Maria Malamatari, Satyanarayana Somavarapu, Kevin M.G. Taylor & Graham Buckton
Introduction: Nanosuspensions combine the advantages of nanotherapeutics (e.g. increased dissolution rate and saturation solubility) with ease of commercialisation. Transformation of nanosuspensions to solid oral and inhalable dosage forms minimises the physical instability associated with their liquid state, enhances patient compliance and enables targeted oral and pulmonary drug delivery.
Areas covered: This review outlines solidification methods for nanosuspensions. It includes spray and freeze drying as the most widely used techniques. Fluidised-bed coating, granulation and pelletisation are also discussed as they yield nanocrystalline formulations with more straightforward downstream processing to tablets or capsules. Spray-freeze drying, aerosol flow reactor and printing of nanosuspensions are also presented as promising alternative solidification techniques. Results regarding the solid state, in vitro dissolution and/or aerosolisation efficiency of the nanocrystalline formulations are given and combined with available in vivo data. Focus is placed on the redispersibility of the solid nanocrystalline formulations, which is a prerequisite for their clinical application.
Expert opinion: A few solidified nanocrystalline products are already on the market and many more are in development. Oral and inhalable nanoparticle formulations are expected to have great potential especially in the areas of personalised medicine and delivery of high drug doses (e.g. antibiotics) to the lungs, respectively.
Nanocomposite microparticles are intelligent carriers utilised for pulmonary drug delivery. These carriers are composed of drug-encapsulated nanoparticles dispersed in microstructures of polysaccharides. Upon administration, the inhaled microparticles can penetrate and be deposited deeply in the lung due to their adjusted aerodynamic particle size. Subsequently, the nanoparticles are released into the lung and are retained there for a prolonged time due to their resistance to immunological opsonisation, engulfment and digestion.
Nanocomposite microparticles may be prepared by spray drying, spray freeze drying, spray drying fluidised bed granulation or dry coating techniques. The selection of the included excipients, preparation technique and optimisation of the operational parameter play a significant role in the determination of the aerodynamic particle size, redispersibility of the nanoparticles, morphology, yield, moisture content, flowability and in vitro drug release. Moreover, the in vivo behaviour of this novel carrier may be optimised and traced by studying the lung deposition of the inhaled particles and the biological activity of the encapsulated drug.
Nanocomposite microparticles have been found to be superior to both nanoparticles and microparticles and may represent a promising carrier for pulmonary drug delivery.
Nanoparticle-based pharmaceutical products are currently finding their way onto the market as a popular strategy to improve the therapeutic efficacy of numerous drugs, hereunder medications for a targeted treatment of severe diseases (e.g., cancer). Drug-loaded polymer and lipid nanoparticles are typically produced via solventbased methods and result in colloidal suspensions, which often suffer from physical and chemical instability (e.g., formation of aggregates) resulting in loss of functionality. There are various ways to stabilize such nanoparticlebased formulations including addition of ionic materials to provide electrostatic repulsion or polymer materials forming a steric barrier between the particles. However, for long-term stability often water needs to be removed to obtain a dry product. For this purpose atomization-based techniques such as spray-drying and spray freeze-drying are frequently used to remove water from the nanoparticle suspensions and to form tailored powder products (e.g., nanoembedded microparticles (NEMs)). NEMs provide an excellent vehicle for both stabilization of nanoparticles and delivery of the nanoparticles to their intended site of action. Excipients such as sugars and biocompatible polymers are used to prepare the surrounding, stabilizing matrix. Further, these “Trojan” vehicles are compatible with a wide range of therapeutic molecules, nanocarriers and applications for different routes of administration. The preparation, properties and stability of these NEMs are described in this review and their application and future development are discussed.
Carlos F. Gutierrez-Gonzalez, Nestor W. Solis Pinargote, Said Agouram, Pavel Y. Peretyagin, Sonia Lopez-Esteban and Ramon Torrecillas
This work describes a whole processing route for obtaining dense and nanostructured zirconia-nickel composites with low contents of metallic phase (1–3.5 vol%). For the processing route, a combinationof spray-freezing and lyophilization has been proposed. After the calcination and reduction of the resultingpowders an X-ray and HRTEM characterization has been performed. This showed the formation of pure zirconia and nickel, well dispersed and homogeneously distributed, nanostructured phases. The obtainedpowders were subsequently sintered by Spark Plasma Sintering (SPS). As a result, dense ZrO2 Ni composites were obtained, revealing that the sizes of the metal particles were kept in the nanometer rangeand appear homogeneously and well dispersed into the ceramic matrix. The mechanical behavior of these materials was evaluated by means of the Vickers hardness, showing and increment of about 25% with
respect to pure zirconia with only a Ni concentration of 1 vol%.
Otake H, Okuda T, Hira D, Kojima H, Shimada Y, Okamoto H
The purpose of this study was to develop inhalable particles that can reach deep into the lungs efficiently independent of inhalation patterns of patients and inhalation devices. We prepared porous particles including L-leucine (Leu), a dispersive agent, by a spray-freeze-drying (SFD) method and examined the influence of inspiratory flow patterns and inhalation devices with various inhalation resistances.
Four types of SFD powder with different Leu contents (0-10%) were prepared. Scanning electron microscopy and laser diffraction were used to measure the morphology and size distribution of the powders. In-vitro inhalation characteristics were determined using a twin-stage liquid impinger equipped with an inspiratory flow pattern simulator. The effects of Leu on the adhesion force and electrostatic property of the particles were evaluated.
