Level Box-Behnken Design Research Articles

Influence of Pregelatinized Breadfruit Starch-Alginate Blend as a Sustained Release Polymer in Theophylline Microbeads Using Box Behnken Design

Background: Apart from the coating property of modified starches on drugs, these natural polymers also acts as release rate retardants.Objectives: To evaluate the potential of pregelatinized breadfruit (Artocarpus altilis) starch as a carrier in microbead formulations of theophylline using different blend combinations with sodium alginate and to determine the optimized formulation using Box-Behnken design.Method: Theophylline microbeads were prepared using the ionic gelation method. The 3 factor-3 level Box-Behnken design was employed for constructing polynomial models to optimize the microbeads, involving 3 independent variables (polymer type, X1, polymer: drug ratio, X2, and concentration of calcium chloride, X3) and 2 dependent variable (entrapment efficiency and quantity of drug released in 12 h, Q12).Results: Entrapment efficiency was 35 - 71 % while the values of Q12 was 38 - 88 %. The three variables, X1, X2 and X3, were positive for entrapment efficiency but negative for Q12, implying that increase from low to medium and then to high level resulted in an increase in entrapment but a decrease in Q12 (sustained release), both desirable effects. Factor X1 had the most significant influence on entrapment efficiency and Q12 (p = 0.002; p = 0.0001, respectively). The optimized formulation with starch:polymer 2:1, polymer:drug 3:1 and 7.5%w/v calcium chloride solution gave an entrapment efficiency 65% with Q12 of 38.75%.Conclusion: Pregelatinized breadfruit starch enhanced entrapment efficiency while retarding drug release, showing its potential as a polymer for sustained release in microbead formulations.
 Keywords: Box-Behnken design; Breadfruit starch; Ionic gelation, Microbeads, Pregelatinization

Photocatalytic degradation of atenolol with graphene oxide/zinc oxide composite: Optimization of process parameters using statistical method

A four factor three level Box-Behnken design (BBD) was analysed to define the photocatalytic degradation of atenolol in an aqueous solution in slurry mode. The four different process variables under consideration in BBD model included synthesized Graphene Oxide-ZnO (GO/ZnO) catalyst dose, pH, Atenolol concentration and variation of light intensity. The model predicted the optimum value for maximum degradation rate with conditions set at 1.2 g/L catalyst concentration, pH of 4, 25 mg/l substrate concentration and 940 W light intensity. The first-order reaction rate at this optimum reaction condition is 0.845 min−1. The substrate concentration and light intensity showed highest positive effect on atenolol degradation while pH and catalyst concentration showed negative effect towards atenolol degradation. The data obtained from 29 experiments suggest that maximum rate of reaction (0.783 min−1) has been achieved within 1 h under solar irradiation at pH 6.5 using 25 ppm atenolol concentration and catalyst concentration of 1.25 g/L at light intensity of 1000 W. The model shows high correlation (R2 > 0.953) between experimental and predicted values. It was observed that the rate of degradation with GO/ZnO composite is faster when compared to Graphene/TiO2 composite.

PROCESS OPTIMIZATION AND CHARACTERIZATION OF MANILA TAMARIND SEED OIL EXTRACTED BY THE SOXHLET METHOD

This work mainly presents an experimental investigation of the extraction of oil from Manila tamarind seeds (Pithecellobium dulce (Roxb.) Benth) using a Soxhlet-assisted solvent extraction method. Different factors that affect the extraction of oil were analyzed and optimized using the response surface methodology (RSM). Three process variables, namely, solvent volume, extraction time, and powder weight, were adopted in a three level Box-Behnken design. Based on the experimental design, 17 experimental runs were performed to evaluate the effect of selected variables on the oil yield. A polynomial model is suggested and found to be significant. From the results of analysis of variance (ANOVA), it is found that the powder weight and solvent volume significantly affect the yield of the produced oil. The results showed that the oil yield could be maximized under the optimized conditions of powder weight, solvent volume, and extraction time of 40 g·s, 314 mL, and 6 h, respectively. The physicochemical properties of extracted oil showed that it is brownish yellow liquid with specific gravity and refractive index of 0.92 and 1.4631, respectively. Similarly, the moisture content, acid value, unsaponifiable matter, iodine value, free fatty acid, saponification value, and peroxide value were found to be 0.12%, 8.32 mg/g KOH of oil, 0.4%, 83.9 g I2/100 g of oil, 4.16 mg/g KOH of oil, 175.4 mg/g KOH of oil, and 6.10 meq O2/kg, respectively. The results also revealed that the presence of stearic fatty and saturated palmitic acids were the major fractions in the Manila tamarind seed oil (MTSO) along with other unsaturated fatty acids.

