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Jet-vortex spray freeze drying for the production of inhalable lyophilisate powders

Wanning S, Süverkrüp R, Lamprecht A

Abstract

Spray-freeze-dried powders were suggested for nasal, epidermal (needle-free injection) or pulmonary application of proteins, peptides or nucleic acids. In spray-freeze-drying processes an aqueous solution is atomized into a refrigerant medium and subsequently dried by sublimation. Droplet-stream generators produce a fast stream of monodisperse droplets, where droplets are subject to collisions and therefore the initial monodispersity is lost and droplets increase in diameter, which reduces their suitability for pulmonary application. In jet-vortex-freezing, a droplet-stream is injected into a vortex of cold process gas to prevent droplet collisions. Both the injection position of the droplet-stream and the velocity of the cold gas vortex have an impact on the size distributions of the resulting powders. A model solution containing mannitol (1.5%m/V) and maltodextrin (1.5%m/V) was sprayed at 5 droplet-stream positions at distances between 1mm and 30mm from the gas jet nozzle and 5 gas velocities (0.8-6.8m/s) at a process temperature of -100°C. Mean geometric diameters of the highly porous particles (bulk density: 0.012±0.007g/cm3) ranged between 55±4 and 98±4μm. Evaluation of the aerodynamic properties by Next-Generation-Impactor (NGI) analysis showed that all powders had high emitted doses (98±1%) and fine-particle fractions ranged between 4±1% and 21±2%. It was shown that jet-vortex freezing is a suitable method for the reproducible production of lyophilized powders with excellent dispersibility in air, which has a high potential for nasal and pulmonary drug delivery.

KEYWORDS

Droplet collision; Droplet-stream generator; Lyophilization; Porous particles; Protein formulations; Pulmonary drug delivery; Spray freeze drying

Inhalable clarithromycin liposomal dry powders using ultrasonic spray freeze drying

Tiantian Yea, Jiaqi Yub, Qiuhua Luoa, Shujun Wanga, Hak-Kim Chanb

Abstract

Liposomal dry powder inhalation for the pulmonary administration has a great potential to improve the efficacy of antibiotics while reducing adverse effects. To improve aerosolisation efficiency of liposomal dry powders, we prepared clarithromycin liposomal powder formulations (CLA-Lips-DPIs) by an ultrasonic spray freeze drying (USFD) method using 15% mannitol and 5% sucrose (W:V) as combination lyoprotectants (co-lyoprotectants). The formulation had a porous structure, comprising micron-sized particles with uniform drug content and high drug recovery. Co-lyoprotectants could modulate the liposomal powder from absorbing moisture, resulting in moisture absorption being < 15% (W/W) when stored at 75% relative humility for 2 h. The interaction of CLA, lyoprotectant and lipids of CLA-Lips-DPIs was investigated by differential scanning calorimetry. The reconstituted liposome suspension showed a high entrapment efficiency of up to 80% and a narrow size distribution due to the co-lyoprotectants protection. CLA-Lips-DPIs formulations remained unchanged after 3-month storage at 60% RH and 25 °C with a high aerosol efficiency (emitted dose > 85%, fine particle fraction 43%–50%). These results demonstrated the aerosolisation efficiency and storage of the CLA-Lips-DPIs formulation. Liposomal powder formulations prepared by USFD can potentially be an effective drug delivery system for delivering antibiotics.

Keywords

Ultrasonic spray freeze drying; Liposomes; Clarithromycin; Dry powder inhaler (DPI); Inhalation aerosols; Aerosolisation efficiency

Spray freeze-dried nanofibrillated cellulose aerogels with thermal superinsulating properties

Clara Jiménez-Saelicesa, Bastien Seantiera, Bernard Cathalab, Yves Grohensa

Abstract

Nanofibrillated cellulose (NFC) aerogels were prepared by spray freeze-drying (SFD). Their structural, mechanical and thermal insulation properties were compared to those of NFC aerogels prepared by conventional freeze-drying (CFD). The purpose of this investigation is to develop superinsulating bioaerogels by reducing their pore size. Severe reduction of the aerogel pore size and skeleton architecture were observed by SEM, aerogels prepared by SFD method show a fibril skeleton morphology, which defines a mesoporous structure. BET analyses confirm the appearance of a new organization structure with pores of nanometric sizes. As a consequence, the thermal insulation properties were significantly improved for SFD materials compared to CFD aerogel, reaching values of thermal conductivity as low as 0.018 W/(m K). Moreover, NFC aerogels have a thermal conductivity below that of air in ambient conditions, making them one of the best cellulose based thermal superinsulating material.

