High-loading cannabidiol powders for inhalation.

ABSTRACT

Limited attempts have been made previously to develop high-loading CBD inhalable powders, which are essential for high dose delivery. Therefore, this study aimed to develop and characterise inhalable powders with ≥ 95 % w/w CBD by wet ball milling. The effects of magnesium stearate (2 % and 5 %) and inhaler resistance (low-resistance and high-resistance RS01 inhalers) on aerosol performance were also compared. Wet ball milling produced CBD powders with > 50 % production yield. The milled particles showed irregular shapes. The powders were crystalline with minimal amorphous content, low residual solvent level (<1%), and low moisture sorption (<4%). Magnesium stearate improved both the emitted and fine particle fractions. The aerodynamic particle size distribution of the formulations differed between the low-resistance and high-resistance RS01 inhalers. The latter decreased throat deposition but increased inhaler retention. The dissolution profiles showed that all three formulations released CBD steadily and plateaued at 30 min. The best scenario was CBD with 5 % magnesium stearate dispersed from the high resistance RS01 inhaler, showing the highest FPF with the lowest throat deposition. This combination may be tested in vivo in the future to investigate its pharmacokinetic profile.