Solubility enhancement of miconazole nitrate: binary and ternary mixture approach

Context: Enhancement of aqueous solubility of very slightly soluble Miconazole Nitrate (MN) is required to widen its application from topical formulation to oral/mucoadhesive formulations.

Objective: Aim of the present investigation was to enhance the aqueous solubility of MN using binary and ternary mixture approach.

Materials and methods: Binary mixtures such as solvent deposition, inclusion complexation and solid dispersion were adopted to enhance solubility using different polymers like lactose, beta-cyclodextrin (β-CD) and polyethylene-glycol 6000 (PEG 6000), respectively. Batches of binary mixtures with highest solubility enhancement potentials were further mixed to form ternary mixture by a simple kneading method. Drug polymer interaction and mixture morphology was studied using the Fourier transform infrared spectroscopy and the scanning electron microscopy, respectively along with their saturation solubility studies and drug release.

Results: An excellent solubility enhancement, i.e. up to 72 folds and 316 folds of MN was seen by binary and ternary mixture, respectively. Up to 99.5% drug was released in 2?h from the mixtures of MN and polymers.

Discussion: Results revealed that solubility enhancement by binary mixtures is achieved due to surface modification and by increasing wettability of MN. Tremendous increase in solubility of MN by ternary mixture could possibly be due to blending of water soluble polymers, i.e. lactose and PEG 6000 with β-CD which was found to enhance the solubilizing nature of β-CD.

Conclusion: Owing to the excellent solubility enhancement potential of ternary mixtures in enhancing MN solubility from 110.4?μg/ml to 57?640.0?μg/ml, ternary mixture approach could prove to be promising in the development of oral/mucoadhesive formulations.     

Revealing characteristics of mixed consortia for azo dye decolorization: Lotka-Volterra model and game theory

This study provides a novel explanation to put forward, in Lotka-Volterra competition model and game theory, interspecific competition in bioaugmentation using constructed mixed consortia for azo dye decolorization. As mixed cultures are regularly used in industrial dye-laden wastewater treatment, understanding species competition of mixed consortia is apparently of great importance to azo dye decolorization. In aerobic growth conditions, Escherichia coli DH5alpha owned a growth advantage to out-compete Pseudomonas luteola due to preferential growth rate of DH5alpha. However, in static decolorization conditions DH5alpha surrendered some proportion of its advantage (i.e., a decrease in its competitive power for metabolite stimulation) to enhance color removal of P. luteola for total coexistence. In aerobic growth, DH5alpha had its growth advantage to exclude P. luteola for dominance (i.e, conflict strategy) according to competitive exclusion principle. In static decolorization conditions, as the removal of a common dye threat was crucial to both species for survival, both species selected cooperation strategy through metabolite stimulation of DH5alpha to enhance effective decolorization of P. luteola for long-term sustainable management. This analysis of game theory clearly unlocked unsolved mysteries in previous studies.     

D-optimal mixture design: optimization of ternary matrix blends for controlled zero-order drug release from oral dosage forms

The objective of the present study was to develop a tablet formulation with a zero-order drug release profile based on a balanced blend of three matrix ingredients. To accomplish this goal, a 17-run, three-factor, two-level D-Optimal mixture design was employed to evaluate the effect of Polyox^™ (X₁), Carbopol® (X₂), and lactose (X₃) concentrations on the release rate of theophylline from the matrices. Tablets were prepared by direct compression and were subjected to an in vitro dissolution study in phosphate buffer at pH 7.2. Polynomial models were generated for the responses Y₄ (percent released in 8 h) and Y₆ (similarity factor or f₂). Fitted models were used to predict the composition of a formulation that would have a similar dissolution profile to an ideal zero-order release at a rate of 8.33% per hour. When tested, dissolution profile of the optimized formulation was comparable to the reference profile (f₂ was 74.2, and n [release exponent] was 0.9). This study demonstrated that a balanced blend of matrix ingredients could be used to attain a zero-order release profile. Optimization was feasible by the application of response surface methodology, which proved efficient in designing controlled-release dosage forms.     