Keywords

Nanofibrillated cellulose (NFC); Aerogel; Freeze-drying; Nano structure formation; Thermal superinsulation

A new class of closed-cell aluminium foams reinforced with carbon nanotubes

I. Duartea, E. Venturaa, S. Olherob, J.M.F. Ferreirab

Abstract

This manuscript reports on the fabrication of closed-cell aluminium alloy foams reinforced with carbon nanotubes (CNTs) through a novel approach that combines the powder metallurgy method with colloidal processing step that grants uniform dispersion of CNTs into the aqueous suspension of all powder components. Spraying the as prepared suspension into liquid nitrogen followed by lyophilisation enables obtaining homogeneous spherical granules to be used in the powder metallurgy method. Besides ensuring good dispersion of all powder components in the system, the non-agglomerated form of CNTs and the expansion upon foaming foster their structural integrity under stretched conditions in the final foams for an efficient load transfer.

Keywords

reinforced aluminium foams; carbon nanotubes; freeze-granulation; powder metallurgy

Enhancement of oral bioavailability of vitamin E by spray-freeze drying of whey protein microcapsules

Parthasarathi S., C. Anandharamakrishnana

Abstract

Vitamin E microcapsules were effectively prepared using three different techniques: spray drying, freeze-drying and spray freeze-drying with whey protein isolate as an encapsulating agent. The quality of microcapsules was evaluated by particle size distribution, surface morphology, encapsulation efficiency, moisture content, flow properties (Hausner ratio), dissolution properties and in vivo oral bioavailability. Vitamin E microcapsules prepared by spray drying, freeze-drying and spray freeze-drying techniques showed maximum encapsulation efficiencies of 89.6 ± 2.58, 86.1 ± 1.44, and 89.3 ± 2.56 respectively. Both freeze-dried and spray freeze-dried microcapsules showed excellent dissolution behavior with higher ODmax and dissolution rates (k0) than the spray-dried microcapsules due to the presence of numerous porous internal structures. Oral bioavailability study performed in male Wistar rats showed enhanced values of maximum plasma concentration (Cmax) and area under the curve (AUC) for spray freeze-dried microcapsules. The overall results demonstrate that the spray freeze-drying based microencapsulation technique could be a promising strategy to enhance the oral bioavailability of poorly water-soluble bioactive compounds like vitamin E.

Keywords

Vitamin E; Microcapsules; Spray freeze drying; Morphology; Dissolution; Bioavailability

Aerodynamic Droplet Stream Expansion for the Production of Spray Freeze-Dried Powders

Wanning S, Süverkrüp R, Lamprecht A

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.

KEYWORDS

flowable lyophilized powders; lyophilization; porous particles; protein formulations; spray freeze-drying

Aerosol assisted self-assembly as a route to synthesize solid and hollow spherical lignin colloids and its utilization in layer by layer deposition

Mishra PK, Wimmer R

Abstract

Lignin, a major constituent of plant cell-wall and by-product of paper based industries is traditionally used for low value applications (heat or electricity generation), but its potential in high value utilization has also been widely reported. In this work, we synthesized lignin colloidal particles using ultrasonic spray-freezing route without any chemical functionalization of material, and stabilized it by electrostatic route. As per our knowledge, this technique is the first reported method which yields hollow/solid lignin colloids having good particle size control without any chemical functionalization of material. Dioxane soluble fraction of Alkali lignin (d-lignin) was used without any further chemical functionalization. d-lignin dissolved in DMSO was sprayed upon liquid nitrogen cooled copper plate using an ultrasonic nebulizer. The resulting frozen droplets were collected and found to possess hollow and solid morphology. Particles thus obtained were characterized for their size distribution and morphology, and compared to theoretically anticipated values. Size tunability of particles in relation to concentration of sprayed lignin solution was also studied. In addition to that, six layers of lignin colloids were deposited on quartz slide with the aid of negligible UV absorbing polyelectrolyte aqueous solution PDADMAC [Poly (diallyldimethylammonium chloride)]. Gradation in UV absorbing ability of lignin with increase in number of layers could be clearly observed. Hollow and solid lignin colloids, apart from their application in sunscreen cosmetics owing to their UV absorbing ability, show potential applications in drug delivery also.

