Molecular architecture influences on material properties of pharmaceutical compounds

Salt formation has extensively been studied as a strategy to improve drug solubility but it has not been explored as a strategy to improve mechanical properties. A better understanding of which factors of the solid state can have an influence in the mechanical properties of pharmaceutical powders can help to optimise and reduce cost of tablet manufacturing. The aim of this study was to form different series of amine salts of flurbiprofen, gemfibrozil and diclofenac and to establish predictive relationships between architectural characteristics and physicochemical and mechanical properties of the salts. For this purpose, three different carboxylic acid drugs were selected: flurbiprofen, gemfibrozil and diclofenac, similar in size but varying in flexibility and shape and three different series of counterions were also chosen: one with increasing bulk and no hydroxyl groups to limit the hydrogen bonding potential; a second one with increasing number of hydroxyl groups and finally a third series, related to the latter in number of hydroxyl groups but with different molecular shape and flexibility. Physico-chemical characterization was performed (DSC, TGA, solubility, intrinsic dissolution rate, particle size, true density) and mechanical properties measured using a compaction replicator. Strained molecular conformations produce weaker compacts as they have higher energy than preferred conformations that usually lie close to energy minimums and oppose plastic deformation. It was observed that slip planes, which correspond to regions of weakest interaction between the planes, were associated with improved plasticity and stronger compacts. Apart from hydrogen bonds, profuse van der Waals forces can result in ineffective slip planes. Salts displaying two-dimensional densely hydrogen bonded layers produced stronger compacts than salts showing one-dimensional networks of non-bonded columns, probably by reducing the attachment energy between layers. When hydrogen bonds are created intramolecularly, it is possible that the mechanical properties are compromised as they do not contribute so much to create twodimensional densely bonded layers and they can force molecules into strained conformations. Some types of hydrogen bonding network may be associated with improved mechanical properties, such as type II, or R (10) 3 4 using graph-set notation, versus type III, or R (12) 4 8 , columns. This work clearly demonstrates the potential of investigating crystal structure-mechanical property relationship in pharmaceutical materials.

Investigation of ultrafast laser-photonic material interactions: Challenges for directly written glass photonics

Currently, direct-write waveguide fabrication is probably the most widely studied application of femtosecond laser micromachining in transparent dielectrics. Devices such as buried waveguides, power splitters, couplers, gratings, and optical amplifiers have all been demonstrated. Waveguide properties depend critically on the sample material properties and writing laser characteristics. In this paper, we discuss the challenges facing researchers using the femtosecond laser direct-write technique with specific emphasis being placed on the suitability of fused silica and phosphate glass as device hosts for different applications.

The effect of care solutions on the bulk and surface properties of soft contact lenses

Purpose: Soft contact lenses for continuous wear require the use of cleaning regimes which utilise hydrogen peroxide systems or multipurpose cleaning solutions (MPS). The compositions of MPS are becoming increasingly complex and often include disinfectants, cleaning agents, preservatives, wetting agents, demulcents, chelating and buffering agents. Recent research on solution–lens interactions has focused on specific ocular parameters such as corneal staining. However the effect of a solution on the lens, particularly silicone hydrogel lenses, itself has received less attention. The purpose of this work was to establish and understand the effects that care solutions have on selected bulk and surface material properties. Methods: Selected bulk and surface properties of each material (etafilcon A, vifilcon A, balafilcon A, senofilcon A, lotrafilcon A and lotrafilcon B, galyfilcon A) were measured after a 24 h soak in a variety of care solutions. Additionally the lenses were soaked for 24 h in hyperosmolar (680 mOsm L-1) and hyposmolar (170 mOsm L-1) PBS. A bulk property parameter the total diameter (TD) was measured using an Optimec contact lens analyser. The surface property related CoF of soaked lenses was measured on a nano-tribometer with conditions of load 30 mN, at a distance of 20 mm and speed 30 mm/min. Results: In terms of bulk properties, change is related to the EWC of the lens, the higher the EWC of the lens the greater the TD changes. Silicone hydrogel lenses have EWCs of <47% and little or no TD changes were observed; lotrafilcon A exhibited no change irrespective of the cleaning solution. Conventional contact lenses have higher EWCs (58% for etafilcon A and 55% for vifilcon A) and the TD was seen to change to a greater extent, for example the etafilcon A material in ReNu MPS had an increase to 14.45± 0.07 mm from the cited 14.2 mm. Other lenses increased or decreased in TD depending on the solution used. The osmolarity of the solution although important is not the only factor governing change in the TD, for example soaking senofilcon A in hyperosmolar PBS (680 mOsm L-1) for 24 h increased the TD of the lens (+0.25 ± 0.07 mm), however when the same lens type was soaked for 24 h in a MPS with a lower osmolarity there was a similar effect. Biotribology measurements demonstrated that some solution–lens combinations can reduce the CoF by 55%, when compared with biotribology with the native packing solution. An increase in the CoF was observed for other solution–lens combinations. Conclusions: There is a dramatic difference in bulk and surface performance of specific lens materials with particular care solutions. Individual components of the care solutions have effects on the bulk and surface properties of contact lenses. The affects are not as great with the silicone hydrogel as compared with conventional hydrogels.

