Statistical Mixture Design Research Articles

Synthesis and optimization of molecular weight of chitosan and carboxymethyl cellulose based polyurethanes

For the first time in this research, using a mixture design approach, polyurethanes (PUs) based on chitosan (CSN) and carboxymethyl cellulose (CMC) were synthesized to develop a high molecular weight polymer. In the synthesis process, a reaction between isophorone diisocyanate (IPDI) and hydroxyl-terminated polybutadiene was carried out to synthesize a prepolymer containing free NCO groups at the corners. This prepolymer was further reacted with changing moles ratio of CSN and CMC following the principles of statistical mixture design. The structural confirmation of the developed PUs was carried out through spectroscopic techniques (FTIR and NMR). The molecular weights of the PU specimens were characterized using gel permeation chromatography. The findings demonstrated that the interaction between CMC and CSN led to a notable increase in the molecular weights of the samples, supported by a significant p-value of 0.006. Additionally, the analysis of variance (ANOVA) disclosed that the employed mixture design and the resulting interaction model effectively account for 98 % of the total variation observed in the molecular weights. The sample labeled as PUS-3 (CMC0.50:CSN0.50) emerged as the most significant formulation, exhibiting a noteworthy 27.9 % improvement in the polymer molecular weight compared to the base sample, denoted as PUS-1 (CMC1.00:CSN0.00).

Aligned electrospun starch-pullulan-protein fibers

Electrospun nanofiber mats with potential utility as functionalized scaffolding for cultivated meat were fabricated from octenyl succinic anhydride (OSA) modified starch, pullulan, and either glycomacropeptide (GMP) or whey protein isolate (WPI). A statistical mixture design was used to establish the influence of polymer composition on spinning dope properties including conductivity, surface tension, shear viscosity, and elasticity and relate these properties to spun fiber morphology. Component composition varied – starch 16–24 %, pullulan 4–6 %, protein 0–10 % – while maintaining the overall polymer content at 30 % w/w. The propensity for fiber beading was inversely associated with a timescale for bead formation dependent on the ratio of viscosity to surface tension and directly to a timescale for fiber solidification/drying altered by adjusting relative humidity. Smooth, continuous nanofibers, average diameter of 461–526 nm, were obtained from mixtures that contained less than 4% (w/w) protein, whereas mixtures with greater than 6% (w/w) protein resulted in fibers with beading. Generally, GMP-containing nanofibers exhibited less beading than WPI-containing nanofibers. Aligned fiber mats were produced using a rotating drum collector at different speeds varying from 3600 to 5600 rpm that may serve to template cell growth.

Assessing the Environmental Sustainability of UHPC in Modern Construction Practices

A comprehensive examination was undertaken to investigate various aspects related to the development and application of Ultra-High-Performance Concrete (UHPC). The research explored eco-friendly approaches, such as incorporating supplementary cementitious materials and nanoparticles, optimizing binder systems, and assessing chemical activators. These modifications improved mechanical properties and reduced environmental impact, including embodied CO2 emissions. Additionally, the utilization of waste materials like CRT glass showed energy savings and reduced emissions. Studies focused on optimizing UHPC mix designs, emphasizing a balance between performance and environmental impact. Techniques like statistical mixture design methods and dynamic testing assessed UHPC's environmental and economic impacts, highlighting significant energy savings and reduced CO2 emissions with waste material recycling. Overall, the research contributes valuable insights into UHPC development and its ecological footprint in construction

Thermally-treated asbestos-cement wastes as supplementary precursor for geopolymeric binders: CO2 emission and properties

This article explores the impact of thermally treated asbestos-cement waste (ACWT) on metakaolin-based geopolymers, using liquid sodium silicate (LSS) and liquid potassium silicate (LKS) as alkali activators. Through statistical mixture design, various formulations were tested for rheological parameters, mineralogical composition, efflorescence mass, electrical conductivity, compressive strength, and CO2 emissions. Formulations with sodium silicate exhibited higher yield stress compared to those with potassium silicate, while flash setting occurred in LKS-activated mixtures with high ACWT content. Alkali activator content significantly affected mechanical strength and leachate electrical conductivity. CO2 emissions were higher for LKS-activated formulations but lower for those with more ACWT. Finally, by incorporating ACWT, it was possible to optimize the formulations, resulting in high compressive strength, reduced free ions, and reduced negative environmental impact.