QUALITY BY DESIGN APPROACH FOR DEVELOPMENT AND OPTIMIZATION OF NITRENDIPINE LOADED NIOSOMAL GEL FOR ACCENTUATED TRANSDERMAL DELIVERY

Objective: The purpose of the present investigation was to develop and optimize nitrendipine loaded niosomal gel for transdermal delivery using quality by design approach.
 Methods: Niosomal formulations were developed by application of the thin-film hydration method using different ratios of span 60, cholesterol, temperature, and optimized by three factors-three levels Box-Behnken statistical design. The independent variables were non-ionic surfactant, cholesterol, and temperature, while vesicle size, polydispersity index, and entrapment efficiency were dependent variables. The nitrendipine loaded optimized formulation was incorporated into gel and evaluated for in vitro release, ex-vivo skin permeation, confocal laser scanning microscopy, and histopathological studies.
 Results: The optimized formulation showed the vesicular size of 226.1±4.36 nm, polydispersity index of 0.282±0.012, and entrapment efficiency of 95.34±3.18% with spherical morphology. The optimized niosomal gel formulation showed transdermal flux 127.60 µg/cm2h through albino Wistar rat skin. Niosomal gel was proved significantly superior by confocal laser scanning microscopy for satisfactory permeation and distribution of gel, deep into the rat skin. Furthermore, dermal safety was confirmed by histopathological studies for transdermal application.
 Conclusion: It was concluded that the developed niosomal gel overcomes the limitation of low penetration through rat skin and could be a potential nano vesicular system for transdermal delivery.

Box-Behnken design for removal of uranium(VI) from aqueous solution using poly(ethylene glycol) based dicationic ionic liquid impregnated chitosan.

Poly(ethylene glycol) bis(methylimidazolium) di[bis(trifluoromethylsulfonyl)imide] was synthesized as an ionic liquid and impregnated onto chitosan. The removal of uranium(VI) ions from aqueous solution was investigated with batch sorption tests using ionic liquid impregnated chitosan. Response surface methodology based on 3 level Box–Behnken design was applied to analyze the effect of initial pH (4–6), initial concentration (20–60 mg L-1), contact time (15–105 min), and temperature (30–50 °C) on the uptake capacity of uranium(VI). Main effect of initial concentration, quadratic effect of contact time, and dual effect of initial pH and contact time were found statistically significant based on analysis of variance (ANOVA). Probability F-value (F = 1.49 ×10-6) and correlation coefficient (R2 = 0.96) point out that the proposed model is compatible with experimental data. The maximum uptake capacity of uranium(VI) was found as 28.48 mg g-1 at initial pH 4, initial concentration 60 mg L-1, contact time of 70 min, and a temperature of 50 °C. Sorption kinetics followed a pseudo-second-order model and Freundlich model was obtained to fit the sorption data. The presence of competing ions slightly reduced uranium(VI) sorption and the selectivity order can be given as UO22+>Zn2+>Ni2+.

Application of artificial neural network (ANN) and response surface methodology (RSM) for modeling and optimization of the contact angle of rice leaf surfaces

In this paper, a novel method for modeling and optimization of the contact angle of rice leaf surfaces by comparing the analytical result of the artificial neural network (ANN) and response surface methodology (RSM), to minimize the contact angle of the rice leaf surfaces. Three factors and three levels Box-Behnken design was used to analyze the external factors influencing the contact angle of the rice leaf surfaces, which consisted of temperature, humidity and the chemical pesticide concentration. By optimizing the designing parameters, the optimum input parameters were obtained. The best input conditions were temperature (25.96 °C), humidity (60.00%), chemical pesticide concentration (131.89 mg/L), and a minimum contact angle of 103.565° was obtained. Moreover, the ANN sensitivity analysis was used to study the weight of three external factors affecting the contact angle. Experiments showed the concentration of chemical pesticides to be the chief factor, as it has a weight is 55.61%, followed by humidity with a weight of 31.15% and temperature with 13.24%. Finally, the reliability of the RSM and ANN methods in modeling and predicting the contact angle was compared by analyzing the value of mean squared error (MSE) and determination coefficient (R2).The result showed that both models have better performance, and both RSM and ANN have better determination coefficients. The experiments also illustrated that the ANN method get better results than RSM in fitting experimental data, prediction and modeling.

