Design of oral drug delivery systems – Past,present and future

Abstract

This paper reviews the past and the present thinking about peroral delivery research and development and how future approaches may be significantly different, both qualitatively and quantitatively. The future should involve the use of comprehensive models capable of incorporating physico-chemical data and biological information such as gastrointestinal flow, how and where drug absorption occurs, and whether and where metabolism of the drug occurs during gastrointestinal transit. Special challenges would involve the use of such models in research protocols in the optimization of drug delivery systems.     

Increasing the efficiency of systems for the detection of the contours of parts on the basis of Hough’s transformation

Hough’s transformation, which is used in systems for the detection and control of the geometric parameters of parts, along with the complex influence of different sets of filters in a contour detection system are considered. The basic methods of filtration that promote suppression of noise, the elimination of false contours, tapering of the edges of contours, and the removal of residual noise in the form of unconnected points of a contour are described. A quantitative estimate of the efficiency gained with the use of these filters is given from the results of tests.     

An analytic solution to the coupled pressure–temperature equations for modeling of photoacoustic trace gas sensors

Trace gas sensors have a wide range of applications including air quality monitoring, industrial process control, and medical diagnosis via breath biomarkers. Quartz-enhanced photoacoustic spectroscopy and resonant optothermoacoustic detection are two techniques with several promising advantages. Both methods use a quartz tuning fork and modulated laser source to detect trace gases. To date, these complementary methods have been modeled independently and have not accounted for the damping of the tuning fork in a principled manner. In this paper, we discuss a coupled system of equations derived by Morse and Ingard for the pressure, temperature, and velocity of a fluid, which accounts for both thermal effects and viscous damping, and which can be used to model both types of trace gas sensors simultaneously. As a first step toward the development of a more realistic model of these trace gas sensors, we derive an analytic solution to a pressure–temperature subsystem of the Morse–Ingard equations in the special case of cylindrical symmetry. We solve for the pressure and temperature in an infinitely long cylindrical fluid domain with a source function given by a constant-width Gaussian beam that is aligned with the axis of the cylinder. In addition, we surround this cylinder with an infinitely long annular solid domain, and we couple the pressure and temperature in the fluid domain to the temperature in the solid. We show that the temperature in the solid near the fluid–solid interface can be at least an order of magnitude larger than that computed using a simpler model in which the temperature in the fluid is governed by the heat equation rather than by the Morse–Ingard equations. In addition, we verify that the temperature solution of the coupled system exhibits a thermal boundary layer. These results strongly suggest that for computational modeling of resonant optothermoacoustic detection sensors, the temperature in the fluid should be computed by solving the Morse–Ingard equations rather than the heat equation.     

Developments in the tools for the investigation of mixing in particulate systems – A review

Mixing of powders and granular materials of different functions and/or properties is frequently encountered by engineers and scientists. Nevertheless, the guidelines for the selections of particle mixers are still not fully developed and predictions of the mixture quality after mixing operations are still not possible. These are largely due to the fact that the tools for particle mixing studies are far from well developed. In the last decades, advances in experimental and computational methods have brought lights to better particle mixer design and operation. This paper reviews the tools for the investigation of mixing in particulate systems.     

Aseptic loosening of femoral components – Materials engineering and design considerations

Aseptic loosening is one of the main reasons for the revision of a total knee replacement (TKR). The design of the key component of a TKR, the femoral component, is particularly problematic because its failure can be the result of different causes. This makes the development of new biomaterials for use in the femoral component a challenging task. This paper focuses on the engineering design aspects in order to understand the limitations of current materials and design deficiencies. The paper describes the introduction of a new biomaterial for a femoral component and justifies the recommendation to use multi-functional materials as a possible solution to aseptic loosening. The potential advantages of applying functionally graded biomaterials (FGBMs) in prosthetic femur are explained by reducing the leading causes of failure including wear, micro-motion and stress-shielding effect. The ideas presented in this paper can be used as the basis for further research on the feasibility and advantages of applying FGBM in other superior implant designs.     

Design of laser micromachined single crystal 6H–SiC diaphragms for high-temperature micro-electro-mechanical-system pressure sensors

A 248-nm, 23-ns pulsed excimer laser was used to micromachine 50 μm thick diaphragms in 6H–SiC wafers. The diaphragms were then subjected to high-pressure (0.7–7 MPa) and high temperature (500 K) tests to obtain the pressure-deflection curves. A finite element model was used to predict the stresses and displacements as a function of temperature and pressure. Model data is in good agreement with experiments. The stresses, strains and displacements were determined in order to facilitate the design of high-temperature micro-electro-mechanical-system pressure sensors.     

