Insights from a Box–Behnken Optimization Study of Microemulsions with Salicylic Acid for Acne Therapy

The present study brings to attention a method to develop salicylic acid-based oil in water (O/W) microemulsions using a tensioactive system based on Tween 80, lecithin, and propylene glycol (PG), enriched with a vegetable oat oil phase and hyaluronic acid. The systems were physically characterized and the Quality by design approach was applied to optimize the attributes of microemulsions using Box–Behnken modeling, combined with response surface methodology. For this purpose, a 33 fractional factorial design was selected. The effect of independent variables namely X1: Tween 80/PG (%), X2: Lecithin (%), X3: Oil phase (%) was analyzed considering their impact upon the internal structure and evaluated parameters chosen as dependent factors: viscosity, mean droplet size, and work of adhesion. A high viscosity, a low droplet size, an adequate wettability—with a reduced mechanical work—and clarity were considered as desirable for the optimal systems. It was found that the optimal microemulsion which complied with the established conditions was based on: Tween 80/PG 40%, lecithin 0.3%, oat oil 2%, salicylic acid 0.5%, hyaluronic acid 1%, and water 56.2%. The response surface methodology was considered an appropriate tool to explain the impact of formulation factors on the physical properties of microemulsions, offering a complex pattern in the assessment of stability and quality attributes for the optimized formulation.

Increase in Fermentable Sugars of Olive Tree Pruning Biomass for Bioethanol Production: Application of an Experimental Design for Optimization of Alkaline Pretreatment

Olive Tree Pruning (OTP) biomass can be considered a suitable source of fermentable sugars for the production of second-generation bioethanol. The present study proposes a remarkable alternative for the valorization of olive tree pruning residues. OTP biomass was processed using a sequential calcium hydroxide pretreatment/enzymatic hydrolysis. A 24–1 half fractional factorial design was adopted for the screening of process variables and a central composite design was used for the optimization stage. Temperature and lime loading resulted statistically significant. The following optimal conditions were obtained: 0.01 g of Ca(OH)2/g of dry material, 20 g of H2O/g of dry material at 160 °C for 2 h. The mathematical model that governs this alkaline pretreatment was obtained with a 76% adjusted determination coefficient, which means that it is a good representation of the process. Under optimal operating conditions, 13% of the cellulose and 88% of the hemicellulose was solubilized. Moreover, the fermentable sugar content increased 1800% compared with the initial conditions, obtaining 240 g of glucose per kg of OTP residue. The fermentable sugars obtained after the calcium hydroxide pretreatment and enzymatic hydrolysis of OTP biomass yielded 2.8 g of ethanol/100 g of raw material.

Resveratrol Nanocrystal Incorporated into Mesoporous Material: Rational Design and Screening through Quality-by-Design Approach

Bioflavonoids from grape seeds feature powerful antioxidant and immunostimulant activities, but they present problems related to solubility and bioavailability. Nanocrystal (NC) incorporated into a mesoporous carrier is a promising strategy to address these issues. However, the preparation of this formulation involves the selection of factors affecting its critical quality attributes. Hence, this study aimed to develop an NC formulation incorporating resveratrol into a soluble mesoporous carrier based on rational screening design using a systematic and continuous development process, the quality-by-design paradigm. A mesoporous soluble carrier was prepared by spray-drying mannitol and ammonium carbonate. The NC was obtained by introducing the evaporated solvent containing a drug/polymer/surfactant and mesoporous carrier to the medium. A 26−2 fractional factorial design (FFD) approach was carried out in the screening process to understand the main effect factors. The type and concentration of polymer and surfactant, resveratrol loading, and solvent were determined on the NC characteristics. The results indicated that drug loading, particle size, and solubility were mainly affected by RSV loading, PEG concentration, and Kolliphor EL concentration. The polymer contributed dominantly to reducing the particle size and enhancing solubility in this screening design. The presence of surfactants in this system made it possible to prolong the supersaturation process. According to the 26−2 FFD, the factors selected to be further developed using a statistical technique according to the quality-by design-approach, Box Behnken Design, were Kolliphor EL, PEG400, and RSV loading.

