Predicting the Strength of Cohesive and Adhesive Interparticle Interactions for Dry Powder Inhalation Blends of Terbutaline Sulfate with α-Lactose Monohydrate.

Grid-based systematic search methods are used to investigate molecule-molecule, molecule-surface, and surface-surface contributions to interparticle interactions in order to identify the crystal faces that most strongly affect particle behavior during powder blend formulation and delivery processes. The model system comprises terbutaline sulfate (TBS) as an active pharmaceutical ingredient (API) and α-form lactose monohydrate (LMH). A combination of systematic molecular modeling and X-ray computed tomography (XCT) is used to determine not only the adhesive and cohesive interparticle energies but, also the agglomeration behavior during manufacturing and de-agglomeration behavior during delivery after inhalation. This is achieved through a detailed examination of the balance between the adhesive and cohesive energies with the XCT results confirming the blend segregation tendencies, through the particle-particle de-agglomeration process. The results reveal that the cohesive interaction energies of TBS-TBS are higher than the adhesive energies between TBS and LMH, but that the cohesive energies of LMH-LMH are the smallest between molecule and molecule, molecule and surface, and surface and surface. This shows how systematic grid-search molecular modeling along with XCT can guide the digital formulation design of inhalation powders in order to achieve optimum aerosolization and efficacy for inhaled medicines. This will lead to faster pharmaceutical design with less variability, higher quality, and enhanced performance.

Stability test of novel combined formulated dry powder inhalation system containing antibiotic: physical characterization and in vitro-in silico lung deposition results.

Objective: The aim was to study the stability of dry powder inhaler (DPI) formulations containing antibiotic with different preparation ways - carrier-based, carrier-free, and novel combined formulation - and thereby to compare their physicochemical and in vitro-in silico aerodynamical properties before and after storage. Presenting a novel combined technology in the field of DPI formulation including the carrier-based and carrier-free methods, it is the most important reason to introduce this stable formulation for the further development of DPIs. Methods: The structure, the residual solvent content, the interparticle interactions, the particle size distribution and the morphology of the samples were studied. The aerodynamic values were determined based on the cascade impactor in vitro lung model. We tested the in silico behavior of the novel combined formulated samples before and during storage. Results: The physical measurements showed that the novel combined formulated sample was the most favorable. It was found that thanks to the formulation technique and the use of magnesium stearate (MgSt) has a beneficial effect on the stability compared with the carrier-based formulation without MgSt and carrier-free formulations. The results of in vitro and in silico lung models were consistent with the physical results, so the highest deposition was found for the novel combined formulated sample during the storage. Conclusions: It can be established that after the storage a novel combined formulated DPI contained amorphous drug to have around 2.5 µm mass median aerodynamic diameter and nearly 50% fine particle fraction predicted high lung deposition in silico also.

Self-Assembly of Quantum Dot-Gold Heterodimer Nanocrystals with Orientational Order.

The self-assembly of nanocrystals into ordered superlattices is a powerful strategy for the production of functional nanomaterials. The assembly of well-ordered target structures, however, requires control over the building blocks' size and shape as well as their interactions. While nanocrystals with homogeneous composition are now routinely synthesized with high precision and assembled into various ordered structures, high-quality multicomponent nanocrystals and their ordered assemblies are rarely reported. In this paper, we demonstrate the synthesis of quantum dot-gold (QD-Au) heterodimers. These heterodimers possess a uniform shape and narrow size distribution and are capped with oleylamine and dodecyltrimethylammonium bromide (DTAB). Assembly of the heterodimers results in a superlattice with long-range orientational alignment of dimers. Using synchrotron-based X-ray measurements, we characterize the complex superstructure formed from the dimers. Molecular dynamics simulations of a coarse-grained model suggest that anisotropic interactions between the quantum dot and gold components of the dimer drive superlattice formation. The high degree of orientational order demonstrated in this work is a potential route to nanomaterials with useful optoelectronic properties.