Analysis of powder caking in multicomponent powders using atomic force microscopy to examine particle properties

Atomic force microscopy has been used to study the surface properties of model spray dried powders. Phase imaging, nanoindentation and force modulation microscopy have differentiated between the different surface material properties of the particles, revealing a regular dispersion of soft, oil rich areas distributed across the particles' surface. Humidity and temperature cycling effects on the caking behavior of the particles have also been investigated, with significant morphology changes and onset of caking found to occur within relatively short periods of time.

A decade of silicone hydrogel development:surface properties, mechanical properties, and ocular compatibility

Since the initial launch of silicone hydrogel lenses, there has been a considerable broadening in the range of available commercial material properties. The very mobile silicon–oxygen bonds convey distinctive surface and mechanical properties on silicone hydrogels, in which advantages of enhanced oxygen permeability, reduced protein deposition, and modest frictional interaction are balanced by increased lipid and elastic response. There are now some 15 silicone hydrogel material variants available to practitioners; arguably, the changes that have taken place have been strongly influenced by feedback based on clinical experience. Water content is one of the most influential properties, and the decade has seen a progressive rise from lotrafilcon-A (24%) to efrofilcon-A (74%). Moduli have decreased over the same period from 1.4 to 0.3 MPa, but not solely as a result of changes in water content. Surface properties do not correlate directly with water content, and ingenious approaches have been used to achieve desirable improvements (e.g., greater lubricity and lower contact angle hysteresis). This is demonstrated by comparing the hysteresis value of the earliest (lotrafilcon-A, >40°) and most recent (delefilcon-A, <10°) coated silicone hydrogels. Although wettability is important, it is not of itself a good predictor of ocular response because this involves a much wider range of physicochemical and biochemical factors. The interference of the lens with ocular dynamics is complex leading separately to tissue–material interactions involving anterior and posterior lens surfaces. The biochemical consequences of these interactions may hold the key to a greater understanding of ocular incompatibility and end of day discomfort.

Fracture and viscoelastic properties of asphalt binders during fatigue and rest periods

Viscoelastic asphalt binder plays an important role in bonding individual aggregate particles and contributes to the durability and stability of asphalt pavement. When asphalt binder is subjected to cyclic loading, deformation and fracture may develop simultaneously within it, leading to the deterioration of material properties and eventually fatigue failure. Research has found that some degree of recovery may develop if rest periods are applied after fatigue deterioration. However, it is not clear whether such recovery is caused by fracture healing, viscoelastic recovery, or both. This paper presents an analysis to differentiate the contributions of fracture healing and viscoelastic recovery to the asphalt binder during rest periods. It also evaluates the damage caused by deformation and fracture during a fatigue process. It is found that viscoelastic recovery plays an important role in the instant increase in the dynamic shear modulus at the beginning of the rest period. The effect of fracture healing on dynamic shear modulus recovery is more dominant in the long term. A healing index is developed based only on the fracture healing of asphalt binder, excluding the effect of viscoelastic recovery. It can be used to evaluate the true healing properties of different asphalt binders. Copyright © 2014 by ASTM International.

