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

Gravimetric water vapor absorption isotherms for raw tacrolimus, pure dipalmitoylphosphatidylcholine (DPPC), pure sodium dipalmitoylphosphatidylglycerol (DPPG) and organic solution advanced co-spray-dried lung surfactant mimic particles of tacrolimus for dry powder inhalation (tacrolipo25 and tacrolipo75).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3569053&req=5

f12-dddt-7-059: Gravimetric water vapor absorption isotherms for raw tacrolimus, pure dipalmitoylphosphatidylcholine (DPPC), pure sodium dipalmitoylphosphatidylglycerol (DPPG) and organic solution advanced co-spray-dried lung surfactant mimic particles of tacrolimus for dry powder inhalation (tacrolipo25 and tacrolipo75).

Mentions: As shown in Figure 12, at low RH levels of 0%–20% RH, the absorption profiles were similar for DPPC, raw tacrolimus, tacrolipo25, and tacrolipo75. Sodium DPPG absorbed much less water, due to its tightly packed bilayer as a result of favorable electrostatic interactions between the cationic sodium ion and anionic polar headgroup, and is in good agreement with our earlier report.52 At intermediate RH regions, the weight change percentage of DPPG showed a plateau, with an increasing RH between 20%–70%, but increased significantly when the RH exceeded ~70%. The plateau region is indicative of a phase transition, as has been described earlier by these authors.52 A similar profile was observed for DPPC. When RH was between 20% and 65%, the percentage weight change of DPPC was higher than DPPG and is in good agreement with our earlier report.52 When RH level exceeded ~65%, the percentage weight change of DPPC increased significantly with an increasing RH and is in good agreement with our earlier report.52 For the organic solution advanced co-spray-dried tacrolipo25 and tacrolipo75 respirable lung surfactant mimic powders, the profiles were similar to each another and approached the raw DPPC absorption curve when the RH level exceeded ~70% RH.


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)

Gravimetric water vapor absorption isotherms for raw tacrolimus, pure dipalmitoylphosphatidylcholine (DPPC), pure sodium dipalmitoylphosphatidylglycerol (DPPG) and organic solution advanced co-spray-dried lung surfactant mimic particles of tacrolimus for dry powder inhalation (tacrolipo25 and tacrolipo75).
© Copyright Policy
Related In: Results  -  Collection

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

f12-dddt-7-059: Gravimetric water vapor absorption isotherms for raw tacrolimus, pure dipalmitoylphosphatidylcholine (DPPC), pure sodium dipalmitoylphosphatidylglycerol (DPPG) and organic solution advanced co-spray-dried lung surfactant mimic particles of tacrolimus for dry powder inhalation (tacrolipo25 and tacrolipo75).
Mentions: As shown in Figure 12, at low RH levels of 0%–20% RH, the absorption profiles were similar for DPPC, raw tacrolimus, tacrolipo25, and tacrolipo75. Sodium DPPG absorbed much less water, due to its tightly packed bilayer as a result of favorable electrostatic interactions between the cationic sodium ion and anionic polar headgroup, and is in good agreement with our earlier report.52 At intermediate RH regions, the weight change percentage of DPPG showed a plateau, with an increasing RH between 20%–70%, but increased significantly when the RH exceeded ~70%. The plateau region is indicative of a phase transition, as has been described earlier by these authors.52 A similar profile was observed for DPPC. When RH was between 20% and 65%, the percentage weight change of DPPC was higher than DPPG and is in good agreement with our earlier report.52 When RH level exceeded ~65%, the percentage weight change of DPPC increased significantly with an increasing RH and is in good agreement with our earlier report.52 For the organic solution advanced co-spray-dried tacrolipo25 and tacrolipo75 respirable lung surfactant mimic powders, the profiles were similar to each another and approached the raw DPPC absorption curve when the RH level exceeded ~70% RH.

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