Process Parameter Optimization to Achieve Higher Impact Strength in SS316 Wire-Mesh and SiCp Reinforced Aluminum Composite Laminates Produced by Explosive Cladding

In this research paper, an empirical relationship is developed to envisage the impact strength of stainless steel wire-mesh and SiCp reinforced aluminum composite laminates produced through the explosive cladding. The process parameters viz., stand-off distance, explosive loading ratio, wire-mesh orientation and wt% of SiCp were optimized in four factors, three levels Box–Behnken design with full appropriateness. Analysis of Variance indicates that the wt% of SiCp possess the greatest sway on impact strength, trailed by stand-off distance, explosive loading ratio and wire-mesh orientation. The interfacial microstructure of the optimized condition reveals the presence of silicon carbide (SiC) as the wt% of SiCp is increased from 0 to 3%. X-ray diffraction analysis of the clad interface shows the absence of brittle intermetallic compounds. The impact fracture faces of the optimized clad reveals a ductile manner of fracture with elevated impact strength.

Improvement of Ocular Efficacy of Levofloxacin by Bioadhesive Chitosan Coated PLGA Nanoparticles: Box-behnken Design, In-vitro Characterization, Antibacterial Evaluation and Scintigraphy Study.

Conjunctivitis is considered as a common infection of ocular surfaces. Eye drop is most commonly used for treatment of conjunctivitis, but has some drawback like 95% drug eliminated after administration. Administration of levofloxacin to the anterior site in form of chitosan coated poly (lactic-co-glycolic acid) nanoparticles (LFV-CS-PLGA-NPs) expected to overcome these problem and increasing corneal contact time and permeability for effective treatment of bacterial conjunctivitis. The Nanoparticles were developed by single emulsion solvent evaporation technique and optimized for different variables (chitosan, poly (lactide-co-glycolic acid) and polyvinyl alcohol concentration) by employing three factors, three levels Box–Behnken statistical design. The nanoparticles were evaluated for particle size, drug loading, entrapment efficiency, drug release, ex-vivo permeation, ocular tolerance, antimicrobial study, confocal laser microscopy, and Gamma scintigraphy study. The particle size and PdI of the optimized nanoparticles were 169.968 ± 15.23 nm and 0.13 ± 0.03, respectively, where as entrapment efficiency and drug loading is 49.54 ± 2.43% and 11.29 ± 2.13% with extended release profile and strong mucoadhesion. DSC data indicated levofloxacin formed molecular dispersion within coated nanoparticles. Corneal flux showed significantly (P < 0.05) higher permeation as compared to marketed formulation. Formulation was nonirritant and possessed good antibacterial activity. Gamma Scintigraphy showed slow drainage compared to drug solution, indicating reduction in nasolachrymal drainage. The Gamma Scintigraphy study indicated the CS coated PLGA-NPs have high corneal residence time as compared to drug solution. So, it is revealed that LFV-CS-PLGA-NPs increase the drug concentration over ocular tissue and potential usefulness for sustained drug delivery.

Hydrothermal co-gasification of sorghum biomass and çan lignite in mild conditions: An optimization study for high yield hydrogen production

In this study, response surface methodology (RSM) combined with a 3–factor and 3–level Box–Behnken design (BBD) was performed to obtain high yield hydrogen production from hydrothermal co–gasification of sorghum biomass and low rank Çan lignite in a batch type reactor at 500 °C. The individual and the combined effects of the process parameters of coal amount (%) of the coal/biomass mixtures, initial water volume (mL) of the reactor and amount of the coal/biomass mixtures (kg) on system pressure, total gas yield, hydrogen production and product distribution were determined. Water volume directly affected the system pressure and the reaction medium was supercritical water medium above 48.2 mL with a pressure of 22.06 MPa. The highest values of both total gas volume and hydrogen gas volume were reached by gasification of 5.0 g of feedstock. It has been observed that total gas volume and hydrogen volume were directly affected by the water volume in the reactor and the coal ratio of the coal-biomass mixtures. The highest total gas and hydrogen volumes can be achieved under the conditions where the higher levels of water volume of the reactor and lower levels of coal percentage of the coal/biomass mixture were combined. Optimum conditions for maximum hydrogen production with 5.0 g of coal/biomass mixture were determined with numerical optimization as coal percentage of 25.6% and initial water volume of 68.5 mL. By combining the impregnated K2CO3 (3%, (w/w)) and CaO catalysts an excellent hydrogen selectivity was achieved. The hydrogen selectivity was drastically increased from 32.0% to 70.8% by capturing more than 99% of CO2 with a H2/CO2 mol ratio of 88.5.

