Solubilising and Aerosolising Cannabidiol Using Methyl β-Cyclodextrin and Human Serum Albumin

Pulmonary delivery can deliver cannabidiol (CBD) with high bioavailability and fast onset of action. One formulation obstacle is the low aqueous solubility of CBD, so solubilsers are necessary. This study aimed to develop inhalable CBD powders using excipients that help dissolving CBD. The solubilisation effects of human serum albumin (HSA), β-cyclodextrin, 2-hydroxypropyl-β-cyclodextrin, and methyl-β-cyclodextrin (mbCD) were investigated with phase solubility test. MbCD showed the highest CBD solubilisation ability at all tested concentrations, followed by HSA. Therefore, mbCD and HSA were co-spray freeze dried with CBD to obtain CBD + mbCD and CBD + HSA powders, respectively. Both powders were amorphous, had < 3% residual solvent, and contained CBD in complexes. CBD + mbCD maintained its amorphicity at < 70% relative humidity. On the other hand, CBD + HSA resisted recrystallisation even at 90% relative humidity. However, although both formulations emitted about 90% of CBD, CBD + HSA was less dispersible than CBD + mbCD (fine particle fraction < 5 µm: 30.2 ± 1.0% vs 53.5 ± 1.5%). The higher level of CBD solubility enhancement and better aerosol performance from mbCD indicated that it was an effective excipient to deliver CBD and potentially other cannabinoids in the future.