A statistical experiment design approach for advanced oxidation of Direct Red azo-dye by photo-Fenton treatment

Advanced oxidation of an azo-dye, Direct Red 28 (DR 28) by photo-Fenton treatment was investigated in batch experiments using Box-Behnken statistical experiment design and the response surface analysis. Dyestuff (DR 28), H(2)O(2) and Fe(II) concentrations were selected as independent variables in Box-Behnken design while color and total organic carbon (TOC) removal (mineralization) were considered as the response functions. Color removal increased with increasing H(2)O(2) and Fe(II) concentrations up to a certain level. High concentrations of H(2)O(2) and Fe(II) adversely affected the color and TOC removals due to hydroxyl radical scavenging effects of high oxidant and catalyst concentrations. Both H(2)O(2) and Fe(II) concentration had profound effects on decolorization. Percent color removal was higher than TOC removal indicating formation of colorless organic intermediates. Complete color removal was achieved within 5min while complete mineralization took nearly 15min. The optimal reagent doses varied depending on the initial dyestuff dose. For the highest dyestuff concentration tested, the optimal H(2)O(2)/Fe(II)/dyestuff ratio resulting in the maximum color removal (100%) was predicted to be 715/71/250 (mgL(-1)), while this ratio was 1550/96.5/250 for maximum mineralization (97.5%).     

3D numerical simulations of thermodiffusion experiment for a ternary mixture on-board foton

The phenomenon of mass flux in a mixture due to a temperature gradient is known as the Soret effect. Accurate experimental and theoretical models are needed for a better understanding and effective characterisation of situations involving coupled transport processes as in hydrocarbon reservoirs. This requires precise knowledge of the transport coefficients particularly the Fick and Soret diffusion coefficients. We have investigated the effect of residual-g and (very) low-frequency g-jitters encountered on-board spacecraft FOTON on mass-thermo-fluid dynamics in the presence of Soret effect. Results revealed that the diffusion process is slightly affected by the g-jitter on board the FOTON platform, which indicates that FOTON is a good platform to conduct near perfect microgravity environment.     

Oral bioavailability enhancement of raloxifene by developing microemulsion using D-optimal mixture design: optimization and in-vivo pharmacokinetic study

The objective of this work was to utilize a potential of microemulsion for the improvement in oral bioavailability of raloxifene hydrochloride, a BCS class-II drug with 2% bioavailability. Drug-loaded microemulsion was prepared by water titration method using Capmul MCM C8, Tween 20, and Polyethylene glycol 400 as oil, surfactant, and co-surfactant respectively. The pseudo-ternary phase diagram was constructed between oil and surfactants mixture to obtain appropriate components and their concentration ranges that result in large existence area of microemulsion. D-optimal mixture design was utilized as a statistical tool for optimization of microemulsion considering oil, S_mix, and water as independent variables with percentage transmittance and globule size as dependent variables. The optimized formulation showed 100?±?0.1% transmittance and 17.85?±?2.78?nm globule size which was identically equal with the predicted values of dependent variables given by the design expert software. The optimized microemulsion showed pronounced enhancement in release rate compared to plain drug suspension following diffusion controlled release mechanism by the Higuchi model. The formulation showed zeta potential of value ?5.88?±?1.14?mV that imparts good stability to drug loaded microemulsion dispersion. Surface morphology study with transmission electron microscope showed discrete spherical nano sized globules with smooth surface. In-vivo pharmacokinetic study of optimized microemulsion formulation in Wistar rats showed 4.29-fold enhancements in bioavailability. Stability study showed adequate results for various parameters checked up to six months. These results reveal the potential of microemulsion for significant improvement in oral bioavailability of poorly soluble raloxifene hydrochloride.     