Exploring the synergistic effect of carboxymethyl cellulose and chitosan in enhancing thermal stability of polyurethanes through statistical mixture design approach

The thermal stability of polyurethanes, known for its limitations, was addressed in this research by seeking improvement through the introduction of carbohydrate-based chain extenders. In this research paper, we systematically sought to improve the thermal resistance of polyurethanes by incorporating carboxymethyl cellulose and chitosan, representing a pioneering application of the mixture design approach in their preparation. In this synthesis, hydroxyl-terminated polybutadiene and isophorone diisocyanate (IPDI) were reacted to prepare –NCO terminated prepolymer, which was subsequently reacted with varying mole ratios of CMC and CSN to develop a series of five PU samples. The prepared PU samples were characterized using the Fourier-transformed infrared spectroscopic technique. Thermal pyrolysis of PU samples was examined using thermal gravimetric analysis (TGA). It was observed that, among all the samples, PUS-3 showed remarkable thermal stability over a wide temperature range. A comprehensive statistical analysis was conducted to substantiate the experimental findings. It was estimated that CMC and CSN significantly enhance the thermal stability of the samples when involved in an interaction fashion. The ANOVA Table for the mixture design demonstrates that over 90 % of the total variation in thermal stability is explained by the mixture model across a wide temperature range. Moreover, PSU-3 exhibited 4 % more thermal stability over a wide range of temperatures on average, as compared to contemporary samples.

Castor-oil biobased foam: the effect of the composition on the physical and mechanical properties via a statistical mixture design.

PU foams are versatile materials that find applications in a wide range of products, from upholstery to packaging and construction. These foams consist primarily of two components, polyol and prepolymer, and their concentrations play a crucial role in determining their physical and mechanical properties. A second-order mixture design approach is used in this work to identify the significant components and their contributions on the physical-mechanical properties of biodegradable castor oil-based foams. The experimental design includes three components: two types of polyols and one prepolymer. These components are varied in nine distinct conditions to evaluate their effects on properties such as expansion rate, bulk density, compressive strength, and tensile strength. The Scheffé's quadratic model coefficients exhibit R-squared values higher than 0.84 in most cases. Chemical analysis using infrared spectroscopy confirms the successful formation of the urethane bond during the manufacturing process. The biobased foams developed in this work have densities ranging between 61 and 100 kg m-3, compressive modulus of 11-15 MPa and compressive strength between 273 and 429 kPa. The tensile modulus varies between 3.2 and 4.9 MPa, with a tensile strength in the range of 370-500 kPa. These results highlight the potential of biodegradable castor oil-based foams as promising alternative materials to traditional synthetic foams.

Theoretical and Experimental Strategy for the Control and Mitigation of Efflorescence in Metakaolin-Based Geopolymer

Compared with portland-cement-based matrices, the high mechanical strength, satisfactory durability, and sustainable features of geopolymeric matrices have brought great interest in the civil construction sector. Excessive activator content in a geopolymer mixture can cause efflorescence, a phenomenon related to the unreacted alkalis that compromise the mechanical properties and aesthetics of the structures. This article proposes applying statistical mixture design (SMD), associated with simultaneous optimization for the dosage of geopolymeric matrices, to evaluate and mitigate efflorescence. Based on the extreme vertices screening design, the formulations were made using metakaolin as a precursor, NaOH and sodium silicate as the activator, and sand and superplasticizer. The formulation with the lowest efflorescence formation, highest compressive strength, and adequate workability was the one whose molarity of NaOH was equal to 9.02 M, and the ratios Na2O/Al2O3, SiO2/Al2O3, and H2O/Na2O were equivalent to 1.43, 2.65, and 8.36, respectively. In addition, the Na2O/Al2O3 ratio was the predominant factor for efflorescence occurrence. SMD associated with simultaneous optimization is a technically viable alternative for minimizing free sodium in geopolymeric matrices.

