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®).     

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.     

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.     

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.     

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.     

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.     

Designing amorphous formulations of polyphenols with naringin by spray-drying for enhanced solubility and permeability

Naringin (NAR), a major flavanone (FVA) glycoside, is a component of food mainly obtained from grapefruit. We used NAR as a food additive to improve the solubility and permeability of hydrophobic polyphenols used as supplements in the food industry. The spray-dried particles (SDPs) of NAR alone show an amorphous state with a glass transition temperature (T_g) at 93.2 °C. SDPs of hydrophobic polyphenols, such as flavone (FVO), quercetin (QCT), naringenin (NRG), and resveratrol (RVT) were prepared by adding varying amounts of NAR. All SDPs of hydrophobic polyphenols with added NAR were in an amorphous state with a single T_g, but SDPs of hydrophobic polyphenols without added NAR showed diffraction peaks derived from each crystal. The SDPs with NAR could keep an amorphous state after storage at a high humidity condition for one month, except for SDPs of RVT/NAR. SDPs with NAR enhanced the solubility of hydrophobic polyphenols, especially NRG solubility, which was enhanced more than 9 times compared to NRG crystal. The enhanced solubility resulted in the increased membrane permeability of NRG. The antioxidant effect of the hydrophobic NRG was also enhanced by the synergetic effect of NAR. The findings demonstrated that NAR could be used as a food additive to enhance the solubility and membrane permeability of hydrophobic polyphenols.     

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.     

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.     

Recent breakthroughs and perspectives of high-energy layered oxide cathode materials for lithium ion batteries

Ni-rich layered oxides (NRLOs) and Li-rich layered oxides (LRLOs) have been considered as promising next-generation cathode materials for lithium ion batteries (LIBs) due to their high energy density, low cost, and environmental friendliness. However, these two layered oxides suffer from similar problems like capacity fading and different obstacles such as thermal runaway for NRLOs and voltage decay for LRLOs. Understanding the similarities and differences of their challenges and strategies at multiple scales plays a paramount role in the cathode development of advanced LIBs. Herein, we provide a comprehensive review of state-of-the-art progress made in NRLOs and LRLOs based on multi-scale insights into electrons/ions, crystals, particles, electrodes and cells. For NRLOs, issues like structure disorder, cracks, interfacial degradation and thermal runaway are elaborately discussed. Superexchange interaction and magnetic frustration are blamed for structure disorder while strains induced by universal structural collapse result in issues like cracks. For LRLOs, we present an overview of the origin of high capacity followed by local crystal structure, and the root of voltage hysteresis/decay, which are ascribed to reduced valence of transition metal ions, phase transformation, strains, and microstructure degradation. We then discuss failure mechanism in full cells with NRLO cathode and commercial challenges of LRLOs. Moreover, strategies to improve the performance of NRLOs and LRLOs from different scales such as ion-doping, microstructure designs, particle modifications, and electrode/electrolyte interface engineering are summarized. Dopants like Na, Mg and Zr, delicate gradient concentration design, coatings like spinel LiNi_0.5Mn_1.5O₄ or Li₃PO₄ and novel electrolyte formulas are highly desired. Developing single crystals for NRLOs and new crystallographic structure or heterostructure for LRLOs are also emphasized. Finally, remaining challenges and perspectives are outlined for the development of NRLOs and LRLOs. This review offers fundamental understanding and future perspectives towards high-performance cathodes for next-generation LIBs.     

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.     

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.     

Metal-organic framework derived hexagonal layered cobalt oxides with {1 1 2} facets and rich oxygen vacancies: High efficiency catalysts for total oxidation of propane

A cobalt-based metal–organic framework was used as a precursor to synthesize Co₃O₄ catalysts exhibiting a hexagonal layered morphology by calcination at varying temperatures. Various characterization techniques, such as XRD, SEM, Raman, H₂-TPR, O₂-TPD and N₂ adsorption–desorption, were used to study the effects of calcination temperature on the grain size, surface area, and pore volume of the catalysts. The Co₃O₄ catalyst obtained by calcination at 350 °C (Co₃O₄-350) exhibited the highest catalytic activity for the total oxidation of propane. Furthermore, the small grain size and layered structure of Co₃O₄-350 allowed it to possess a high specific surface area, a highly exposed {1 1 2} facets, and abundant oxygen defects that facilitated a favorable low-temperature reducibility and oxygen mobility, thereby improving catalytic activity. This research offers a simple strategy for synthesis of Co₃O₄ with layered structure, highly exposed {1 1 2} facets and rich oxygen defects.     

Virus meet metal-organic frameworks: A nanoporous solution to a world-sized problem?

Laboratory diagnosis of pathologies caused by virus plays a critical role in outbreak response efforts and establishing safe and expeditious testing strategies. Detection of pathogenic virus using commercial solutions require specific tools and laborious laboratory procedures. This makes the day-to-day on time detection of virus infections the limiting step in any outbreak. The need for new diagnostic tools easily available to poor and rural underdeveloped areas where health infrastructure and trained personnel are scarce is highly desirable. The widely known intrinsic properties of Metal-Organic Frameworks (MOFs) embody them with the potential to overcome some of the challenges inherent to virus detection. MOFs are already components of functional devices capable of perform an uninterrupted detection of molecular targets in real time. In this review, we summarise the few studies concerning the reported MOFs used as sensors for pathogenic virus. We emphasise the structural and physical properties of these materials which can open the possibility for their use in this type of sensors and conclude on how the field can progress to envisage the usage of MOFs by the pharmaceutical industry to develop new sensors for these sub-microscopic infectious agents.     

