Centroid Mixture Design Research Articles

Stationary-phase optimized selectivity in supercritical fluid chromatography using a customized Phase OPtimized Liquid Chromatography kit: comparison of different prediction approaches.

The use of stationary-phase optimized selectivity in liquid chromatography (SOS-LC) was shown to be successful for HPLC to analyze complex mixtures using a Phase OPtimized Liquid Chromatography (POPLC) kit. This commercial kit contains five stationary-phase types of varying lengths, which can be coupled to offer an improved separation of compounds. Recently, stationary-phase optimized selectivity supercritical fluid chromatography (SOS-SFC) has been introduced, transferring the methodology to SFC. In this study, the applicability of a customized POPLC expert kit for isocratic SFC runs was explored. Five stationary-phase chemistries were selected as potentially most suitable for achiral separations of polar compounds: aminopropyl (amino), cyanopropyl (CN), diol, ethylpyridine (EP), and silica. The retention factors (k) on the individual stationary phases were used for the prediction of the best stationary-phase combination, based on the POPLC algorithm (via the included software). As an alternative, the best column combination was predicted using multiple linear regression (MLR) models on the results obtained from a simplex centroid mixture design with only three stationary-phase types (amino, silica, and EP). A third approach applied the isocratic POPLC algorithm on the same three stationary-phase data. The proposed combinations were assembled and tested. The predicted and experimental retention factors were compared. The predictions based on the POPLC algorithm provided a stationary phase showing a complete separation of the mixture. The stationary phase suggested by the MLR models, on the other hand, showed co-elution of two compounds, due to an unexpected experimental retention shift. Overall, the customized POPLC kit showed good potential to be applied in SFC. Graphical abstract.

NiO, Fe2O3, and MoO3 Supported over SiO2 Nanocatalysts for Asphaltene Adsorption and Catalytic Decomposition: Optimization through a Simplex–Centroid Mixture Design of Experiments

The main objective of this study was to evaluate the effect of functionalized silica nanoparticles with Fe2O3, NiO, and MoO3 metal oxides on the decomposition of asphaltenes, through an experimental simplex–centroid mixture design for surface area, asphaltene adsorption, and activation energy. The experimental nanoparticle surface area was measured by adsorption of N2. Adsorption isotherms, and the subsequent oxidation process of asphaltenes, were performed through batch adsorption experiments and thermogravimetric analysis, respectively. Among the monometallic systems, the presence of iron increased the affinity between the nanoparticle and the asphaltenes, and a higher metal oxide load increased the adsorptive capacity of the system. For the pairings evaluated, there was better synergy between iron and nickel, with the participation of the former being slightly superior. In the mixture design that included three transition elements, the participation of molybdenum was not significant, and the adsorption of asphaltenes was dominated by the active sites formed by the other two transition element oxides. The mixture design created to minimize the activation energy showed that the interaction of the three transition elements is important and can be evidenced in the interaction coefficients.

Effect of solvent composition and its interaction with ultrasonic energy on the ultrasound-assisted extraction of phenolic compounds from Mango peels (Mangifera indica L.)

Ultrasound has been used to intensify the extraction of phenolic compounds from many agro-food products. However, there is still a lack of understanding on how the ultrasonic energy is influenced by blends of different solvents and how this impacts the extraction process. This work studied the effect of ethanol, acetone and hexane blends on the ultrasonic power density (UPD) generated during the extraction of phenolic compounds from Mango peel, using an ultrasonic-assisted extraction (UAE) and a conventional solvent extraction (CSE). A simplex centroid mixture design and a special cubic regression model were used to evaluate the total phenolic compounds (TPC), antioxidant activity (AA) and ultrasonic intensity (UI) as a function of the solvents proportions. The greatest TPC was obtained with the ethanol–acetone blend (60–40%) for CSE (205.08mg GAE/100g DM) and UAE (1493.01mg GAE/100g DM). Likewise, an increase (avg. 630%) was observed in TPC when the ultrasound was applied for all solvents and their blends. The TPC showed a good correlation (r=0.81) with the UPD, with higher UPD resulting in larger amounts of TPC extracted. Nevertheless, for the ethanol–acetone blend there was a decrease of 14.2% of the AA for the UAE, which could be due to the sonochemical reactions taking place at the high UPD achieved for that blend. The results of this work indicate that the solvent composition and use of ultrasound should be carefully selected to achieve the desired extraction objectives.

Effect of Solvent Composition on the Extraction of Phenolic Compounds and Antioxidant Capacity of Bacaba Juice (Oenocarpus bacaba Mart.)

