LAUSR

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&mgr;m with ˜3&mgr;m 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.