The mechanical behaviour of cylindrical GRP panels

Glass reinforced plastic (GRP) is now an established material for the fabrication of sonar windows. Its good mechanical strength, light weight, resistance to corrosion and acoustic transparency, are all properties which fit it for this application. This thesis describes a study, undertaken at the Royal Naval Engineering College, Plymouth, into the mechanical behaviour of a circular cylindrical sonar panel. This particular type of panel would be used to cover a flank array sonar in a ship or submarine. The case considered is that of a panel with all of its edges mechanically clamped and subject to pressure loading on its convex surface. A comprehensive program of testing, to determine the orthotropic elastic properties of the laminated composite panel material is described, together with a series of pressure tests on 1:5 scale sonar panels. These pressure tests were carried out in a purpose designed test rig, using air pressure to provide simulated hydrostatic and hydrodynamic loading. Details of all instrumentation used in the experimental work are given in the thesis. The experimental results from the panel testing are compared with predictions of panel behaviour obtained from both the Galerkin solution of Flugge's cylindrical shell equations (orthotropic case), and finite element modelling of the panels using PAFEC. A variety of appropriate panel boundary conditions are considered in each case. A parametric study, intended to be of use as a preliminary design tool, and based on the above Galerkin solution, is also presented. This parametric study considers cases of boundary conditions, material properties, and panel geometry, outside of those investigated in the experimental work Final conclusions are drawn and recommendations made regarding possible improvements to the procedures for design, manufacture and fixing of sonar panels in the Royal Navy.

An experimental analysis of operating conditions in cold roll-forming

A detailed literature survey confirmed cold roll-forming to be a complex and little understood process. In spite of its growing value, the process remains largely un-automated with few principles used in set-up of the rolling mill. This work concentrates on experimental investigations of operating conditions in order to gain a scientific understanding of the process. The operating conditions are; inter-pass distance, roll load, roll speed, horizontal roll alignment. Fifty tests have been carried out under varied operating conditions, measuring section quality and longitudinal straining to give a picture of bending. A channel section was chosen for its simplicity and compatibility with previous work. Quality measurements were measured in terms of vertical bow, twist and cross-sectional geometric accuracy, and a complete method of classifying quality has been devised. The longitudinal strain profile was recorded, by the use of strain gauges attached to the strip surface at five locations. Parameter control is shown to be important in allowing consistency in section quality. At present rolling mills are constructed with large tolerances on operating conditions. By reduction of the variability in parameters, section consistency is maintained and mill down-time is reduced. Roll load, alignment and differential roll speed are all shown to affect quality, and can be used to control quality. Set-up time is reduced by improving the design of the mill so that parameter values can be measured and set, without the need for judgment by eye. Values of parameters can be guided by models of the process, although elements of experience are still unavoidable. Despite increased parameter control, section quality is variable, if only due to variability in strip material properties. Parameters must therefore be changed during rolling. Ideally this can take place by closed-loop feedback control. Future work lies in overcoming the problems connected with this control.

Finite element analysis of particle impact problems

Particle impacts are of fundamental importance in many areas and there has been a renewed interest in research on particle impact problems. A comprehensive investigation of the particle impact problems, using finite element (FE) methods, is presented in this thesis. The capability of FE procedures for modelling particle impacts is demonstrated by excellent agreements between FE analysis results and previous theoretical, experimental and numerical results. For normal impacts of elastic particles, it is found that the energy loss due to stress wave propagation is negligible if it can reflect more than three times during the impact, for which Hertz theory provides a good prediction of impact behaviour provided that the contact deformation is sufficiently small. For normal impact of plastic particles, the energy loss due to stress wave propagation is also generally negligible so that the energy loss is mainly due to plastic deformation. Finite-deformation plastic impact is addressed in this thesis so that plastic impacts can be categorised into elastic-plastic impact and finite-deformation plastic impact. Criteria for the onset of finite-deformation plastic impacts are proposed in terms of impact velocity and material properties. It is found that the coefficient of restitution depends mainly upon the ratio of impact velocity to yield Vni/Vy0 for elastic-plastic impacts, but it is proportional to [(Vni/Vy0)*(Y/E*)]-1/2, where Y /E* is the representative yield strain for finite-deformation plastic impacts. A theoretical model for elastic-plastic impacts is also developed and compares favourably with FEA and previous experimental results. The effect of work hardening is also investigated.