Monitoring of scaling in dilute phase pneumatic conveying systems using non-intrusive acoustic sensors – A feasibility study

Scale formation in pneumatic conveying systems is a major industrial challenge. The underlying scale formation mechanisms can be intricate as they often involve a combination of several mutually enhancing binding forces and can be affected by a number of different factors. A non-intrusive monitoring technique capable of measuring scale growth would be a valuable tool to investigate different scaling mechanisms. In this study, the feasibility of an active acoustic sensor technique for monitoring of scale growth in a pneumatic conveying system is evaluated. Tests are performed in a pilot scale pneumatic conveying system transporting sand in dilute phase. The acoustic sensors conducts measurements on test pipes which are coated with a primer/powder mixture, one layer after the other, to simulate scale progression. Reference measurements of the coating layer thickness in the test pipes are obtained by a laser imaging technique for each added coating layer. A multivariate method is used to calibrate prediction models of the scale thickness using acoustic measurements as independent variables and the reference measurements as the dependent variable. Results show that the active monitoring method is capable of monitoring scale growth in pneumatic conveying systems and that dilute phase conveying of sand does not affect the precision of predictions made by the method.     

Analysis of coupled dissipative dynamic systems of engineering using extended Hamiltonian \mathcal{H} for classical and nonconservative Hamiltonian H ∗n for higher order Lagrangian systems

Lagrange and Hamilton formalisms derived from variational calculus can be applied nearly in all engineering sciences. In this study, the reader is introduced using tensorial variables in covariant and contravariant forms, to the extended Lagrangian $\mathcal{L}$ and herewith to the modified momentum ${p}_{{k}}^{*}$ . Through both, the extended Hamiltonian $\mathcal{H}$ of a dissipative engineering system is derived to analyze the engineering system in an analytical way. In addition, a nonconservative Hamiltonian H ^?n for systems with elements of higher order is introduced in a similar manner. Moreover, different forms of extended Hamiltonian are represented. How these forms are achieved and how to derive the equations of generalized motion in different forms is also explained. As an example, a coupled electromechanical system in different formulations is given on behalf of the reader. The example is even extended to a case including some elements of higher order.     

Clarifying the debate on selection methods for engineering: Arrow’s impossibility theorem, design performances, and information basis

To demystify the debate about the validity of selection methods that utilize aggregation procedures, it is necessary that contributors to the debate are explicit about (a) their personal goals and (b) their methodological aims. We introduce three additional points of clarification: (1) the need to differentiate between the aggregation of preferences and of performances, (2) the application of Arrow’s theorem to performance measures rather than to preferences, and (3) the assumptions made about the information that is available in applying selection methods. The debate about decision methods in engineering design would be improved if all contributors were more explicit about these issues.     

Effects of pressure sensitivity on the η factor and the J integral estimation for compact tension specimens

In this paper, the effects of pressure-sensitive yielding on the factor and the J integral estimation for compact tension specimens are investigated. The analytical expressions for and J for pressure-insensitive von Mises materials are generalized to pressure-sensitive Drucker-Prager materials using a lower bound approach. The factor as a function of the pressure sensitivity and the normalized crack depth for compact tension specimens is derived under plane stress and plane strain conditions. The numerical results indicate that the factor decreases as the pressure sensitivity increases. The effects are more pronounced under plane strain conditions than under plane stress conditions. However, the effects of the pressure sensitivity on are found to be mild in general. For rigid perfectly-plastic materials, the J estimation for pressure-sensitive materials is also reduced to a simple expression of the tensile yield stress times the crack tip opening displacement as for the von Mises materials.     

Study of the monopolar RWG and monopolar n×RWG basis functions for electromagnetic scattering analysis

In this paper, we study the accuracy and the efficiency of the monopolar divergence-conforming Rao–Wilton–Glisson (RWG) and the monopolar curl-conforming n×RWG basis functions for the magnetic field integral equation (MFIE). Similar to cases using RWG and n×RWG basis functions for the MFIE, there are two impedance matrix elements calculation schemes if the monopolar RWG and monopolar n×RWG basis functions are used to the MFIE, respectively. The monopolar basis functions and the implementation schemes used for the MFIE are discussed. The scattering cross section data as well as the CPU time needed to fill the corresponding impedance matrix obtained from numerical solutions of these implementation schemes using monopolar basis functions are investigated. For the monopolar basis functions and the implementation schemes considered, the first scheme of the MFIE using the monopolar curl-conforming n×RWG basis functions gives most accurate results and it is the best choice for the use of the monopolar basis functions to the MFIE.     

Microstructural topology optimization for minimizing the sound pressure level of structural–acoustic coupled systems with multi-scale random parameters

The main aim of this article is to present a robust microstructural topology optimization methodology for structural–acoustic coupled systems with multi-scale random parameters. During the microstructural topology optimization, both the uncertainty at the macro-scale, which comes from the physical parameters of the acoustic medium or the external load, and the uncertainty existing in the constituent material properties of the microstructure at the micro-scale are considered as random parameters. A homogenization-based probabilistic finite element method (HPFEM) is first developed for quantifying the structural–acoustic system with multi-scale random parameters. The use of the HPFEM transforms the problem of microstructural topology optimization with multi-scale random parameters to an augmented deterministic microstructural topology optimization problem. This provides a computationally cheap alternative to Monte Carlo-based optimization algorithms. A numerical example of a hexahedral box is given to demonstrate the efficiency of the proposed method.     

