The objective of the work was to produce a new excipient based on D-leucine to improve the aerosolization properties of the poorly flowable micronized budesonide. The D-leucine powders produced by a nano spray-dryer were characterized in terms of dimensions, morphology, thermal behavior, X-ray powder diffraction and infrared spectroscopy. Then, micronized budesonide was mixed with the different leucine powders obtained or commercial D-leucine at different weight ratios (1:1, 5:1, 10:1) to investigate their aerodynamic characteristics using a glass twin-stage impinger. Commercial D-leucine powder is composed of large flattened crystals of about 30 μm with ~3 μm thickness, while micronized budesonide appeared as small irregular crystals. After spray-drying, D-leucine particles appeared wrinkled and porous. Particle sizes were mainly influenced by the amino acid concentration. Aerodynamic assessment showed that D-leucine was able to improve the aerodynamic behavior of micronized budesonide from about 28 to 45% emitted fraction. The best aerodynamic properties were obtained with D-leucine powdered from a water:ethanol (1:1, v:v) solution and using micronized budesonide:leucine weight ratio of 5:1. The direct physical mixing of the atomized D-leucine with the micronized active pharmaceutical ingredient is a valid and economic alternative for the production of carrier-free dry powders for inhalation.
D-leucine microparticles as an excipient to improve the aerosolization performances of dry powders for inhalation
Schoubben, Aurélie;Vivani, Riccardo;Paolantoni, Marco;Gioiello, Antimo;Macchiarulo, Antonio;Ricci, Maurizio
2019
Abstract
The objective of the work was to produce a new excipient based on D-leucine to improve the aerosolization properties of the poorly flowable micronized budesonide. The D-leucine powders produced by a nano spray-dryer were characterized in terms of dimensions, morphology, thermal behavior, X-ray powder diffraction and infrared spectroscopy. Then, micronized budesonide was mixed with the different leucine powders obtained or commercial D-leucine at different weight ratios (1:1, 5:1, 10:1) to investigate their aerodynamic characteristics using a glass twin-stage impinger. Commercial D-leucine powder is composed of large flattened crystals of about 30 μm with ~3 μm thickness, while micronized budesonide appeared as small irregular crystals. After spray-drying, D-leucine particles appeared wrinkled and porous. Particle sizes were mainly influenced by the amino acid concentration. Aerodynamic assessment showed that D-leucine was able to improve the aerodynamic behavior of micronized budesonide from about 28 to 45% emitted fraction. The best aerodynamic properties were obtained with D-leucine powdered from a water:ethanol (1:1, v:v) solution and using micronized budesonide:leucine weight ratio of 5:1. The direct physical mixing of the atomized D-leucine with the micronized active pharmaceutical ingredient is a valid and economic alternative for the production of carrier-free dry powders for inhalation.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
