Novel preparation approach with a 2-step process for spherical particles with high drug loading and controlled size distribution using melt granulation: MALCORE®

A novel approach for preparing drug-containing particles (DCPs) with controlled size distribution and high drug loading was developed using melt granulation. This approach comprises two steps. First, melting component adsorbed particles (MAs) were prepared by mixing and heating the melting components with a porous carrier using a high shear granulator. Second, DCPs were prepared by layering the drug on MAs using a fluidized bed rotor granulator. The time taken for both steps was within 30 min. Adding the polymer in the second step remarkably increased the viscosity of the mixture of melting components and the polymer. Therefore, DCPs could be successfully loaded with a high amount of drug (70% w/w). The particle size distribution of the DCPs was narrow, and it depended on that of the MAs. The flowability of the DCPs was excellent, and the sphericity was close to 1. A unique particle formulation mechanism was suggested based on the observation of DCPs using scanning electron microscopy. The manufacturing time and DCP characteristics were not affected by the manufacturing scale. In conclusion, we have successfully developed a highly efficient novel approach for preparing optimal DCPs through melt granulation, named “Melt Adsorption and Layering with Porosity Core” (MALCORE®).     

Influence of the solvent evaporation rate on the β-Phase content of electrosprayed PVDF particles and films studied by a fast Multi-Overtone QCM

A combination of an electrospray setup and a quartz crystal microbalance with dissipation monitoring (QCM-D) was employed to study the drying of droplets of poly(vinylidene fluoride) (PVDF) dissolved in dimethylformamide (DMF). A novel variant of the QCM was used, which interrogates the resonance frequency and the resonance bandwidth on four overtones at the same time, achieving a time resolution of 2 ms. This instrument allowed to elucidate the mechanism of β-phase formation in electrospray deposition of PVDF. When the distance between the nozzle and the substrate was small, the droplets landed in a partially wet state, as evidenced from an increase in the resonance bandwidth. No such increase in bandwidth was observed when the distance was large. From the flight time (milliseconds) and the drying time on the substrate (seconds), one concludes that drying in the plume is faster than drying on the substrate. IR spectra show that the β–phase content is close to 100 % for particles, which dried in the plume. It is less than 50 % for particles having dried on the substrate. Fast drying promotes the formation of the β-phase. Follow-up experiments with thicker films on steel substrates also show increased β-phase content for larger distances.     

Stabilizing effect of the cyclodextrins additive to spray-dried particles of curcumin/polyvinylpyrrolidone on the supersaturated state of curcumin

Although curcumin is considered to have various therapeutic effects, its use as a functional food or supplement is restricted owing to its low water solubility and bioavailability. To increase the solubility of curcumin in water, the use of polyvinylpyrrolidone (PVP) and vinylpyrrolidone-vinyl acetate copolymers with a pyrrolidone skeleton was noted to be promising. In particular, the bi-component formulations of curcumin/PVP prepared through spray drying exhibited an amorphous state in powder X-ray diffraction observations and temporally increased the apparent solubility of curcumin to over 5000 times that of untreated curcumin; nevertheless, after 24 h, the solubility decreased owing to the unstable supersaturated state of curcumin. The addition of α-cyclodextrin (α-CyD) in the bi-component curcumin/PVP formulation helped maintain the supersaturated state of curcumin, whereas the addition of β- and γ-CyD led to the collapse of the supersaturated state. The addition of α-CyD can likely help inhibit the nucleation and crystal growth of curcumin, through the interaction among the solubilized units of curcumin/PVP and α-CyD.     

