Spray‐freeze‐drying for protein powder preparation: Particle characterization and a case study with trypsinogen stability

Sonner, Christine; Maa, Yuh‐Fun; Lee, Geoffrey

doi:10.1002/jps.10204

Cited by 83 publications

(72 citation statements)

References 23 publications

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“…Sonner et al 7 reported on the use of SFV/L to make particles containing protein for epidermal delivery, in which the stability of trypsinogen during SFV/L was influenced by the composition of the formulation. Maa et al 8 compared spray drying and SFV/L for producing protein powders for inhalation and found that SFV/L produced protein particles with light and porous characteristics.…”

Section: Methodsmentioning

confidence: 99%

Investigation of processing parameters of spray freezing into liquid to prepare polyethylene glycol polymeric particles for drug delivery

et al. 2003

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INTRODUCTIONThe objective of this study was to investigate the influence of processing parameters on the morphology, porosity, and crystallinity of polymeric polyethylene glycol (PEG) microparticles by spray freezing into liquid (SFL), a new particle engineering technology. Processing parameters investigated were the viscosity and flow rate of the polymer solution, nozzle diameter, spray time, pressure, temperature, and flow rate of the cryogenic liquid. By varying the processing parameters and feed composition, atomization and heat transfer mechanisms were modified resulting in particles of different size distribution, shape, morphology, density, porosity, and crystallinity. Median particle diameter (M50) varied from 25 µm to 600 µm. Particle shape was spherical or elongated with highly irregular surfaces. Granule density was between 0.5 and 1.5 g/mL. In addition to producing particles of pure polymer, drug particles were encapsulated in polymeric microparticles. The encapsulation efficiency of albuterol sulfate was 96.0% with a drug loading of 2.4%, indicating that SFL is useful for producing polymeric microparticles for drug delivery applications. It was determined that the physicochemical characteristics of model polymeric microparticles composed of PEG could be modified for use as a drug delivery carrier.Particle engineering techniques to make pharmaceutical powders have been reviewed recently. 1 Relatively new solution-based particle formation techniques were discussed that involved the use of conventional liquids, compressed gases, near-critical liquids, or supercritical fluids functioning either as solvents, antisolvents, or cryogenic media for freezing. These techniques were shown to involve phase separation of solvent and active pharmaceutical ingredient (API), either by evaporation, rapid expansion, change in solvent composition, or solidification by freezing. The spray configuration in many of these processes produces atomized droplets with high surface areas. Thus, phase separation and rapid nucleation result in small primary particles or highly porous microparticles.

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Section: Methodsmentioning

confidence: 99%

Investigation of processing parameters of spray freezing into liquid to prepare polyethylene glycol polymeric particles for drug delivery

et al. 2003

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“…No change in particle appearance could be seen in the SEM pictures with increasing dextran (150 kDa) content. This type of collapsed morphology has been described in the literature for formulations containing dextran or hydroxyethyl starch and depends on the viscosity of the amorphous structure above its glass transition temperature (Sonner et al 2002;Maa et al 2004;Rochelle & Lee 2007). Primary drying temperatures above the glass transition temperature (T g 0 ) of the amorphous freeze concentrate of frozen SFD formulations can lead to particle morphologies deviating from the original spherical shape of the frozen droplets, in particular, if polymers such as dextran or hydroxyethyl starch are present.…”

mentioning

confidence: 94%

“…This has been explained by Sonner et al (2002) as the result of collapse of the amorphous TMD 10kDa phase during primary drying. No change in particle appearance could be seen in the SEM pictures with increasing dextran (150 kDa) content.…”

mentioning

confidence: 99%

“…High concentrations of sugars and polymers in the initial liquid formulation are necessary (often around 350 mg ml 21 ) to obtain sufficient particle density and mechanical strength (Sonner et al 2002;Maa et al 2004). In particular, polymers such as dextran or hydroxyethyl starch in the formulation are essential ingredients for the maximization of particle robustness (Rochelle & Lee 2007).…”

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confidence: 99%

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Spray-freeze-drying of nanosuspensions: the manufacture of insulin particles for needle-free ballistic powder delivery

Schiffter

Condliffe

Vonhoff

2010

J. R. Soc. Interface.

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The feasibility of preparing microparticles with high insulin loading suitable for needle-free ballistic drug delivery by spray-freeze-drying (SFD) was examined in this study. The aim was to manufacture dense, robust particles with a diameter of around 50 mm, a narrow size distribution and a high content of insulin. Atomization using ultrasound atomizers showed improved handling of small liquid quantities as well as narrower droplet size distributions over conventional two-fluid nozzle atomization. Insulin nanoparticles were produced by SFD from solutions with a low solid content (,10 mg ml 21 ) and subsequent ultra-turrax homogenization. To prepare particles for needle-free ballistic injection, the insulin nanoparticles were suspended in matrix formulations with a high excipient content (.300 mg ml 21) consisting of trehalose, mannitol, dextran (10 kDa) and dextran (150 kDa) (abbreviated to TMDD) in order to maximize particle robustness and density after SFD. With the increase in insulin content, the viscosity of the nanosuspensions increased. Liquid atomization was possible up to a maximum of 250 mg of nano-insulin suspended in a 1.0 g matrix. However, if a narrow size distribution with a good correlation between theoretical and measurable insulin content was desired, no more than 150 mg nano-insulin could be suspended per gram of matrix formulation. Particles were examined by laser light diffraction, scanning electron microscopy and tap density testing. Insulin stability was assessed using size exclusion chromatography (SEC), reverse phase chromatography and Fourier transform infrared (FTIR) spectroscopy. Densification of the particles could be achieved during primary drying if the product temperature (T prod ) exceeded the glass transition temperature of the freeze concentrate (T g 0 ) of 229.48C for TMDD (3 : 3 : 3 : 1) formulations. Particles showed a collapsed and wrinkled morphology owing to viscous flow of the freeze concentrate. With increasing insulin loading, the d (v, 0.5) of the SFD powders increased and particle size distributions got wider. Insulin showed a good stability during the particle formation process with a maximum decrease in insulin monomer of only 0.123 per cent after SFD. In accordance with the SEC data, FTIR analysis showed only a small increase in the intermolecular b-sheet of 0.4 per cent after SFD. The good physical stability of the polydisperse particles made them suitable for ballistic injection into tissue-mimicking agar hydrogels, showing a mean penetration depth of 251.3 + 114.7 mm.

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“…15 Although not determined in this work, we expect SFD sucrose/LN2 to be similarly amorphous. Sucrose contains less nonfrozen water at T 0 g than does trehalose and can therefore loose less water during 18 drying.…”

mentioning

confidence: 90%

Gravimetric Measurement of Momentary Drying Rate of Spray Freeze-Dried Powders in Vials

Gieseler

Lee

2009

Journal of Pharmaceutical Sciences

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Spray‐freeze‐drying for protein powder preparation: Particle characterization and a case study with trypsinogen stability

Cited by 83 publications

References 23 publications

Investigation of processing parameters of spray freezing into liquid to prepare polyethylene glycol polymeric particles for drug delivery

Investigation of processing parameters of spray freezing into liquid to prepare polyethylene glycol polymeric particles for drug delivery

Spray-freeze-drying of nanosuspensions: the manufacture of insulin particles for needle-free ballistic powder delivery

Gravimetric Measurement of Momentary Drying Rate of Spray Freeze-Dried Powders in Vials

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