Abstract
In spray freeze-srying (SFD), a solution is sprayed into a refrigerant medium, frozen, and subsequently sublimation dried, which allows the production of flowable lyophilized powders. SFD allows commonly freeze-dried active pharmaceutical ingredients (e.g., proteins and peptides) to be delivered using new applications such as needle-free injection and nasal or pulmonary drug delivery. In this study, a droplet stream was injected into a vortex of cold gas in order to reduce the risk of droplet collisions and therefore droplet growth before congelation, which adversely affects the particle size distribution. Droplets with initial diameters of about 40–50 μm were frozen quickly in a swirl tube at temperatures around −75°C and volumetric gas flow rates between 17 and 34 L/min. Preliminary studies that were focused on the evaluation of spray cone footprints were performed prior to SFD. A 23 factorial design with a model solution of mannitol (1.5% m/V) and maltodextrin (1.5% m/V) was used to create flowable, low density (0.01–0.03 g/cm3) spherical lyophilisate powders. Mean particle diameter sizes of the highly porous particles ranged between 49.8 ± 6.6 and 88.3 ± 5.5 μm. Under optimal conditions, the mean particle size was reduced from 160 to 50 μm (decrease of volume by 96%) compared to non-expanded streams, whereas the SPAN value did not change significantly. This method is suitable for the production of lyophilized powders with small particle sizes and narrow particle size distributions, which is highly interesting for needle-free injection or nasal delivery of proteins and peptides.
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Wanning S, Süverkrüp R, Lamprecht A. Pharmaceutical spray freeze drying. Int J Pharm. 2015;488(1–2):136–53.
Schiffter H, Condliffe J, Vonhoff S. Spray-freeze-drying of nanosuspensions: the manufacture of insulin particles for needle-free ballistic powder delivery. J R Soc Interface. 2010;7(Suppl_4):S483–500.
Wang SH, Kirwan SM, Abraham SN, Staats HF, Hickey AJ. Stable Dry powder formulation for nasal delivery of anthrax vaccine. J Pharm Sci. 2012;101(1):31–47.
Bi R, Shao W, Wang Q, Zhang N. Spray-freeze-dried dry powder inhalation of insulin-loaded liposomes for enhanced pulmonary delivery. J Drug Target. 2008;16(9):639–48.
Eggerstedt SN, Dietzel M, Sommerfeld M, Süverkrüp R, Lamprecht A. Protein spheres prepared by drop jet freeze drying. Int J Pharm. 2012;438(1–2):160–6.
Hu J, Johnston KP, Williams RO. Spray freezing into liquid (SFL) particle engineering technology to enhance dissolution of poorly water soluble drugs: organic solvent versus organic/aqueous co-solvent systems. Eur J Pharm Sci. 2003;20(3):295–303.
Maa Y-F, Nguyen P-A, Sweeney T, Shire SJ, Hsu CC. Protein inhalation powders: spray drying vs spray freeze drying. Pharm Res. 1999;16(2):249–54.
Ali ME, Lamprecht A. Spray freeze drying for dry powder inhalation of nanoparticles. Eur J Pharm Biopharm. 2014;87(3):510–7.
Eggerstedt S. Sprühgefriertrocknung zur Herstellung von Protein-Inhalanda [Dissertation]. Rheinische Friedrich-Wilhelms-Universität Bonn; 2014.
Niwa T, Mizutani D, Danjo K. Spray freeze-dried porous microparticles of a poorly water-soluble drug for respiratory delivery. Chem Pharm Bull (Tokyo). 2012;60(7):870–6.
Mueannoom W, Srisongphan A, Taylor KMG, Hauschild S, Gaisford S. Thermal ink-jet spray freeze-drying for preparation of excipient-free salbutamol sulphate for inhalation. Eur J Pharm Biopharm. 2012;80(1):149–55.
Sharma G, Mueannoom W, Buanz ABM, Taylor KMG, Gaisford S. In vitro characterisation of terbutaline sulphate particles prepared by thermal ink-jet spray freeze drying. Int J Pharm. 2013;447(1–2):165–70.
Rochelle C. Spray-freeze-dried powders for needle-free injection [Dissertation]. Friedrich-Alexander-Universität Erlangen-Nürnberg; 2005.
Maa Y-F, Ameri M, Shu C, Payne LG, Chen D. Influenza vaccine powder formulation development: spray-freeze-drying and stability evaluation. J Pharm Sci. 2004;93(7):1912–23.
Süverkrüp R, Eggerstedt SN, Gruner K, Kuschel M, Sommerfeld M, Lamprecht A. Collisions in fast droplet streams for the production of spherolyophilisates. Eur J Pharm Sci. 2013;49(4):535–41.
Süverkrüp R, Eggerstedt S, Wanning S, Kuschel M, Sommerfeld M, Lamprecht A. Collisions and coalescence in droplet streams for the production of freeze-dried powders. Colloids Surf B. 2016;141:443–9.
Rasband WS, ImageJ US. National Institutes of Health, Bethesda, Maryland, USA. 1997–2016. http://imagej.nih.gov/ij/.
Walzel P. Zerstäuben von Flüssigkeiten. Chem Ing Tech. 1990;62(12):983–94.
Garmise RJ, Staats HF, Hickey AJ. Novel dry powder preparations of whole inactivated influenza virus for nasal vaccination. AAPS PharmSciTech. 2007;8(4):2–10.
Acknowledgments
The authors are grateful for the financial support of the “Deutsche Forschungsgemeinschaft” (DFG) in the framework of SPP1423 (grant no. LA1362/2-1) and would also like to thank Franz-Josef Willems, Thomas Vidua, and Jürgen Hohmann for technical assistance.
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R. Süverkrüp: German Patent Application # 2015 0409 11542100 DE “Vorrichtung und Verfahren zur Erzeugung monodisperser gefrorener Tropfen”
(Apparatus and method for the generation of mono-disperse frozen droplets)
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Fig. S1
Epicyclical positioner. a Scheme. b View (JPG 145 kb)
ESM 1
(GIF 4747 kb)
Fig. S2
Spray cone expansion test setup. 1. Droplet generator. 2. Epicyclical positioner. 3. Swirl tube. 4. Shutter surfaces. 5. Target surface (GIF 8493 kb)
Supplementary Table S1
Results (DOC 35 kb)
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Wanning, S., Süverkrüp, R. & Lamprecht, A. Aerodynamic Droplet Stream Expansion for the Production of Spray Freeze-Dried Powders. AAPS PharmSciTech 18, 1760–1769 (2017). https://doi.org/10.1208/s12249-016-0648-2
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DOI: https://doi.org/10.1208/s12249-016-0648-2