Full-loop study of a dual fluidized bed cold flow system: Hydrodynamic simulation and validation

The unsteady behaviors of the air-silica sand flow in a lab-scale dual fluidized bed gasification cold flow system have been studied. A two-dimensional computational fluid dynamics full-loop model with poly-size distribution in solid phases was developed as an innovation of this study to investigate the effects of crucial parameters on system hydrodynamics. The results showed a decrease in the mixture static pressure from the bottom to the upper regions of the system, which maintained the system operations stable. The riser air inlet velocity and the gasifier static bed height were found to play considerable roles in enhancing the total sand flow rates. The same tendencies in the prediction and experiment of both the mixture pressure and the sand flow rate showed the feasibility of the proposed model. Besides, the residual evaluation enhanced data reliability and supported model validation. Especially, undesirable phenomena possibly occurring in the system operation under improper conditions could also be predicted. Accordingly, the inventory of bed material and the fluidizing gas flow rates should be suitably regulated to maintain pressure balances, trouble-free continuous flow, optimal sand circulation rate, and low solids loss. Furthermore, the obtained results in this study can be used as a reference for optimizing the designs and operational conditions of large-scale plants.     

Three-dimensional periodic structures of gold nanoclusters in the interstices of sub-100 nm polymer particles toward surface-enhanced Raman scattering

Regularly ordered polymer nanoparticle (PNP) assemblies incorporating gold nanoparticle (Au NP) clusters into the PNP interstices were fabricated by a simultaneous deposition of PNPs and Au NPs on a glass substrate. Monodisperse PNPs with an average size of 66 nm were employed as a template in the co-assembly to create the sub-100 nm periodic Au nanostructures on the substrate. First, mono-layering of PNP array with incorporation of 14 nm Au NPs was performed by a drop-casting to examine the number ratio of Au NPs to PNPs for multi-layering. Absorption spectra of the mono-layered co-assemblies of PNPs and Au NPs were employed to characterize the clustered state of Au NPs in the interstices of mono-layered PNPs. The number ratio suitable for homogeneous incorporation of Au NPs clustered in the interstice was found to be ranged from 6 to 8 in the characterization. Then, multi-layered co-assemblies of PNPs and clustered Au NPs were fabricated by a vertical deposition method with the Au NP number ratio of 8 to PNPs. Lifting rate of the substrate on which the PNPs were deposited was varied in the vertical deposition method to tune the film thickness of NP co-assembly. A decrease in the lifting rate to 1 μm/s could thicken the film to 0.71 μm corresponding to 13 layers of PNPs, resulting in the fabrication of periodic structures of Au NP clusters with a high packing density. Signal-to-noise ratio in the Raman measurement using p-mercaptobenzoic acid as a target molecule was successfully enhanced by multi-layering of the co-assembly, indicating that Au NP clusters were homogeneously incorporated into the interstices of PNPs in the co-assemblies.     

Machine learning aided nanoindentation: A review of the current state and future perspectives

The solution of instrumented indentation inverse problems by physically-based models still represents a complex challenge yet to be solved in metallurgy and materials science. In recent years, Machine Learning (ML) tools have emerged as a feasible and more efficient alternative to extract complex microstructure-property correlations from instrumented indentation data in advanced materials. On this basis, the main objective of this review article is to summarize the extent to which different ML tools have been recently employed in the analysis of both numerical and experimental data obtained by instrumented indentation testing, either using spherical or sharp indenters, particularly by nanoindentation. Also, the impact of using ML could have in better understanding the microstructure-mechanical properties-performance relationships of a wide range of materials tested at this length scale has been addressed.The analysis of the recent literature indicates that a combination of advanced nanomechanical/microstructural characterization with finite element simulation and different ML algorithms constitutes a powerful tool to bring ground-breaking innovation in materials science. These research means can be employed not only for extracting mechanical properties of both homogeneous and heterogeneous materials at multiple length scales, but also could assist in understanding how these properties change with the compositional and microstructural in-service modifications. Furthermore, they can be used for design and synthesis of novel multi-phase materials.     

