°C, corresponding to the gel-to-ripple bilayer pretransition and to the bilayer main transition Tm (ie, due to the hydrophobic acyl chain melting event) between the rippled-gel and liquid crystalline phases, respectively.52 DPPG powders showed three endothermic phase transitions consisting of two low-enthalpy pretransitions at ~55.3°C and ~79.5°C and a high-enthalpy main phase transition at 125°C, which correspond to the crystal-to-gel bilayer phase transition, gel-to-ripple bilayer phase transition, and rippled-to-liquid crystalline bilayer main phase transition (Tm), respectively.52 Co-spray-dried samples of tacrolipo25 and tacrolipo75 containing lung surfactant mimic DPPC/DPPG (3:1) exhibit the main bilayer phase transition temperature at 66.2°C and 67.4°C, respectively, which are slightly below the Tm values of pure DPPC and DPPG powders. All co-spray-dried lung surfactant mimic particles did not exhibit the characteristic tacrolimus endothermic melting peak, suggesting a loss of crystallinity in tacrolimus following organic solution advanced spray drying.


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

Wu X, Hayes D, Zwischenberger JB, Kuhn RJ, Mansour HM - Drug Des Devel Ther (2013)

Differential scanning calorimetry thermograms at 5.00°C/minute heating scan rate of raw tacrolimus, pure dipalmitoylphosphatidylcholine (DPPC), pure sodium dipalmitoylphosphatidylglycerol (DPPG), and organic solution advanced co-spray-dried lung surfactant mimic inhalable particles (tacrolipo25 and tacrolipo75) for dry powder inhalation.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3569053&req=5

f5-dddt-7-059: Differential scanning calorimetry thermograms at 5.00°C/minute heating scan rate of raw tacrolimus, pure dipalmitoylphosphatidylcholine (DPPC), pure sodium dipalmitoylphosphatidylglycerol (DPPG), and organic solution advanced co-spray-dried lung surfactant mimic inhalable particles (tacrolipo25 and tacrolipo75) for dry powder inhalation.
Mentions: The thermograms of raw tacrolimus and organic solution advance co-spray-dried lung surfactant mimic powders are shown in Figure 5. DPPC powders exhibit two endothermic phase transitions at 66.9°C and 73°C, corresponding to the gel-to-ripple bilayer pretransition and to the bilayer main transition Tm (ie, due to the hydrophobic acyl chain melting event) between the rippled-gel and liquid crystalline phases, respectively.52 DPPG powders showed three endothermic phase transitions consisting of two low-enthalpy pretransitions at ~55.3°C and ~79.5°C and a high-enthalpy main phase transition at 125°C, which correspond to the crystal-to-gel bilayer phase transition, gel-to-ripple bilayer phase transition, and rippled-to-liquid crystalline bilayer main phase transition (Tm), respectively.52 Co-spray-dried samples of tacrolipo25 and tacrolipo75 containing lung surfactant mimic DPPC/DPPG (3:1) exhibit the main bilayer phase transition temperature at 66.2°C and 67.4°C, respectively, which are slightly below the Tm values of pure DPPC and DPPG powders. All co-spray-dried lung surfactant mimic particles did not exhibit the characteristic tacrolimus endothermic melting peak, suggesting a loss of crystallinity in tacrolimus following organic solution advanced spray drying.

Bottom Line: Increasing the pump rate percent of tacrolimus solution resulted in a larger particle size.Conclusively, advanced spray-drying particle engineering design from organic solution in closed mode was successfully used to design and optimize solid-state particles in the respirable size range necessary for targeted pulmonary delivery, particularly for the deep lung.These particles were dry, stable, and had optimal properties for dry powder inhalation as a novel pulmonary nanomedicine.

View Article: PubMed Central - PubMed

Affiliation: University of Kentucky, College of Pharmacy, Department of Pharmaceutical Sciences-Drug Development Division, Lexington, KY 40536-0596 , 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 interfacial properties. Water vapor uptake and lyotropic phase transitions in the solid state at varying levels of relative humidity were determined by gravimetric vapor sorption technique. Water content in the various powders was very low and well within the levels necessary for dry powder inhalation, as quantified by Karl Fisher coulometric titration. Conclusively, advanced spray-drying particle engineering design from organic solution in closed mode was successfully used to design and optimize solid-state particles in the respirable size range necessary for targeted pulmonary delivery, particularly for the deep lung. These particles were dry, stable, and had optimal properties for dry powder inhalation as a novel pulmonary nanomedicine.

Show MeSH
Related in: MedlinePlus