Inhalable N-acetylcysteine dry powder formulations as potential adjuvant treatment for COVID-19

Alessandra Rossi, Teresa Greco, Chiara Ogliari, Arianna Ferrari, Marianna Boraschi & Matteo Incerti

Department of Food and Drug, University of Parma, Parco Area delle Scienze 27/A, Parma, 43121, Italy

Summary

N-acetylcysteine (NAC), a mucolytic drug with antioxidant and anti-inflammatory properties, has been recently proposed as adjuvant in the treatment of SARS-CoV-2 infection. In this study spray-dried powders of NAC for inhalation with 75% drug loading were prepared. NAC and the excipients were dissolved at acid pH and the solution was subjected to a spray drying process in close loop under nitrogen atmosphere. The effect of polyvinylpyrrolidone (PVP) or lactose in the spray dried powders and the variation of aspiration rate on the stability of NAC and powder aerosolization performance was investigated. The spray dried powders were characterized in terms of process yield, drug content, residual water content, particle size distribution, particle morphology and thermal behaviour. In vitro aerodynamic performance was evaluated using Fast Screening Impactor. The results showed that NAC was stable under nitrogen atmosphere during the spray drying process, as confirmed by the drug content values in the spray dried powders between 95 % and 105 %. The aspirator rate did not affect the overall properties of the spray dried powders. However, even if the lactose-containing spray dried powders exhibited the lower value of residual water respect to those with PVP, the better aerosolization performance was observed with the spray dried powders containing PVP.

Key Message

The combination of NAC solution in acid environment and the spray drying process in close loop under nitrogen atmosphere protects the drug from degradation and allowed the manufacturing of spray dried NAC microparticles. Lactose decreased the residual water content of the spray dried powders, while PVP reduces the aggregation of spray dried microparticles and increased the in vitro respirability of the powders.