Steel slag waste combined with melamine pyrophosphate as a flame retardant for rigid polyurethane foams

To explore the potential application of industrial waste, steel slag powder in combination with melamine pyrophosphate (MPP) was adopted to improve the flame retardancy of rigid polyurethane foam (RPUF). The incorporation of steel slag slightly reduced the thermal conductivity of the resulting flame-retardant RPUF samples. The addition of MPP and/or steel slag did not significantly alter the thermal stability in terms of T_-10% and T_max but did obviously increase the T_-50% value, suggesting the improved thermal resistance of the residues. The coaddition of MPP and steel slag into RPUF resulted in higher LOI values and lower peak heat release rates than the samples incorporating either MPP or steel slag alone. The superior flame retardancy could be attributed to MPP promoting char formation, which then acted as a barrier at the beginning of RPUF thermal decomposition; simultaneously, the thermally stable inorganics in the steel slag powder strengthened the thermal resistance of this char layer.     

pH-responsive dual-functional hydrogel integrating localized delivery and anti-cancer activities for highly effective therapy in PDX of OSCC

As one of the most promising localized drug delivery systems for enhancing therapeutic efficacy and reducing systemic toxicity, supramolecular hydrogels self-assembled from natural products have recently attracted tremendous attention. However, the intricate drug loading process, limited drug entrapment efficacy, and lack of stimulus responsiveness considerably impede their potential for biological applications and raise the need for advanced hydrogel-based delivery systems. Therefore, the development of updated materials that integrate localized delivery and drug activity into a single system is extremely desired and has great potential to overcome the aforementioned shortcomings. In this study, a pH-responsive dual-functional isoG-based supramolecular hydrogel with both localized delivery and anti-cancer activity in one molecule is successfully developed in one pot by following a simple and green procedure. The isoguanosine-phenylboronic-guanosine (isoGPBG) hydrogel exhibits exceptional stability (more than one year), outstanding pH-responsiveness and excellent sustained release capability. Both in vitro and in vivo experiments demonstrate that the isoGPBG hydrogel not only shows acceptable biocompatibility and biodegradability but also significantly inhibit tumor growth (approximately 60% inhibition of tumor growth) and improve overall survival, especially in preclinical patient-derived xenograft (PDX) model of oral squamous cell carcinoma (OSCC). Therefore, the isoGPBG hydrogel, to the best of our knowledge, is the first example of pH-responsive dual-functional isoG-based supramolecular hydrogel integrating localized delivery and anti-cancer activity in one molecule. It is implied that the isoGPBG hydrogel could act as a smart dual-functional localized delivery system in the future for clinical cancer therapy.     

Breaking behaviour and interactions in maize and soybean meal while grinding of a hammer mill

The objective of the present study was to investigate whether mixing ratio of maize and soybean meal (SBM) affects the breaking behaviour during hammer-milling in terms of the nutrient properties and in vitro digestibility of fractionated particles. Mixtures of maize and SBM with different proportions (% Maize:SBM; 0:100, 25:75, 50:50, 75:25, 100:0) were hammer milled using a 2-mm screen. The obtained powder was sieved into seven fractions with size ranges from 0.149 to 1.190 mm. Results show that energy consumption of grinding mixtures increased from 3.8 to 48.4 kJ/kg with the maize proportion increasing from zero to 100%. Mixing proportion of maize and SBM showed significant effects on nutrient content of fractionated material. For hammer milled material <595 µm, the in vitro digestibility of crude protein (CP) and organic matter (OM) of fractionated material decreased with increasing particle size. Additionally grinding fractionated particles ≥595 µm over a 1-mm sized screen before in vitro digestion analysis increased the digestibility of OM and CP. Equivalent particle size (EPS) and geometric standard deviation (GSD) of hammer milled maize and SBM and their mixtures correlated better than geometric mean diameter (GMD) to OM and CP in vitro digestibility in a linear regression model. In summary, the mixing ratio of maize and SBM had a significant effect on the breaking behaviour of ingredients and in vitro digestibility of CP and OM of the isolated fractions. Mixing ingredients before grinding is suggested in terms of saving energy consumption. The GSD/EPS of ground material should be considered while studying the effects of particle size distribution on the in vitro digestibility of nutrients.     

