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An optimum carrier rugosity is essential to achieve a satisfying drug deposition efficiency for the carrier based dry powder inhalation (DPI). Therefore, a non-organic spray drying technique was firstly used to prepare nanoporous mannitol with small asperities to enhance the DPI aerosolization performance. Ammonium carbonate was used as a pore-forming agent since it decomposed with volatile during preparation. It was found that only the porous structure, and hence the specific surface area and carrier density were changed at different ammonium carbonate concentration. Furthermore, the carrier density was used as an indication of porosity to correlate with drug aerosolization. A good correlation between the carrier density and fine particle fraction (FPF) (r2 = 0.9579) was established, suggesting that the deposition efficiency increased with the decreased carrier density. Nanoporous mannitol with a mean pore size of about 6 nm exhibited 0.24-fold carrier density while 2.16-fold FPF value of the non-porous mannitol. The enhanced deposition efficiency was further confirmed from the pharmacokinetic studies since the nanoporous mannitol exhibited a significantly higher AUC0-8h value than the non-porous mannitol and commercial product Pulmicort. Therefore, surface modification by preparing nanoporous carrier through non-organic spray drying showed to be a facile approach to enhance the DPI aerosolization performance.

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In response to the epidemic and pandemic threats caused by emerging respiratory viral infections, a safe and efficient broad‐spectrum antiviral therapy at early onset of infection can significantly improve patients’ outcome. Inhaled dry powder is easy to administer and delivers antiviral agent directly to the primary site of infection, thereby minimizing systemic side effects. Here, spray freeze drying (SFD) technique is employed to formulate tamibarotene, a retinoid derivative with broad‐spectrum antiviral activity, as inhalable powder. The SFD tamibarotene powder exhibits desirable physicochemical and aerodynamic properties for inhalation. Pulmonary delivery of tamibarotene powder results in rapid absorption and higher bioavailability compared with intraperitoneal injection of unformulated drug in animals. More importantly, inhalation or intranasal delivery of SFD tamibarotene formulation displays broad‐spectrum antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), Middle East respiratory syndrome coronavirus, and pandemic 2009 influenza A virus (H1N1) in mouse and hamster models by targeting lower or upper airways, and the efficacy is comparable or superior to the commercially available antivirals remdesivir and zanamivir against specific virus. These results present a promising strategy to combat various respiratory viral infections including SARS‐CoV‐2 and influenza virus, or even co‐infection.