Less Is More: Enhancement of Second-Harmonic Generation from Metasurfaces by Reduced Nanoparticle Density.

We investigate optical second-harmonic generation (SHG) from metasurfaces where noncentrosymmetric V-shaped gold nanoparticles are ordered into regular array configurations. In contrast to expectations, a substantial enhancement of the SHG signal is observed when the number density of the particles in the array is reduced. More specifically, by halving the number density, we obtain over 5-fold enhancement in SHG intensity. This striking result is attributed to favorable interparticle interactions mediated by the lattice, where surface-lattice resonances lead to spectral narrowing of the plasmon resonances. Importantly, however, the results cannot be explained by the improved quality of the plasmon resonance alone. Instead, the lattice interactions also lead to further enhancement of the local fields at the particles. The experimental observations agree very well with results obtained from numerical simulations including lattice interactions.

Dynamically Tuning Particle Interactions and Assemblies at Soft Interfaces: Reversible Order-Disorder Transitions in 2D Particle Monolayers.

Particles trapped at fluid interfaces experience long-range interactions that determine their assembly behavior. Because particle interactions at fluid interfaces tend to be unusually strong, once particles organize themselves into a 2D assembly, it is challenging to induce changes in their microstructure. In this report, a new approach is presented to induce reversible order-disorder transitions (ODTs) in the 2D monolayer of colloidal particles trapped at a soft gel-fluid interface. Particles at the soft interface, consisting of a nonpolar superphase and a weakly gelled subphase, initially form a monolayer with a highly ordered structure. The structure of this monolayer can be dynamically varied by the addition or removal of the oil phase. Upon removing the oil via evaporation, the initially ordered particle monolayer undergoes ODT, driven by capillary attractions. The ordered monolayer can be recovered through disorder-to-order transition by simply adding oil atop the particle-laden soft interface. The possibility to dynamically tune the interparticle interactions using soft interfaces can potentially enable control of the transport and mechanical properties of particle-laden interfaces and provide model systems to study particle-laden soft interfaces that are relevant to biological tissues or organs.

De Novo Atomistic Discovery of Disordered Mechanical Metamaterials by Machine Learning.

Architected materials design across orders of magnitude length scale intrigues exceptional mechanical responses nonexistent in their natural bulk state. However, the so-termed mechanical metamaterials, when scaling bottom down to the atomistic or microparticle level, remain largely unexplored and conventionally fall out of their coarse-resolution, ordered-pattern design space. Here, combining high-throughput molecular dynamics (MD) simulations and machine learning (ML) strategies, some intriguing atomistic families of disordered mechanical metamaterials are discovered, as fabricated by melt quenching and exemplified herein by lightweight-yet-stiff cellular materials featuring a theoretical limit of linear stiffness-density scaling, whose structural disorder-rather than order-is key to reduce the scaling exponent and is simply controlled by the bonding interactions and their directionality that enable flexible tunability experimentally. Importantly, a systematic navigation in the forcefield landscape reveals that, in-between directional and non-directional bonding such as covalent and ionic bonds, modest bond directionality is most likely to promotes disordered packing of polyhedral, stretching-dominated structures responsible for the formation of metamaterials. This work pioneers a bottom-down atomistic scheme to design mechanical metamaterials formatted disorderly, unlocking a largely untapped field in leveraging structural disorder in devising metamaterials atomistically and, potentially, generic to conventional upscaled designs.

Quantification of polystyrene microsphere attachment probability at the oil‒water interface using a microfluidic platform.

This study investigates the effects of interparticle interactions and wettability on the particle attachment efficacy to the oil‒water interface. Three types of PS particles with different surface functional groups were examined at varying salt concentrations and the number of particles injected into the interface. Based on the microfluidic method and the surface coverage measurement, we found that the two contributing factors significantly influenced particle attachment efficiency to the interface, while the wettability factor has a major contribution. This research contributes to the understanding of physicochemical aspects of particle assembly at fluid interfaces and can offer strategies for forming tailored structures with desired interfacial properties.

