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

2010 ◽  
Vol 7 (suppl_4) ◽  
Author(s):  
Heiko Schiffter ◽  
Jamie Condliffe ◽  
Sebastian Vonhoff
Keyword(s):  
Size Distribution ◽  
Freeze Drying ◽  
Size Exclusion ◽  
Insulin Content ◽  
Size Distributions ◽  
Narrow Size Distribution ◽  
Matrix Formulation ◽  
Tap Density ◽  
Spray Freeze Drying ◽  
Insulin Stability

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 µm, 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 −1 ) 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 −1 ) 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 ′) of −29.4°C 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 β-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 µm.

Characterization of Booming Sands

2002 ◽  
Vol 759 ◽  
Author(s):  
Katherine S. Brantley ◽  
Melany L. Hunt ◽  
Christopher E. Brennen ◽  
Steven S. Gao
Keyword(s):  
United States ◽  
Moisture Content ◽  
Size Distribution ◽  
Sand Dunes ◽  
The United States ◽  
Size Distributions ◽  
Narrow Size Distribution ◽  
Dune Sands ◽  
The Mean

ABSTRACTMany sand dunes – at least seven in the United States – make loud booming noises when they avalanche. Records of the sound are centuries old, but the cause remains a mystery. This study examines properties of both the sand and the sound.Properties of the sand reveal clues about the source of the booming. Sand must be extremely dry to boom, but low moisture content alone is not sufficient to facilitate booming. Although the mean grain diameters of both booming and silent dune sands range from 0.20 – 0.40mm, the booming samples have smaller standard deviations. However, synthetic sands with similar size distributions do not boom, so a narrow size distribution cannot be solely responsible for the booming. Studies of the roundness and sphericity of the grains are currently underway.Air microphone and geophone recordings of the booming indicate that the fundamental frequency varies between 80–105 Hz depending on the dunes. This is consistent with previous measurements. Laboratory recordings of the “burping” sound that booming sand makes when shaken in a jar reveal a broad peak between 150–300 Hz.

Narrowing sputtered nanoparticle size distributions

1993 ◽  
Vol 8 (5) ◽  
pp. 995-1000 ◽  
Author(s):  
F.H. Kaatz ◽  
G.M. Chow ◽  
A.S. Edelstein
Keyword(s):  
Size Distribution ◽  
Mean Free Path ◽  
Particle Formation ◽  
Distribution Functions ◽  
Size Distributions ◽  
Narrow Size Distribution ◽  
Linear Arrangement ◽  
Nanocrystalline Particle ◽  
The Mean ◽  
Potential Use

By adjusting the sputtering rate and gas pressure, it is possible to form nanoparticles of different sizes, phases, and materials. We have investigated the spatial distribution of sputtered particle formation using a vertical, linear arrangement of substrates. Collecting the particles soon after they are formed, before they have time to grow and agglomerate, allows one to obtain a narrow size distribution. In the case of molybdenum, a narrow distribution of cubic particles is formed at relatively large distances (8 cm) from the source. These cubic particles collide and self-assemble in the vapor into arrays of larger cubic particles. The particle size histograms are fitted to lognormal distribution functions. How supersaturation occurs is discussed qualitatively as a function of the distance from the substrate, sputtering rate, and the mean free path in the vapor. This method of nanocrystalline particle formation has potential use in magnetic and opto-electronic (quantum dot) applications, where a narrow size distribution is required.

Comparison of Flowability and Sinterability Among Different Binder Jetting Feedstock Powders: Nanopowder, Micropowder, and Granulated Powder

2021 ◽  
Vol 9 (2) ◽  
Author(s):  
Wenchao Du ◽  
Guanxiong Miao ◽  
Zhijian Pei ◽  
Chao Ma
Keyword(s):  
Particle Size ◽  
Flow Rate ◽  
Freeze Drying ◽  
Volumetric Flow Rate ◽  
Granule Size ◽  
Hausner Ratio ◽  
Tap Density ◽  
Spray Freeze Drying ◽  
Binder Jetting ◽  
High Flowability

