Development of Remdesivir as a Dry Powder for Inhalation by Thin Film Freezing

Published: July 27, 2020, 5:01 a.m.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.26.222109v1?rss=1 Authors: Moon, C., Sahakijpijarn, S., Koleng, J. J., Williams, R. O. Abstract: Remdesivir, an investigational broad-spectrum antiviral agent, has shown in vitro activity against SARS-CoV-2. To maximize direct delivery to the target site, the lungs, we aim to develop remdesivir as a dry powder for inhalation using thin film freezing (TFF). TFF produces a brittle matrix of nanostructured aggregates that can be sheared into respirable low-density microparticles upon aerosolization from a passive dry powder inhaler. In vitro aerodynamic testing demonstrated that drug loading and excipient type affected the aerosol performance of remdesivir. Remdesivir combined with optimal excipients (e.g. Captisol, mannitol, lactose, leucine) exhibited suitable aerosol performance (up to 92.4% FPF and 0.86 micron MMAD). Remdesivir was amorphous after the TFF process, which we hypothesize will provide a benefit for drug dissolution once administered to the lungs. Neither the organic/water processing cosolvent or the rapid freezing rate used during the TFF process affected the chemical stability of remdesivir during processing. In conclusion, TFF is a suitable technology for producing remdesivir dry powder formulations suitable for pulmonary administration. Copy rights belong to original authors. Visit the link for more info