Face-centered Composite Design Research Articles

Optimization on dry sliding wear behavior of yellow brass using face centered composite design

The proposed research has investigated the dry sliding wear behavior at ambient temperature atmosphere on yellow brass intended for locks, gears, bearings, ammunition casings, and valves. The experiments were conducted based on the central composite design. The wear experiments were performed using the pin-on-disc tribometer by varying the applied load, the sliding velocity, and the sliding distance. The obtained wear results were examined using the multiple regression non-linear model and then the results were validated by performing the confirmation test. It was found that the predicted wear based on the developed regression model was well correlated with the confirmation results. Further, the detailed microstructures of as-received and worn surfaces were examined and reported. In addition, the plotted surface graphs between the input independent parameters and the responses showed that the wear rate started to vary linearly with the function of load whereas it was varied non-linearly with the function of the sliding velocity and the sliding distance.

Development of a multiplex forensic identity panel for massively parallel sequencing and its systematic optimization using design of experiments

The application of massively parallel sequencing (MPS) in forensic sciences enables high-resolution short tandem repeat (STR) genotyping for the characterization of biological evidence. While MPS supports multiplexing of a large number of forensic markers, the performance of an MPS-STR panel depends on good primer design and optimal PCR conditions. However, conventional strategies for multifactorial assay optimization are labor-intensive and do not necessarily allow the experimenter to identify optimum factor settings.Here we describe our new multiplex PCR assay, monSTR, which supports the simultaneous amplification of 21 forensic markers followed by targeted sequencing on the Illumina MiSeq. The selection of STR markers adapts on the expanded European Standard Set (ESS), including the highly polymorphic locus SE33, for compatibility with existing forensic DNA databases. Primer engineering involved bioinformatics tools to create a multiplex-compatible primer set. Primer quality was evaluated in silico and in vitro. We demonstrate the systematic optimization of multiplex PCR thermocycling conditions using Design of Experiments (DOE) methodology. The objective was to yield a specific, balanced, low-noise amplification of forensic targets. A central composite face design of experiments enabled an efficient simultaneous investigation of multiple critical process parameters and their interactions. Optimal multiplex PCR conditions were predicted using software-aided modelling based on DOE data. Verification experiments suggested a balanced, reproducible amplification of all markers with reduced formation of artefacts. Fully concordant STR profiles were obtained for the investigated reference samples even with challenging input DNA concentrations. We found that application of DOE principles enabled an experimentally practical and economically justifiable assay development and optimization, even beyond the field of forensic genetics.

Experimental optimization of geometrical parameters on heat transfer and pressure drop inside sinusoidal wavy channels

The response surface methodology (RSM) is firstly employed to investigate the geometric and flow parameters on heat transfer, pressure drop and thermal performance of sinusoidal wavy channels with different phase shifts. The investigated flow and geometric parameters are axial Reynolds number 1106<Rea<2530, wave’s amplitude ratio 0.2<b/H<0.6, phase shift 0∘<φ<180∘ and number of waves 5<Nw<15, respectively. The experiments are carried out by using face central composite design (FCCD). The geometric parameters are optimized and general correlations for pressure drop and Nusselt number inside sinusoidal channels are presented. The influence of each parameter on the heat transfer and pressure drop of sinusoidal wavy channel is also investigated. It is found that the heat transfer to pressure drop ratio is maximum for b/H=0.54, Nw=11, φ/π=0 and the corresponding value of η is 1.21. This optimization gives a lot of freedom to engineers to choose the optimal geometric parameters of plate heat exchangers.

Modeling of biodiesel production: Performance comparison of Box–Behnken, face central composite and full factorial design

