Level Box-Behnken Design Research Articles

Mathematical Modeling and Simulation of Enzyme Assisted Bioactive Compound Extraction from Allium Cepa Using Response Surface Methodology

In this present study, an attempt was made to investigate the enzyme assisted extraction process to extract the phenolic compounds from onion (Allium cepa) under various operating conditions such as temperature, extraction time and enzyme concentration. Three factors three level Box-Behnken response surface design (BBD) coupled with desired function methodlogy was used to optimize and model the extraction process. Optimum extracting conditions for the maximum phenloic compounds were determined and it was found to be: temperature of 40 0C, extraction time of 16 hour and enzyme concentration of 2 %. Under these conditions, 9.25 % of phenolic compound was extracted. Extracted phenolic compounds can be regarded as the promising antioxidants to scavenge the DPPH free radicals.

Chitosan coated PLGA nanoparticles amplify the ocular hypotensive effect of forskolin: Statistical design, characterization and in vivo studies

PurposeEnhancing the ocular hypotensive effect of forskolin (FK) by means of biodegradable chitosan (CS) coated poly lactic-co-glycolic acid (PLGA) nanoparticles (NP's). MethodsOne step emulsion-sonication process was employed for the formulation of CS-PLGA NP's with optimization being carried out by employing a four factor four level Box Behnken Design. The physical and spectral characterization, drug release, permeation, confocal and ocular tolerance studies (ex-vivo &in vivo) were performed. The corneal retention was assessed by gamma scintigraphic analysis and dexamethasone induced glaucamotous rabbit's intraocular pressure (IOP) was measured by means of Schiotz tonometer. Results and discussionParticle size of optimized CS-PLGA NP's was found as 201.56 ± 10.92 nm with a good PDI and positive zeta potential value. Entrapment efficiency and drug loading were found to be 72.32 ± 1.12% and 28.39 ± 1.67% respectively. Spectral characterization confirmed the purity and encapsulation of the drug within polymeric system. Sustained drug release and enhanced permeation profile was observed with maximum depth penetration. Ocular tolerance studies explicated its safe use. Scintigraphy studies indicated longer retention of CS-PLGA NP's while increased effectiveness after single instillation in reducing the intraocular pressure was observed. ConclusionCS-PLGA-NP's could be successfully formulated and are an excellent vehicle for FK in ocular delivery.

Application of Response Surface Methodology in the Preparation of Pectin-Caseinate Nanocomplexes for Potential Use as Nutraceutical Formulation: A Statistical Experimental Design Analysis

Background: The formation of electrostatic complexes between two types of biopolymers, sodium Caseinate (a derivative from most abundant milk protein) and Pectin (a natural hetro polysaccharide), was studied as a function of biopolymers concentrations and pH of solutions (3.9- 4.3). Method: The size and morphology of the resulted complexes were investigated by using of laser light scattering and transmission electron microscopy, respectively. Response surface methodology (A three-factor, three levels Box-Behnken design) was used for the optimization procedure with pH, pectin and sodium Caseinate concentrations as independent variables. Particle size and polydispersity index of nanocomplexes were considered as dependent variables. Results: Negatively charged nanocomplexes were produced below the isoelectric point of protein (5.4), at pH 4.1 with a suitable colloidal stability and average particle size of about 100 nm. It was found that the particle size of nanocomplexes could be controlled by changing in variables. Conclusion: In conclusion response surface methodology are simple, rapid and beneficial approach for preparation, optimization and investigation of the effect of independent variables on the properties of products.