High-energy sensitivity enhancement in panchromatic photopolymers for holography using a mixture of visiblelight photoinitiators

Abstract

A new aqueous photopolymer containing the monomers acrylamide, N,N'-methylenbisacrylamide and zinc acrylate, the initiators 4,5-diiodosuccinylfluorescein (2ISF) and methylene blue (MB), and the coinitiator sodium p-toluenesulphinate is described. This formulation exhibits a clear enhancement of the high-energy sensitivity upon irradiation with 514 or 633 nm light (Ar⁺ laser or He–Ne laser respectively), with respect to the same mixture but with only one of the two dyes, reaching maximum diffraction efficiencies of 15–20% with 15–60 mJ cm^?2. This enhancement is explained by the more efficient photogeneration of initiator radicals by the ground-state formation of an ion-pair complex between cationic (MB) and anionic (2ISF) chromophores. This must compensate the observed decrease in the absorbance of the mixture of the two dyes at 514 nm, with respect to the absorbance of the same medium but with only 2ISF (maximum absorption at 490 nm). A clear absorbance increase at 633 nm, with respect to the absorbance of this system with only MB (maximum absorption at 660 nm), must also favour photopolymerization.     

Optimization of process variables for decolorization of Disperse Yellow 211 by Bacillus subtilis using Box-Behnken design

Decolorization of textile azo dye Disperse Yellow 211 (DY 211) was carried out from simulated aqueous solution by bacterial strain Bacillus subtilis. Response surface methodology (RSM), involving Box-Behnken design matrix in three most important operating variables; temperature, pH and initial dye concentration was successfully employed for the study and optimization of decolorization process. The total 17 experiments were conducted in the study towards the construction of a quadratic model. According to analysis of variance (ANOVA) results, the proposed model can be used to navigate the design space. Under optimized conditions the bacterial strain was able to decolorize DY 211 up to 80%. Model indicated that initial dye concentration of 100 mgl(-1), pH 7 and a temperature of 32.5 degrees C were found optimum for maximum % decolorization. Very high regression coefficient between the variables and the response (R(2)=0.9930) indicated excellent evaluation of experimental data by polynomial regression model. The combination of the three variables predicted through RSM was confirmed through confirmatory experiments, hence the bacterial strain holds a great potential for the treatment of colored textile effluents.     

Use of ejectors in a multi-evaporator refrigeration system for performance enhancement

In this study, an improved cooling cycle for a conventional multi-evaporators simple compression system utilizing ejector for vapour precompression is analyzed. The ejector-enhanced refrigeration cycle consists of multi-evaporators that operate at different pressure and temperature levels. A one-dimensional mathematical model of the ejector was developed using the equations governing the flow and thermodynamics based on the constant-area ejector flow model. The model includes effects of friction at the constant-area mixing chamber. The energy efficiency and the performance characteristics of the novel cycle are theoretically investigated. The comparison between the novel and conventional system was made under the same operating conditions. Also, a comparison of the system performances with environment friendly refrigerants (R290, R600a, R717, R134a, R152a, and R141b) is made. The theoretical results show that the COP of the novel cycle is better than the conventional system.     

主动减振器结构参数优化设计

主动减振系统由3个以上减振器构成,其固有频率直接决定了系统隔振带宽,且减振器水平向隔振广泛采用摆机构。柔性杆直径及杆长是影响摆机构水平向刚度的主要几何参数。根据材料弹性变形理论建立了摆机构的水平向刚度模型及最大拉应力模型。在给定的负载质量范围内,以主动减振系统水平向固有频率与目标值的均方差最小作为优化目标,将许用拉应力和最大尺寸作为设计约束,应用序列二次规划法求解该非线性优化模型,得出摆机构的最优设计参数及对应的均方差。基于3σ准则,可估计主动减振系统的水平向固有频率分布范围。在许用固有频率范围约束下,得到摆机构参数的允许范围。实验结果表明:减振系统固有频率的测试值与理论分析值的差异小于10%;加入主动控制后,振动传递率的共振峰小于0dB,大于6Hz的振动传递率小于-20dB。     