Theoretical modelling of the sulcated spring

Replacement of the traditional coil spring with one of more fibre-reinforced plastic sulcated springs is a future possibility. Spring designers of metallic coil springs have design formulae readily available, and software packages specific to coil spring design exist. However, the sulcated spring is at the prototype stage of development, so literature on these springs is very sparse. The thesis contains information on the market for sulcated springs, and their advantages and disadvantages. Literature on other types of fibre reinforced plastic springs has also been reviewed. Design software has been developed for the sulcated spring along similar lines to coil spring design software. In order to develop the software, a theoretical model had to be developed which formed the mathematical basis for the software. The theoretical model is based on a choice of four methods for calculating the flexural rigidity; beam theory, plate theory, and lamination theory assuming isotropic and orthoropic material properties. Experimental results for strain and spring stiffness have been compared with the theoretical model, and were in good agreement. Included in the design software are the results of experimental work on fatigue, and design limiting factors to prevent or warn against impractical designs. Finite element analysis has been used to verify the theoretical model developed, and to find the better approximation to the experimental results. Applications and types of assemblies for the sulcated spring were discussed. Sulcated spring designs for the automotive applications of a suspension, clutch and engine valve spring were found using the design computer software. These sulcated spring designs were within or close to the space of the existing coil spring and yield the same performance. Finally the commercial feasibility of manufacturing the sulcated spring was assessed and compared with the coil spring, to evaluate the plausibility of the sulcated spring replacing the coil spring eventually.

Morphology modification of polyethylene/clay nanocomposite samples under convergent flow

The morphology of PE/CL nanocomposite samples subjected to convergent flows is studied. Elongational flow – the typical flow involved in spinning and film-blowing processing operations – significantly increases with the reduction of the capillary diameter. The values of the convergent extensional stress (calculated by Cogswell's formula) for the PE/CL systems, for all the adopted capillary geometries, are greater than the calculated values for pure polyethylene. The applied convergent flow, at the entrance of the capillary, is able to change the clay morphology and consequently the final material properties on the PE/CL system with limited affinity between the matrix and organo-modified clay particles.

Direct measurement of coherency limits for strain relaxation in heteroepitaxial core/shell nanowires

The growth of heteroepitaxially strained semiconductors at the nanoscale enables tailoring of material properties for enhanced device performance. For core/shell nanowires (NWs), theoretical predictions of the coherency limits and the implications they carry remain uncertain without proper identification of the mechanisms by which strains relax. We present here for the Ge/Si core/shell NW system the first experimental measurement of critical shell thickness for strain relaxation in a semiconductor NW heterostructure and the identification of the relaxation mechanisms. Axial and tangential strain relief is initiated by the formation of periodic a/2 〈110〉 perfect dislocations via nucleation and glide on {111} slip-planes. Glide of dislocation segments is directly confirmed by real-time in situ transmission electron microscope observations and by dislocation dynamics simulations. Further shell growth leads to roughening and grain formation which provides additional strain relief. As a consequence of core/shell strain sharing in NWs, a 16 nm radius Ge NW with a 3 nm Si shell is shown to accommodate 3% coherent strain at equilibrium, a factor of 3 increase over the 1 nm equilibrium critical thickness for planar Si/Ge heteroepitaxial growth. © 2012 American Chemical Society.