Sustainable ultrasound-assisted ultralow liquor ratio dyeing of cotton fabric with natural turmeric dye

Natural dyes are environmentally friendly and have become important alternatives to synthetic dyes in some dyeing products. Therefore, better extraction and dyeing techniques need to be developed for the dyeing process of natural dyes. In this work, cotton fabric was dyed using turmeric extraction solution under an ultralow liquor ratio (materials to liquor ratio of 1:5) and ultrasonic-assisted conditions. Dye extraction using different dispersants and pH values has been investigated and three-factor-three–level Box–Behnken design was employed to explore the dyeing conditions. It was found that sodium dodecyl sulfate systems and ultrasonic waves can effective improve the dyeing depth under neutral condition. The K/ S value can reach 2.53 with ultrasonic power of 200 W, dyeing time of 30 min and temperature of 40℃. Scanning electron microscope images showed that the application of ultrasound did not cause obvious fiber damage. The developed technique could be used in the textile industry to make dyeing cotton fibers with natural dyes more sustainable than it is at present.

Optimization by design of etoposide loaded solid lipid nanoparticles for ocular delivery: Characterization, pharmacokinetic and deposition study

The present study was to develop etoposide loaded solid lipid nanoparticles (SLN) and optimize it for effective ocular delivery to the posterior eye. SLN were prepared by melt-emulsification and ultrasonication technique. Etoposide loaded SLN were optimized by using three-factor three levels Box-Behnken design to establish the functional relationships between variables on responses of particle size, polydispersity index (PDI) and entrapment efficiency (EE). SLN were characterized for size & surface morphology, entrapment efficiency and in vitro release. Further the pharmacokinetic study of optimized formulation after intravitreal administration was evaluated in Wister rats. The deposition in the ocular tissues was checked by scintigraphic analysis in Albino rabbits. Histology was also done to evaluate morphological changes if any occur after treatment. The particle size, PDI and EE obtained for the optimized formulation (Z15) were 239.43 ± 2.35 nm, 0.261 ± 0.001 and 80.96 ± 2.21% respectively. Single intravitreal administrations of SLN were able to give sustained etoposide concentration in the vitreous for 7 consecutive days which was also supported by the results of Gamma scintigraphic study. Histology of posterior ocular tissues do not showed any serious toxic effect. Therefore it can concluded that etoposide loaded SLN was able to maintain vitreous concentration of drug without any serious toxic effect to the surrounding ocular tissues after an intravitreous administration in rat eye.

Development of bioactive compounds-loaded chitosan films by using a QbD approach – A novel and potential wound dressing material

In the present study, a Quality by Design (QbD) approach was applied in order to develop and optimize a chitosan film formulation loaded with bioactive compounds, intended for further use as an aid in the acceleration of wound healing. Chitosan was chosen as film forming polymer, polyethylene glycol was used as plasticizer, while polyvinyl alcohol was added to improve the bioadhesive properties of the films. Risk assessment strategy was applied to identify the critical formulation variables, which were further introduced as factors of a 3 level Box Behnken design of experiments.The optimal film formulation registered a film thickness of 0.09 mm, solubility in water of 44.9% and a high swelling degree of 2157.4%. The optimized formulation, as well as a placebo formulation without bioactive compounds proved to have a good antibacterial activity. We conclude that in the current study, the QbD approach was successfully applied in order to ensure a good understanding of the manufacturing process, as well as to optimize the formulation of chitosan films. To the best of our knowledge, this is the first time when a QbD approach has been applied in order to develop and optimize a film formulation as a novel wound dressing material.

Syngas production from biomass using Fe-based oxygen carrier: Optimization

Chemical looping gasification is a promising technology to convert biomass into syngas with low adverse effects by heat loss and production dilution. This study utilized 60% loading Fe2O3/Al2O3 oxygen carrier (OC) for gasification tests on four biomass samples: rice straw, corn stalk, peanut shell and wheat straw under OC/biomass (OC/B) ratio of 1.0, steam/biomass (S/B) ratio of 2.8, reaction time of 20 min, and reaction temperature of 850 °C. All biomass samples yielded similar gasification performances: CO content 19.2–23.1%, H2 content 36.5–41.1%, carbon conversion rate 72.3–82.2% and gas yield 0.78–1.04 L/g. The gasification performance using rice straw was optimized on maximum H2/CO ratio using three levels Box-Behnken experimental design: 899.6 °C, 20.3 min, OC/B = 1.02 and S/B = 2.89, leading to maximum H2/CO value of 2.20. Verification tests confirmed this prediction. The adopted Fe-based OC can be applied to generate syngas from the tested biomass with promising outcomes.