A new tolerance design method for a secondary rechargeable battery using design of experiments with mixture

Mixing errors in the manufacturing process of a mixture may cause a sizeable variation in the performance of the product, leading to the need for the tolerance design. Even though a variety of procedures have been proposed for the optimal tolerance design based on quality loss and manufacturing costs, there are no available tolerance design methods when mixing errors exist in the manufacturing process of a mixture. In this article, we propose a new tolerance design method for the case where mixing errors are involved in massive manufacturing process of a secondary rechargeable battery. Using an approximation method, we derive quality loss function, reflecting the effects of mixing errors on the product performances. Statistical design of mixture experiments is applied to build empirical models of performances as functions of component proportions in the corresponding quality loss function. A real‐life case study on the tolerance design of a secondary battery is provided for the illustration of the proposed method. The results show the efficiency of the proposed method in designing the tolerances to minimize the quality loss and manufacturing costs. Copyright © 2008 John Wiley & Sons, Ltd.     

Fraction of design space plots for evaluating ridge estimators in mixture experiments

When the component proportions in mixture experiments are restricted by lower and upper bounds, the design space can become an irregular region that can induce multicollinearity among the component proportions. Thus, we suggest the use of ridge regression as a means of stabilizing the estimates of the coefficients in the fitted model. We use fraction of design space plots and violin plots to illustrate and evaluate the effect of ridge regression estimators with respect to the prediction variance and to guide the decision about the value of ridge constant k. We illustrate the methods with three examples from the literature. Copyright © 2010 John Wiley & Sons, Ltd.     

Mortar fatigue model for meso-mechanistic mixture design of ravelling resistant porous asphalt concrete

This paper presents the development of a practical mortar fatigue model on the basis of the dissipated energy concept. A specially designed test setup was developed for characterization of mortar fatigue at meso-scale by means of dynamic shear rheometer. Test results showed that mortar fatigue models based on the dissipated energy concept can be developed for the purpose of life predictions under complicated loading conditions. The dissipated energy per cycle in the initial phase of fatigue tests is a practical indicator for fatigue life determination purposes than the total energy dissipated during a fatigue test. Since a mortar fatigue model based on the initial dissipated energy per cycle was adopted, effects of random stress and strain signals on mortar fatigue can be taken into account.     

Kinetic study approach of remazol black-B use for the development of two-stage anoxic-oxic reactor for decolorization/biodegradation of azo dyes by activated bacterial consortium

The laboratory-isolated strains Pseudomonas aeruginosa, Rhodobacter sphaeroides, Proteus mirabilis, Bacillus circulance, NAD 1 and NAD 6 were observed to be predominant in the bacterial consortium responsible for effective decolorization of the azo dyes. The kinetic characteristics of azo dye decolorization by bacterial consortium were determined quantitatively using reactive vinyl sulfonated diazo dye, remazol black-B (RB-B) as a model substrate. Effects of substrate (RB-B) concentration as well as different substrates (azo dyes), environmental parameters (temperature and pH), glucose and other electron donor/co-substrate on the rate of decolorization were investigated to reveal the key factor that determines the performance of dye decolorization. The activation energy (E(a)) and frequency factor (K(0)) based on the Arrhenius equation was calculated as 11.67 kcal mol(-1) and 1.57 x 10(7)mg lg MLSS(-1)h(-1), respectively. The Double-reciprocal or Lineweaver-Burk plot was used to evaluate V(max), 15.97 h(-1) and K(m), 85.66 mg l(-1). The two-stage anoxic-oxic reactor system has proved to be successful in achieving significant decolorization and degradation of azo dyes by specific developed bacterial consortium with a removal of 84% color and 80% COD for real textile effluents vis-à-vis >or=90% color and COD removal for synthetic dye solution.     