Studying the phytochemical composition and bioactive potential of underexploited species is of great importance for promoting their valorization and for broadening the range of sources of bioactive compounds in the human diet. In this study, we used a simplex centroid mixture design to determine an optimal extraction solvent composition (using mixtures of water, acetone, and ethanol) for maximizing the extraction of phenolic compounds and the antioxidant capacity of bacaba juice (Oenocarpus bacaba). The compounds were identified and quantified by high-performance liquid chromatography coupled with mass spectrometry. Taxifolin, orientin, and isoorientin were identified and quantified in bacaba juice for the first time. It was possible to evidence the high potentiality of the bacaba regarding the contents of syringic, vanillic, ferulic, 3,4-dihydroxybenzoic acids, and orientin, which have significantly contributed to the antioxidant capacity of the extracts. Thus, this study indicates that bacaba juice can provide antioxidant compounds. Moreover, the determined extraction conditions can be applied for obtaining extracts rich in potential bioactive properties for food and pharmaceutical applications.

A statistical design optimization study of a multi-chamber reactive type silencer using simplex centroid mixture design

This study aims to optimize the acoustic performance of a silencer with baffles having extension tubes. It considers the position, the number and the extension geometry of the baffles as design variables and sound transmission loss as the response variable to be optimized. The finite element analysis software ABAQUS is used to compute the response values for different combinations of design variables. The statistical design of the experiments provides a mathematical framework for such computer design optimization studies with multiple design variables. Yet, it has not been used for design optimization of silencers in the literature. In this study, simplex centroid mixture designs, a type of response surface method, are used in the statistical design of experiments. They can provide faster convergence on the optimization problem. The design involves one, two and three baffles with different positions and extension tube lengths. The outcome of this study indicates that obtaining ABAQUS software solutions at design points for each baffle number allows constructing nonlinear regression equations expressing the response variable as a function of the design variables. The equations obtained are then used to compute optimal values. Further evaluation of these equations indicates that better sound transmission loss values are obtained when the baffle number is increased, and the lengths of the extension tubes are set at high values. Moreover, it is possible to use the statistical experimental design approach implemented in this study for other types of silencers with different baffle geometries and design variables.

Enhancing of Copper (II) Adsorption Efficiency by Mixing Plantain and Orange Peelings as Bio-Sorbent Support

The present study focuses on the valorization of plantain and orange peels in the field of water treatment contaminated by heavy metals, especially copper (II). To carry out this study, simplex centroid mixture design was used to determine best mixture from plantain and orange peelings through iodine number, specific surface area and point of zero charge. The influence of contact time, adsorbed amount, bio-sorbent mass, medium temperature and medium pH were equally investigated from best mixture and thermodynamic parameters were also carried out. The results show that R2, Absolute Average Deviation (AAD), biais factor and exactitude factor are respectively 89.39%, 0.01, 1.00 and 1.00 for iodine number, 94.13%, 0.03, 0.99 and 0.99 for Specific surface Area (SA) and 97.05%, 0.01, 1.00 and 1.00 for Point of Zero Charge (PZC). These values are in agreement with the interval set to validate the model. Besides, desirability is 1.00, 0.80 and 0.77 respectively for specific surface area, iodine number and zero point of charge and closer to 1. The best mixture from this study is 90% of orange peelings proportion and 10% of plantain peelings proportion. The results also show that contact time is 10 min, adsorbed amount of copper ions (II) increases with initial copper concentration, bio-sorbent mass and medium temperature. Adsorbed amount increases for pH between 3 and 5 and decreases for pH greater than 5. The efficiency of Copper (II) removal is about 88.11% for the native bio-sorbent and 97.04% for activated bio-sorbent. These efficiencies are higher than those obtained from orange and plantain peelings taken individually and are ranged between 70 and 85%. The pseudo second order describes perfectly the adsorption mechanism followed by intra particular diffusion while the isotherm adsorption is well described by Langmuir and Freundlich model. The thermodynamic parameters indicate that adsorption reaction is spontaneous, reversible and endothermic.

Artificial neural network employment for element determination in Mugil cephalus by ICP OES in Pontal Bay, Brazil.

Fish are important sources of protein, making them very significant in the human diet. Although the consumption of this food is beneficial for health, it is essential that the product does not contain inorganic components above the limits recommended by the current legislation. Therefore, a method for determination of elements in fish (Mugil cephalus) samples was optimized. A simplex centroid mixture design with restriction was applied for optimization of the acid digestion of samples in an open system under reflux in order to evaluate the best ratio between the reagents HNO3, H2O2 and H2O. The results indicated that more intense analyte signals were obtained when a mixture containing 3.6 mL of HNO3 (65% v/v), 0.4 mL of H2O2 (30% v/v) and 6.0 mL of H2O was used. The accuracy of the method was assessed with a CRM of oyster tissue (NIST 1566b). The method presented relative standard deviations (RSDs) of 3.54%; 3.82%; 4.81% and 3.50% for Zn, Fe, Cu and S, respectively. The detection limits were 0.002 mg kg-1 for Cu and Zn and 0.02 mg kg-1 for Fe and S. The proposed method was applied for the determination of Zn, Fe, Cu and S in fish samples. A Kohonen Self-Organizing Map (KSOM) with K-means implementation was applied to better delimit the boundary between groups and the spatial and temporal influence on how concentrations of the chemical elements were perceived. To verify the separation, the Davies-Bouldin and Silhouette indices were used, obtaining 0.5374 and 0.8541, respectively, indicating satisfactory separation.