KEYWORDS

Hollow and solid lignin colloids; Layer by layer deposition; UV absorbance by lignin

Spray freeze drying as an alternative technique for lyophilization of polymeric and lipid-based nanoparticles

Mohamed Ehab Alia, Alf Lamprechta

Abstract

The use of nanoparticles for drug delivery is still restricted by their limited stability when stored in an aqueous medium. Freeze drying is the standard method for long-term storage of colloidal nanoparticles; however the method needs to be elaborated for each formulation. Spray freeze drying (SFD) is proposed here as a promising alternative for lyophilizing colloidal nanoparticles. Different types of polymeric and lipid nanoparticles were prepared and characterized. Afterwards, samples were spray freeze dried by spraying into a column of cold air with a constant concentration of different cryoprotectants, and the frozen spherules were collected for further freeze drying. Similar samples were prepared using the commonly used technique, freeze drying, as controls. Using SFD, fast-dissolving, spherical and porous nanocomposite microparticles with remarkably high flowability (CI ≤ 10) were produced. On the contrary to similar samples prepared using the freeze drying technique, the investigated polymeric and lipid nanoparticles were completely reconstituted (Sf/Si ratio <1.5) after SFD. SFD proved to be an effective platform for improving the long-term stability of colloidal nanoparticles.

Keywords

Spray freeze drying; Stability; Freeze drying; Polymeric nanoparticles; Lipid nanocapsules; Solid lipid nanoparticles; Liposomes

Improved transparency and hardness in α-alumina ceramics fabricated by high-pressure SPS of nanopowders

Shaghayegh Ghanizadeha, Salvatore Grassob, Prabhu Ramanujamc, Bala Vaidhyanathana, Jon Binnerc, Peter Brownd, Judah Goldwassere

Abstract

Nanocrystalline alumina powder with an average crystallite size of ≤50 nm has been consolidated by spark plasma sintering (SPS) and hot pressing (HP) with a view to achieving dense, fine grained alumina bodies that display transparency. When as-synthesised powder was densified directly, excessive grain growth resulted from both the SPS and HP techniques and hence a large final grain size was observed. Attempts to improve the uniformity of the green microstructure prior to densification were unsuccessful when spray freeze dried granules were used, whether pre-pressed into a compact or not. The use of 53% dense slip cast green compacts, however, enabled final density of ~99.96% and a mean grain size of ~0.32 µm to be achieved when SPS conditions of 1200 °C and 500 MPa were applied for 20 min. These samples offered in-line transmittance values of up to ~80% and microhardness values of 22 GPa.

Keywords

Nanocrystalline; Alumina; SPS; Hot press; Transparent

Effect of cryogenic freezing by liquid nitrogen on the quality and microstructure of Portunus trituberculatus

Hori T, Odaka S, Oba H, Mizutani T, Kawakami E, Tsutsui T.

Abstract

The freezing conditions for preparation of frozen canine semen by the plunging method were investigated with regard to the period of sensitization in liquid nitrogen (LN2) vapor and the height from LN2, and the semen qualities after thawing were compared with those of canine semen prepared by the simple freezer method previously reported by us. In the plunging method, 9 semen straws were prepared under the same conditions, horizontally kept at 5, 7, and 10 cm above the LN2 surface in a styrene foam box for 5, 10, and 15 min, and then plunged into LN2. The semen qualities immediately after thawing were high in the 7 cm/10 min (cooling rate: -4 to -22 degrees C/min) and 10 cm/15 min groups (cooling rate: -6 to -10 degrees C/min). On comparison of frozen semen prepared by the plunging method (7 cm/10 min) with frozen semen prepared by the simple freezer method, sperm motility and viability were significantly higher for the frozen semen prepared by the plunging method. The cooling rate in freezing was higher for the simple freezer method (cooling rate: -6 to -50.9 degrees C/min) than the plunging method. Based on these findings, horizontal placement of canine semen straws above LN2 to reduce the temperature at a slow cooling rate of about -10 degrees C/min, followed by plunging into LN2 after sensitization for 10-15 min, provides good semen qualities after thawing.