Optimization of gliclazide loaded alginate-gelatin beads employing central composite design

Abstract

Objective: The aim of this study was to optimize the formulation of alginate-gelatin (AL-GL) beads containing gliclazide (GLZ) employing design of experiments (DOE).

Significance: DOE enabled identification of the interaction between the studied factors, deep understanding of GLZ release pattern and acceleration of the optimization process.

Methods: A three-factor, three-level face centered design was employed. The effects of GLZ content (GLZ%, X₁), polymer ratio (AL:GL ratio, X₂), crosslinker concentration (glutaraldehyde, GA%, X₃), and their interaction on incorporation efficiency (IE) and release rate were studied. The optimized formulation was prepared using numerical optimization and evaluated by DSC, FT-IR, SEM and release rate studies.

Results: Increasing GA% (X₃) decreased IE (Y₁) with the highest magnitude of effect among the studied factors. On the other hand, increasing alginate content in AL:GL ratio (X₂) increased IE (Y₁). The amount of GLZ released Q_0.5h, Q_2h(pH 1.2) and Q_4h(pH 7.4) decreased by increasing GLZ% (X₁) and AL:GL ratio (X₂). Both drug content and AL:GL ratio appeared to affect water penetration into the gel matrix and drug release. Generally, there was a direct relationship between GA% (X₃) and GLZ release in pH 1.2 (Q_0.5h and Q_2h). However, in pH 7.4 (Q_4h), increasing GA% decreased GLZ release. In addition, increasing GA% caused deviation from zero-order release model. The actual responses of the optimized formulation were in close agreement with the predicted ones.

Conclusion: The selected factors and their levels studied in the optimization design were useful for tailoring the anticipated formulation characteristics and GLZ release pattern.     

Robust design employing a genetic algorithm

The minimization of variability in a key design feature or performance measure, in the presence of variability in the realized values of design parameters, is discussed and an analytic solution for quadratic performance measures is provided. Solutions are based on the determination of optimum nominal (or design point) values for the design parameters, subject to constraints in the form of a given nominal performance at the design point and limits on the nominal values of the design parameters, which preserve the design concept. The more general, numerical, problem solution is addressed and a previously described deterministic procedure which generated multiple local optima is improved by the replacement of a simplex search method with a sophisticated genetic algorithm which, with suitable parameter values and choice of Lagrange multiplier, converges only to the required global minimum within the specified design parameter limits. Further improvements are discussed. Copyright © 2000 John Wiley & Sons, Ltd.     

Interphase coordination design in carbamate-siloxane/vaterite composite microparticles towards tuning ion-releasing properties

Siloxane-containing vaterite (SiV) microparticles were prepared with controlling the degree of aminopropyl-functionalization in the siloxane; they are aiming for applications as bone regenerative devices. The aim of this work was to evaluate the structure at siloxane/vaterite interphase and to control the solubility of particles by the structural tuning of siloxane. The particles were spherical with average diameters of 1.1–1.4 μm. Differential infrared spectrometry revealed the transformation of aminopropyl terminals in the siloxane into carbamate (NH-COO^?) groups. Moreover, the vaterite crystallites in the particles were slightly oriented towards the (0 0 1) plane. These results describe the interphase structure, with the carbamate groups coordinating on the Ca²⁺ ion face in the (0 0 1) plane of neighbouring vaterite. Upon soaking in buffer solution, the particles exhibited a rapid initial release of Ca²⁺ ions within 30 min and of soluble silica within 2 h. The vaterite in this particle survived for more than 6 h. The chemical stability of the siloxane was enhanced by incorporating tetraethoxysilane-derived siloxane with fractions of 24 mol% or 50 mol%. This enhancement controlled the initial release of not only soluble silica but also Ca²⁺ ions.     