Preparation and evaluation of naringin-loaded polycaprolactone microspheres based oral suspension using Box-Behnken design

The objective of the current investigation was to study the outcome of the concentration of polycaprolactone (PCL), the concentration of polyvinyl alcohol (PVA) and the concentration of hydroxypropyl methylcellulose (HPMC) on the average particle size of microspheres and the drug entrapment efficiency of naringin-loaded polycaprolactone microspheres based oral suspension. Naringin-loaded polycaprolactone microspheres based oral suspension were prepared by solvent evaporation method. Further, in this work optimization of the formulation was done using a three factors, three levels Box-Behnken design (BBD). Drug-loaded microsphere suspension was prepared by employing solvent evaporation technique. Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC) analysis was carried out to determine any incompatibility between the naringin and other components used in the formulations. Polymer alone (PVA concentration) or interaction effects of polymers (PCL-HPMC, PCL-PVA, HPMC-PVA, and PCL in higher order) have a substantial influence on particle size of microspheres. Amount of PVA and HPMC have a significant effect on entrapment efficiency of microspheres. The optimal conditions of PCL concertation were 7.7% w/v; HPMC concentration was 3.2% w/v and PVA concentration was 0.081% w/v. The optimized suspension showed particle size of 24μm with drug entrapment efficiency 96%. As a result, due to uniform distribution of microspheres, drug entrapment efficiency was achieved in optimized suspension.

Investigation on dry sliding wear behavior of Selective Inhibition Sintered HDPE parts using simulated annealing algorithm

Owing to the dependency of multiple process parameters in additive manufacturing (AM) techniques, it is tedious to determine optimal processing conditions for improving quality characteristics of fabricated functional pats. Hence, optimization of process parameters is an important aspect in AM techniques to achieve desired properties of prototypes. The present study focuses on optimization of four key contributing parameters such as layer thickness, heater energy, heater feedrate, and printer feedrate on dry sliding wear behavior of high density polyethylene (HDPE) parts fabricated through a novel AM technique namely selective inhibition sintering (SIS) process. The experiments are conducted on the basis of response surface methodology (RSM) and four factor-three level box-behnken design. The significance of the developed models and contribution of each process parameters on wear rate is estimated through analysis of variance (ANOVA). The results suggested that, the wear rate is influenced principally by the layer thickness and heater energy. The quadratic regression model of RSM associated with simulated annealing (SA) algorithm is employed to find optimum levels of process parameters.

Ultrasound-assisted extraction of oil from Moringa oleifera Lam. seed using various solvents

ABSTRACTThe present research analyzes the extraction of oil from Moringa oleifera Lam. seed using ultrasound-assisted extraction (UAE) technique under different operating conditions such as temperature, solvent type, and time. Three factors with three levels Box-Behnken response surface design was employed to optimize and investigate the effect of process variables on the response (oil yield). The independent variables showed significant effect on the extraction process. Interactive effects of the extraction process variables were analyzed by Pareto analysis of variance (ANOVA), and second-order polynomial model was used to plot the 3D response surface plot. Optimum extraction conditions for the maximizing the extraction yield of oil (59%) was found to be: temperature of 35°C, solvent type of 2, and time of 20 min. FT-IR was used to analysis the oil. From the results, it can be concluded that the UAE is the effective technique to extract the oil from Moringa oleifera Lam. seed.

Optimizing the Maximum Recovery of Dihydromyricetin from Chinese Vine Tea, Ampelopsis grossedentata, Using Response Surface Methodology.

This work provides an optimized extraction approach intended to maximize the recovery of dihydromyricetin (DHM) from Chinese vine tea (Ampelopsis grossedentata) leaves. The presented work adopts a Box-Behnken design as a response surface methodology to understand the role and influence of specific extraction parameters including: time, temperature, and solvent composition/ethanol (%) on DHM final yields. Initially, single factor experiments were used to delineate the role of above factors (temperature, time, and solvent composition) before proceeding with three factors-three levels Box-Behnken design with 17 separate runs to assess the effect of multifactorial treatments on DHM recovery rates. The collected data shows that independent variables (solvent composition, time, and temperature) can significantly affect DHM recovery rates with maximum yields resulting from a combined 60 °C, 60% aqueous ethanol, and 180 min treatment. From the empirical point of view, the above optimized extraction protocol can substantially enhance processing and profitability margins with a minimum need of interventions or associated costs.

