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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.

Atmospheric Spray Freeze-Drying: Numerical Modeling and Comparison With Experimental Measurements

Israel Borges Sebastião, Thomas D. Robinson, Alina Alexeenko

Abstract

Atmospheric spray freeze-drying (ASFD) represents a novel approach to dry thermosensitive solutions via sublimation. Tests conducted with a second-generation ASFD equipment, developed for pharmaceutical applications, have focused initially on producing a light, fine, high-grade powder consistently and reliably. To better understand the heat and mass transfer physics and drying dynamics taking place within the ASFD chamber, 3 analytical models describing the key processes are developed and validated. First, by coupling the dynamics and heat transfer of single droplets sprayed into the chamber, the velocity, temperature, and phase change evolutions of these droplets are estimated for actual operational conditions. This model reveals that, under typical operational conditions, the sprayed droplets require less than 100 ms to freeze. Second, because understanding the heat transfer throughout the entire freeze-drying process is so important, a theoretical model is proposed to predict the time evolution of the chamber gas temperature. Finally, a drying model, calibrated with hygrometer measurements, is used to estimate the total time required to achieve a predefined final moisture content. Results from these models are compared with experimental data.

Keywords

spray freeze-drying; thermodynamics; simulations; proteins; freeze-drying/lyophilization; powder technology; mathematical model

Hydroxypropylcellulose as matrix carrier for novel cage-like microparticles prepared by spray-freeze-drying technology

Shaofeng Weia, Yueqin Mab, Jing Luoa, Xiaoru Hea, Pengfei Yuea, Zhiyu Guana, Ming Yanga

Abstract

The objective of this study is to design novel dissolution-enhanced microparticles loaded poorly soluble drug nanocrystals used a low viscosity of hydroxypropylcellulose (HPC) as matrix carrier. An interesting approach combined homogenization and the spray-freeze-drying technique was developed. The results demonstrated that the ratio of HPC to drug played an important role in size-reduction efficiency of drug during homogenization. And the formation of cage-like structure of the composite particles depended on ratio of HPC to drug. The spray-freeze-dried composite particles with HPC ratio of 1:2, 1:1 and 2:1 possessed excellent redispersibility, which attributed to its porous matrix and large surface area (3000 m2/g). The dissolution of spray-freeze-dried composite particles with higher ratios of HPC (1:2 and 1:1) was significantly enhanced, which attributed to the particle size reduction of drug. The HPC could immobilize drug nanocrystals in its cage-like structure and prevent it from the subsequent agglomeration during storage. In conclusion, the prepared cage-like microparticles is a promising basis for further formulation development.

Keywords

Hydroxypropylcellulose; Nanocrystals; Cage-like microparticles; Spray-freeze-drying; Redispersibility