新型炭／T型分子筛复合膜材料的设计、制备及应用

以聚酰胺酸为有机前驱，两种不同形貌的T型分子筛为杂化物经高温热解制备了新型的炭／T型分子筛复合膜材料。利用TG、XRD、SEM等分析手段对所制备的复合膜的微结构进行了研究。结果表明，T型分子筛在炭相中分散良好，其晶体结构在热解过程中没有被破坏，同时形成了稳定的无机，无机复合结构。单组分气体（CO2，O2，N2和CH4）以及混合气体（CO2／CH4，O2／N2）的渗透实验表明，分子筛减小了气体分子在膜中的扩散阻力从而大大提高了复合膜对气体分子的渗透能力，其中，复合膜对CO2和O2渗透系数可达1302Barrer[1Barrer=1×10^-10cm^3（STP）·cm／cm^2·s·cmHg]和334Barrer，同时CO2／CH4混合气体分离系数达到62，O2／N2分离系数达到8左右。这些数据表明该复合膜是一种可实现大规模二氧化碳以及空气分离的理想膜材料。     

复合材料帽型加筋壁板的失效机制分析与改进设计

为了准确预测复合材料帽型加筋壁板的后屈曲承载能力,针对压缩载荷下筋条端头斜削的复合材料帽型加筋壁板结构的失效机制及失效载荷进行了研究。首先利用物理试验,研究了端头斜削的复合材料帽型加筋壁板失效过程,然后构建了考虑蒙皮/缘条胶接界面以及复合材料层板失效的非线性损伤分析模型,详细地研究了损伤起始、扩展和失效的全过程。在此基础上,提出了包覆层对蒙皮/缘条界面进行增强的设计方案,并基于数值仿真和试验研究了包覆层对复合材料帽型壁板的破坏模式和承载能力的影响。数值分析和试验结果表明,包覆层设计能够明显提高结构的屈曲载荷和后屈曲承载能力,分析结果与试验值吻合良好,且预测的破坏模式也与试验结果一致。     

Optimal design of a composite structure

This paper presents a design methodology for a laminated composite stiffened panel, subjected to multiple in-plane loads and bending moments. Design variables include the skin and stiffener ply orientation angles and stiffener geometry variables. Optimum designs are sought which minimize structural weight and satisfy mechanical performance requirements. Two types of mechanical performance requirements are placed on the panel, maximum strain and minimum strength. Minimum weight designs are presented which document that the choice of mechanical performance requirements cause changes in the optimum design. The effects of lay-up constraints which limit the ply angles to user specified values, such as symmetric or quasi-isotropic laminates, are also investigated.     

Innovative design of a tunable laser using liquid crystal tuning elements

An innovative non-mechanical and low power consumption tunable external cavity laser (ECL) using liquid crystal tuning elements is proposed. This contains a gain chip, a collimating lens, tuning elements and a partial-reflection mirror. The proposed tunable ECL can achieve both coarse tuning and fine tuning, and it is designed to lase at wavelength matching the International Telecommunication Union (ITU) channels, which is one of the important requirements in optical communication. The tuning elements include an ITU etalon, a liquid crystal Fabry–Pérot interferometer (LC-FPI) and a fine tuner. Only two parameters are required to tune the wavelength over the whole C-band, namely the voltage over the LC-FPI and the fine tuner. This high reliability cost-effective design proposes a theoretical tuning range of about 80?nm. The LC tuning elements including LC-FPI and fine tuner has been fabricated and tested.     

高阶调谐齿轮参数设计及动态响应研究EI北大核心CSCD

提出一种高阶调谐齿轮传动原理,定义了调谐齿轮的错时相位角。基于动态啮合力开展高阶调谐齿轮参数设计研究,推导出调谐齿轮最佳传动参数,验证调谐齿轮错时相位角、调谐阶数对动态响应的影响;结合具体案例,进行高阶调谐齿轮的动力学数值模拟,研究高阶调谐齿轮传动参数对系统动态啮合力以及振动响应的影响。研究结果表明,当调谐阶数为2(二阶调谐齿轮)、错时相位角为1/2个齿距时,调谐齿轮时变啮合刚度和接触力波动最小,振动位移以及振动加速度波动最小,从理论上验证了二阶调谐齿轮具有明显的减振作用。     

A Josephson logic design employing current-switched junctions

A logic scheme using Josephson tunnel junctions in a current-steering mode is described. Switching from voltageV = 0toV neq 0is accomplished by adding a fraction of the control-line currents to the bias current. In one form the addition is accomplished by shunting the junction to be switched with a loop containing a second junction serving a diode-like function and causing one or more control lines to possess inductive coupling to the loop. A five-element circuit demonstrating AND, OR and INVERSION operations carried out by this approach has been fabricated and works as expected.     