Immersed-boundary/soft-sphere method for particle–particle-fluid interaction in a viscous flow: An OpenFOAM solver

We developed a stable OpenFOAM solver for Immersed Boundary Method based on direct forcing and regularized delta function. The soft-sphere model and a lubrication model were implemented to consider particle–particle collision in a viscous flow. We proposed a fluid–structure interaction (FSI) coupling method to accurately calculate the fluid forcing term and particle velocity. Our solver was validated for fixed and moving bodies, including rotation. The accuracy of various FSI schemes was evaluated in predicting the solid and fluid flow behavior in a viscous flow. It was demonstrated that neglecting or simplifying the fluid momentum change affects the accuracy of the solid velocity and fluid flow dynamic; for higher solid-to-fluid density ratios, a larger deviation was predicted. Furthermore, the FSI schemes highly influenced the behavior of the formed vortices.The solver was validated to predict the effective restitution coefficient of particles in a viscous flow as a function of the Stokes number. We also thoroughly analyzed the dynamic flow behavior of colliding particles through the pressure and velocity field and fluid force. This analysis helped us accurately determine the rebound velocity of particles in case of high Stokes numbers when the effect of viscous force is significant.     

Changes in the oxygen content,morphology, and microstructure of Mo-10Nb composite powders during mechanical alloying

The prefabrication of Mo-Nb composite powders is an effective way of improving the homogeneity of Mo-10Nb targets, which have broad application prospects in the photoelectric sensor industry. However, this aspect has been rarely addressed so far. Therefore, we prepared Mo-10Nb composite powders by mechanical alloying (MA), and investigated the effects of the experimental parameters such as the milling speed and duration on the particle morphology, size distribution, compositional homogeneity, crystallite size, inner strain, and oxygen content. High-quality Mo-10Nb composite powders with 3-μm spherical particles of narrow size distribution, homogeneous elemental distribution, and nanometric crystalline structure were obtained by implementing optimum MA parameters, viz., a milling speed of 250 rpm and duration of 36 h using an MITR QM-QX-4L omnidirectional ball mill. The mechanically alloyed Mo-10Nb composite powders were prone to oxidation when exposed to air, which led to a sharp increase in the oxygen content to ~5400 ppm. X-ray photoelectron spectroscopic analysis revealed the presence of Nb₂O₅, MoO₂, and MoO₃ on the surface of the Mo-10Nb particle. We believe that this study demonstrates an interesting strategy for the fabrication of high-quality Mo-10Nb targets.     

Measurement and analysis of impact dynamics suitable for modelling pneumatic transport of metallic powder flow through a directed energy deposition nozzle

In blown powder directed energy deposition (DED) additive manufacturing powdered metal feedstock is pneumatically conveyed to the meltpool via a nozzle. DED nozzles have been the subject to a growing number of research efforts using computational fluid dynamics (CFD) with multiphase flows to study and optimize powder flow. However, many research papers published to date contain powder – nozzle impact dynamics behavior that is not realistic or not derived from experiments that resemble the powder conveyance process in the DED nozzle being studied. To provide a set of data representative of DED powder flow through a nozzle particle image velocimetry (PIV) experiments were conducted using 316L stainless steel metal powder and flat targets with varying surface roughness made of oxygen free copper, mild steel, P20 tool steel, 316L stainless steel, Inconel 718, and Ti-Al6-V4. Normal coefficients of restitution (COR) were calculated and compared to several analytical and empirical models in literature.     