Abstract The performances of the response surface methodology (RSM) in connection with the Box–Behnken, face central composite or full factorial design (BBD, FCCD or FFD, respectively) were compared for the use in modeling of the NaOH-catalyzed sunflower oil ethanolysis. The influence of temperature, catalyst loading, and ethanol-to-oil molar ratio (EOMR) on fatty acid ethyl esters (FAEE) content was evaluated. All three multivariate strategies were efficient in the statistical modeling and optimization of the influential process variables but BBD and FCCD realization involved less number of experiments, generating smaller costs, requiring less work and consuming shorter time than the corresponding FFD. All three designs resulted in the same optimal catalyst loading (1.25% of oil) and EOMR (12:1). The reduced two-factor-interaction (2FI) models based on the BBD and FCCD defined a range of optimal reaction temperature (25 °C–75 °C) and 25 °C, respectively while the same model based on the 33 FFD appointed 75 °C. The predicted FAEE content of about 97%–98.0% was close to the experimentally obtained FAEE content of about 97.0%–97.6% under the optimal reaction conditions. Therefore, the simpler BBD or FCCD might successfully be applied for statistical modeling of biodiesel production processes instead of the more extensive, more laborious and more expensive FFD.

Impact of pH on the high-pressure inactivation of microbial transglutaminase

Microbial transglutaminase (MTG) is an enzyme largely used in the food industry, mainly to improve food texture. However, many globular proteins show low susceptibility to the action of this enzyme. High-pressure processing (HPP), being able to change protein conformation, may be a useful tool to increase the accessibility of globular proteins to the action of MTG. Nevertheless, HPP conditions need to be carefully optimized to avoid the expected decrease of enzymatic activity observed above certain conditions of pressure (P), treatment time (t) or temperature (T). Pressure inactivation of MTG under different HPP conditions (200–600 MPa; 20–40 °C; 10–30 min) was evaluated employing a face-centered composite design at four different pH values (4–7). The regression models obtained presented high coefficients of determination and high F values, although they could not explain some of the associated variability. At all the pH values tested, the three main factors (P, T, and t) significantly (p < 0.05) affected the activity of MTG. At least 20% of MTG was inactivated when low pressures (200 MPa) were used at pH 4 and 5, whereas a higher pressure above 400 MPa was needed to obtain a similar inactivation at pH 6 or 7. MTG pressure-inactivation followed first-order kinetics under all tested conditions. Inactivation rate constants decreased with increasing pressure at constant temperature and pH 4, with a positive activation volume (Va), while the opposite was verified for the other pH values. Both activation energy (Ea) and Va were dependent on pH, however, at the lower pH values, Ea and Va did not vary significantly with pressure and temperature, respectively. Overall, MTG can be considered relatively resistant to pressure, particularly near its optimal pH.

Spectroscopic characterization of tablet properties in a continuous powder blending and tableting process

By the advent of continuous pharmaceutical manufacturing, fast and accurate characterization of product quality has become of a major interest. Although it also promotes the real-time release testing approach, so far mainly content uniformity studies were performed by near-infrared (NIR) spectroscopy. This paper proposes the simultaneous application of NIR and Raman spectroscopy to nondestructively analyze the critical quality attributes of continuously produced tablets in a real-time release testing procedure. A face-centered composite design was applied to determine the impact of lubrication and compression force on the properties of a tablet formulation containing caffeine, glucose-monohydrate and magnesium stearate and to provide a systematic comparison of the applicability of spectroscopic methods. Quantitative methods were developed to evaluate different lubrication approaches in a continuous blending and tableting line. The simultaneous application of NIR and Raman spectroscopy revealed that NIR spectroscopy is more suitable to follow the changes of compression force, while Raman spectroscopy could be successfully applied for the detection of overlubrication. The presented approach can be a part of a comprehensive real-time release strategy, where NIR and Raman spectroscopy provide complementary information about multiple critical quality attributes, such as content uniformity, tablet hardness, friability and dissolution.

Optimizing the extraction of polyphenols from Sideritis montana L. using response surface methodology

Sideritis montana L. endemic of Turkey was screened for its polyphenols content and antioxidant activity. Factor analysis and experimental design have been applied to understand the structure of the separation process, to determine the effective parameters, and to accomplish the performance improvement. Face-centred composite design (FCD) of response surface methodology (RSM) was applied to evaluate the influences of solvent concentration, solvent amount, extraction time, and stirring speed of homogenizer-assisted extraction (HAE) as well as to model and to optimize the HAE. Quadratic models were highly significant (p < 0.0001) for the responses studied with high coefficients of determination (R2) of 0.9440, 0.9415 and 0.9521. The result of the study suggests that 15.02 mL of 22.69% EtOH solution (v/v), 70.16 s, and 9524.52 rpm of mixing speed are the optimal conditions to obtain the highest yield of total polyphenols (TPC) and flavonoids (TFC), and the best antioxidant activity (AA). Rosmarinic acid was identified as the most abundant component.

