Selection of Small Amounts of Glidant Capable of Improving the Tensile Strength of Ibuprofen Tablets.

This study examined the selection of small amounts of excipients capable of improving the compactability of ibuprofen, thereby enabling the miniaturization of ibuprofen tablets. Various glidants in amounts of 1% of the total volume were added to dry surface-modified ibuprofen, and the tensile strengths of the resulting tablets were evaluated. The characteristics of the excipients that affected the tensile strengths of the tablets were then extracted using a tensile strength prediction model. We confirmed that the effective angle of the internal friction of the mixed powder, the coating form of the glidant, the packing fraction of the raw material, and the mixed powder affect the tensile strength of the tablet. A smooth particle layer was formed on the surface of the ibuprofen particles when a glidant with a packing fraction of <0.05 was used. In the sample with a smooth particle layer, the angle of the critical state line increased significantly and the tensile strength improved. We inferred that the smoothness of the particle layer allowed the ibuprofen particles to come into close contact with each other. Consequently, the number of junctions increased, and the frictional force between the particles improved, resulting in tablets with improved tensile strengths. In conclusion, the compactability of ibuprofen was improved by adding 1% glidant with a packing fraction of <0.05. The reduction in excipients will allow the creation of smaller tablets, making them easier to swallow. Therefore, the medication adherence of customers will be improved.

Analyses of protein cores reveal fundamental differences between solution and crystal structures.

There have been several studies suggesting that protein structures solved by NMR spectroscopy and X-ray crystallography show significant differences. To understand the origin of these differences, we assembled a database of high-quality protein structures solved by both methods. We also find significant differences between NMR and crystal structures-in the root-mean-square deviations of the C α atomic positions, identities of core amino acids, backbone, and side-chain dihedral angles, and packing fraction of core residues. In contrast to prior studies, we identify the physical basis for these differences by modeling protein cores as jammed packings of amino acid-shaped particles. We find that we can tune the jammed packing fraction by varying the degree of thermalization used to generate the packings. For an athermal protocol, we find that the average jammed packing fraction is identical to that observed in the cores of protein structures solved by X-ray crystallography. In contrast, highly thermalized packing-generation protocols yield jammed packing fractions that are even higher than those observed in NMR structures. These results indicate that thermalized systems can pack more densely than athermal systems, which suggests a physical basis for the structural differences between protein structures solved by NMR and X-ray crystallography.

Estimation of bottle filling counts for conventional pharmaceutical tablets and capsules.

A method has been developed using commonly available data for estimating the number of tablets or hard shell capsules that can be filled into bottles. The single unit volumes of conventional pharmaceutical biconvex tablets and capsules can be calculated from simple geometric relationships, which then can be used to determine the packing fraction of the units in bottles. The packing fractions of capsules and tablets studied in this work ranged from 0.53 to 0.63 and 0.56 to 0.62, respectively, and were dependent on bottle size and shape. This method can be used to assess a variety of packaging configurations computationally during drug product development.

Microstructural and Rheological Transitions in Bacterial Biofilms.

Biofilms are aggregated bacterial communities structured within an extracellular matrix (ECM). ECM controls biofilm architecture and confers mechanical resistance against shear forces. From a physical perspective, biofilms can be described as colloidal gels, where bacterial cells are analogous to colloidal particles distributed in the polymeric ECM. However, the influence of the ECM in altering the cellular packing fraction (ϕ) and the resulting viscoelastic behavior of biofilm remains unexplored. Using biofilms of Pantoea sp. (WT) and its mutant (ΔUDP), the correlation between biofilm structure and its viscoelastic response is investigated. Experiments show that the reduction of exopolysaccharide production in ΔUDP biofilms corresponds with a seven-fold increase in ϕ, resulting in a colloidal glass-like structure. Consequently, the rheological signatures become altered, with the WT behaving like a weak gel, whilst the ΔUDP displayed a glass-like rheological signature. By co-culturing the two strains, biofilm ϕ is modulated which allows us to explore the structural changes and capture a change in viscoelastic response from a weak to a strong gel, and to a colloidal glass-like state. The results reveal the role of exopolysaccharide in mediating a structural transition in biofilms and demonstrate a correlation between biofilm structure and viscoelastic response.

Modeling the Impact of the Variation in Peripheral Nerve Anatomy on Stimulation.