How does the Earth system generate and maintain thermodynamic disequilibrium and what does it imply for the future of the planet?

The Earth's chemical composition far from chemical equilibrium is unique in our Solar System, and this uniqueness has been attributed to the presence of widespread life on the planet. Here, I show how this notion can be quantified using non-equilibrium thermodynamics. Generating and maintaining disequilibrium in a thermodynamic variable requires the extraction of power from another thermodynamic gradient, and the second law of thermodynamics imposes fundamental limits on how much power can be extracted. With this approach and associated limits, I show that the ability of abiotic processes to generate geochemical free energy that can be used to transform the surface-atmosphere environment is strongly limited to less than 1?TW. Photosynthetic life generates more than 200?TW by performing photochemistry, thereby substantiating the notion that a geochemical composition far from equilibrium can be a sign for strong biotic activity. Present-day free energy consumption by human activity in the form of industrial activity and human appropriated net primary productivity is of the order of 50?TW and therefore constitutes a considerable term in the free energy budget of the planet. When aiming to predict the future of the planet, we first note that since global changes are closely related to this consumption of free energy, and the demands for free energy by human activity are anticipated to increase substantially in the future, the central question in the context of predicting future global change is then how human free energy demands can increase sustainably without negatively impacting the ability of the Earth system to generate free energy. This question could be evaluated with climate models, and the potential deficiencies in these models to adequately represent the thermodynamics of the Earth system are discussed. Then, I illustrate the implications of this thermodynamic perspective by discussing the forms of renewable energy and planetary engineering that would enhance the overall free energy generation and, thereby 'empower' the future of the planet.     

Development of an interactive simulation system for the determination of the pressure–time relationship during the filling in a low pressure casting process

An interactive computer simulation system has been developed in this study to aid the determination of the pressure–time relationship during the filling of a low pressure casting to eliminate filling-related defects while maintaining its productivity. The pressure required to fill a casting in a low pressure casting process can be separated into two stages. The first stage is to exert pressure to force the molten metal to rise in the riser tube up to the gate of the casting die, which varies from casting to casting due to the drop of the level of the molten metal in the furnace, whilst the second stage is to add an additional pressure to push the molten metal into the die cavity in a way that will not cause much turbulence and have the proper filling pattern to avoid the entrapment of gas while maintaining productivity.One of the major efforts in this study is to modify the filling simulation system with the capability to directly predict the occurrence of gas porosity developed earlier to interactively determine the proper gate velocity for each and every part of the casting. The pressure required to fill the die cavity can then be obtained from the simulations.The operation principles and the interactive analysis system developed are then tested on an automotive wheel made by the low pressure casting process to demonstrate how the system can aid in determining the proper pressure–time relations, the p–t curve, required to produce a sound casting without sacrificing productivity.     

The impact assessment ‘arms race’ and visions for the future

In this commentary on Morrison-Saunders et al.'s [Morrison-Saunders A, Pope J, Gunn JAE, Bond A, Retief F. 2014. Strengthening impact assessment: a call for integration and focus. Impact Assess Project Appraisal. 44] position paper we focus on two main issues: their (1) call for unification and (2) assessment of the implications for impact assessment (IA) of the better regulation agenda. The importance of names and naming, plus the existence of genuine differences between IA tools and IA communities lead us to problematize the goal of unification. We argue that their ‘call to arms’ is based on a partial analysis of drivers of deregulation and is unnecessarily alarmist. Our commentary concludes with recommendations for a future agenda that prioritizes creativity arising from a vibrant community of practice.     

Fabrication of Pd–DNA and Pd–CNT hybrid nanostructures for hydrogen sensors

This review reports fabrication methods for ordered metallic nanostructures such as nanowires and nanoparticles based on deoxyribonucleic acid (DNA) templates. The phosphate groups in DNA are negatively charged; consequently, the DNA conformation may mineralize metals, e.g., palladium (Pd) at a relatively high metal concentration. We successfully form unique spherically shaped moss-like hybrid Pd nanoparticles using the small compacted globular state of DNA by controlling the reductive reaction. Pd can absorb hydrogen to become PdH_x, and hydrogen storage increases the electrical resistance and volume of Pd materials. Hence, the use of this material is attracting growing interest as a reliable, cheap, ultracompact, and safe hydrogen sensor. Pd–DNA hybrid nanoparticles can be used as highly sensitive hydrogen sensors, which exhibit a switch response that depends on the volume expansion in a cyclic atmosphere exchange. This paper also shows the fabrications of Pd–carbon nanotube (CNT) hybrid nanostructures.