Modelling the human accommodation system using finite element analysis

The human accommodation system has been extensively examined for over a century, with a particular focus on trying to understand the mechanisms that lead to the loss of accommodative ability with age (Presbyopia). The accommodative process, along with the potential causes of presbyopia, are disputed; hindering efforts to develop methods of restoring accommodation in the presbyopic eye. One method that can be used to provide insight into this complex area is Finite Element Analysis (FEA). The effectiveness of FEA in modelling the accommodative process has been illustrated by a number of accommodative FEA models developed to date. However, there have been limitations to these previous models; principally due to the variation in data on the geometry of the accommodative components, combined with sparse measurements of their material properties. Despite advances in available data, continued oversimplification has occurred in the modelling of the crystalline lens structure and the zonular fibres that surround the lens. A new accommodation model was proposed by the author that aims to eliminate these limitations. A novel representation of the zonular structure was developed, combined with updated lens and capsule modelling methods. The model has been designed to be adaptable so that a range of different age accommodation systems can be modelled, allowing the age related changes that occur to be simulated. The new modelling methods were validated by comparing the changes induced within the model to available in vivo data, leading to the definition of three different age models. These were used in an extended sensitivity study on age related changes, where individual parameters were altered to investigate their effect on the accommodative process. The material properties were found to have the largest impact on the decline in accommodative ability, in particular compared to changes in ciliary body movement or zonular structure. Novel data on the importance of the capsule stiffness and thickness was also established. The new model detailed within this thesis provides further insight into the accommodation mechanism, as well as a foundation for future, more detailed investigations into accommodation, presbyopia and accommodative restoration techniques.

Weak form equation–based finite-element modeling of viscoelastic asphalt mixtures

The objective of this study is to demonstrate using weak form partial differential equation (PDE) method for a finite-element (FE) modeling of a new constitutive relation without the need of user subroutine programming. The viscoelastic asphalt mixtures were modeled by the weak form PDE-based FE method as the examples in the paper. A solid-like generalized Maxwell model was used to represent the deforming mechanism of a viscoelastic material, the constitutive relations of which were derived and implemented in the weak form PDE module of Comsol Multiphysics, a commercial FE program. The weak form PDE modeling of viscoelasticity was verified by comparing Comsol and Abaqus simulations, which employed the same loading configurations and material property inputs in virtual laboratory test simulations. Both produced identical results in terms of axial and radial strain responses. The weak form PDE modeling of viscoelasticity was further validated by comparing the weak form PDE predictions with real laboratory test results of six types of asphalt mixtures with two air void contents and three aging periods. The viscoelastic material properties such as the coefficients of a Prony series model for the relaxation modulus were obtained by converting from the master curves of dynamic modulus and phase angle. Strain responses of compressive creep tests at three temperatures and cyclic load tests were predicted using the weak form PDE modeling and found to be comparable with the measurements of the real laboratory tests. It was demonstrated that the weak form PDE-based FE modeling can serve as an efficient method to implement new constitutive models and can free engineers from user subroutine programming.

Functionalised particles using dry powder coating in pharmaceutical drug delivery:promises and challenges

Introduction: Production of functionalised particles using dry powder coating is a one-step, environmentally friendly process that paves the way for the development of particles with targeted properties and diverse functionalities. Areas covered: Applying the first principles in physical science for powders, fine guest particles can be homogeneously dispersed over the surface of larger host particles to develop functionalised particles. Multiple functionalities can be modified including: flowability, dispersibility, fluidisation, homogeneity, content uniformity and dissolution profile. The current publication seeks to understand the fundamental underpinning principles and science governing dry coating process, evaluate key technologies developed to produce functionalised particles along with outlining their advantages, limitations and applications and discusses in detail the resultant functionalities and their applications. Expert opinion: Dry particle coating is a promising solvent-free manufacturing technology to produce particles with targeted functionalities. Progress within this area requires the development of continuous processing devices that can overcome challenges encountered with current technologies such as heat generation and particle attrition. Growth within this field requires extensive research to further understand the impact of process design and material properties on resultant functionalities.