Processing design space is critical for voriconazole nanoaggregates for dry powder inhalation produced by thin film freezing

• Published in: Journal of drug delivery science and technology 2019-12, Vol.54, p.101295, Article 101295
• Main Authors: Moon, Chaeho, Sahakijpijarn, Sawittree, Koleng, John J., Williams, Robert O.
• Format: Article
• Language: English
• Subjects: Antifungal; Dry powder inhalation; Nanoaggregates; Surface modification; Thin film freezing; Voriconazole
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2019.101295

We previously developed high-potency (up to 97%) crystalline voriconazole nanoaggregates intended for dry powder inhalation. A process using thin film freezing was designed such that nanoparticles of mannitol on the surface of voriconazole nanoaggregates modified the surface texture of the voriconazole nanoaggregates and thus the aerosolization properties of the powder. Identifying the process design space is absolutely critical for the development of the voriconazole nanoaggregates into a pharmaceutical product. Thus, we evaluated several critical parameters of the process design space, including: solvent system composition, processing temperature, solid loading, and scale. We also evaluated aerosolization of the powder with different devices, namely high and low resistance RS01 and RS00 DPIs. The solvent composition with a higher amount of water and a low processing temperature (−150 °C) was favorable to aerosolization. Higher solid loadings resulted in lower aerosol performance, while powder conditioning improved aerosolization. The 450-fold larger manufacture scale presented no differences in physicochemical and aerodynamic properties. While a low resistance RS00 device performed the best at a high flow rate, a high resistance RS00 device presented consistent aerosolization over the flow rate of 60 L/min and 30 L/min, and a dosing range of 10–20 mg per capsule. [Display omitted]