Mixing of menthol-based hydrophobic deep eutectic solvents as a novel method to tune their properties

Due to the limited number and water-immiscibility of hydrophobic deep eutectic solvents (hDESs), new methods of expanding the repertoire and tuning the properties of these solvents are required. Here, menthol was combined with organic acids or alcohols to produce nine hDESs, all of which were freely miscible with each other. Three of the hDESs, vis. ML, MB, and MT (containing menthol combined with levulinic acid, 1,3-butanediol, and tert-butanol, respectively) were selected as the least to most non-polar solvents. Two and three of these hDESs were mixed at equal volume ratios to produce three binary mixtures (namely, LB, BT, and LT) and one ternary mixture (LBT), respectively, via simplex centroid mixture design. The properties of these mixtures as extraction solvents were characterized using Ginko biloba leaves (GBLs) as a model plant. Mixtures containing ML exhibited high capability for extracting phenolic compounds and flavonoids, comparable to that of methanol and 70% methanol. They provided wide extraction coverage with reliability, as evidenced by the high numbers of variables with coefficients of variation within 30%. The liquid chromatography-mass spectrometry-based profiles of 47 secondary metabolites showed that MB and BT presented similar results to methanol and 70% methanol based on heatmap and hierarchical cluster analysis. This study shows that combining the menthol-based hDESs furnishes properties that differ from those of the individual components; in this way, the repertoire of hDESs can be expanded, and therefore, the hDESs and their mixtures can be used as green task-specific extraction solvents as substitutes for volatile organic solvents.

Microencapsulation optimization of cinnamon essential oil in the matrices of gum Arabic, maltodextrin, and inulin by spray‐drying using mixture design

AbstractA simple centroid mixture design was used to optimize the ratio of the wall materials for the production of the cinnamon essential oil microcapsules by spray‐drying. Gum Arabic (GA), maltodextrin (MD), and inulin (IN) were used as wall materials. Four parameters were evaluated as responses, containing the surface cinnamaldehyde, the encapsulation efficiency of cinnamaldehyde, the release of cinnamaldehyde (RC), and powder recovery (PR). The cinnamon essential oil was purely formed of cinnamaldehyde (about 99.96%), based on results obtained from the gas chromatography device. The multiple response optimization analysis showed that the optimum compound concentration for walls will be 27.87% wt/wt GA, 27.59% MD, and 44.53% IN. It can be concluded that the optimal compound was suitable to the RC in the mouth medium due to its Tg. The microscopy images of the optimal compound showed a smooth surface, spherical, and slight crack in the microparticles. Furthermore, the optimum compound improved the stability of antioxidant activity compared to the pure oil during 30 days storage. It was observed that the Fickian diffusion was the main mechanism involved in the release process of the microencapsulated cinnamon essential oil in the mouth medium.Practical ApplicationsIn the food industry, the major aromatic components utilized are essential oils, synthetic flavoring agents, and natural oleoresin. The key constituent of cinnamon essential oil is cinnamaldehyde. Cinnamaldehyde is often used as a flavoring agent, but its importance as a natural antimicrobial, antioxidant, and antiseptic agent has recently been established. The knowledge of encapsulation techniques allows the control of the bioactive components, the release time, and the dosage of essential oil in the structure of the food. Moreover, the encapsulation of essential oils helps to reduce the oxidation of process by exposure to the environment, increasing the shelf life and the solubility. The results of this work lead to the use of flavored components for implementation in similar products, thereby improving their flavor.

An In Situ Gelling System for the Local Treatment of Inflammatory Bowel Disease (IBD). The Loading of Maqui (Aristotelia Chilensis) Berry Extract as an Antioxidant and Anti-Inflammatory Agent.