Urease producing microorganisms for coal dust suppression isolated from coal: Characterization and comparative study

In order to promote the biomineralization technology application to the field of coal dust inhibition, two strains of urease producing bacteria from coal were screened in this study. They are X3 with extracellular enzyme and X4 with intracellular enzyme. The ITS and 16S rDNA sequencing showed that the strains X3 and X4 were highly similar to Aspergillus sydowii and Bacillus DB-6. Strains X3 and X4 had their maximum urease activity at the initial 0.5 M urea concentration and slightly alkaline (pH 8) and neutral (pH 7) initial pH, respectively. Their mineralized products have a spherical structure and conform to the elemental composition of calcium carbonate. The dust suppression effect showed that both X3 and X4 bacteria liquid can effectively bind coal dust to form coal dust consolidation bodies containing calcite and vaterite type calcium carbonate. Interestingly, the coal dust consolidation body treated with the strain X4 is more resistant to wind and rain. The screening, mineralization and dust suppression potential analysis of the two strains of urease bacteria provided empirical support for the application of microbial induced calcium carbonate precipitation technology in the coal dust suppression.     

Data-driven parameter optimization for the synthesis of high-quality zeolitic imidazolate frameworks via a microdroplet route

As an emerging strategy for the synthesis of metal-organic frameworks (MOFs), a microdroplet-based spray method holds merits of improved heat and mass transfer rates, which allows the formation of MOF crystals in a much faster manner. To optimize the spray route for the MOF synthesis, further exploration is needed to understand the dominant variables controlling the quality of the products. With a series of experiments and advanced computational analysis, we present here general guidance for the synthesis of representative zeolitic imidazolate frameworks (i.e., ZIF-8 and ZIF-67) using the spray route.     

Improving hydrothermal performance of hybrid nanofluid in double tube heat exchanger using tapered wire coil turbulator

Tapered wire coil insert is proposed as a novel enhancer in the double tube heat exchanger and experimental studies on Al₂O₃ + MgO hybrid nanofluid flowing under the turbulent condition are performed to investigate the hydrothermal characteristics. Effects of using tapered wire coil turbulator and hybrid nanofluid on the hydrothermal behaviors are examined for different coil configurations (Converging (C) type, Diverging (D) type and Conversing-Diverging (C-D) type) and hybrid nanofluid inlet temperatures and volume flow rates. Results show that D-type wire coil insert promotes better hydrothermal performance as compared to C-type and C-D type. Nusselt number and friction factor of hybrid nanofluid using D-type, C-D type and C-type wire coil inserts enhance up to 84%, 71% and 47%, and 68%, 57% and 46%, respectively than that of water in tube without insert. The entropy generation of hybrid nanofluid is lower than that of base fluid in all cases. The thermal performance factor for hybrid nanofluid is found more than one with all inserts. The thermal performance factor is observed a maximum of 1.69 for D-type coil. The study reveals that the hybrid nanofluid and tapered wire coil combination is promising option for improving the hydrothermal characteristics of double pipe heat exchanger.     

Text mining as a tool for real-time technology assessment: Application to the cross-national comparative study on artificial organ technology

This study proposed a methodology that integrate sociotechnical systems (STS) and media big data analysis using text mining for the new, real-time technology assessment (TA). The essential steps of this method are composed of data collection using a cultural map, analysis with trends and patents, and synthesis using media big data. By applying this methodology to artificial organs, first, we have shown that STS can be apply to biosocial technical systems beyond the sustainability transition. The result reveals that a media discourse structures, in which eight countries began to form socio-technical regimes around technologies with their respective strengths, in an objective way. Each technology corresponded to the vested interests in each country's socio-technical regimes. These discourse structures helped us to identify substitution, two types of transformation, and reconfiguration as transition pathways. More importantly, our analysis results have also shown that the methodology helps to overcome the anticipation dilemma, saving the time and resources required for TA. Our integrated methodology has achieved similar results by using 23% of the budget, 25% of the time, and 14% of the work hours used for official TA. Lastly, the “objectivity” and “agenda setting” of this methodology can provide a breakthrough in overcoming the control dilemma.     