Influence of Nano Powder Mixed Dielectric Fluid on Surface Finish in Micro Electro Discharge Machining of Zirconia

Background: Powder mixed dielectric fluid is being used recently to cut difficult to cut ceramic materials such as aluminium oxide (Al2O3) and zirconium oxide (ZrO2) where process development and optimization are found to be critical issues. Object: This paper investigates and compares the average surface roughness (Ra) in micro electrical discharge machining (EDM) of electrically nonconductive zirconium oxide (ZrO2) ceramic using clean and tantalum carbide (TaC) nano powder mixed kerosene dielectric fluid. Method: The design of experiment was applied by response surface methodology with face centred composite design. The gap voltage, capacitance and concentration of TaC powder are considered as the variable parameters for the investigation while other conditions are kept constant. Results: The study shows that the powder concentration has a significant negative effect on the average surface roughness of ZrO2. Conclusion: The optimized values of gap voltage and powder concentration are found to be 100 pF, 94.4 V and 6.3 g/l, respectively for a minimum surface roughness in micro-EDM of ZrO2. Without powder introduction, a minimum Ra surface roughness of 170 nm achieves 100 pF and 81 V.

Application of Quality by Design to optimize a stability-indicating LC method for the determination of ticagrelor and its impurities

Simultaneous analysis of drug compounds and their impurities of degradation and synthesis became constant in the modern pharmaceutical analysis. Likewise, analytical techniques must improve sensitivity and selectivity for the monitoring of pharmaceutical products, allowing a full assessment of impurities in drug products and, therefore, ensure safety and efficacy of pharmacological treatments. The application of Quality by Design (QbD) principles has proved to be feasible on the elaboration of analytical methods, allowing the comprehensive evaluation and measurement of different analytical parameters and their effects on critical properties of the methodology in development. QbD approach was applied to the development of a fast and selective HPLC method for the analysis of the antiplatelet aggregation drug ticagrelor and its degradation products in presence of three impurities of synthesis. Fractional factorial resolution V was the screening experimental design applied to five method parameters. Response surface methodology was carried by central composite star face design on the two critical method parameters selected. Analytical design space, established after the application of Monte-Carlo simulations, verified whether predicted results were in accordance with critical quality attributes. The developed and validated HPLC method with DAD detection at 225 nm was able to resolve eight related compounds in less than three minutes.

Improvement of Bending Strength of Resin Coated Sand

This research proposed a method to improve bending strength of RCS used in hollow core production by finding the optimal levels of factors in the mixing process. Process factors under study were temperature of sand, time to release phenolic resin, time to release hexamine solution, time to start air blowing, air blowing time duration, and time to release calcium stearate. Experiments with Central Composite Face-centered (CCF) design were performed to save the number of experimental runs. Then, backward elimination regression analysis was performed to find out the relationship equation of bending strength and significant process factors. Next, the optimization technique was applied to determine the optimal setting of those significant process factors. The comfirmatory result showed that bending strength was significantly improved.

QSRR modeling for the chromatographic retention behavior of some β-lactam antibiotics using forward and firefly variable selection algorithms coupled with multiple linear regression

The justified continuous emerging of new β-lactam antibiotics provokes the need for developing suitable analytical methods that accelerate and facilitate their analysis. A face central composite experimental design was adopted using different levels of phosphate buffer pH, acetonitrile percentage at zero time and after 15 min in a gradient program to obtain the optimum chromatographic conditions for the elution of 31 β-lactam antibiotics. Retention factors were used as the target property to build two QSRR models utilizing the conventional forward selection and the advanced nature-inspired firefly algorithm for descriptor selection, coupled with multiple linear regression. The obtained models showed high performance in both internal and external validation indicating their robustness and predictive ability. Williams-Hotelling test and student’s t-test showed that there is no statistical significant difference between the models’ results. Y-randomization validation showed that the obtained models are due to significant correlation between the selected molecular descriptors and the analytes’ chromatographic retention. These results indicate that the generated FS-MLR and FFA-MLR models are showing comparable quality on both the training and validation levels. They also gave comparable information about the molecular features that influence the retention behavior of β-lactams under the current chromatographic conditions. We can conclude that in some cases simple conventional feature selection algorithm can be used to generate robust and predictive models comparable to that are generated using advanced ones.

