Dry powder inhaler delivery of amorphous drug nanoparticles: Effects of the lactose carrier particle shape and size

Stable amorphous drug nanoparticles represent a new bioavailability enhancement strategy of poorly soluble drugs. Herein we present dry powder inhaler (DPI) formulations of amorphous drug nanoparticles, where the effects of the lactose carrier particle shape (i.e. tomahawk, needle, and pollen) in two size ranges (i.e. ≈ 50–70 μm and 14–20 μm) on the aerosolization efficiency of the drug-carrier particle blends are investigated. Spherical ciprofloxacin nanoparticles (≈ 300 nm) prepared by drug-polyelectrolyte complexation are used as the amorphous nanoparticle model. The aerosolization efficiency is characterized by the emitted dose (ED), dispersibility, fine particle fraction (FPF), and mass median aerodynamic diameter (MMAD). Contrary to the findings in DPI delivery of drug microparticles, where the needle (NL) and pollen (PL) shaped lactose particles are often reported to exhibit superior aerosolization efficiency than the commercial tomahawk (CL) lactose particles, our results at two theoretical drug loadings (i.e. 10 and 20%) indicate that the CL particles yield equivalent aerosolization efficiencies as the NL and PL particles for the large and small carrier particle size ranges, respectively. The ED, dispersibility, FPF, and MMAD of the better drug-carrier particle blends (i.e. large/small CL, small PL, and large NL) are ≈ 70–80%, 20–30%, 16–18%, and 5.7–6.2 μm, respectively.

The effect of lactose carrier particle shape on the aerosolization efficiency of drug nanoparticles is distinct from its effect for drug microparticles. The tomahawk shaped lactose particles, depending on its size range, can have equal aerosolization efficiency as the needle and pollen shaped lactose particles, which were previously found to be superior for delivering drug microparticles. The effect of lactose carrier particle shape on the aerosolization efficiency of drug nanoparticles is distinct from its effect for drug microparticles. The tomahawk shaped lactose particles, depending on its size range, can have equal aerosolization efficiency as the needle and pollen shaped lactose particles, which were previously found to be superior for delivering drug microparticles.Figure optionsDownload as PowerPoint slideHighlights
► Traditional tomahawk shaped lactose particles are as efficient as other particle shapes.
► Effects of carrier shape and size are different between nano and microparticles.
► Needle shaped lactose particles exhibit loading and size dependent aerosolization.
► Pollen shaped particles do not always improve aerosolization for drug nanoparticles.