Optimization of a New Antioxidant Formulation Using a Simplex Lattice Mixture Design of Apium graveolens L., Coriandrum sativum L., and Petroselinum crispum M. Grown in Northern Morocco.

A statistical Simplex Lattice Mixture design was applied to develop a new formulation based on a combination of three plants grown in northern Morocco: Apium graveolens L., Coriandrum sativum L., and Petroselinum crispum M. We examined the extraction yield, total polyphenol content (TPC), 2'2-diphenyl-l-picrylhydrazyl (DPPH) radical scavenging activity, and total antioxidant capacity (TAC). The results of this screening study showed that C. sativum L. had the highest content of DPPH (53.22%) and TAC (37.46 ± 0.29 mg Eq AA/g DW) compared to the other two plants, while P. crispum M. showed the highest TPC (18.52 ± 0.32 mg Eq GA/g DW). Furthermore, the ANOVA analysis of the mixture design showed that all three responses (DPPH, TAC, and TPC) were statistically significant, with determination coefficients of 97%, 93%, and 91%, respectively, and fit the cubic model. Moreover, the diagnostic plots showed good correlation between the experimental and predicted values. Therefore, the best combination obtained under optimal conditions (P1 = 0.611, P2 = 0.289, P3 = 0.100) was characterized by DPPH, TAC, and TPC of 56.21%, 72.74 mg Eq AA/g DW, and 21.98 mg Eq GA/g DW, respectively. The results of this study reinforce the view of stimulating the effect of plant combinations to achieve better antioxidant activities, thus providing a better formulation using designs of mixtures for the food industry and in cosmetic and pharmaceutical applications. Moreover, our findings support the traditional use of the Apiaceae plant species in managing many disorders cited in the Moroccan pharmacopeia.

Asbestos-cement wastes as supplementary precursors of NaOH-activated binders

The need to remove, eliminate the hazard, and correctly dispose of asbestos-cement artifacts found in buildings or incorrectly in the environment is considered a global problem. Processes of inerting asbestos-cement waste (ACW) and application thereof are research priorities. In this sense, this article proposes the production of alkali-activated binders (AAB) with partial metakaolin replacement by heat-treated asbestos-cement wastes (ACWT) as a sustainable alternative for the ACW disposal. To produce AAB, metakaolin, ACWT, and liquid sodium silicate were used. Through the statistical mixture design (SMD), the mineralogical phases formation, the compressive strength, and the skeletal density of the mixtures were evaluated. In addition, an indirect method to determine the unreacted sodium content based on the electrical conductivity and the mass of efflorescent material of the pastes was proposed. The results showed that the presence of ACWT can promote the formation of new alkali-activation products, although it does not significantly influence mechanical strength and efflorescence formation. The paste with the lowest efflorescence mass and lowest electrical conductivity presented higher compressive strength, equal to 61.3 MPa. The determination of electrical conductivity is an accurate method for quantifying unreacted sodium. The incorporation of ACWT in the geopolymer matrices increased the sustainable character of this binder.

One-part alkali-activated binder produced from inertized asbestos cement waste

Owing to its carcinogenic potential and the environmental impacts associated with its disposal, the search for inertization technologies that enable the reuse of asbestos cement waste (ACW) is a priority in several countries. Among the proposed methods, optimized heat treatment is a promising methodology. However, there is a lack of studies aimed at the application of asbestos cement waste, even after proper treatment. Thus, this study investigates the potential use of heat-treated asbestos-cement waste (ACWT) as a precursor of one-part alkali-activated binders. Eleven formulations were established using the I-Optimal algorithm, strategically varying the mass fractions of ACWT, solid sodium metasilicate (SSM) with a molar ratio of SiO2/Na2O equal to 0.98, and water. These formulations served as the basis for the construction of models that relate the properties of pastes with the proportion of materials. The pastes were evaluated by isothermal calorimetry, X-ray diffraction, autogenous shrinkage, drying shrinkage, and compressive strength. The results show that the formulations with an SSM concentration of approximately 5% and molarities close to 1 M presented the best mechanical properties. The addition of SSM had a strong influence on the accumulated heat rate, with the formulations containing the activator showing superior mechanical behavior compared to the mixtures without the activator. Furthermore, the pastes without an activator exhibited lower drying shrinkage and chemical shrinkage. It was possible to verify that ACWT can be applied for the production of alkali-activated binders and that the statistical mixture design is an efficient method for predicting the evaluated properties.