Structural design of a composite bicycle fork

Despite the wide literature on the mechanical behaviour of carbon/epoxy composites, it is rare to find practical methodological approaches in finite element design of structural components made by laminate layup. Through the case study of a special bicycle fork needed in a Student Team prototype, this paper proposes a simplified methodology as starting point for educational and manufacturing purposes. In order to compare two manufacturing solutions in terms of stiffness, strength and failure mode, a numerical model was implemented. Since the project requirements imposed to avoid standard destructive testing, the model validation was based on a posteriori linear stiffness comparison with the manufactured component. The slight discrepancies between experimental and numerical results were discussed in order to check their origin and to assess the reliability of the model. The overall methodology, even if complain with only a part of the safety standard requirements, shows to be reliable enough and can be the basis for further extension and refinement.     

Computational design of nanostructured steels employing irreversible thermodynamics

Abstract

Recent theory demonstrates that the Kocks–Mecking formulation of plasticity has a foundation in multiscale irreversible thermodynamics. The key terms in the formulation can be obtained form experiments and from fundamental calculations. This offers two advantages to materials scientists and alloy designers: the Kocks–Mecking approach goes beyond being a phenomenological approach, gaining a solid physical foundation in multiscale computational physics; the new formulation can be employed to conceive new alloys displaying complex synergistic interactions at several scales and among several phases. This approach is ideal for designing and modelling nanostructured steels. This work incorporates four concomitant strengthening effects: solid solution, Hall–Petch, dislocation forest and precipitation. The new formulation is applied to nanostructured martensitic, dual phase and twinning induced plasticity steels, describing with excellent accuracy of their stress–strain behaviour.     

Fracture mechanism in a SiCw-6061 Al composite

The dynamic fracture processes of hot-extruded SiCw-6061 Al composite were observed using scanning electron microscopy (SEM). The effect of the off-axis angle on the strength and the fracture mechanism of the composite was studied in detail. On the basis of the SEM observations, two tensile fracture models, namely the brittle fracture model and the shear fracture model, are discussed.     

High-pressure triggered quantum tunneling tuning through classical percolation in a single nanowire of a binary composite

In the era of miniaturization, the one-dimensional nanostructures presented numerous possibilities to realize operational nanosensors and devices by tuning their electrical transport properties. Upon size reduction, the physical properties of materials become extremely challenging to characterize and understand due to the complex interplay among structures, surface properties, strain effects, distribution of grains, and their internal coupling mechanism. In this report, we demonstrate the fabrication of a single metal-carbon composite nanowire inside a diamond-anvil-cell and examine the in situ pressure-driven electrical transport properties. The nanowire manifests a rapid and reversible pressure dependence of the strong nonlinear electrical conductivity with significant zero-bias differential conduction revealing a quantum tunneling dominant carrier transport mechanism. We fully rationalize our observations on the basis of a metal-carbon framework in a highly compressed nanowire corroborating a quantum-tunneling boundary, in addition to a classical percolation boundary that exists beyond the percolation threshold. The structural phase progressions were monitored to evidence the pressure-induced shape reconstruction of the metallic grains and modification of their intergrain interactions for successful explanation of the electrical transport behavior. The pronounced sensitivity of electrical conductivity to an external pressure stimulus provides a rationale to design low-dimensional advanced pressure sensing devices.