The inhalation performance of the powders was improved by the addition of Leu. The powders with Leu showed a high inhalation performance regardless of inspiratory flow patterns and devices. The addition of Leu decreased the adhesion force and increased the surface potential of the powders.
The SFD particles with Leu showed high inhalation performance regardless of the inhalation patterns and devices, which was attributed to the decreased adhesion force between particles and increased dispersibility.
Agata Sidorowicz, Magdalena Nakielska, Anna Wajler, Helena Węglarz, Katarzyna Jach, Andrzej Olszyna
The aim of this work has been to obtain transparent Tm, Ho:YAG ceramics (thulium doping range: 2–6 at.%, holmium doping range: 0.1–1.0 at.%) by reaction sintering using commercial powders. It has been proved that the particle size, purity and degree of agglomeration of the powders used are crucial from the point of view of the optical quality of ceramics. The spectroscopic measurements of Tm, Ho:YAG ceramics with different concentration of active ions (including transmission and emission spectra measurements) have been presented and discussed. As has been found, both concentration of holmium and thulium separately as well as the balance between them are of great importance. Energy transfer between Tm and Ho ions has been demonstrated.
Abstract: Spray freeze granulation is an improved method based on spray granulation, solving many limitations of spray granulation. In this work, spray freeze granulation of submicron alumina is performed to explore the possibility of industrial-scale production of dense alumina via spark plasma sintering. Powder pretreatment such as sedimentation and the selection of granules with the appropriate size are employed for the maximum use of the high qualified as-prepared granules and granule sliding, which would provide a guidance for the industrial-scale production. Debound granules were densified via SPS and the corresponding sintering behaviors such as the recorded shrinkage and shrinkage rate were discussed. The comparison of sintering behaviors between granulated and as-received powder are conducted to identify the role of spray freeze granulation in sinterability for dense alumina. The Vickers hardness (Hv) and the fracture toughness (KIC) of the freeze granulated body are higher than the corresponding properties of the as-received body due to the more homogenous microstructure with little agglomeration in the particle packing after freeze granulation.
Second day at CERAMITEC 2015 on Oct 21th with good discussions upon processing of different powder material by Freeze Granulation and the advantages regarding granule homogeneity and the impact on the ultimate material performance it brings.
Recently, enormous efforts have been done within the development of Li-ion batteries for use in portable electric devices from small scale applications such as mobile phones, digital cameras, laptop computers, to large scale applications like electrical vehicles (EVs) and hybrid electric vehicles (HEVs). LiFePO4 as an active material in cathode materials in Li-ion batteries has shown outstanding advantages compare to other cathode materials such as low cost, low toxicity and environmental compatibility, good thermal stability, high theoretical specific capacity of 170 mAh/g and operating reversibility at 3.4V. Still, it is a need to develop the manufacture of the cathode material to achieve improved performance reliability by using environmental sustainable processes in order to meet future demands in large scale production and uses of Li-ion batteries. The aim of this work was to develop a non-toxic, cheap, efficient and environmentally friendly process for synthesis of high quality active cathode material based on LiFePO4 for Li-ion batteries. Water based suspensions/solutions containing various reactant constituents have been homogenized, granulated and calcined. Freeze granulation was applied as the key tool for the synthesis of LiFePO4 with integrated carbon in order to produce granules with high degree of homogeneity prior to calcination. The resulting powder materials have been evaluated by XRD, carbon and conductivity measurements and characterization of other physical properties such as density and specific surface area. The promising version was used for manufacture of cathode material by tape casting, cell assembling and evaluation of the performance by charge/discharge cycling of the cells. For the best sample in our experiment the XRD results revealed a high degree of purity, homogeneity and crystallinity of LiFePO4. The produced LiFePO4/C composite also had a high specific surface area and, therefore, considered as a promising material for cathode manufacturing and cell assembly. A discharge capacity of 155 and 140 mAh/g was achieved at the fifth cycle at 0.1C rate at room temperature for the cathodes which were made with NMP (solvent based) and water system, respectively. The long-term stability test indicated good result with no loss in capacity for at least 390 cycles. The satisfactory discharge capacity should be attributed to the homogenous nano-sized particles with a conductive porous carbon structure that was provided by the freeze granulation process and adapted calcination process.
Keywords: Li-ion batteries, LiFePO4, cathode active material, specific capacity, freeze granulation, calcination, LiFePO4/C composite, cell assembly.
Use of freeze granulated powders is successfully used as an industrially viable alternative to loose powder sintering for transparent polycrystalline alumina (PCA). Freeze granulation with narrow granule size distribution was realized after suspension condition optimization, with very good ﬂowability and regular spherical shapes. The key factors are low viscosity slurries linked to the complex interactions between the organic processing additives and their interaction with dopant ions in solution. Real in-line transmittances (RITs) of 52% were achieved by pulsed electric current sintering (PECS) of dry pressed green bodies from doped granulated powders. This is the ﬁrst example of a high RIT (>50%) alumina produced from simple dry pressing of a granulated powder. The results indicate that higher granule solid loads and lower organic additive concentrations give better RITs after PECS. Aging of the powder slurry before freeze granulation proves a crucial step for the optical performance of the ﬁnal transparent PCA.