Use of RSM for the multivariate, simultaneous multiobjective optimization of the operating conditions of aliphatic carboxylic acids ion-exclusion chromatography column: Quantitative study of hydrodynamic, isotherm, and thermodynamic behavior

The present study evaluates the capability of ion exclusion chromatography (IEC) of short chain aliphatic carboxylic acids using a cation exchange column (8% sulfonated cross-linked styrene-divinylbenzene copolymer) in different experimental conditions. Since one of the prerequisites to the development of an efficient carboxylic acid separation process is to obtain the optimum operational conditions, response surface methodology (RSM) was used to develop an approach to evaluate carboxylic acids separation process in IEC columns. The effect of the operating conditions such as column temperature, sulfuric acid concentration as the mobile phase, and the flow rate was studied using Central Composite Face (CCF) design. The optimum operating conditions for the separate injection of lactic acid and acetic acid is temperature of 75 °C, sulfuric acid concentration of 0.003 N for both acids and flow rate of 0.916 (0.886) mL/min for acetic acid (lactic acid). Likewise, the optimum conditions for the simultaneous injection of acetic and lactic acid mixture are the column temperature of 68 °C, sulfuric acid concentration of 0.0003 N, and flow rate of 0.777 mL/min. In the next step, the adsorption equilibria of acetic acid and lactic acid on the stationary phase were investigated through a series of Frontal Analysis (FA), Frontal Analysis by Characteristic Points (FACP), and using Langmuir isotherm model. The results showed an excellent agreement between the model and experimental data. Finally, the results of thermodynamic studies proved that the IEC process for separation of acetic and lactic acid is a spontaneous, feasible, exothermic, and random process with a physical adsorption mechanism.The results of the current paper can be a valuable information in the stages of designing IEC columns for separation of aliphatic carboxylic acids.

Effect of Cutting Parameters on Cutting Force under Different Conditions in Hard Turning of AISI4340

In the present study, an attempt was made to investigate the effect of cutting parameters on cutting force under different conditions (dry condition, wet and solid lubricant condition) in finish hard turning of AISI 4340 steel. The material with 60HRC was used for experimentation. Its applications have been found in making dies and mould, roller and ball bearings, automobile and aircraft parts. Water based lubricant was used as wet lubricant and boric acid in powder form was used as a solid lubricant. The machining experiments were conducted to understand the relative advantages of different conditions; based on RSM (Response Surface Methodology) and sequential approach using face CCD (Central Composite Design). It was found from experimental results that solid lubricating conditions were effective in bringing down the cutting force.

Development of solidified self-microemulsifying drug delivery systems containing l-tetrahydropalmatine: Design of experiment approach and bioavailability comparison

The study first aimed to apply a design of experiment (DoE) approach to investigate the influences of excipients on the properties of liquid self-microemulsifying drug delivery system (SMEDDS) and SMEDDS loaded in the pellet (pellet-SMEDDS) containing l-tetrahydropalmatine (l-THP). Another aim of the study was to compare the bioavailability of l-THP suspension, liquid SMEDDS and pellet-SMEDDS in the rabbit model. By using Central Composite Face design (CCF), the optimum ratio of Capryol 90, and Smix `(Cremophor RH 40: Transcutol HP) in the formulation of SMEDDS was determined. This optimum SMEDDS was absorbed on the solid carrier (Avicel or Aerosil) for the preparation of pellet-SMEDDS by extrusion and spheronization method. The ANOVA table indicated that Avicel was more effective than Aerosil, the traditional solid carrier, in both terms of preservation of dissolution rate of l-THP from the original SMEDDS and pelletization yield. Results obtained from scanning electron microscopy (SEM) indicated that the existence of liquid SMEDDS droplets on the surface of pellet-SMEDDS was due to the absorption on Avicel. The powder X-ray diffractometry proved the amorphous state of l-THP in pellet-SMEDDS. Pharmacokinetic study in the rabbit model using liquid chromatography tandem mass spectrometry showed that the SMEDDS improved the oral bioavailability of l-THP by 198.63% compared to l-THP suspension. Besides, pharmacokinetics study also proved that the mean relative bioavailability (AUC) and mean maximum concentration (Cmax) of pellet-SMEDDS were not significantly different from the original liquid SMEDDS (p > 0.05).

