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CBD Aerosols with Methyl β-Cyclodextrin for Lung Delivery

By May 5, 2025No Comments

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. 2025 Apr 30;26(5):120.

doi: 10.1208/s12249-025-03121-8.

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

Waiting Tai 1, Dipesh Khanal 1, Jonathon Carl Arnold 2 3, Hak-Kim Chan 1, Philip Chi Lip Kwok 4
Affiliations 

Abstract

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.

Keywords: cannabidiol, human serum albumin, methyl-β-cyclodextrin, pulmonary delivery, spray freeze dry

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Conflict of interest statement

Declarations. Conflicts of interest: The authors declare no conflicts of interest.

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CBD Delivery Enhanced with Cyclodextrins for Pulmonary Use

To overcome cannabidiol’s poor water solubility, researchers developed inhalable powders using solubility-enhancing carriers. Among the tested excipients, methyl β-cyclodextrin (mbCD) significantly outperformed others, offering higher CBD solubilisation and superior aerosol dispersion. When co-spray freeze dried with CBD, both mbCD and human serum albumin (HSA) stabilized amorphous formulations, but CBD + mbCD delivered over 50% of its content as fine particles suitable for deep lung delivery. These findings suggest mbCD is a promising excipient for clean, efficient cannabinoid inhalation therapies.

CBD Aerosols enhanced by mbCD offer better solubility, stability, and lung delivery for cleaner cannabinoid formulations.Stay informed with the latest scientific insights, evidence-based independent research and discoveries on the ECS, cannabis medicine and more

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