Multi-response optimization of oil extraction from pine nut (Pinus pinea L.) by response surface methodology: Extraction efficiency, physicochemical properties and antioxidant activity

Effects of solvent extraction conditions on the extraction efficiency, physicochemical properties and antioxidant activity of pine nut oil were investigated and optimized by using three level Box-Behnken design (BBD). Temperature (25–65 °C), time (10–60 min) and solvent/sample (S/S) ratio (5–20 mL g−1) were chosen as the independent variables while the dependent variables were extraction efficiency, yellowness index (YI), peroxide value (PV), p-anisidine value (p-AnV), totox value (TV), DPPH-hydrophilic fraction (DPPH-HF), DPPH-lipophilic fraction (DPPH-LF) and DPPH-oil to obtain pine nut oil with high oil yield, and desirable physicochemical properties and antioxidant activity. N-hexane was found to be the most effective solvent for the extraction. Extraction efficiency, physicochemical properties and antioxidant activity of pine nut oil were highly affected by temperature, time and S/S ratio. Desirability function approach was used to determine optimum conditions. The optimum conditions for the production of pine nut oil with solvent extraction were attained at the extraction temperature of 39.3 °C, extraction time of 33.4 min and S/S ratio of 10.8:1 (mL g−1). At optimum conditions, the predicted values for the extraction efficiency, YI, PV, p-AnV, TV, DPPH-HF, DPPH-LF and DPPH-oil yielded 80.03%, 59.89, 1.05 meq peroxide kg−1 oil, 0.92, 3.02, 8.60%, 65.07% and 73.35%, respectively.

Prediction and Experimental Validation of Peak Temperature in Friction Stir Welded AA2024 with AA5083 by Response Surface Methodology

Objective: The work aims at prediction of the peak temperature using Response Surface Methodology. Methods/ Statistical Analysis: Dissimilar Aluminum Alloys AA2024 and AA5083 O were friction stir welded. A fifteen run 3 factorial 3 level Box Behnken design was conducted and temperature generated were measured at both sides of the alloys. Thermocouples were employed for the same. The temperature was recorded and studies conducted. Response surface plots were used to obtain the peak temperature and effect of various parameters. Findings: The relationship between the process parameters and the temperature were established using ANNOVA. Mathematical models were development which can apply for future predictions. The traverse speed, rotational speed and the tool profile contributed to the temperature generation. The peak temperature was obtained at 1200 rpm, 25 m/min and threaded cylindrical tool pin profile. Application/Improvements: The temperature at the re-treating side was recorded to be higher compared to the advancing side. Keywords: Anova, Heat Input, Mathematical Modeling. Peak Temperature, RSM

Thermosonication and inactivation of viable putative non-culturableLactobacillus acetotoleransin beer

This work compares the inactivation by thermosonication of exponentially growing Lactobacillus acetotolerans cells with viable putative non-culturable (VPNC) cells in beer. The critical process parameters were optimised using response surface methodology using a three-factor three level Box–Behnken design. The three independent variables were volumetric power (2.7, 5.8 and 8.9 W/mL), temperature (40, 50 and 60°C) and treatment time (2, 4 and 6 minutes) with the output of log reduction in viable cell number of L. acetotolerans cells growing exponentially or in the VPNC state. The results showed that under different conditions of volumetric acoustic power–temperature–time combination, cells of L. acetotolerans in the VPNC state were more resistant to thermosonication than exponential cells. This insight will be of value to the design of appropriate thermosonication conditions to pasteurise beer and other beverages. © 2018 The Institute of Brewing & Distilling

Process design and potential use of a regenerable biomagsorbent for effective decolorization process

Abstract Aquatic pollution caused by synthetic dyes poses a significant threat to environment and public health. Efficient and convenient removal of dye contaminants from aquatic environment is a challenge for environmental protection. Biosorption process is a promising way to remove such chemicals from contaminated media. Herein, a new biomagsorbent based on Lactarius salmonicolor cells (MagLS) was simply designed by combining magnetic separation and biosorption techniques. Technical feasibility of the prepared biomagsorbent for Reactive Yellow 2 retention was examined. The interactive effects of batch process variables were evaluated by 4 − level Box–Behnken design. Kinetic analysis indicated applicability of the pseudo − second − order model. qmax value was noted as 115.23 mg/g and retention of RY2 was endothermic and spontaneous in nature. IR, SEM/EDX analysis and zeta potential measurements were employed for the characterization. Flowthrough experiments indicated that MagLS has a high decolorization potential. Regeneration experiments carried out in 25 consecutive cycles revealed that MagLS can be easily regenerated and reused for at least 15 cycles with high sorption (∼70%) and desorption (∼80%) yield. Furthermore, after 25 cycling process, a recovery yield of RY2 dye was maintained at around 80%.