Anisotropy in Near-Spherical Colloidal Nanoparticles.

Two major aspects of functional colloidal nanoparticles are their colloidal stability (dispersion) and controlled assembly of nanoparticles into ordered structures. Simplifying colloidal nanoparticles as isotropically interacting spheres is unsuitable for small nanoparticles capped with hydrocarbon chain ligands in which the ligand-ligand interaction plays a prominent role in the assembly processes. However, experimentally characterizing the ligand shell structure in solution presents significant challenges, and computer simulations yield divergent results without effective validation. Moreover, the connection between detailed information regarding ligand shell structures and interparticle interactions, in relation to the diverse dynamical behaviors of colloidal nanoparticles, remains poorly understood. In this study, we reveal the relationship between the ligand shell structures, interparticle interactions, and dynamical behaviors of few-nm-sized near-spherical nanoparticles capped with hydrocarbon chain ligands immersed in nonpolar solvents. Our study shows a transformation of the interparticle interactions from anisotropic attractions to isotropic repulsions as a result of the change in the ligand shell structures from order to disorder caused by varying temperature and other factors. The interplay between anisotropic attractions from ligand bundles and isotropic repulsions from disordered ligands dictates the nanoparticle dynamical behaviors of dispersion, uncontrolled aggregation, and controlled assembly.

Tuning the rheology and microstructure of particle-laden fluid interfaces with Janus particles.

HYPOTHESIS: Particle-laden fluid interfaces are the central component of many natural and engineering systems. Understanding the mechanical properties and improving the stability of such interfaces are of great practical importance. Janus particles, a special class of heterogeneous colloids, might be used as an effective surface-active agent to control the assembly and interfacial rheology of particle-laden fluid interfaces. EXPERIMENTS: Using a custom-built interfacial stress rheometer, we explore the effect of Janus particle additives on the interfacial rheology and microscopic structure of particle-laden fluid interfaces. FINDINGS: We find that the addition of a small amount of platinum-polystyrene (Pt-PS) Janus particles within a monolayer of PS colloids (1:40 number ratio) can lead to more than an order-of-magnitude increase in surface moduli with enhanced elasticity, which improves the stability of the interface. This drastic change in interfacial rheology is associated with the formation of local particle clusters surrounding each Janus particle. We further explain the origin of local particle clusters by considering the interparticle interactions at the interface. Our experiments reveal the effect of local particle structures on the macroscopic rheological behaviors of particle monolayers and demonstrate a new way to tune the microstructure and mechanical properties of particle-laden fluid interfaces.

Dependence of Exchange Bias on Interparticle Interactions in Co/CoO Core/Shell Nanostructures.

This article reports the dependence of exchange bias (EB) effect on interparticle interactions in nanocrystalline Co/CoO core/shell structures, synthesized using the conventional sol-gel technique. Analysis via powder X-Ray diffraction (PXRD) studies and transmission electron microscope (TEM) images confirm the presence of crystalline phases of core/shell Co/CoO with average particle size ≈ 18 nm. Volume fraction (φ) is varied (from 20% to 1%) by the introduction of a stoichiometric amount of non-magnetic amorphous silica matrix (SiO2) which leads to a change in interparticle interaction (separation). The influence of exchange and dipolar interactions on the EB effect, caused by the variation in interparticle interaction (separation) is studied for a series of Co/CoO core/shell nanoparticle systems. Studies of thermal variation of magnetization (M-T) and magnetic hysteresis loops (M-H) for the series point towards strong dependence of magnetic properties on dipolar interaction in concentrated assemblies whereas individual nanoparticle response is dominant in isolated nanoparticle systems. The analysis of the EB effect reveals a monotonic increase of coercivity (HC) and EB field (HE) with increasing volume fraction. When the nanoparticles are close enough and the interparticle interaction is significant, collective behavior leads to an increase in the effective antiferromagnetic (AFM) CoO shell thickness which results in high HC and HE. Moreover, in concentrated assemblies, the dipolar field superposes to the local exchange field and enhances the EB effect contributing as an additional source of unidirectional anisotropy.