Introduction: The peripheral nervous system has a complex anatomical structure. Stimulation of nerve fibers in the peripheral nervous system depends on the fiber diameter and myelination as well as its location within the nerve, packing fraction and fascicle distribution within the nerve bundle. This paper analyzes the impact of the variation in peripheral nervous system anatomy and the distance of the stimulating electrodes on the probability of generating an action potential. Methods: A mathematical model for effective fascicle conductivity has been developed to capture the variation in the packing fraction and fiber diameter. A linear activating function is utilized to analyze the impact of this effective conductivity and fascicle distribution as an indicator of generating an action potential. Results: Finite element simulations are performed for the nerve-electrode configuration to evaluate the electric field. The simulation results are used to analyze the activating function for different packing fractions and type of nerve fibers. The effect of electrode distance on activating function and the total current through a nerve bundle has also been studied. Discussion: The simulation results indicate that the peripheral nerve anatomy and electrode distance have a significant effect on the action potential generation.

Random sequential adsorption: An efficient tool for investigating the deposition of macromolecules and colloidal particles.

Random Sequential Adsorption (RSA) is one of the most efficient theoretical models used to investigate adsorption of macromolecules and particles, with a long-standing tradition in the field of colloid and interface science. In the first part of this paper, we demonstrate how the RSA model can be applied to interpret the experimental data and extract information about the density of the adsorption monolayer, the kinetics of its growth, and microstructural properties such as pair-correlation function and monolayer roughness. We briefly summarized the most important generalizations of the RSA model for monolayers and reviewed its extensions considering, e.g., various particle shapes, the introduction of electrostatic interaction, or adsorption on non-uniform substrates. We thoroughly scrutinized the extended RSA model developed for bilayer and multilayer formation. We collected the mean saturated packing fractions of various two- and three-dimensional objects and provided the most accurate result for two-dimensional disk packing. In the second part of this paper, we summarize various numerical algorithms and techniques that allow one to effectively implement RSA algorithms. We describe efficient methods for detecting intersections of various shapes and techniques enabling generation of strictly saturated RSA packings built of a wide range of different shapes. We hinted at how an inherently sequential RSA scheme can be parallelized. Finally, we critically discuss the limitations of the model and possible directions for future studies.

Practical Limits for Two Fundamental Approaches to Designing Particle Size Distributions to Address a Specific Physical Property like Viscosity.

It has previously been shown that optimum particle size distributions with a maximum packing fraction can be achieved from a straight line plot of the accumulated sum of particle volume fractions versus the square root of particle size. This study addresses practical limits for two dominant fundamental approaches to designing particle size distributions to address the effect on a specific physical property such as viscosity. The two fundamental approaches to obtain such a straight line would include: the first design approach would be generated utilizing the same initial particle size, Dmin, but by using different ultimate particle sizes, Dmax. The second design approach would be generated where each distribution starts with the same initial particle size, Dmin, and ends with the same ultimate particle size, Dmax. The first design approach is particularly useful to identify the possible slopes available based on the smallest and largest particle sizes available. The second design approach can be utilized to identify the preferred ratio between particles, Z, and the number of different particle sizes, n, to be utilized in the final particle blend. The extensive empirical experimental evaluations of particle size distributions generated by McGeary were then utilized to confirm the limits.

Mechanism Influencing the Drying Behavior of Bitumen Emulsion.

The drying process of bitumen emulsion largely dominates the strength development of emulsion-based mixtures for pavement structure, thus it can be used to judge the quality of bitumen emulsion. However, the drying behaviour of bitumen emulsions was seldom considered. The emulsion drying and film formation theory are employed to study the drying process of different bitumen emulsions with a thin layer. Results indicated the drying process of bitumen emulsion can be divided into three stages: (a) an initial high evaporation rate stage; (b) an intermediate stage with a rapidly decreasing evaporation rate; (c) a final stage with a very small evaporation rate. The boundaries among the three stages can be identified by studying the water evaporation rate. Three drying parameters, i.e., the critical volume fractions of bitumen defining the boundaries among the three stages and the maximum packing fraction of bitumen droplets, are proposed to quantitatively characterize the drying behavior of bitumen emulsion. High values of these parameters indicate a bitumen emulsion that has rapid drying behavior. Therefore, these parameters are independent of the emulsifier type, but they are highly dependent on the bitumen's droplet size. These drying parameters increase with a decrease in bitumen droplet size. Therefore, bitumen emulsion with a smaller size distribution of bitumen droplets can have a more rapid drying behavior, which is recommended in real engineering.

