Preparation of Excipient-Free Molnupiravir Microparticles for Pulmonary Drug Delivery and Process Evaluation via...

Background/Objective: Molnupiravir (EIDD-2801) was originally designed to treat influenza A virus and showed broad-spectrum antiviral activity, including against influenza virus, Ebola virus, coronavirus and other viruses. Methods: In this study, molnupiravir microparticles were firstly prepared by spray freeze-drying (SFD) and jet milling (JM) methods. Meanwhile, machine learning methodology was applied to evaluate the influence of process parameters such as feeding rate, concentration, and nebulization pressure on powder properties. Results: According to SEM images, the microparticles prepared by SFD presented a porous and near-spherical structure. Moreover, the fine particle fraction (FPF) and mass median aerodynamic diameter (MMAD) of the optimal inhalable powder reached up to 70.19 ± 2.06% and 2.80 ± 0.16 μm, proving the excellent aerodynamic performance. Conclusions: The molnupiravir micropowder showed preliminary short-term storage behavior after storage for 28 days at 25 °C and 60% RH.