Testing an Iron Oxide Nanoparticle-Based Method for Magnetic Separation of Nanoplastics and Microplastics from Water.

Nanoplastic pollution is increasing worldwide and poses a threat to humans, animals, and ecological systems. High-throughput, reliable methods for the isolation and separation of NMPs from drinking water, wastewater, or environmental bodies of water are of interest. We investigated iron oxide nanoparticles (IONPs) with hydrophobic coatings to magnetize plastic particulate waste for removal. We produced and tested IONPs synthesized using air-free conditions and in atmospheric air, coated with several polydimethylsiloxane (PDMS)-based hydrophobic coatings. Particles were characterized with scanning electron microscopy (SEM), transmission electron microscopy (TEM), superconducting quantum interference device (SQUID) magnetometry, dynamic light scattering (DLS), X-ray diffraction (XRD) and zeta potential. The IONPs synthesized in air contained a higher percentage of the magnetic spinel phase and stronger magnetization. Binding and recovery of NMPs from both salt and freshwater samples was demonstrated. Specifically, we were able to remove 100% of particles in a range of sizes, from 2-5 mm, and nearly 90% of nanoplastic particles with a size range from 100 nm to 1000 nm using a simple 2-inch permanent NdFeB magnet. Magnetization of NMPs using IONPs is a viable method for separation from water samples for quantification, characterization, and purification and remediation of water.

Colloidal particle aggregation: mechanism of assembly studied via constructal theory modeling.

The assembly of colloidal particles into ordered structures is of great importance to a variety of nanoscale applications where the precise control and placement of particles is essential. A fundamental understanding of this assembly mechanism is necessary to not only predict, but also to tune the desired properties of a given system. Here, we use constructal theory to develop a theoretical model to explain this mechanism with respect to van der Waals and double layer interactions. Preliminary results show that the particle aggregation behavior depends on the initial lattice configuration and solvent properties. Ultimately, our model provides the first constructal framework for predicting the self-assembly of particles and could be expanded upon to fit a range of colloidal systems.

Development of an Innovative, Carrier-Based Dry Powder Inhalation Formulation Containing Spray-Dried Meloxicam Potassium to Improve the In Vitro and In Silico Aerodynamic Properties.

Most of the marketed dry powder inhalation (DPI) products are traditional, carrier-based formulations with low drug concentrations deposited in the lung. However, due to their advantageous properties, their development has become justified. In our present work, we developed an innovative, carrier-based DPI system, which is an interactive physical blend of a surface-modified carrier and a spray-dried drug with suitable shape and size for pulmonary application. Meloxicam potassium, a nonsteroidal anti-inflammatory drug (NSAID), was used as an active ingredient due to its local anti-inflammatory effect and ability to decrease the progression of cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). The results of the in vitro and in silico investigations showed high lung deposition in the case of this new formulation, confirming that the interparticle interactions were changed favorably.

Co-doped MnFe2O4 nanoparticles: magnetic anisotropy and interparticle interactions.

The effect of cobalt doping on the magnetic properties of Mn1- x Co x Fe2O4 nanoparticles was investigated. All samples consist of ensembles of nanoparticles with a spherical shape and average diameter of about 10 nm, showing small structural changes due to the substitution. Besides having the same morpho-structural properties, the effect of the chemical composition, i.e., the amount of Co doping, produces marked differences on the magnetic properties, especially on the magnetic anisotropy, with evident large changes in the coercive field. Moreover, Co substitution has a profound effect on the interparticle interactions, too. A dipolar-based interaction regime is detected for all samples; in addition, the intensity of the interactions shows a possible relation with the single particle anisotropy. Finally, the sample with the strongest interaction regime shows a superspin glass state confirmed by memory effect dynamics.

