Cannabidiol and Hydroxypropyl-β-Cyclodextrin for the Development of Deflated Spherical-Shaped Inhalable Powder

In addition to the known therapeutic indications for cannabidiol, its administration by inhalation appears to be of great interest. Indeed, there is evidence of cannabidiol's efficacy in several physiological pathways, suggesting its potential for a wide range of applications for both local and systemic pulmonary administration like cancers. Significant advances in pulmonary drug delivery have led to innovative strategies to address the challenges of increasing the respirable fraction of drugs and standardizing inhalable products. Among different devices, dry powder inhalers offer significant advantages including high stability and ease of use. Particle engineering using techniques such as spray drying is now the focus of research and is expected to improve upon, rather than completely replace, traditional carrier-based formulations. The development of carrier-free powders (without lactose-carrier) is mainly used for medicines with low active ingredient doses, which limits the technology. Previously, we demonstrated the benefits of using a cyclodextrin to obtain deflated spherical-shaped powders by spray drying. In this study the potential of this excipient with a very poorly water-soluble active molecule was investigated. Inhalable cannabidiol powders were developed by spray drying, using the solubility enhancers hydroxypropyl-beta-cyclodextrin and ethanol to optimize cannabidiol water-solubility. Electron microscopy images revealed consistent deflated spherical shapes, while particle size analysis showed low polydispersity and suitable sizes for deep lung deposition (2 µm). The selected engineered powders (without ethanol) had very high fine particle fractions (> 60%) due to their deflated surface. Finally, the powder was instantly solubilized leading to drug dissolution, which is important for therapeutic efficacy. In conclusion, this study successfully develops a cannabidiol inhalation powder by particle engineering having suitable aerosolization behavior. Due to the speed of the process and the performance of the finished product, this work opens the door for future studies. It has been shown that active molecules that are only slightly soluble in water can be formulated effectively as a powder for inhalation. Other molecules could be tested and subsequent in vivo studies conducted to demonstrate correlation with these in vitro results.