Electrochemical treatment of soil-washing effluent with boron-doped diamond electrodes: A review

In recent years, electrochemical technologies have been widely used to remove contaminants at lab-scale and semi-pilot scale. Boron-doped diamond (BDD) electrodes have been considered as efficient materials for the abatement of persistent organic pollutants owing to their outstanding properties, such as rapid rates of electron-transfer for soluble redox systems, wide electrochemical potential window for water discharge reactions in aqueous and non-aqueous electrolytes, and high stability. Similar to other applications of electrochemical technology, wastes display medium to high ionic conductivity. Therefore, one of the applications highlighted for the electrolysis with these new electrodes is the treatment of soil-washing fluids, because in the polluted streams, washing of polluted soils provides a suitable conductivity to the effluent. In this context, this review summarizes the application of conductive diamond anodes for the electrochemical treatment of soil-washing effluents contaminated with different persistent organic pollutant such as pesticides, hydrocarbons, dyes, and organochlorine compounds, in single anodic oxidation processes and in other more complex processes such as electro-Fenton, photoelectrolysis, or sonoelectrolysis. Finally, the challenges and future research directions of electrochemical technology are discussed and outlined at pilot and prototype scale.     

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.     

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.     

3D printing vertically: Direct ink writing free-standing pillar arrays

Over the last three decades, a variety of additive manufacturing techniques have gradually gained maturity and will potentially play an important role in future manufacturing industries. Among them, direct ink writing has attracted significant attention from both material and tissue engineering areas, where the colloidal ink is extruded and dispensed according to a pre-designed path, usually in the X-Y plane with suitable increments in the Z direction. Undoubtedly, this way of disassembling geometries, simple or complex, can facilitate most of the printing process. However, for one extreme case, i.e. pillar arrays, the size resolution can deviate from both nozzle and design if the common way of slicing and additive manufacturing is used. Therefore, a different printing path is required – directly depositing pillars in a converse gravitational direction. This paper gives multiple examples of printing viscoelastic colloidal ceramic and metal inks uniaxially and periodically into free-standing and height-adjustable pillar arrays. It is expected to inspire the additive manufacturing community that more versatile degrees of freedom and complex printing paths, not confined within only complex shapes, can be achieved by ink-based 3D printing.     

Granulation of ibuprofen/isonicotinamide co-crystals by continuous spray granulator (CTS-SGR)

The importance of granulation is paramount for tablet manufacturing, and is based on the fact that granulated powders are characterized by improved flowability, compressibility, segregation, and dust reduction. The aim of this study was to prepare and characterize continuous granules of high drug content by using a continuous-spray granulator (CTS-SGR). Ibuprofen (IBU), a drug of low-flowability, was selected as the model drug. As IBU has a low melting point and cannot easily granulate on its own, we employed isonicotinamide (INA) as a coformer that would allow us to prepare co-crystal granules containing 60 % IBU. The results of the undertaken differential scanning calorimetry and powder X-ray diffraction revealed that the IBU and the INA in the granules formed co-crystals. The granulation conditions affected the particle size and the yield of the granules; in fact, a low air supply temperature, a low atomizing air rate, and a high solution flow rate ensured a high granulation efficiency. Moreover, continuous granulation increased the yields of the formulations compared to those obtained through a short-run granulation, and high yields were obtained after applying a low atomizing air rate. The circularity of the granules exceeded 90 %, and their flowability improved when compared to that of the IBU bulk. The undertaking of dissolution studies revealed no change in the elution amount of IBU as a result of the co-crystallization. Our study shows that it is possible to produce high-content IBU granules in a direct and continuous manner through the co-crystallization of IBU and the use of a CTS-SGR.     

3D HCN nanotexture with synergistic effect of nickel and hole scavengers for enhancing photocatalytic H2 production: Role of morphology and influential parameters

Well-designed three-dimensional (3D) nanotextures of graphitic carbon nitride (g-C₃N₄), synthesized using template free single step method and mediated with nickel as a noble free metal, for solar hydrogen production, has been investigated. The photoactivity was investigated in a slurry type continuous flow photoreactor system by using different influential parameters such as hole scavengers, diffusion effects, time, and mass transfer. Compared to bulk g-C₃N₄, H₂ yield was increased with 3D hierarchical carbon nitride (HCN) nanotexture. The H₂ evolution rate was reached to 1310 µmol g^?1 h^?1 with optimized 2 % Ni loading to 3D HCN. This H₂ evolution rate was 19.8 and 24.9 times higher than it was generated using 3D HCN and g-C₃N₄, respectively. The special interlayer opening, more light penetration and suppressed charge carrier recombination were the main contributors for this photoactivity enhancement. Among the different influential parameters, lower viscosity, higher number of protons and less diffusion effects were promising to give significantly higher H₂ production. The stability of nanotextures was entirely dependent on the attached reactants over the nickel reactive sites, which was more promising for Triethanolamine (TEOA) than using methanol. This newly developed low-cost 3D HCN can be promising in solar energy conversion and other energy applications.