Feasibility study to control fiber distribution for enhancement of composite properties via three-dimensional printing

The distribution of fibers in the composite (which takes into account both their locations and orientations) is one of the important factors that affect the mechanical properties of FRCs. However, this parameter depends on various factors during composite fabrication, and controlling the distribution of fibers in the produced material represents a significant challenge. In this study, the applicability of three-dimensional (3D) printing technique for controlling fiber distributions was evaluated. The fibers fabricated using a 3D printer were placed inside a mold to produce cementitious composites. Three-point bending tests were conducted and the results of the experiment were discussed.     

Critical parameters in design of active magnetocaloric regenerators for magnetic refrigeration applications

A new way to evaluate the performance of the active magnetocaloric regenerator (AMR) was developed based on a few critical parameters proposed in this study. The critical parameters were derived from the energy equations that have been used to describe the transient energy transfer processes in the AMR for both the magnetocaloric materials and the heat transfer fluid. Each parameter is corresponding to a specific energy transfer mechanism in the AMR and can be easily implemented to evaluate the contribution from each term, including axial conduction and remnant energy storage in the magnetocaloric materials, axial conduction, remnant energy storage and fluid dissipation in the heat transfer fluid, and internally regenerated energy. Parametric studies were carried out to explore the impact of geometric and operating parameters and to determine whether or not a certain heat transfer mechanism is significant to the overall system performance.     

Gradation design of porous asphalt mixture (PAM) for low-strength application in wet environment

Porous asphalt mixture (PAM) is potentially suitable for application in wet environment given its excellent performance in drainage due to the typical open-graded design, whilst ravelling and clogging are the two major issues directly related to the functional service life of PAM pavements. With the increasing up-build of non-motorised transport facility in Singapore which is a tropical country with frequent thunderstorms during monsoon periods, it deserves research into designing well-performing PAM for low-strength pavements such as pedestrian and cycling pathways. In this research, two areas are researched on designing appropriate PAM: firstly, relationship between gradation design and permeability performance is established and 7% content of fine aggregates is selected to achieve adequate coefficient of permeability for Singapore; secondly, four aggregate gradations with different packing structures created by the coarse aggregates were designed, and the performance was evaluated in the aspect of permeability, mechanical strength, resistance to ravelling and resistance to clogging. Three testing scenarios were applied in ravelling and clogging tests, which were unconditioned, ageing-conditioned and moisture-conditioned. It is found that moisture exposure is a more severe condition than ageing on PAM’s performance. On the whole, PAM with high content of intermediate size aggregates (i.e. 6.3–4.75 mm) in the coarse fraction and low content (i.e. lower than 7%) of fine fraction is suggested for low-strength PAM pavement in Singapore.     

Use of modified hybrid PSOGSA for optimum design of RC frame

A realistic and optimum design of reinforced concrete structural frame, by hybridizing enhanced versions of standard particle swarm optimization (PSO) and standard gravitational search algorithm (GSA) is presented in this paper. PSO has been democratized by considering all good and bad experiences of the particles, whereas GSA has been made self-adaptive by considering a specific range for certain parameters like ‘gravitational constant’ and ‘set of agents with best fitness value.’ Optimal size and reinforcement of the members have been found by employing the technique in a computer-aided environment. Use of self-adaptive GSA together with democratic PSO technique has been found to provide two distinct advantages over standard PSO and GSA, namely better capability to escape from local optima and faster convergence rate. The entire formulation for optimal cost design of frame includes the cost of beams and columns. In this approach, variables of each element of structural frame have been considered as continuous functions and rounded off appropriately to imbibe practical relevance to the study. An example has been considered to emphasize the validity of this optimum design procedure and results have been compared with earlier studies.     

Use of the manufacturing system design decomposition for comparative analysis and effective design of production systems

The focus of this paper is on the use of the Manufacturing System Design Decomposition (MSDD) to make effective cost and production system design decisions. A comparative study is conducted to illustrate how and why the total cost is reduced when the functional requirements defined by the MSDD are achieved. The ultimate goal of this research was to advance manufacturing and production system development to being guided by engineering science and design rather than the common practice of duplicating another person’s or entity’s notion of the best physical implementation.