Dynamics of Magnetic Fluids in Crossed DC and AC Magnetic Fields.

In this study, we derived the equations describing the dynamics of a magnetic fluid in crossed magnetic fields (bias and alternating probe fields), considering the field dependence of the relaxation times, interparticle interactions, and demagnetizing field has been derived. For a monodisperse fluid, the dependence of the output signal on the bias field and the probe field frequency was constructed. Experimental studies were conducted in a frequency range up to 80 kHz for two samples of fluids based on magnetite nanoparticles and kerosene. The first sample had a narrow particle size distribution, low-energy magneto dipole interactions, and weak dispersion of dynamic susceptibility. The second sample had a broad particle size distribution, high-energy magneto dipole interactions, and strong dispersion of dynamic susceptibility. In the first case, the bias field led to the appearance of short chains. In the second case, we found quasi-spherical clusters with a characteristic size of 100 nm. The strong dependence of the output signal on the particle size allowed us to use the crossed field method to independently estimate the maximum diameter of the magnetic core of particles.

Microstructure and rheology of particle stabilized emulsions: Effects of particle shape and inter-particle interactions.

Using fumed and spherical silica particles of similar hydrodynamic size, we investigated the effects of particle shape and inter-particle interactions on the formation, stability and rheology of bromohexadecane-in-water Pickering emulsions. The interparticle interactions were varied from repulsive to attractive by modifying the salt concentration in the aqueous phase. Optical microscope images revealed smaller droplet sizes for the fumed silica stabilized emulsions. All the emulsions remained stable for several weeks. Cryo-SEM images of the emulsion droplets showed a hexagonally packed single layer of particles at oil-water interfaces in emulsions stabilized with silica spheres, irrespective of the nature of the inter-particle interactions. Thus, entropic, excluded volume interactions dominate the fate of spherical particles at oil-water interfaces. On the other hand, closely packed layers of particles were observed at oil-water interfaces for the fumed silica stabilized emulsions for both attractive and repulsive interparticle interactions. At the high salt concentrations, attractive inter-particles interactions led to aggregation of fumed silica particles, and multiple layers of these particles were then observed on the droplet surfaces. A network of fumed silica particles was also observed between the emulsion droplets, suggesting that enthalpic interactions are responsible for the determining particle configurations at oil-water interfaces as well as in the aqueous phase. Steady shear viscosity measurements over a range of shear stresses, as well as oscillatory shear measurements at 1Hz confirm the presence of a network in fumed silica suspensions and emulsions, and the lack of such a network when spherical particles are used. The fractal structure of fumed silica leads to several contact points and particle interlocking in the water as well as on the bromohexadecane-water interfaces, with corresponding effects on the structure and rheology of the emulsions. The attenuation of droplet motion due to the formation of a particle network can be exploited for stabilizing emulsions and for modulating their rheology.

Influence of particle properties on powder bulk behaviour and processability.

Understanding interparticle interactions in powder systems is crucial to pharmaceutical powder processing. Nevertheless, there remains a great challenge in identifying the key factors affecting interparticle interactions. Factors affecting interparticle interactions can be classified in three different broad categories: powder properties, environmental conditions, and powder processing methods and parameters. Although, each of these three categories listed is known to affect interparticle interactions, the challenge remains in developing a mechanistic understanding on how combination of these three categories affect interparticle interactions. This review focuses on the recent advances on understanding the effect of powder properties, particularly particle properties, its effect on interparticle interactions and ultimately on powder bulk behaviour. Furthermore, this review also highlights how particle properties are affected by the particle processing route and parameters. Recent advances in developing a particle processing route to prepare particles with desired properties allowing desired interparticle interaction to deliver favoured powder bulk behaviour are also discussed. Perspectives for the development of potential particle processing approaches to control interparticle interaction are presented.