Paper mulberry fruit juice: a novel biomass resource for bioethanol production

By way of broadening the use of diverse sustainable bioethanol feedstocks, the potentials of Paper mulberry fruit juice (PMFJ), as a non-food, sugar-based substrate, were evaluated for fuel ethanol production. The suitability of PMFJ was proven, as maximum ethanol concentration (56.4 g/L) and yield (0.39 g/g) were achieved within half a day of the start of fermentation, corresponding to very high ethanol productivity of 4.7 g/L/hr. The established potentials were further optimally maximized through the response surface methodology (RSM). At the optimal temperature of 30 °C, yeast concentration of 0.55 g/L, and pH of 5, ethanol concentration, productivity, and yield obtained were 73.69 g/L, 4.61 g/L/hr, and 0.48 g/g, respectively. Under these ideal conditions, diverse metal salts were afterward screened for their effects on PMFJ fermentation. Based on a two-level fractional factorial design, nutrient addition had no positive impact on ethanol production. Thus, under the optimal process conditions, and without any external nutrient supplementation, bioethanol from PMFJ compared favorably with typical sugar-based energy crops, highlighting its resourcefulness as a high-value biomass resource for fuel ethanol production. Graphical Abstract

Fractional Factorial Design Study for the Extraction of Cannabinoids from CBD-Dominant Cannabis Flowers by Supercritical Carbon Dioxide

The optimization of the supercritical fluid extraction (SFE) of cannabinoids, using supercritical carbon dioxide (scCO2), was investigated in a fractional factorial design study. It is hypothesized that four main parameters (temperature, pressure, dry flower weight, and extraction time) play an important role. Therefore, these parameters were screened at predetermined low, medium, and high relative levels. The density of scCO2 was used as a factor for the extraction of cannabinoids by changing the pressure and temperature. The robustness of the mathematical model was also evaluated by regression analysis. The quantification of major (cannabidiol (CBD), cannabidiolic acid (CBDA), delta 9-tetrahydrocannabinol (Δ9-THC), delta 8-tetrahydrocannabinol (Δ8-THC), and delta 9-tetrahydrocannabinol acid (THCA-A)) and minor (cannabidivann (CBDV), tetrahydrocannabivann (THCV), cannabigerolic acid (CBG), cannabigerol (CBGA), cannabinol (CBN), and cannabichomere (CBC)) cannabinoids in the scCO2 extract was performed by RP-HPLC analysis. From the model response, it was identified that long extraction time is a significant parameter to obtain a high yield of cannabinoids in the scCO2 extract. Higher relative concentrations of CBD(A) (0.78 and 2.41% w/w, respectively) and THC(A) (0.084 and 0.048% w/w, respectively) were found when extraction was performed at high relative pressures and temperatures (250 bar and 45 °C). The higher yield of CBD(A) compared to THC(A) can be attributed to the extract being a CBD-dominant cannabis strain. The study revealed that conventional organic solvent extraction, e.g., ethanol gives a marginally higher yield of cannabinoids from the extract compared to scCO2 extraction. However, scCO2 extraction generates a cleaner (chlorophyll-free) and organic solvent-free extract, which requires less downstream processing, such as purification from waxes and chlorophyll.

Screening factors affecting chitosan extraction from mud crab (Scylla sp.) shell using microwave irradiation for the Response Surface Approach

Extracting chitosan from crab shell using conventional method requires processing in strong acid and alkali conditions under high temperature with long reaction time. Microwave-based extraction proposes shorter processing time, and hence energy and cost efficient. This study intended to screen factors affecting the extraction of chitosan from mud crab shell using microwave irradiation. The factors would be used in Response Surface Methodology (RSM) approach to obtain the optimum conditions for chitosan extraction. Microwave irradiation was employed in all of the three steps of chitosan extraction, the demineralization, deproteination, and deacetylation processes. A fractional factorial design was used to screen eight independent factors to determine the most significant ones to be optimized to determine the maximum value of four responses, which were yield, mineral removal, degree of deacetylation and moisture content. The results show that all of the main independent variables were significant in affecting minimal one of the 4 responses (P < 0.05). Mud crab chitosan had the degree of deacetylation of 87.72 – 95.13 %. Results of the screening analysis concluded, the main independent factors that are going to be applied in the optimization study are NaOH concentration, microwave oven power, and reaction time in deacetylation process.

