The importance of boundary conditions in the simulation of dissolution in the USP dissolution apparatus

As shown in previous papers, mathematical simulation can be useful in the design of drug delivery systems. We present a finite-difference approximation to the drug mass transfer rate from dissolving cylindrical drug-containing compacts, consisting of alternating layers of drug and inert material. Results are compared with a recent analytical solution to the same problem and with experiment. The two theoretical estimates differ by about 10%, a result of different implementations of a derivative surface boundary condition. The finite-difference model is more physically realistic but the analytical solution is usefully accurate.     

Study on structural optimum design of implantable drug delivery micro-system

In this paper, design, modeling, and simulation of a new type of controlled drug delivery system based on biodegradable polymers is report. The system consists of arrays of micro-chambers for drug storage to achieve linear release. The micro-chambers were fabricated with biodegradable polymer using the UV-LIGA technology and the controlled release process is the combined results of design of the micro-chambers and the biodegradable characteristics of the polymer. This type of drug delivery system has some unique advantages in controlled long-term drug delivery, such as improved efficiency, reduced side effect, on-spot delivery, and convenient therapy. Mathematical model has been developed for two kind of biodegradable polymer micro-system respectively, and numerical simulations were conducted to analyze the biodegradation and the controlled release process. The mathematical model can be used to optimize the structural design for controlled-release system with the desired release characteristics.     

Finite element modeling of multi-pass welding and shaped metal deposition processes

This paper describes the formulation adopted for the numerical simulation of the shaped metal deposition process (SMD) and the experimental work carried out at ITP Industry to calibrate and validate the proposed model. The SMD process is a novel manufacturing technology, similar to the multi-pass welding used for building features such as lugs and flanges on fabricated components (see Fig. 1a and b). A fully coupled thermo-mechanical solution is adopted including phase-change phenomena defined in terms of both latent heat release and shrinkage effects. Temperature evolution as well as residual stresses and distortions, due to the successive welding layers deposited, are accurately simulated coupling the heat transfer and the mechanical analysis. The material behavior is characterized by a thermo-elasto-viscoplastic constitutive model coupled with a metallurgical model. Nickel super-alloy 718 is the target material of this work. Both heat convection and heat radiation models are introduced to dissipate heat through the boundaries of the component. An in-house coupled FE software is used to deal with the numerical simulation and an ad-hoc activation methodology is formulated to simulate the deposition of the different layers of filler material. Difficulties and simplifying hypotheses are discussed. Thermo-mechanical results are presented in terms of both temperature evolution and distortions, and compared with the experimental data obtained at the SMD laboratory of ITP.     

基于Monte Carlo模型的微型PLGA给药系统建模及仿真

多腔体的微型可降解高分子聚合物PLGA药物缓释系统是一种新型植入式给药微器件,其载体结构是结合药物释放的要求和高分子聚合物生物降解特性进行设计并利用MEMS工艺制备.为了解微型给药系统实际释药的性能,需要对其进行建模和仿真研究.基于体溶蚀的Monte Carlo溶蚀模型,建立了具有多腔体的微型PLGA给药载体的释药模型,并对腔体结构为圆形的微型给药系统进行了释药过程仿真.仿真结果表明本文建立的微系统释药模型可以较为准确的描述微系统的释药过程,仿真模型对进一步开发微型PLGA给药系统有重要的参考价值.     

圆柱绕流的二维数值模拟和尾迹分析

为指导机械设计中参数和布局的选择,研究固定在水流中的圆柱结构件的受力情况和流场分布．利用FLUENT中的三种湍流模型对雷诺数为3900的圆柱绕流进行二维数值模拟并进行对比,得到升力因数、阻力因数、分离角、斯特劳哈尔数和涡街尺寸等参数的模拟结果,与参考文献中的实验结果对比验证二维模拟的预测精度．RKE（Realizable k-ε）和雷诺应力模型（Reynolds Stress Model,RSM）均能在此雷诺数下得出接近实验结果的流场,RSM模型使用POWER LAW离散格式的结果优于QUICK格式．与三维模拟的对比表明二维模拟适合在设计初期的快速估算,能够快速得到合适精度的模拟结果．     