Exogenous application of bioregulators in Coffea arabica beans during ripening: Investigation of UV–Visible and NIR mixture design-fingerprints using AComDim-ICA

Bioregulators are substances applied to various types of crops to optimize their quantity and quality. Their external application could affect the plant metabolome by triggering metabolic changes and consequently modifying the quality of beverage. The present study investigated the metabolomic modifications observed in the spectral fingerprints of raw coffee beans dependent on bioregulator applications (BIO, Gibberellin, and Ethephon) over the stratified vertical canopy profile (STR). Principal components analysis (PCA) was used to identify the discriminating solvent, obtained from statistical mixture design, for each applied technique. When analyzing both the near-infrared (NIR) and UV–Visible (UV–Vis) spectra, E (ethanol) and ED (ethanol/dichloromethane) were the most discriminating solvents. The NIR and UV spectra obtained from the statistical mixture design were interpreted by using a modification of analysis of variance-common dimensions analysis (AComDim), where the usual PCA step within ComDim was replaced by an independent components analysis (ICA), i.e., AComDim-ICA. AComDim-ICA showed that ED extractor was the most efficient in bioregulator effect discrimination, while E was the most efficient for the stratification and the BIO x STR interactions. AComDim-ICA indicated that gibberellin gave the greatest differentiation compared to the other BIO treatments (Ethephon and Control), with a possible influence on phenolic compounds. AComDim-ICA indicated that berries harvested at strata up to 1 m (highly shaded) were different than berries harvested at higher strata (2 m and 3 m), that are related to metabolites such are caffeine, lipids, sugars, and diterpenes. Caffeine from the highest stratum (3 m) treated with Ethephon differed from that of the Control for the same stratum, in relation to caffeine. The use of these multivariate methods expands the metabolomic analysis of the plants, producing more information about the system.

Statistical mixture design for carbide residue activated blast furnace slag foamed lightweight concrete

Carbide residue activated blast furnace slag is a relatively new kind of eco-friendly construction materials. This work addresses the design of foamed lightweight concrete as road embankment material using such material. A statistical mixture design approach was adopted to assess the influence of each ingredient as well as the interaction between these on the spreadability and compressive strength and thus allowing mixture design. The fitted models were validated using analysis of variance, residual analysis and confirmed by the experiments. Afterwards, the proposed models were used to optimize the mixture. The mixture with the highest compressive strength and the maximum content of carbide residue that allows the mixture to meet the required properties were obtained, respectively.

Statistical mixture designs for media development with agro-industrial residues – Supporting the circular bioeconomy

Nutrient-rich side streams can be used in fermentation media to produce biomaterials, biofuels and other high-value products, contributing to the circular bioeconomy. However, the efficient valorization of side streams requires media optimized for the fermentation organism and the desired product. In an exemplary process, we investigated statistical mixture designs for the development of a medium containing food-grade agro-industrial residues (whey, molasses and cornsteep powder (CSP)). The yeast Kluyveromyces lactis was used to convert these residues into biomass and a model-protein (β-galactosidase). With the obtained response surface, the effects and interactions of the residues and mixtures thereof on growth rate, biomass and β-galactosidase production could be determined. Two-thirds CSP with one-third molasses produced the most biomass, whereas 88% CSP with 12% whey achieved the optimal β-galactosidase production rate. The side streams used fulfilled cell-specific requirements and the mixture design even led to the identification of synergistic effects between residues. The models were verified in confirmation runs, showing that statistical mixture designs are ideal for targeted and resource-efficient media development. Expanding the use of mixture designs to other side streams, biocatalysts, and products increases the attractiveness and efficiency of using agro-industrial residues in fermentation media and thus can be beneficial in supporting the circular bioeconomy.