Abstract Feedstock powders used in binder jetting additive manufacturing include nanopowder, micropowder, and granulated powder. Two important characteristics of the feedstock powders are flowability and sinterability. This paper aims to compare the flowability and sinterability of different feedstock powders. Three powders were compared: nanopowder (with a particle size of ∼100 nm), micropowder (with a particle size of 70 μm), and granulated powder (with a granule size of ∼70 μm) made from the nanopowder by spray freeze drying. Flowability metrics employed included apparent density (AD), tap density (TD), volumetric flow rate (VFR), mass flow rate (MFR), Hausner ratio (HR), Carr index (CI), and repose angle (RA). Sinterability metrics employed included sintered bulk density (SBD), volumetric shrinkage (VS), and densification ratio (DR). Results show that the granulated powder has a higher flowability than the nanopowder and a higher sinterability than the micropowder. Moreover, different flowability metric values of the granulated powder are close to those of the micropowder, indicating that these two powers have a comparably high flowability. Similarly, different sinterability metric values of the granulated powder are close to those of the nanopowder, indicating that these two powders have a comparably high sinterability.

scholarly journals A new purification technique to obtain specific size distribution of giant lipid vesicles using dual filtration

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254930
Author(s):  
Mohammad Abu Sayem Karal ◽  
Tawfika Nasrin ◽  
Marzuk Ahmed ◽  
Md. Kabir Ahamed ◽  
Shareef Ahammed ◽  
...  
Keyword(s):  
Size Distribution ◽  
Fluorescent Probe ◽  
Lognormal Distribution ◽  
Lipid Vesicles ◽  
Water Soluble ◽  
Size Distributions ◽  
Narrow Size Distribution ◽  
Purification Technique ◽  
Polycarbonate Membranes ◽  
Filtration Technique

A new purification technique is developed for obtaining distribution of giant unilamellar vesicles (GUVs) within a specific range of sizes using dual filtration. The GUVs were prepared using well known natural swelling method. For filtration, different combinations of polycarbonate membranes were implemented in filter holders. In our experiment, the combinations of membranes were selected with corresponding pore sizes–(i) 12 and 10 μm, (ii) 12 and 8 μm, and (iii) 10 and 8 μm. By these filtration arrangements, obtained GUVs size distribution were in the ranges of 6−26 μm, 5–38 μm and 5–30 μm, respectively. In comparison, the size distribution range was much higher for single filtration technique, for example, 6−59 μm GUVs found for a membrane with 12 μm pores. Using this technique, the water-soluble fluorescent probe, calcein, can be removed from the suspension of GUVs successfully. The size distributions were analyzed with lognormal distribution. The skewness became smaller (narrow size distribution) when a dual filtration was used instead of single filtration. The mode of the size distribution obtained in dual filtration was also smaller to that of single filtration. By continuing this process of purification for a second time, the GUVs size distribution became even narrower. After using an extra filtration with dual filtration, two different size distributions of GUVs were obtained at a time. This experimental observation suggests that different size specific distributions of GUVs can be obtained easily, even if GUVs are prepared by different other methods.

Macrostructure and microphysics of Saturn's E-ring

1984 ◽  
Vol 75 ◽  
pp. 607-613 ◽  
Author(s):  
Kevin D. Pang ◽  
Charles C. Voge ◽  
Jack W. Rhoads
Keyword(s):  
Size Distribution ◽  
Spherical Shape ◽  
Mie Scattering ◽  
Narrow Size Distribution ◽  
Electrostatic Levitation ◽  
Volcanic Origin ◽  
Micron Diameter

Abstract.All observed optical and infrared properties of Saturn's E-ring can be explained in terms of Mie scattering by a narrow size distribution of ice spheres of 2 - 2.5 micron diameter. The spherical shape of the ring particles and their narrow size distribution imply a molten (possibly volcanic) origin on Enceladus. The E-ring consists of many layers, possibly stratified by electrostatic levitation.

scholarly journals Intratracheal inoculation of AHc vaccine induces protection against aerosolized botulinum neurotoxin A challenge in mice

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Changjiao Gan ◽  
Wenbo Luo ◽  
Yunzhou Yu ◽  
Zhouguang Jiao ◽  
Sha Li ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Clostridium Botulinum ◽  
Freeze Drying ◽  
Botulinum Neurotoxin ◽  
Secretory Iga ◽  
Immune Protection ◽  
Dry Powder ◽  
Botulinum Neurotoxin A ◽  
Spray Freeze Drying