Modeling and simulation of drug delivery from a new type of biodegradable polymer micro-device

In this paper, modeling and simulation of a new type of controlled drug delivery micro-device based on biodegradable polymers is reported. The micro-device consists of micro-chambers arrays for drug storage to achieve linear release. The micro-chambers are fabricated with polyanhydrides (CPP-SA) using the UV-LIGA technology and the controlled release process are the combined results of the design of the micro-chambers and the biodegradable characteristics of the polymer. This type of drug delivery system has some unique advantages in controlled long-term drug delivery, such as larger loading volume than the matrices release systems, easier control for the release rate, etc. It is necessary to optimize the structure for the long-term and zero-order drug release. Based on the Monte Carlo erosion model, the drug release model is founded for the drug delivery system and using the new model, the drug release profiles from the delivery systems with different structures are simulated. The simulated results indicate that the effect of the drug delivery is dependent on the micro-structure of the delivery system and the simulated drug profiles of coaxial rings micro-cavity shape equal to zero-order released model approximatively. The simulated results are very important to the application research of the new biodegradable polymer micro-device.     

Application of the Gaussian mixture model to drug dissolution profiles prediction

In this paper, the radial basis function-based Gaussian mixture model (GMM) is applied to model and predict drug dissolution profiles in a time-series approach. The Parzen-window method is embedded into the GMM for determining whether the network predictions are derived from interpolation or extrapolation of the training data. A benchmark study on time-series prediction is first used to evaluate and compare the GMM performance with those from other models. The GMM is then used to predict dissolution profiles of a matrix-controlled release theophylline pellet preparation. Performance of the GMM is assessed using the difference and similarity factors, as recommended by the United States Food and Drug Administration for dissolution profile comparison. In addition, bootstrapping is employed to estimate the confidence intervals of the network predictions. The experimental results are analyzed and compared, and implications of the GMM for pharmaceutical product formulation tasks are discussed.     

Application of DPD in the design of polymeric nano-micelles as drug carriers

Developing new drug carrier systems are of a great importance in the treatment approach for a wide range of diseases. The simulation techniques can be valuable for decreasing the time and cost of developing novel drug carriers. Among the simulation methods there are a vast number of studies using dissipative particle dynamics (DPD) method for the prediction of different aspects of polymeric nano-micelles for encapsulating drugs. Here, we reviewed the results of the studies employing DPD for the simulation of drug loading and release in different polymeric micelles carriers. In some cases the simulation results were compared with the experimental results by the authors that were demonstrated the reliability of the DPD predictions.     

Modeling and simulation of drug release from multi-layer biodegradable polymer microstructure in three dimensions

Multi-layer biodegradable polymer drug delivery microstructures with micro-chambers have many exceptional advantages in a long-term controlled drug delivery. In this paper, a mathematical model for the drug release from this type of three-dimensional (3D) drug delivery microstructures is presented by using 3D cellular automata and discrete iterations. The validity of the model is proved by comparing with the Gőpferich’s simulated profiles for the same composite polymer cylinder matrices. Based on this model, furthermore, the simulations are done to describe the dynamic behavior of drug release from this type of microstructures. The simulation results show that this 3D mathematical model can describe accurately the drug release behavior and therefore can provide a new optimal design tool for this kind of multi-layer biodegradable polymer drug delivery microstructure.     

Numerical modeling of a novel degradable drug delivery system with microholes

Based on UV-LIGA technology, a novel drug delivery microsystem is proposed to eliminate the time lag in initial drug release. With proper microholes in bonding membrane, the drug release rate can be controlled at a stable level in the whole release process. This microsystem is fabricated by degradable polymer and suitable for subcutaneous implants. As a significant parameter, the demarcation time of polymer absorption/erosion is estimated by comparing the experimental results of polymer erosion and in vitro release. By considering diffusion, swelling and erosion mechanisms simultaneously, a numerical drug releasing model is developed to investigate the effect of microholes on drug release and impact factors of linear drug releasing. The simulation results show that the microholes are beneficial to eliminate the time lag, and furthermore, the area of microholes and the initial drug loading have great impact on the release time and the linear drug release rate.     