Optimised Reduction of Surgical Gloves Pinholes using Forward Search Method

This research investigates the factors that affect the existence of pinholes in surgical gloves during the manufacturing process. Since eight factors affect the existence of pinholes in surgical gloves, a two-level fractional factorial design 28-4 was used to study the main effects and the first-order interactions of the multiple variables. Multiple linear regressions are used to model the data. This paper also examines the presence of influential points in the data using the influential measures in linear regression such as Cook’s Distance, DFFITS, DFBETAS, Studentized Residual, Standardized Residual, Hadi's measure, and the robust forward search. The impact of influential points is further assessed through deletion of potential influential points and model selection using adjusted R2, information criterion, and stepwise selection to see whether these influential points significantly improved the existing model.

Removal of Copper, Nickel, and Zinc Ions from an Aqueous Solution through Electrochemical and Nanofiltration Membrane Processes

Heavy metal contamination in water is a major health concern, directly related to rapid growth in industrialization, urbanization, and modernization in agriculture. Keeping this in view, the present study has attempted to develop models for the process optimization of nanofiltration (NF) membrane and electrocoagulation (EC) processes for the removal of copper, nickel, and zinc from an aqueous solution, employing the response surface methodology (RSM). The variable factors were feed concentration, temperature, pH, and pressure for the NF membrane process; and time, solution pH, feed concentration, and current for the EC process, respectively. The central composite design (CCD), the most commonly used fractional factorial design, was employed to plan the experiments. RSM models were statistically analyzed using analysis of variance (ANOVA). For the NF membrane, the rejection of Zn, Ni, and Cu was observed as 98.64%, 90.54%, and 99.79% respectively; while the removal of these through the EC process was observed as 99.81%, 99.99%, and 99.98%, respectively. The above findings and a comparison with the conventional precipitation and adsorption processes apparently indicate an advantage in employing the NF and EC processes. Further, between the two, the EC process emerged as more efficient than the NF process for the removal of the studied metals.

Magnetic Ion Imprinted Polymers (MIIPs) for Selective Extraction and Preconcentration of Sb(III) from Environmental Matrices

Antimony(III) is a rare element whose chemical and toxicological properties bear a resemblance to those of arsenic. As a result, the presence of Sb(III) in water might have adverse effects on human health and aquatic life. However, Sb(III) exists at very ultra-trace levels which may be difficult for direct quantification. Therefore, there is a need to develop efficient and reliable selective extraction and preconcentration of Sb(III) in water systems. Herein, a selective extraction and preconcentration of trace Sb(III) from environmental samples was achieved using ultrasound assisted magnetic solid-phase extraction (UA-MSPE) based on magnetic Sb(III) ion imprinted polymer-Fe3O4@SiO2@CNFs nanocomposite as an adsorbent. The amount of antimony in samples was determined using inductively coupled plasma optical emission spectrometry (ICP-OES). The UA-MSPE conditions were investigated using fractional factorial design and response surface methodology based on central composite design. The Sb(III)-IIP sorbent displayed excellent selectivity towards Sb(III) as compared to NIIP adsorbent. Under optimised conditions, the enrichment factor, limit of detection (LOD) and limit of quantification (LOQ) of UA-MSPE/ICP-OES for Sb(III) were 71.3, 0.13 µg L−1 and 0.44 µg L−1, respectively. The intra-day and inter-day precision expressed as relative standard deviations (%RSDs, n = 10 and n = 5) were 2.4 and 4.7, respectively. The proposed analytical method was applied in the determination of trace Sb(III) in environmental samples. Furthermore, the accuracy of the method was evaluated using spiked recovery experiments and the percentage recoveries ranged from 95–98.3%.