Modeling and prediction of optimal process parameters in wear behaviour of selective inhibition sintered high density polyethylene parts

Owing to the dependency of multiple process parameters in additive manufacturing (AM) techniques, it is tedious to determine optimal processing conditions for improving quality characteristics of fabricated functional pats. The present study focuses on optimization of four key contributing parameters such as layer thickness, heater energy, heater feedrate, and printer feedrate on dry sliding wear behaviour of high-density polyethylene (HDPE) parts fabricated through a novel selective inhibition sintering (SIS) process. The experiments are conducted on the basis of response surface methodology (RSM) and four factor-three level box-behnken design. The significance of the developed models and contribution of each process parameters on wear rate are estimated through analysis of variance (ANOVA). The results suggested that wear rate is influenced principally by the layer thickness and heater energy. The quadratic regression model of RSM associated with the desirability approach is employed to determine optimum levels of process parameters. The morphologies of worn surfaces are observed using scanning electron microscope. Sensitivity analysis has been performed to measure the relative impact of SIS process parameters on wear rate.

Development and optimization of methotrexate-loaded lipid-polymer hybrid nanoparticles for controlled drug delivery applications

Lipid-polymer hybrid nanoparticles (LPHNPs) are emerging platforms for drug delivery applications. In the present study, methotrexate loaded LPHNPs consisted of PLGA and Lipoid S100 were fabricated by employing a single-step modified nanoprecipitation method combined with self-assembly. A three factor, three level Box Behnken design using Design-Expert® software was employed to access the influence of three independent variables on the particle size, drug entrapment and percent drug release. The optimized formulation was selected through numeric optimization approach. The results were supported with the ANOVA analysis, regression equations and response surface plots. Transmission electron microscope images indicated the nanosized and spherical shape of the LPHNPs with fair size distribution. The nanoparticles ranged from 176 to 308nm, which increased with increased polymer concentration. The increase in polymer and lipid concentration also increased the drug entrapment efficiency. The in vitro drug release was in range 70.34–91.95% and the release mechanism follow the Higuchi model (R2=0.9888) and Fickian diffusion (n<0.5). The in vitro cytotoxicity assay and confocal microscopy of the optimized formulation demonstrate the good safety and better internalization of the LPHNPs. The cell antiproliferation showed the spatial and controlled action of the nanoformulation as compared to the plain drug solution. The results suggest that LPHNPs can be a promising delivery system envisioned to safe, stable and potentially controlled delivery of methotrexate to the cancer cells to achieve better therapeutic outcomes.

Formulation and optimization of lacidipine loaded niosomal gel for transdermal delivery: In-vitro characterization and in-vivo activity

The aim of the present research work is to formulate lacidipine (LAC) loaded niosomes formulation for the management of hypertension by thin film hydration technique. The developed formulations were statistically optimized by four factors, three levels Box–Behnken design and were evaluated for vesicle size, entrapment efficiency, and flux. The optimized LAC niosomes was further evaluated for permeation depth by confocal laser scanning microscopy (CLSM) and converted to gel formulation. Further, the optimized LAC niosomes gel was evaluated for ex-vivo permeation study, skin irritation study, stability study and pharmacodynamics study. The optimized LAC niosomes formulation showed vesicle size, entrapment efficiency and flux value of 676.98±10.92nm, 82.77±4.34% and 38.43±2.43μg/cm2/h respectively, with spherical morphology. The comparative CLSM study showed that optimized LAC niosomes formulation has shown maximum permeation (70.75μm) as compare to LAC liposomes formulation (58.26μm). The optimized LAC niosomes gel showed skin permeation enhancement of 2.15 times as compare to control gel. Furthermore, in vivo antihypertensive activity showed significantly higher (p<0.001) reduction in blood pressure compared to oral suspension. Indeed, it was found that niosomal vesicles represented to be an efficient nano vesicular carrier for transdermal delivery of lacidipine.