Analytical, numerical and experimental investigations of mixing fluids in microchannel

This work presents theoretical analysis, numerical simulation, fabrication and test of a micromixer chip for mixing fluids in microchannel. A three-dimensional analytical model is developed using a different mathematical approach to study passive laminar mixing phenomena and predict concentration distribution in a microchannel. The analytical model is validated by comparing with experimental and simulation results. The process of mixing fluids in a microchannel is simulated by solving the continuity, momentum and mass diffusion equations. The simulation results are validated and then parametric studies are performed to investigate the effects of channel aspect ratio, Reynolds number and diffusion coefficient on the mixing performance. The micromixer chip is fabricated with patterned SU-8 photoresist as the microchannel layer on a PMMA substrate using a combination of photolithography and micro-milling. Experiments are performed with different mixing fluids and the results were compared with that obtained from the theoretical model and simulation results.     

Agent-Based Simulation of Animal Behaviour

In the biological literature on animal behaviour, in addition to real experiments and field studies, also simulation experiments are a useful source of progress. Often specific mathematical modelling techniques are adopted and directly implemented in a programming language. Modelling more complex agent behaviours is less adequate using the usually adopted mathematical modelling techniques. The literature on AI and Agent Technology offers more specific methods to design and implement (also more complex) intelligent agents and agent societies on a conceptual level. One of these methods is the compositional multi-agent system design method DESIRE. In this paper it is shown how (depending on the complexity of the required behaviour) a simulation model for animal behaviour can be designed at a conceptual level in an agent-based manner. Different models are shown for different types of behaviour, varying from purely reactive behaviour to pro-active, social and adaptive behaviour. The compositional design method for multi-agent systems DESIRE and its software environment supports the conceptual and detailed design, and execution of these models. A number of experiments reported in the literature on animal behaviour have been simulated for different agent models.     

传感器网络基于两跳邻居信息的实时路由设计

提出了无线传感器网络基于两跳邻居信息的实时路由.包的截止期要求映射为速率要求的路由决策方法在SPEED 中首先提出,而本文提出的路由决策是基于两跳速率.如果没有节点能够满足给定速率,采用节能的概率丢包策略降低截止期错失率,可以提高能效.如果截止期松弛,嵌入平衡能耗的代价函数缓解某些节点被频繁选为转发节点的情况,以达到网络的能耗平衡.在仿真中模拟了物理层和MAC 层,采用了通过Mica2 Motes 实验得到的损耗链路模型.仿真结果显示,提出的路由方案比基于单跳信息的SPEED-S 路由的截止期错失率更低,能量效率更高,而且在端到端延迟的性能总体上没有降低.该设计可用于对服务质量要求较高的基于传感器网络的实时应用中.     

Numerical simulation study of spallation in reinforced concrete plates subjected to blast loading

In the design of protective structures, concrete walls are often used to provide effective protection against blast from incidental events. With a reasonable configuration and proper reinforcement, the protective structure could sustain a specified level of blast without global failure. However, the concrete wall may generate spallation on the back side of the wall, posing threats to the personnel and equipment inside the structure. For this concern, it is important to establish appropriate concrete spallation criteria in the protective design. Earlier analytical studies have been based on simplified one-dimensional wave theory, which does not consider the complex three-dimensional stress conditions in the case of close-in explosion and the structural effects. This paper presents a numerical simulation study on the concrete spallation under various blast loading and structural conditions. A sophisticated concrete material model is employed, taking into account the strain rate effect. The erosion technique is adopted to model the spallation process. Based on the numerical results, the spallation criteria are established for different levels of spallation. Comparison of the analytical results with experimental data shows a favorable agreement. It is also shown that the structural effects can become significant for relatively large charge weight and longer distance scenarios.     

