Impact of Solid-State Properties on the Aerosolization Performance of Spray-Dried Curcumin Powders.

ABSTRACT

Amorphous and crystalline active pharmaceutical ingredients (APIs) are both widely studied for pulmonary delivery. The past research mainly studied the impact of solid-state properties on pharmacokinetic attributes; however, the influence of solid-state properties on aerosolization performance was much less studied. This study aimed to investigate the different aerosolization performances of amorphous and crystalline curcumin (Cur) stabilized with L-leucine. Cur was spray-dried with different concentrations of L-leucine (0, 5, 20, 35, and 50%, w/w) as both solution-based and suspension-based formulations to acquire amorphous and crystalline Cur powders. The physicochemical properties of the spray-dried powders, including particle size, morphology, and solid-state characteristics, were studied. The aerosolization performance as well as dissolution properties were evaluated. It was found that 35% (w/w) L-leucine or above led to the formation of amorphous Cur in the spray-dried powders, and the amorphous Cur powders exhibited higher FPF (70.8%, with 50% L-leucine, w/w) than the crystalline Cur formulations with an FPF at 56.3% (with 50% L-leucine, w/w). In conclusion, with a high concentration of L-leucine (35% or above) in the formulations, amorphous Cur would exhibit higher aerosolization efficiency than crystalline Cur. However, with a low concentration of L-leucine (20% or less) in the formulations, crystalline Cur would be preferred for more enhanced consideration.