AbstractBotulinum neurotoxin (BoNT), produced by Clostridium botulinum, is generally known to be the most poisonous of all biological toxins. In this study, we evaluate the protection conferred by intratracheal (i.t.) inoculation immunization with recombinant Hc subunit (AHc) vaccines against aerosolized BoNT/A intoxication. Three AHc vaccine formulations, i.e., conventional liquid, dry powder produced by spray freeze drying, and AHc dry powder reconstituted in water are prepared, and mice are immunized via i.t. inoculation or subcutaneous (s.c.) injection. Compared with s.c.-AHc-immunized mice, i.t.-AHc-immunized mice exhibit a slightly stronger protection against a challenge with 30,000× LD50 aerosolized BoNT/A. Of note, only i.t.-AHc induces a significantly higher level of toxin-neutralizing mucosal secretory IgA (SIgA) production in the bronchoalveolar lavage of mice. In conclusion, our study demonstrates that the immune protection conferred by the three formulations of AHc is comparable, while i.t. immunization of AHc is superior to s.c. immunization against aerosolized BoNT/A intoxication.

scholarly journals Effect of Strain-Induced Precipitation on the Recrystallization Kinetics in a Model Alloy

2021 ◽  
Author(s):  
Mo Ji ◽  
Martin Strangwood ◽  
Claire Davis
Keyword(s):  
Grain Size ◽  
Size Distribution ◽  
Grain Size Distribution ◽  
Avrami Exponent ◽  
Model Alloy ◽  
Size Distributions ◽  
Recrystallization Kinetics ◽  
Grain Size Distributions ◽  
Recrystallized Grain Size ◽  
Nb Addition

AbstractThe effects of Nb addition on the recrystallization kinetics and the recrystallized grain size distribution after cold deformation were investigated by using Fe-30Ni and Fe-30Ni-0.044 wt pct Nb steel with comparable starting grain size distributions. The samples were deformed to 0.3 strain at room temperature followed by annealing at 950 °C to 850 °C for various times; the microstructural evolution and the grain size distribution of non- and fully recrystallized samples were characterized, along with the strain-induced precipitates (SIPs) and their size and volume fraction evolution. It was found that Nb addition has little effect on recrystallized grain size distribution, whereas Nb precipitation kinetics (SIP size and number density) affects the recrystallization Avrami exponent depending on the annealing temperature. Faster precipitation coarsening rates at high temperature (950 °C to 900 °C) led to slower recrystallization kinetics but no change on Avrami exponent, despite precipitation occurring before recrystallization. Whereas a slower precipitation coarsening rate at 850 °C gave fine-sized strain-induced precipitates that were effective in reducing the recrystallization Avrami exponent after 50 pct of recrystallization. Both solute drag and precipitation pinning effects have been added onto the JMAK model to account the effect of Nb content on recrystallization Avrami exponent for samples with large grain size distributions.

scholarly journals Post-Processing Techniques for the Improvement of Liposome Stability

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1023
Author(s):  
Ji Young Yu ◽  
Piyanan Chuesiang ◽  
Gye Hwa Shin ◽  
Hyun Jin Park
Keyword(s):  
Freeze Drying ◽  
Protective Agent ◽  
Post Processing ◽  
Additional Process ◽  
Spray Freeze Drying ◽  
The Stability ◽  
Processing Techniques ◽  
The Impact ◽  
Self Aggregation ◽  
Liposome Stability

Liposomes have been utilized as a drug delivery system to increase the bioavailability of drugs and to control the rate of drug release at the target site of action. However, the occurrence of self-aggregation, coalescence, flocculation and the precipitation of aqueous liposomes during formulation or storage can cause degradation of the vesicle structure, leading to the decomposition of liposomes. To increase the stability of liposomes, post-processing techniques have been applied as an additional process to liposomes after formulation to remove water and generate dry liposome particles with a higher stability and greater accessibility for drug administration in comparison with aqueous liposomes. This review covers the effect of these techniques including freeze drying, spray drying and spray freeze drying on the stability, physicochemical properties and drug encapsulation efficiency of dry liposomes. The parameters affecting the properties of liposomes during the drying process are also highlighted in this review. In addition, the impact of using a protective agent to overcome such limitations of each process is thoroughly discussed through various studies.

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