Effect of ultra-sonication on postharvest quality parameters and microbial load on Docynia indica

Freshly harvested Docynia indica fruits were surface cleansed with ultrasonic treatment at different amplitudes. Partly matured fruits were selected for all the experimental studies. The process variables i.e. ultrasonic amplitude, treatment time and temperature selected were optimized using response surface methodology (RSM) by three factor three level Box-Behnken design. Probe type ultra-sonicator with a power density of 600W/cm2 with a constant frequency of 30Hz was used for all the 17 experiments. Optimum independent variables selected by RSM were ultrasonic amplitude (80%), treatment time (5.82min) and solvent temperature (25°C). The corresponding optimum values for all the dependent variables obtained were total plate count (2.82 log CFU/cm2), firmness (65.22N) and respiration rate (43.30mgCO2kg−1h−1 FW). The linear terms, some interaction and quadratic terms were found to be significant (p<0.05). Interaction terms between ultrasonic amplitude and treatment time had showed significant negative effect on total plate count (p<0.001) and firmness (p<0.05). But significant positive effect was obtained for respiration rate (p<0.100). Therefore, from this study it was concluded that the ultra-sonication was found to be an effective technology in reducing surface microbial load. Hence, ultra-sonication treatment extremely useful for extending the shelf-life (58%) and maintaining the quality of freshly harvested Docynia indica by one month at refrigerated temperature (7–8°C). While RSM was proven to be an effective technique in controlling and optimizing the factors responsible for ultrasonic treatment.

Poly(benzoxazine‐co‐sulfur): An efficient sorbent for mercury removal from aqueous solution

ABSTRACTA novel sulfur‐rich adsorbent, poly(BA‐ala‐co‐sulfur), was synthesized by reacting allyl functional benzoxazine (BA‐ala) and elemental sulfur. Simultaneous inverse vulcanization and ring‐opening reactions of benzoxazine generated copolymers in several feed ratios. The adsorption behavior of these copolymers was investigated in aqueous solutions containing Hg2+. A three level Box–Behnken design with four factors was applied in order to examine the interactive effect of Hg2+ concentration (ppm), S % in adsorbent, temperature, and pH. The optimum adsorption conditions were determined as: 10.33 ppm Hg2+, 68% S content, 329 K, and pH 6.3. Common isotherm and kinetic models were applied to the experimental data, where the Langmuir isotherm provided the better fit (qmax = 79.36 mg g−1) and the pseudo‐second order fit indicated chemisorption as the process‐controlling step. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45306.

TiO2/H2O2 mediated UV photocatalysis of Chlorpyrifos: Optimization of process parameters using response surface methodology

Chlorpyrifos (CP), an organophosphate pesticide which is used extensively in agricultural fields of various developing countries, is found to cause neurological and immunological effects on living beings. In this study, TiO2/H2O2 mediated UV photocatalytic oxidation of CP was investigated in a laboratory-scale photo-reactor. Experiments were designed using three level Box-Behnken factorial design (BBD) technique combined with response surface methodology (RSM). Effects of the process parameters such as concentration of TiO2, concentration of H2O2 and initial pH on the response parameters like degradation of chemical oxygen demand (COD) and degradation of CP were analyzed using polynomial regression models. After 3h reaction time, with the optimum process parameters, about 68.29% and 74.38% of COD degradation and CP degradation, respectively were achieved. Kinetic and synergistic studies for different oxidation systems viz., H2O2, UV+H2O2, UV+TiO2 and UV+TiO2+H2O2 were also performed using the optimum conditions. Statistical models developed in this study can be used for optimization of oxidation processes for treatment of industrial as well as agricultural wastewater.

Applications of Box–Behnken experimental design coupled with artificial neural networks for biosorption of low concentrations of cadmium using Spirulina (Arthrospira) spp.

