Needle-Free Delivery of Powdered Protein Vaccines: A New and Rapidly Developing Technique

Ziegler, Andreas

doi:10.1007/s12247-008-9039-x

Cited by 10 publications

(5 citation statements)

References 45 publications

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“…Classical freeze-drying does not lead to distinct particles, but rather to the wellknown cake structure that has to be disaggregated in a subsequent step, usually leading to a very wide particle size distribution with a substantial fine powder fraction that cannot be used for needle-free delivery. A summary of other methods for the manufacture of powders for needle-free injection can be found in the literature (Burkoth et al 1999;Ziegler 2008).…”

Section: Introductionmentioning

confidence: 99%

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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Section: Introductionmentioning

confidence: 99%

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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“…Ziegler (2008) has shown that acceptable DNA vaccination requires the coated micro-particle to penetrate the skin surface with around 20-100 mm penetration depth. It indicated that needle-free biolistic micro-particle injection achieves a more efficient pharmaceutical effect than diffusion delivery.…”

Section: Effects Of Physical Approaches To Drug Deliverymentioning

confidence: 99%

Potential of microneedle-assisted micro-particle delivery by gene guns: a review

2013

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“…The micro‐particles are generally required to penetrate to certain depths within the target to carry out the desired effect of gene delivery and, as such, the penetration depth of the micro‐particles is one of the major variables studied in gene delivery research. Ziegler has indicated that an acceptable DNA delivery requires that the micro‐particles penetrate into the target skin tissue by approximately 20 ± 100 μm. However, the top layer of the skin, that is the stratum corneum , limits the penetration depths for the particles because of its resistance to particle motion.…”

Section: Introductionmentioning

confidence: 99%

Microneedle Assisted Micro-Particle Delivery from Gene Guns: Experiments Using Skin-Mimicking Agarose Gel

Zhang

Das

Rielly

2014

Journal of Pharmaceutical Sciences

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A set of laboratory experiments has been carried out to determine if micro‐needles (MNs) can enhance penetration depths of high‐speed micro‐particles delivered by a type of gene gun. The micro‐particles were fired into a model target material, agarose gel, which was prepared to mimic the viscoelastic properties of porcine skin. The agarose gel was chosen as a model target as it can be prepared as a homogeneous and transparent medium with controllable and reproducible properties allowing accurate determination of penetration depths. Insertions of various MNs into gels have been analysed to show that the length of the holes increases with an increase in the agarose concentration. The penetration depths of micro‐particle were analysed in relation to a number of variables, namely the operating pressure, the particle size, the size of a mesh used for particle separation and the MN dimensions. The results suggest that the penetration depths increase with an increase of the mesh pore size, because of the passage of large agglomerates. As these particles seem to damage the target surface, then smaller mesh sizes are recommended; here, a mesh with a pore size of 178 μm was used for the majority of the experiments. The operating pressure provides a positive effect on the penetration depth, that is it increases as pressure is increased. Further, as expected, an application of MNs maximises the micro‐particle penetration depth. The maximum penetration depth is found to increase as the lengths of the MNs increase, for example it is found to be 1272 ± 42, 1009 ± 49 and 656 ± 85 μm at 4.5 bar pressure for spherical micro‐particles of 18 ± 7 μm diameter when we used MNs of 1500, 1200 and 750 μm length, respectively. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:613–627, 2014

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Needle-Free Delivery of Powdered Protein Vaccines: A New and Rapidly Developing Technique

Abstract: Skin is an attractive tissue for vaccine delivery.Recently, interest has focused on dry powder injectors for needle-free vaccination. This review summarizes the current knowledge on this innovative application technique.

Cited by 10 publications

References 45 publications

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

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

Potential of microneedle-assisted micro-particle delivery by gene guns: a review

Microneedle Assisted Micro-Particle Delivery from Gene Guns: Experiments Using Skin-Mimicking Agarose Gel

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