Statistical Mixture Design for Carbide Residue Activated Blast Furnace Slag Foamed Lightweight Concrete

Statistical Mixture Design for Carbide Residue Activated Blast Furnace Slag Foamed Lightweight Concrete

Formulation and optimization of a phosphogypsum – fly ash – lime composite for road construction: A statistical mixture design approach

This paper investigates the valorization of phosphogypsum and fly ash by-products as a road construction material through lime stabilization. To this end, an extreme vertices design was adopted to model the compaction characteristics, mechanical performance at different curing periods and durability upon wetting/drying (W/D) cycles of the mixture. Statistical analysis of the obtained regression models showed that the measured responses decrease with phosphogypsum addition while fly ash and lime cause them to increase. The increasing effect of fly ash addition was especially noticeable on compressive strengths at early ages (7–28 days), whereas at longer curing periods (90–360 days), these were mainly governed by its interaction with lime following the activation of the pozzolanic reaction where phosphogypsum acted as a catalyst to improve fly ash reactivity. However, a negative impact of excess lime beyond a threshold has been noted. The compressive strength at 28 days combined with weight loss upon W/D cycles were used as optimization responses to detect regions of interest, within the design space, where requirements are met for a subbase utilization.

CO2-binding organic liquids for high pressure CO2 absorption: Statistical mixture design approach and thermodynamic modeling of CO2 solubility using LJ-Global TPT2 EoS

CO2-binding organic liquids (CO2-BOLs) or switchable ionic liquids (SILs) are switchable polarity solvents (SPS) that can be used as non-aqueous, energy efficient solvents for CO2 absorption. In this study, the three-component CO2-BOLs comprised of a single-component CO2-BOL (tertiary alkanolamine) and a two-component CO2-BOL (superbase/alcohol) are introduced. The most efficient equimolar combination of superbase (1,8-diazabicyclo-[5.4.0]-undec-7-ene (DBU)), alcohol (methanol, n-butanol, sec-butanol, tert-butanol and hexanol) and amine (Dimethylethanolamine (DMEA), Diethylethanolamine (DEEA) and N-methyldiethanolamine (MDEA)) are obtained using screening experiments considering CO2 loading (αeq) and absorption rate (αR). The mixture design technique is employed for modeling of αeq and αR as a function of mole fraction of components at 35.0 °C and initial pressure of 25.0 bar. The DBU/DMEA/n-butanol CO2-BOL represented the best performance for CO2 uptake. The experimental CO2 solubility data in DBU/n-butanol, DBU/DMEA and DBU/DMEA/n-butanol BOLs were obtained in the temperature range of 25.0–45.0 °C and the pressure range of 1.0–45.0 bar. The DBU mole fraction was selected to be 0.1 and 0.2 while the molar ratio of DMEA to n-butanol was kept constant at 2 in the three-component BOL. The simultaneous vapor–liquid and chemical equilibrium calculation algorithm using LJ-Global TPT2 equation of state was used for the thermodynamic modeling of CO2 solubility in BOLs. The average absolute relative deviation error (AAD%) for the calculation of total pressure of DBU/n-butanol, DBU/DMEA and DBU/DMEA/n-butanol BOLs were obtained to be 8.5%, 5.8% and 8.6%, respectively.