Atomic-level characterization of free volume in the structure of Cu67Zr33amorphous alloy.

The structure of Cu67Zr33amorphous alloy was investigated in terms of packing density and free volume by using neutron, x-ray diffraction and reverse Monte Carlo (RMC) modelling. The RMC model was analysed by a method of decomposing the three-dimensional atomic configuration into fundamental polyhedral units (termed as 'holes' referencing the Bernal's works) of which faces are all triangles consisting of chemical bonds. Not only tetrahedral and octahedral holes but also other larger holes were identified. Moreover, the atomic packing fractions and free volumes in the respective polyhedral holes were evaluated with reference to those for the corresponding crystal structures. The results show that the distribution of free volumes for the larger holes can be described by the exponential function assuming that there are no energetic interactions between each other. On the other hand, the local structural fluctuations due to densely and loosely packed tetrahedral holes were observed, leading to the negative free volume spaces.

Evaluation of the physical properties of dry surface-modified ibuprofen using a powder rheometer (FT4) and analysis of the influence of pharmaceutical additives on improvement of the powder flowability.

In this study, we examined the characteristics of glidant that affect the improvement of the flowability of APIs by using the dry surface modification of ibuprofen. In addition, the screening method of glidant suitable for improving flowability of APIs was examined. As a result of evaluation of mixed powder with surface modification using various inorganic fine particles with different physical properties, it became clear that the packing fraction had the most influence regardless of the component. This was thought to able to coat the surface with small quantities because the smaller the packing fraction, the more it was able to dispersed from the less contacts between the glidant particles. The packing fraction of glidant was correlated with the (SE/CBD)-1 which was calculated value from the results measured with powder rheometer. From this results, when using any excipient as a glidant for dry surface modification, it is now possible to estimate the effect of improving flowability simply by measuring with a powder rheometer. Based on this study, it is possible to select excipients suitable for improving APIs flowability and to estimate the improvement effect, and therefore, it is expected to improve the efficiency of prescription design work.

Effects of Volume Fraction and Surface Area of Aggregates on the Static Yield Stress and Structural Build-Up of Fresh Concrete.

With increasing interest in the use of additive manufacturing techniques in the construction industry, static rheological properties of fresh concrete have necessarily come into focus. In particular, the knowledge and control of static yield stress (SYS) and its development over time are crucial for mastering formwork-free construction, e.g., by means of layered extrusion. Furthermore, solid understanding of the influences of various concrete constituents on the initial SYS of the mixture and the structural build-up rate is required for purposeful material design. This contribution is concentrated on the effect of aggregates on these rheological parameters. The volume fraction of aggregates was varied in the range of 35% to 55% by volume under condition of constant total surface area of the particles. The total surface area per unit volume of cement paste was equal to 5.00, 7.25 and 10.00 m²/L, conditioned on the constant volume fraction of aggregates. Both variations were enabled by changing the particle size distributions of the aggregates while holding the cement paste composition constant for all concrete mixtures. To characterise the SYS and the structural build-up, constant shear rate tests with a vane-geometry rotational rheometer were performed. It was found that in the ranges under investigation the variation in volume fraction had a more pronounced effect on the static rheological properties of concrete than did the variation in surface area. An accurate mathematical description of the relationship between the initial SYS of concrete and the relative volume fraction of aggregate based on the Chateau-Ovarlez-Trung model was proposed. Challenges in deriving a similar relationship for the structural build-up rate of concrete were highlighted.

Soft Skyrmions, Spontaneous Valence and Selection Rules in Nanoparticle Superlattices.

A number of bewildering paradoxes arise in the field of nanoparticle self-assembly: nominal low density superlattices, strong stability of low coordination sites, and a clear but imperfect correlation between lattice stability and the maximum of hard sphere packing, despite the fact that that nanocrystals themselves are, through their ligands, very much compressible. In this study, I show that by regarding nanocrystals as pseudotopological objects ("soft skyrmions"), it is possible to identify and classify the ligand textures that determine their bonding. These textures consist of interacting vortices, where the total vorticity defines a spontaneous valence (coordination). Furthermore, skyrmion interactions are governed by two simple assumptions, which lead to a set of selection rules for superlattice structure. Besides resolving all the above paradoxes, the predictions are completely supported by more than one hundred sixty experiments gathered from the literature, including a wide range of nanocrystal cores and ligands (saturated or unsaturated hydrocarbons, amines, polystyrene, etc.). How those results can be used for addressing more complex structures and guiding future experiments is also addressed.