     

Complex permittivity measurements of ferroelectrics employing composite dielectric resonator technique

Composite cylindrical TE(0n1) mode dielectric resonator has been used for the complex permittivity measurements of ferroelectrics at frequency about 8.8 GHz. Rigorous equations have been derived that allowed us to find a relationship between measured resonance frequency and Q-factor and the complex permittivity. It has been shown that the choice of appropriate diameter of a sample together with rigorous complex angular frequency analysis allows precise measurements of various ferroelectric. Proposed technique can be used for materials having both real and imaginary part of permittivity as large as a few thousand. Variable temperature measurements were performed on a PbMg(1/3)Nb(2/3)O3 (PMN) ceramic sample, and the measured complex permittivity have shown good agreement with the results of measurements obtained on the same sample at lower frequencies (0.1-1.8 GHz).     

复合材料机翼鲁棒气动弹性优化设计

针对气动弹性结构, 利用遗传-敏度混合算法开展鲁棒优化设计。以大展弦比复合材料机翼的鲁棒气动弹性结构优化设计为例验证了鲁棒设计方法的适用性和有效性, 比较了鲁棒结构优化设计与传统优化设计的区别。研究结果表明: 在设计变量存在不确定性的情况下, 考虑鲁棒性约束优化得到的结构较传统优化结构具有更好的抗干扰性; 但鲁棒性的满足是以增加结构质量为代价的, 鲁棒性要求越高, 结构增重越明显。      

High-power and high-quality, green-beam generation by employing a thermally near-unstable resonator design

We have obtained green-beam quality of M2 = 6.2 at an average output power of 120 W by intracavity frequency doubling of a diode-side-pumped, Q-switched Nd:YAG rod laser with a repetition rate of 10 kHz and an optical-to-optical conversion efficiency of 15.2%. To achieve high-beam quality at high average power, the laser employs a thermally near-unstable resonator design with two-rod birefringence compensation in an L-shaped flat-flat cavity. The output power fluctuation of the green laser remains less than 0.9% in 4 h.     

High speed tuning mechanism for CO2 lidar systems

A method for rapidly tuning lasers is presented. The system utilizes a rotating eight-sided mirror and a fixed grating. It is demonstrated that the entire CO2 lasing spectrum can be tuned at effective rates of up to 400 Hz. It is shown that, although the pulse energy is diminished as the tuning rate is increased, the loss comes from the tail of the pulse, and the peak power is almost unchanged. In addition, the tuning method preserves the spatial beam profile while contributing a minimum of beam steering.     

Adaptive post-buckling response of carbon fibre composite plates employing SMA actuators

Restoration forces, associated with embedded activated pre-strained SMA wires, have successfully been employed to enhance the post-buckling behaviour of laminated plate structures while under the influence of a uniaxial load. The results of which will be presented. The manufacturing methodology of the hybrid SMA-carbon-epoxy plates is outlined. Optical micrographs illustrate the effect of embedding diametrical inclusions within a host composite. Thermal and structural finite-element analysis have been employed to predict the non-uniform temperature profile within the laminates and to provide insight to the SMA-hybrid structure adaptive response. It is shown that by utilizing the considerable control authority generated, even for a small actuator volume fraction, the out-of-plane displacement of the post-buckled laminates can be significantly reduced. Such displacement alleviation allows for the load redistribution away from the plate's unloaded edges i.e. there is a tendency for the plate to conform to the optimal flat configuration beyond its critical buckling load. However, the stability of the adaptive response is very much dependent upon the laminate stacking sequence. It is envisaged that the range of operational performance for such an adaptive hybrid structure may be extended over conventional materials and structures.     

Planar ferrite-piezoelectric composite microwave resonator with electric and magnetic frequency tuning

A planar composite microwave resonator based on a bilayer structure comprising a single-crystal yttrium iron garnet (YIG) ferrite film on a lead magnesium niobate-lead titanate (PMN-PT) piezoelectric plate has been studied. The possibility of electric and magnetic tuning of the resonance frequency in this structure is demonstrated. The magnetic tuning in the frequency range of 2–18 GHz is effected by varying the magnetic bias field and the electric tuning within a 20 MHz bandwidth is achieved by applying a dc bias voltage to the piezoelectric layer. An increase in the central frequency of a YIG/PMN-PT composite resonator is accompanied by a growth in the resonator Q from 110 to 990, while the electric tuning bandwidth remains unchanged