The present study deals with the application of artificial intelligence techniques coupled with Box–Behnken (BB) design to model the processparameters for biosorption of cadmium using live Spirulina (Arthrospira) spp. as adsorbent in open race way pond with Zarrouk medium. Thebiomass concentration of Spirulina spp. decreased to half at 4 ppm Cd (II) after 8 days. Based on the LCt50 values, 3.69 ppm (8th day),Spirulina (Arthospira) maxima showed maximum tolerance. Considerable growth and bioaccumulation of Spirulina spp. is observed below1 ppm and tolerant up to 3 ppm. The cadmium adsorption on Spirulina spp. showed good correlation (R2 = 0.99) when applied to Freundlichequation and data fit into pseudo second order kinetics. A four factorial, three blocks and three level Box–Behnken design with initialconcentration (1 ppb to 5 ppb), biosorbant dosage (0.1 gdw to 0.2 gdw), agitation speed (12 rpm to 16 rpm) and pH (6 to 8) as independentvariables and percentage adsorption as dependent variable were selected for study. The data were further processed using artificial neuralnetwork model and DIRECT algorithm for better optimization. The final Cd (II) concentration of &lt;0.5 ppb was achieved with 1 ppb initialconcentration under optimal conditions. A continuous desorption process was also developed for removal of cadmium from Spirulina (Arthrospira)sp.

Formulation by design based risperidone nano soft lipid vesicle as a new strategy for enhanced transdermal drug delivery: In-vitro characterization, and in-vivo appraisal

The present study was designed to formulate and optimize transdermal risperidone soft lipid vesicles. The formulation optimized with phospholipid, safranal and ethanol were incorporated as permeation and absorption enhancers. The optimized risperidone soft lipid vesicle was further evaluated for skin irritation study, in-vivo pharmacokinetic study and locomotor activity. Three factor three level Box–Behnken design (BBD) was used to statistically optimize soft lipid vesicle using safranal (A), ethanol (B)and phospholipid (C) as independent variable, while their effect was observed for vesicle size (Y1), entrapment efficiency (Y2) and flux (Y3). The optimized risperidone soft lipid vesicle (Ris-opt) showed nanometric vesicle size, high entrapment efficiency and marked enhancement in transdermal flux. The extent of absorption from Ris-opt was greater when compared to oral suspension with relative bioavailability of 177%. The histopathological evaluation revealed developed formulation did not showed skin irritation compared to standard irritant. The significant findings presented here encourage further studies with risperidone soft lipid vesicles for treatment of schizophrenia.

An investigation of laser cutting quality of 22MnB5 ultra high strength steel using response surface methodology

In hot press forming, changes of mechanical properties in boron steel blanks have been a setback in trimming the final shape components. This paper presents investigation of kerf width and heat affected zone (HAZ) of ultra high strength 22MnB5 steel cutting. Sample cutting was conducted using a 4kW Carbon Dioxide (CO2) laser machine with 10.6µm wavelength with the laser spot size of 0.2mm. A response surface methodology (RSM) using three level Box-Behnken design of experiment was developed with three factors of peak power, cutting speed and duty cycle. The parameters were optimised for minimum kerf width and HAZ formation. Optical evaluation using MITUTOYO TM 505 were conducted to measure the kerf width and HAZ region. From the findings, laser duty cycle was crucial to determine cutting quality of ultra-high strength steel; followed by cutting speed and laser power. Meanwhile, low power intensity with continuous wave contributes the narrowest kerf width formation and least HAZ region.

Applications of Box–Behnken experimental design coupled with artificial neural networks for biosorption of low concentrations of cadmium using Spirulina (Arthrospira) spp.

The present study deals with the application of artificial intelligence techniques coupled with Box–Behnken (BB) design to model the process parameters for biosorption of cadmium using live Spirulina (Arthrospira) spp. as adsorbent in open race way pond with Zarrouk medium. The biomass concentration of Spirulina spp. decreased to half at 4 ppm Cd (II) after 8 days. Based on the LCt50 values, 3.69 ppm (8th day), Spirulina (Arthospira) maxima showed maximum tolerance. Considerable growth and bioaccumulation of Spirulina spp. is observed below 1 ppm and tolerant up to 3 ppm. The cadmium adsorption on Spirulina spp. showed good correlation (R2 = 0.99) when applied to Freundlich equation and data fit into pseudo second order kinetics. A four factorial, three blocks and three level Box–Behnken design with initial concentration (1 ppb to 5 ppb), biosorbant dosage (0.1 gdw to 0.2 gdw), agitation speed (12 rpm to 16 rpm) and pH (6 to 8) as independent variables and percentage adsorption as dependent variable were selected for study. The data were further processed using artificial neural network model and DIRECT algorithm for better optimization. The final Cd (II) concentration of <0.5 ppb was achieved with 1 ppb initial concentration under optimal conditions. A continuous desorption process was also developed for removal of cadmium from Spirulina (Arthrospira) sp.