Screening of sugars and cyclodextrins as carriers in montelukast dry powder inhalers processed by spray freeze drying

The purpose of this study was to develop a site targeting montelukast sodium (MTK) microparticles as a respiratory drug delivery system using the spray freeze drying (SFD) process. A range of sugars and cyclodextrins (CDs) were screened as carrier in order to find compatible excipients for the preparation of dry powder inhalers (DPIs). The physical characteristics of collected powders were studied by scanning electron microscopy (SEM), laser light scattering, differential scanning calorimetry (DSC), and X-ray diffraction (XRD). The aerodynamic behavior of the particles was also assessed using twin stage impinge (TSI). In the presence of simple sugars as carriers, highly porous particles in irregular shapes were produced. The use of CDs resulted in the formation of spherical particles with high porosity. Among all carriers that were used during the preparation of powders, raffinose had the best aerodynamic behavior with a fine particle fraction (FPF) of 60 % in sugar groups, while the lowest FPF was related to trehalose as carrier. Powders containing CDs mostly showed proper aerodynamic behavior, especially in formulations containing alfa-cyclodextrin (A-CD), beta-cyclodextrin (β-CD), and highly branched cyclic dextrin (HBCD). Overall, data indicated that the CDs were excellent excipients for use with MTK for respiratory drug delivery.     

Understanding the formation of ultrafine maltodextrin particles under simultaneous convective drying and antisolvent vapour precipitation

Research on simultaneous antisolvent-vapour-induced precipitation and convective drying of a solute-containing droplet was extensively conducted since this technique was introduced. However, the internal droplet compositions, which were suggested to be related to the formation of particle morphologies, had not been explored. Herein, the ethanol-vapour-induced precipitation of multi-solvent droplets containing maltodextrin as the solute was used to analyse internal droplet compositions. The droplet mass and diameter profiles were obtained via an established single-droplet drying experiment, which mimicked the spray drying of droplets. Analysis revealed that the antisolvent concentration increased with time and was higher than solvent concentration towards the end of the process. It is interesting to find out that the final particle morphology was profoundly impacted by the ambient ethanol humidity and also how spontaneous the subsequent drying was during ethanol-vapour-induced precipitation of the solutes. The formation of the porous structure was favoured with the occurrence of spontaneous vaporization once the ethanol was present for precipitation. Therefore, low ethanol humidity (20% ERH in this study) was sufficient. In contrast, higher ethanol humidity (>70% ERH) was preferable to produce spherical particles. This study provides an insight into particle engineering to unveil the internal droplet conditions and physical phenomena during this unique process.     

Investigation of the molecular state of 4-aminosalicylic acid in matrix formulations for dry powder inhalers using solid-state fluorescence spectroscopy of 4-dimethylaminobenzonitrile

Carrier-free method is an alternative approach for dry powder inhaler (DPI) formulations, which overcome poor drug mobility and distribution. Here we investigated the properties of an active pharmaceutical ingredient (API) within composite particles. We used highly-branched cyclic dextrin (HBCD) as the excipient matrix that was prepared using a spray-drying technique. 4-Aminosalicylic acid (4-ASA) and 4-dimethylaminobenzonitrile (DMABN) were selected as a hydrophilic second-line antitubercular agent and a surrogate for 4-ASA as a model compound, respectively. The spray-dried particles (SDPs) containing 4-ASA or DMABN with HBCD had geometric median diameters (D₅₀) of 2.34 ± 0.07 μm and 2.26 ± 0.10 μm, respectively. Further, the in vitro aerodynamic properties were similar for SDPs containing 4-ASA and DMABN with HBCD. To determine the properties of APIs within composite particles, we performed solid-state fluorescence spectroscopy of DMABN. As a candidate excipient, hydroxypropyl methylcellulose (HPMC) was compared to HBCD. We determined the intensity ratio of twisted intramolecular charge transfer (TICT) emission to locally excited emission within the excipient matrix environment. The HBCD matrix environment was better than HPMC to trigger a more robust TICT reaction of DMABN. A potent state-changing interaction of APIs occurred in the HBCD matrix environment versus another excipient environment.