Application of a Recurrent Neural Network to Prediction of Drug Dissolution Profiles

The Elman Recurrent Neural Network was employed for the prediction of in-vitro dissolution profiles of matrix controlled release theophylline pellet preparation, leading to the potential use of an intelligent learning system in the development of pharmaceutical products with desired drug release characteristics. A total of six different formulations containing various matrix ratios of substance to control the release rate of theophylline were used for experimentation. By using the leave-one-out cross-validation approach, the dissolution profiles of all the matrix ratios were consumed for training, except for one set that was taken as a reference profile, with which the network predicted profiles were compared. Performance of the network was assessed using the similarity factor, f ₂ , a criterion for dissolution profile comparison recommended by the United States Food and Drug Administration. Simulation results indicated that the Elman network was capable of predicting dissolution profiles that were similar to the reference profiles with an error of less than 8%. In addition, the Bootstrap method was used to estimate the confidence intervals of the f ₂ values. The results revealed the potential of a neural-network-based intelligent system in solving non-linear time-series prediction problems in pharmaceutical product development.     

Finite-difference lattice Boltzmann model for liquid–vapor systems

A two-dimensional finite-difference lattice Boltzmann model for liquid–vapor systems is introduced and analyzed. Two different numerical schemes are used and compared in recovering equilibrium density and velocity profiles for a planar interface. We show that flux limiter techniques can be conveniently adopted to minimize spurious numerical effects and improve the numerical accuracy of the model.     

离散时间下混合型良性蠕虫的建模仿真分析

为了更好地刻画良性蠕虫的传播过程,采用了离散时间模型。在离散时间下,考虑恶性蠕虫和良性蠕虫传播对网络的影响,对混合型良性蠕虫的传播过程进行分析和数学建模,通过仿真验证传播模型,并引入泰勒公式对关键参数进行分析比较。理论分析和仿真实验表明,在混合型良性蠕虫释放时间和网络性能一定的条件下,存在一个临界值使得切换时间最佳,而网络敏感度足够小时,不同的切换时间对感染类主机数量的变化几乎没有影响。     

Finite-element analysis of a rotary oven for bread

The paper deals with a finite-element analysis of the turbulent forced-convection air flow inside a rotary oven for bread. The code ADINA-F is used for the numerical finite-element simulation. To describe the flow and the heat transfer inside the oven, a two-dimensional model has been adopted. The numerical heat-transfer convection coefficient is in good agreement with the experimental data thus providing a validation of the approximate model formulated in the numerical analysis. A structural change intended to enhance the convective heat transfer has been suggested and numerically tested. The results show a mean Nusselt number enhancement of about 30%. The finite-element analysis is, therefore, a helpful tool in estimating the performances of this kind of oven.     

Structural locking mechanisms and their effect on database management system performance

Database management systems must provide a concurrency control subsystem to protect database consistency in the presence of concurrent readers and writers. The widely accepted method for realizing such protection in centralized database management systems is through a locking mechanism. The design of a locking mechanism for a relational database management systems presents the developer with a considerable number of new alternatives. This paper discusses some of those alternatives and their tradeoffs. A particular model is then presented which supports these alternatives for relational database management system locking mechanisms. A simulation model is described which was used to provide experimental results investigating these design alternatives. Results from a number of simulation experiments are presented demonstrating the effects on performance realized under different locking mechanism designs and transaction behavior profiles.     

Multilevel microwave design optimization with automated model fidelity adjustment

A computationally efficient algorithm for electromagnetic (EM)‐simulation‐driven design optimization of microwave structures is proposed. Our technique exploits variable‐fidelity EM simulations and the multilevel design approach where an approximate optimum of the lower accuracy but faster EM model of the structure under design is used as a starting point for optimizing a more accurate model. Several enhancements of the basic multifidelity method are introduced, including an efficient algorithm of optimizing EM models that is based on local response surface approximations, as well as automated adjustment of model fidelity. Convergence of the procedure to the optimum design is ensured by defaulting to the higher fidelity model whenever the prediction given by the lower fidelity fails to improve the design. Distribution of the computational effort between the models of different fidelity allows for making larger steps in the design space at a low cost, as well as substantial reduction of the number of high‐fidelity model evaluations, because the high‐fidelity model is only referred to in the last design stage. The article provides comprehensive numerical verification of our technique. Substantial computational savings are demonstrated in comparison to the benchmark methods: over 40% on average as compared to a basic version of the multifidelity optimization approach and over 95% as compared to direct optimization of the high‐fidelity model. © 2013 Wiley Periodicals, Inc. Int J RF and Microwave CAE 24:281–288, 2014.