Mass Defect from Nuclear Physics to Mass Spectral Analysis.

Mass defect is associated with the binding energy of the nucleus. It is a fundamental property of the nucleus and the principle behind nuclear energy. Mass defect has also entered into the mass spectrometry terminology with the availability of high resolution mass spectrometry and has found application in mass spectral analysis. In this application, isobaric masses are differentiated and identified by their mass defect. What is the relationship between nuclear mass defect and mass defect used in mass spectral analysis, and are they the same? Graphical Abstract ᅟ.

Linking flowability and granulometry of lactose powders.

The flowing properties of 10 lactose powders commonly used in pharmaceutical industries have been analyzed with three recently improved measurement methods. The first method is based on the heap shape measurement. This straightforward measurement method provides two physical parameters (angle of repose αr and static cohesive index σr) allowing to make a first screening of the powder properties. The second method allows to estimate the rheological properties of a powder by analyzing the powder flow in a rotating drum. This more advanced method gives a large set of physical parameters (flowing angle αf, dynamic cohesive index σf, angle of first avalanche αa and powder aeration %ae) leading to deeper interpretations. The third method is an improvement of the classical bulk and tapped density measurements. In addition to the improvement of the measurement precision, the densification dynamics of the powder bulk submitted to taps is analyzed. The link between the macroscopic physical parameters obtained with these methods and the powder granulometry is analyzed. Moreover, the correlations between the different flowability indexes are discussed. Finally, the link between grain shape and flowability is discussed qualitatively.

Viscosity of soft spherical micro-hydrogel suspensions.

The rheology of soft particle suspensions is considered to be a function of particle micromechanics and phase volume. However, soft particles such as microgels present a challenge because they typically contain solvent in their polymeric network structure, and their specific volume can alter in response to mechanical forces and physiochemical effects. We investigate how particle elasticity affects the viscosity of microgel suspensions as a function of effective phase volume (ϕ0) using non-colloidal hydrogel spheres that, unlike many colloidal-scale microgels, are not highly responsive to physiochemical effects. In our unique approach, we compare the viscosity of microgel suspensions to a theoretical hard sphere viscosity model that defines the maximum packing fraction using the geometric random close packing fraction (ϕrcp) obtained from the measured particle size distribution. We discover that our harder microgels follow the hard sphere model up to random close packing, but softer microgels deviate around ϕ0/ϕrcp∼50% which indicates that their specific volume is decreasing with increasing ϕ0. This effect arises because microgels at high phase volumes do not fully re-swell during their preparation. We conclude that particle elasticity does not directly affect the viscosity of soft sphere suspensions up to the random close packing fraction. We highlight a convenient method for analysing the viscosity of microgel suspensions with potential to be applied to a wide variety of soft sphere suspensions.

A novel characterization of organic molecular crystal structures for the purpose of crystal engineering.

A novel analytical approach is proposed for the characterization of organic molecular crystal structures where close packing is an important factor. It requires the identification of a unique reference axis within the crystal, along which three-dimensional space is divided into close-packed blocks (CPB) and junction zones (JZ). The degree of close packing along the reference axis is quantified by a two-dimensional packing function, ϕ2D, of symmetry determined by the space group. Values of ϕ2D reflect the degree of area-filling in planes perpendicular to this axis. The requirement of close packing within CPB allows the planar structures perpendicular to the reference axis to be analysed as tessellations of area-filling molecular-based cells (MBC), which are generally hexagonal. The form of these cells reflects the molecular shape in the cross-section, since their vertices are given by the centres of the voids between molecules. There are two basic types of MBC, Type 1, of glide or pseudo-glide symmetry, and Type 2, which is formed by lattice translations alone and generally requires a short unit-cell axis. MBC at layers of special symmetry are used to characterize the structures in terms of equivalent ellipses with parameters aell, bell and χell. The ratio aell/bell allows the established α, ß, γ classification to be integrated into the current framework. The values of parameters aell and bell arising from all the structures considered, polynuclear aromatic hydrocarbons (PAH), substituted anthracenes and anthraquinones (SAA) and 2-benzyl-5-benzylidene (BBCP) are mapped onto a universal curve. The division of three-dimensional space into CPB and JZ is fundamentally useful for crystal engineering, since the structural perturbations brought about by substitution at hydrogen positions located within JZ are minimal. A contribution is also made to ongoing debate concerning the adoption of polar space groups, isomorphism and polymorphism.