Photocatalytic and antibacterial potential of silver nanoparticles derived from pineapple waste: process optimization and modeling kinetics for dye removal

Green chemistry offers several benefits over other synthesis routes of nanoparticles due to their eco-friendly attributes during their formulation as well as application stages. In the present study, an aqueous extract of Ananas comosus (Pineapple) peel waste was successfully exploited for the synthesis of ultra small (average size 14–20 nm) silver nanoparticles (AgNPs) without adding any reducing or stabilizing agents. Two major factors, i.e., concentration ratio between silver ion precursor versus peel extract and synthesis pH were found to be influential for achieving monodispersed and stable AgNPs. Biogenic AgNPs adorned with natural moieties demonstrated good photocatalytic activity against methylene blue (MB) dye under sunlight illumination for various conditions. The process variable, e.g., solution pH, initial MB concentration and contact time were optimized using response surface methodology (RSM) based on three levels Box-Behnken design. A maximum MB removal of 98.04% was achieved at optimized values of 9.96 pH, 40 ppm initial dye concentration and 173 min of contact time. The kinetics of MB removal was best fitted to its first order kinetic model (R2 = 0.996) in concurrence with intraparticle diffusion-mediated adsorption. AgNPs were also found to be effective to kill pathogenic bacterial strains, Pseudomonas aeruginosa and Bacillus subtilis as characterized from zone of inhibition (ZoI) and viability tests. Undergoing photochemical reactions, the generation of reactive oxygen species (ROS) was elucidated as the major mechanism of AgNPs’ toxicity modulating membrane permeability. This strategy is not only economically viable and environmentally benign, synthesized AgNPs were capable to remove methylene blue dye almost completely under ambient conditions through solar energy.

Development of Predictive Model for Quality Output of Welding Process of Steel NST 37-2 Using Response Surface Methodology

The present study investigated the effect of operating parameters in modeling the output quality of welding process of steel sample. A three factor, three levels Box-Behnken Design (BBD) of RSM was applied to determine the effects of three independent variables (welding speed (A), welding current (B) and electrode potential (C)) on the tensile strength and to also develop a model for predicting the output quality. Data analysis shows that A, C, AB, BC, A2, B2and C2are the terms which significantly affected the ultimate tensile strength of the sample at 95% confidence level. The experimental values were very close to the predicted values and were not statistically different at p&lt;0.05. The maximum tensile strength of 228 MPa was obtained at 250 A current, electrode diameter of 3.25 mm and 50 cm/min welding speed, respectively. The regression model obtained has provided a basis for selecting optimum process parameters for the improving output quality (tensile strength) of the welded steel sample.

Preparation and Statistical Modeling of Solid Lipid Nanoparticles of Dimethyl Fumarate for Better Management of Multiple Sclerosis.

Purpose: The objective of this study was to synthesize and statistically optimize dimethyl fumarate (DMF) loaded solid lipid nanoparticles (SLNs) for better management of multiple sclerosis (MS).Methods: SLNs were formulated by hot emulsion, ultrasonication method and optimized with response surface methodology (RSM). A three factor and three level box-behnken design was used to demonstrate the role of polynomial quadratic equation and contour plots in predicting the effect of independent variables on dependent responses that were particle size and % entrapment efficiency (%EE).Results: The results were analyzed by analysis of variance (ANOVA) to evaluate the significant differences between the independent variables. The optimized SLNs were characterized and found to have an average particle size of 300 nm, zeta potential value of -34.89 mv and polydispersity index value < 0.3. Entrapment efficiency was found to be 59% and drug loading was 15%. TEM microphotograph revealed spherical shape and no aggregation of nanoparticles. In-vitro drug release profile was an indicative of prolonged therapy. In-vivo pharmacokinetic data revealed that the relative bioavailability was enhanced in DMF loaded SLNs in Wistar rats.Conclusion: This study showed that the present formulation with improved characteristics can be a promising formulation with a longer half-life for the better management of MS.