Induced change in Arthrospira sp. (Spirulina) intracellular and extracellular metabolites using multifactor stress combination approach

The interactive effects of light intensity, NaCl, nitrogen, and phosphorus on intracellular biomass content and extracellular polymeric substance production were assessed for Arthrospira sp. (Spirulina) in a two-phase culture process using principal component analysis and central composite face design. Under high light intensity (120 μmol photons m−2 s−1) and low NaCl (1 gL−1), NaNO3, and K2HPO4 (0.5 g L−1), the carbohydrate content was maximized to 26.61%. Interaction of both K2HPO4 (1.6 gL−1) and NaCl (1.19 gL−1) with low NaNO3 (0.5 gL−1) achieved the maximum content of lipids (15.62%), while high NaCl (40 gL−1), K2HPO4, and NaNO3 (4.5 gL−1) enhanced mainly total carotenoids (0.85%). Conversely, under low light intensity of 10 μmol photons m−2 s−1 combined with 11.76 gL−1 of NaCl, 0.5 gL−1 of NaNO3, and 2.68 gL−1 of K2HPO4, the phycobiliprotein content reached its highest level (16.09%). The maximum extracellular polymeric substance (EPS) production (0.902 gg−1 DW) was triggered under moderate light of 57.25 μmol photons m−2 s−1 and interaction of high NaCl (40 gL−1) and K2HPO4 (4.5 gL−1) with low NaNO3 (0.5 gL−1). The maximization ratios of intracellular biomass content in terms of carbohydrate, lipid, total carotenoid, phycobiliprotein, and EPS production were 3.55-, 1.73-, 9.55-, 2.92-, and 1.46-fold, respectively, greater than those obtained at optimal growth conditions. This study demonstrated that the multiple stress factors applied to the adopted two-phase culture process could be a promising strategy to produce biomass enriched in various high-value compound.

Experimental Design Approach in HPLC Method Development: Application for the Simultaneous Determination of Sacubitril and Valsartan in Presence of Their Impurities and Investigation of Degradation Kinetics

Combination of sacubitril, a novel neprilysin inhibitor, with valsartan, an angiotensin receptor blocker, was approved by FDA as first line treatment of chronic heart failure resulting from hypertension. A selective, rapid, accurate and precise stability indicating RP-HPLC method was developed for the estimation of sacubitril and valsartan in the presence of their impurities in bulk powder and pharmaceutical dosage form. Experimental design using face-centered composite design was applied during method optimization to achieve best resolution with minimum experimental trials. The two independent variables were buffer pH and organic modifier volume in the mobile phase. Chromatographic separation was accomplished using a Zorbax Eclipse C18 Cyano column (150 mm, 4.6 mm, 5 µm) and a mobile phase composed of ammonium acetate buffer (0.02 M, adjusted to pH 4 with acetic acid): acetonitrile (55:45, v/v) at a flow rate 1 mL min−1. Detection was performed at 254 nm. Sharp and well-resolved peaks for sacubitril and valsartan were obtained with retention times 4.91 and 2.53 min, respectively. A complete forced degradation of sacubitril was achieved and degradation kinetics under basic conditions was studied and was found to follow first-order kinetics. Structure elucidation was performed using mass spectrometry. The method was fully validated in terms of selectivity, linearity, accuracy, precision and robustness in agreement with ICH guidelines Q2 (R1).