QUALITY BY DESIGN BASED DEVELOPMENT OF ETRAVIRINE SELF MICRO EMULSIFYING DRUG DELIVERY SYSTEM

Objective: The main objective of the present research work was to develop systematically the Self Micro Emulsifying Drug Delivery system of BCS Class IV drug in a Quality by Design framework.
 Methods: The quality by design-based formulation development proceeds with defining the Quality Target Product Profile and Critical Quality Attributes of dosage form with appropriate justification for the same. The statistical Mixture design was used for the development of the formulation. The independent variables selected for the design were Oleic acid, Labrasol and PEG 6000, whereas droplet size (nm), emulsification time (sec), % drug loading and % drug release at 15 min were considered as the potential quality attributes of the Self Micro Emulsifying System. The eight different batches of Etravirine-Self Micro Emulsifying systems (ETV-SMEDDS) were prepared and checked for the Critical Quality Attributes. The simultaneous optimization of the formulation was done by the global desirability approach.
 Results: The characterization report obtained for all the different batches of formulation was analyzed statistically by fitting into regression models. The statistically significant models determined for droplet size (nm) (R2= 0.96 and p-0.1022), emulsification time (sec) (R2= 0.99 and p-0.0267), % drug loading (R2= 0.93 and p-0.1667) and % drug release at 15 min (R2= 0.96 and p-0.0911) and were statistically significant. The maximal global desirability value obtained was 0.9415 and the value indicates, the selected factors and responses have a good correlation and are significant enough for optimization and prediction of best formulation.
 Conclusion: The QbD approach utilized during the development of ETV-SMEEDS facilitated the identification of Critical Material Attributes and their significant impact on the Critical Quality Attributes of SMEDDS. The concept of building quality into product through the QbD application was utilized successfully in the formulation development.

Statistical Mixture Design for Modelling and Optimization of Feed Mixture in the Chemical Interesterification to produce Cocoa Butter Alternatives

This study aimed to find the optimum feed mixture consist of palm stearin (PS), palm olein (PO), and coconut oil (CO), for chemical interesterification to produce cocoa butter alternatives (CBA) with the most similar melting profile with cocoa butter. The feed mixture was chemically interesterified using sodium ethylate as the catalyst at a temperature of 75°C for 8 hours. Based on the melting profile analysis of the products, the pure coconut oil (CO-100) and pure palm stearin (PS-100) gave the most similar melting profile of cocoa butter alternatives. The CO-100 melting profile gave the least value of Sum of Square Error compared to Cocoa Butter Substitute while the PS-100 melting profile gave a similar result compared to Cocoa Butter Equivalent (CBE) and Cocoa Butter Replacer (CBR). However, PS-100 product does not meet the other specifications, such as Iodine value and slip melting point. Therefore, it can be concluded that pure coconut oil was the best feed for chemical interesterification to produce cocoa butter alternatives (CBA).

An exploratory study of recovery of rare-earth elements from monazite in mild conditions using statistical-mixture design

Monazite is a phosphate mineral, considered an essential source of light rare-earth elements (REE). The present work sought to evaluate different methods of solubilization of REE through the use of different concentrations of inorganic acids (H2SO4, HCl, and HNO3) and organic acids (citric, oxalic, and lactic) in mild conditions at room temperature. According to the results, the inorganic acid solutions favored the solubilization in order of Ce3+, La3+, Nd3+, Pr3+, and Sm3+ elements, while organic acid solutions only favored the solubilization of Ce3+ and La3+. Nitric acid was the more efficient leaching agent for the first group. In the case of organic acids, lactic acid solubilized Ce3+, while mixtures of lactic and citric acids appeared to solubilize La3+.

Application of Statistical Solvent Mixture Design in Optimizing the Solid-Liquid Extraction of Phenolic Compounds from Mango Seed Kernels

Mango seed kernel (MSK) is a waste material of the mango processing industry and is reported to significantly contain phenolic compounds with anti-oxidative properties. In this work, these compounds are isolated via solid-liquid extraction (SLE) in which solvent mixture design approach was used to evaluate the optimal quaternary solvent ratio in relation to the phenolics content of extracts from MSK. The quaternary solvent is composed of ethanol (E), methanol (M), acetone (A), and water (W). The extraction process was implemented at 40°C for 60 minutes with the ratio between solid and solvent at 1:25. Response surface methodology coupled with simplex lattice design was developed to evaluate the optimal solvent system and their interaction effects on the phenolic compounds content. The linear, two-way, and three-way interaction, except for methanol-acetonewater system, resulted in positive effects on the phenolic compounds content. The response model shows that a quaternary mixture with approximately 3:3:3:1 E:M:A:W ratio provided the highest phenolic content. A Scheffé cubic model sufficiently described the extraction process. The results of this study showed that the extraction of phenolic compounds in MSK via SLE using a mixture of solvents is possible. Higher extraction efficiencies can be achieved by optimizing the SLE process, and the optimum conditions can be applied to produce phenolic extracts with positive antioxidant activity.