Optimization of copper extraction from spent LTS catalyst (CuO–ZnO–Al2O3) using chelating agent: Box-behnken experimental design methodology

The objective of the present work is to investigate the extraction of copper from spent low temperature Shift catalyst using EDTA, as chelating agent and optimization of the parameters that influence the extraction of copper. Response surface methodology was applied for designing the experiment and to determine the optimal experimental conditions. Most influencing parameters such as concentration of EDTA, solid to liquid ratio and particle size of catalyst were optimized based on 3 factors 3 levels box behnken design which requires 15 run of experiments for designing a response surface. The high value of regression coefficient R 2 (0.981) indicates a good correlation between predicted and experimental response, which confirms the acceptability of the proposed model.The optimum conditions were found as—concentration of EDTA: 0.5889 M, solid to liquid ratio: 0.02 and particle size: 90 μm. Under these optimum conditions, the experimental value of extraction of copper was estimated as 94.5% which seems very close to predicted response.

Effect of Post-harvest Quality Parameters on Ultra-Sonication Treatment of Khoonphal (Haematocarpus validus) of Meghalaya, North-East India

Freshly harvested khoonphal (Haematocarpus validus) were surface cleansed with ultrasonic treatment. The process variables i.e., ultrasonic amplitude, treatment time and temperature selected were optimized using response surface methodology (RSM) by three factor three level Box-Behnken design. Horn type ultra-sonicator with a power density of 460 W/cm2 with a constant frequency of 30 Hz was used for all the 17 experiments. Optimum independent variables selected by RSM were ultrasonic amplitude (100%), treatment time (5.10 min) and solvent temperature (25°C). The corresponding optimum values for dependent variables obtained were total plate count (2.94 log CFU/cm2), firmness (66.67 N) and respiration rate (42.32 N). Linear terms for all the dependent variables were found to be significant (p<0.05). Similarly, the interaction terms between ultrasonic amplitude and treatment time had showed significant negative effect on total plate count (p<0.001) and firmness (p<0.05). But significant positive effect was obtained for respiration rate (p<0.100). Therefore, from this study it was concluded that the ultra-sonication was found to be an effective technology in reducing surface microbial load. Hence, this may be used for extending the shelf-life and maintaining the quality of freshly harvested khoonphal, while RSM was proven to be an effective technique in controlling and optimizing the factors responsible for ultrasonic treatment.

HOW TO FORMULATE A STABLE AND MONODISPERSE WATER-IN-OIL NANOEMULSION CONTAINING PUMPKIN SEED OIL: THE USE OF MULTIOBJECTIVE OPTIMIZATION

Abstract - The multiobjective optimization method was applied in order to improve the droplet size distribution and stability of water-in-oil emulsions composed of sunflower and pumpkin seed oils as continuous phase, polyglycerol polyricinoleate as emulsifier, water as dispersed phase and sodium chloride as co-stabilizer (lipophobe). Three composition factors were varied based on the three level Box-Behnken design and three characteristics of the obtained emulsions were measured for each experimental run. The mean volume diameter of water droplets and the span of the droplet size distribution, both determined immediately upon preparation of the emulsion, as well as the stability index over a three-month period were interrelated by regression functions with the surfactant concentration, oil composition and the salt content in the water phase of the emulsion. Also, the fourth objective function based on a difference in the prices of pumpkin seed and sunflower oils was considered for optimization. The multiobjective optimum was calculated by using the minimal loss method with weight factors. Additionally, effects of the continuous phase composition and the salt content on the equilibrium interfacial tension of water-oil systems and the changes of the droplet size distribution over time were studied.