Selective adsorption of oleuropein from olive (Olea europaea) leaf extract using macroporous resin

ABSTRACTExtraction, optimization, and adsorption of oleuropein from olive (Olea europaea) leaves were carried out, respectively. Face-centered composite design model was chosen for designing the experimental conditions for extraction of olive leaves through response surface methodology. Olive leaf extract obtained under the optimum conditions was concentrated by several macroporous resins (Amberlites XAD 2, XAD 4, XAD 7HP, and XAD 16). The crude and purified extracts were evaluated according to their total phenolic material (TPM) and oleuropein concentration. XAD 7HP showed the best performance regarding adsorption (91%) and desorption ratio (97%) for oleuropein. Pseudo-first- and second-order and Elovich kinetic models were efficient to represent the experimental data for the adsorption of TPM and oleuropein with high correlation coefficients. Equilibrium data were fitted to Langmuir and Freundlich isotherms at four different temperature values. The antioxidant capacity of the extracts was evaluated with several assays such as Cupric ion reducing antioxidant capacity, 2,2-diphenyl-1-picrylhydrazyl, and 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt.

Chamotte clay as potential low cost adsorbent to be used in the palm kernel biodiesel purification

Solid waste from the red ceramic industry (chamotte clay) was assessed as glycerol adsorbent for biodiesel purification by dry washing. Its structure and composition was analyzed by several techniques, such as X-ray diffraction, FT-IR, scanning electron microscopy and particle size. By using a simulated medium (5w/v% glycerol in an ethanol solution), a face centered composite design was used to analyze the combined effect of chamotte concentration and temperature on glycerol removal. Chamotte levels of 2.5w/v% at 45°C maximized glycerol removal (1282mgglycerolg−1) with minimum loss of adsorbate. Kinetic data on glycerol adsorption by chamotte clay could be adjusted using the pseudo-second order model, which indicates that the rate-limiting step may be chemisorption. Moreover, chamotte clay was used for purifying ethyl biodiesel samples from palm kernel oil by chemical and biochemical catalysis. In the presence of chamotte clay, low glycerol levels (<0.02wt%) were found in comparison with crude biodiesel (0.29±0.03wt%). Chamotte clay was also able to remove residual levels of monoacylglycerols and diacylglycerols and provided samples with properties that are similar to those attained by traditional wet washing.

Comparative study of modeling the stability improvement of sunflower oil with olive leaf extract

Commercially available sunflower oil was enriched in polyphenols by adding olive leaf extract. After extracting the dried and ground olive leaves with the assistance of homogenizer, total phenolic content (TPC) and oleuropein concentration of the extract were determined. The dried extract was partially dissolved into the sunflower oil to increase the quality and shelf-life of the oil enriched by the substances in the plants by means of solid-liquid extraction method. A face central composite design (FCCD) through response surface methodology (RSM) was used to investigate the effects of enrichment conditions (extract content, time and mixing speed) on the responses, TPC and oleuropein concentration of the enriched sunflower oil as well as to design of experiments, to model and to optimize the process. The enriched sunflower oil obtained at optimum conditions was evaluated in terms of its TPC, oleuropein, total carotenoid content (TCC), antioxidant activity (AA), peroxide value (PV) and induction time (IT), depending on those of the crude oil. Furthermore, artificial neural networks (ANN) were also employed to compare the predicted results of RSM.

Temperature and pressure effects on the product distribution of PTFE pyrolysis by means of qualitative, in-line FTIR analysis

The results of the depolymerisation of PTFE under steady operating conditions in a semi-automated, continuous depolymerisation system are presented. The influence of temperature and pressure on the selectivity of the three main products of depolymerisation (tetrafluoroethylene (TFE), hexafluoropropylene (HFP), and octafluorocyclobutane (OFCB)) was investigated via qualitative in-line FTIR analysis. No carrier gas was used, with the PTFE feed rate and experimental run time kept constant. The temperature and pressure ranges investigated were: 650 °C–750 °C and <10 kPa–40 kPa. The optimum operating conditions to maximise the three main products were determined using response surface methodology following a three-level face centered composite design. A TFE mole fraction of 0.95 and higher was achieved at operating conditions of ±675 °C and <10 kPa. HFP mole fractions of 0.19 and higher were achieved within the operating range of 744 °C–750 °C and 32 kPa up to 40 kPa. At operating conditions of 750 °C and 40 kPa, OFCB fractions of 0.5–0.55 were achieved. The OFCB and HFP mole fractions achieved differed from those previously mentioned in the literature. Analysis of the determined product specific kinetics indicates that the predominant HFP production pathway at low residence times (<3 s) is via the reaction of TFE with difluorocarbenes. At higher residence times the dominant reaction pathway is the dissociation OFCB.