Dry powder insufflation of crystalline and amorphous voriconazole formulations produced by thin film freezing to mice

European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V
Nicole A BeinbornRobert O Williams

Abstract

Attention has begun to focus on the pulmonary delivery of antifungal agents for invasive fungal infections as inhalation of the fungal spores is often the initial step in the pathogenesis of many of these infections, including invasive pulmonary aspergillosis (IPA). IPA in immunocompromised patients has high mortality rates despite current systemic (oral or intravenous) therapies. In this study, particulate voriconazole (VRC) formulations were designed with suitable properties for inhalation using thin film freezing (TFF), a particle engineering process capable of producing low-density porous aggregate particles. Nanostructured amorphous morphology of VRC was less favorable in vitro and in vivo than microstructured crystalline morphology, despite being a poorly water-soluble compound. Using a Handihaler dry powder inhaler (DPI), microstructured crystalline TFF-VRC and nanostructured amorphous TFF-VRC-PVP K25 (1:3) had fine particle fractions of 37.8% and 32.4% and mass median aerodynamic diameters of 4.2 and 5.2 μm, respectively. Single dose 24-h pharmacokinetic studies were conducted in ICR mice. AUC(0-24h) in the lung tissue and plasma was 452.6 μg h/g wet lung weight and 38.4 μg h/mL, respectively, following a 10mg/kg insuff...Continue Reading

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Citations

May 27, 2014·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Simone R CarvalhoRobert O Williams
Jan 19, 2016·Advanced Drug Delivery Reviews·Lan ChenHak-Kim Chan
Oct 4, 2015·International Journal of Biological Macromolecules·Hitendra S Mahajan, Prashant R Mahajan
Sep 24, 2015·International Journal of Pharmaceutics·Charan SinghSarasija Suresh
Mar 26, 2013·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Christophe DuretKarim Amighi
Jun 30, 2016·Expert Review of Anti-infective Therapy·Kathleen M JobCatherine M T Sherwin
Mar 18, 2020·Pharmaceutical Development and Technology·Rui ChenXiaohong Xu
Nov 22, 2016·Journal of Drug Delivery·Piyush Mehta
Feb 21, 2019·AAPS PharmSciTech·Chaeho MoonRobert O Williams
Oct 28, 2020·Pharmaceutics·Sawittree SahakijpijarnRobert O Williams Iii
Feb 28, 2021·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Prakash KhadkaShyamal C Das
Apr 4, 2021·Antibiotics·Aidan K Curran, David L Hava
Apr 10, 2021·AAPS PharmSciTech·Khaled AboulFotouhRobert O Williams
Mar 31, 2019·Molecular Pharmaceutics·Chaeho MoonRobert O Williams

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