The aim of the present work was the development of an innovative in situ gelling system, to be applied on the mucosa of the distal colon via rectal route. The system consisted of three polymers having different functions: gellan (GG), able to jellify in presence of ions; methylcellulose (MC), a thermosensitive polymer with a gelation temperature close to 50 °C; and hydroxypropylcellulose (HPC), a mucoadhesive polymer. The three polymers were able to act synergistically, increasing the permanence of the vehicle on the mucosa and forming a protective gel layer. A DoE approach, “simplex centroid mixture design,” was used to identify the optimal quantitative composition of the vehicle. The response variables considered were: vehicle viscosity at room temperature; increase in vehicle viscosity on increasing temperature (from room to physiological value) and upon dilution with simulated colonic fluid (SCF); and viscoelastic behavior, thixotropic area, and mucoadhesion properties of the gel formed at 37 °C upon dilution in SCF. The optimized vehicle was loaded with maqui berry extract (MBE), known for its antioxidant and anti-inflammatory properties. MBE loading (0.5% w/w) into the vehicle improved rheological and mucoadhesive properties of the formulation. Both MBE and the optimized vehicle were not cytotoxic towards human fibroblasts and Caco-2 cells. Moreover, the optimized vehicle did not affect MBE antioxidant properties.

Sequential optimization and large scale production of lipase using tri-substrate mixture from Aspergillus niger MTCC 872 by solid state fermentation

Abstract Tri-substrate mixture of Prosopis juliflora (PJ), red gram husk (RGH) and cotton seed cake (CSC) has been studied for the production of lipase (E.C. 3.1.1.3) using Aspergillus niger MTCC 872 in solid state fermentation. Simplex centroid mixture design (SCMD) was implemented to optimize the tri-substrate mixture composition consisting of PJ, RGH and CSC. Mixture taken in the ratio of 6.66:1.66:1.66 for PJ:RGH:CSC has shown highest lipase activity of 212.20 ± 6.36 U/gds at 30 °C, 7 pH and 70 % initial moisture content (v/w). Sequential optimization of physical parameters was done using the central composite face-centered design (CCFD). The optimum mixture composition has shown the highest lipase activity of 269.87 ± 8.09 U/gds at 35 °C, 7 pH and 70 % initial moisture content (v/w). ANOVA analysis for SCMD and CCFD confirms the model’s significance with R2 values of 0.9989 and 0.968. A 1.27 fold increased lipase activity was obtained after physical parameters optimization. Large scale production using 1 kg substrate was carried out in tray bioreactor with different bed heights and the highest lipase activity of 208.79 ± 6.26 U/gds was obtained. This study signifies the enhancement of lipase production using substrate PJ for lipase production along with the other agricultural residues.

Characterization of Composite Edible Films Based on Pectin/Alginate/Whey Protein Concentrate.

Edible films and coatings gained renewed interest in the food packaging sector with polysaccharide and protein blending being explored as a promising strategy to improve properties of edible films. The present work studies composite edible films in different proportions of pectin (P), alginate (A) and whey Protein concentrate (WP) formulated with a simplex centroid mixture design and evaluated for physico-chemical characteristics to understand the effects of individual components on the final film performance. The studied matrices exhibited good film forming capacity, except for whey protein at a certain concentration, with thickness, elastic and optical properties correlated to the initial solution viscosity. A whey protein component in general lowered the viscosity of the initial solutions compared to that of alginate or pectin solutions. Subsequently, a whey protein component lowered the mechanical strength, as well as the affinity for water, as evidenced from an increasing contact angle. The effect of pectin was reflected in the yellowness index, whereas alginate and whey protein affected the opacity of film. Whey protein favored higher opacity, lower gas barrier values and dense structures, resulting from the polysaccharide-protein aggregates. All films displayed however good thermal stability, with degradation onset temperatures higher than 170 °C.

Optimization of rice bread formulation by mixture design and relationship of bread quality to flour and dough attributes

The bread making aptitude of five rice flours (native and gelatinized) and five gluten substitutes (GS) were prior tested and the best ingredients for mixture design were set. Native flour with a wide distribution of particle size, xanthan gum (XG), guar gum (GG) and sodium alginate (SA) were selected due to their good performance. The effect of formulation on bread volume (BV), cell area fraction (CAF) of breadcrumb and dough rheology was determined by using a simplex centroid mixture design with constrain (2.1 g of GS/100 g of flour). A significant effect of formulation on viscoelasticity of dough was observed. A non-linear relationship between BV and dough viscosity was found with maximum BV at 60000 Pa⋅s. The optimum formulation, from XG to GG mass ratio of 0.71, yields maximum values of BV (4.07 ml/g of flour) and CAF (29%); optimum bread presented good textural attributes and a slightly toasted crust.

Development of gluten-free batter from three Thai rice cultivars and its utilization for frozen battered chicken nugget.

Rice flour based batter (RFBB) formulations were developed for deep-fat fried chicken nugget application. Ten combinations of the waxy rice (Rice Division6, RD6), low apparent amylose content (AAC) (Khao Dawk Mali105, KDML105) and high AAC rice (Rice Division31, RD31) were prepared according to the ten-point augmented simplex centroid mixture design. The AAC of RFBB samples ranged from 5.93 to 29.46% and contained less than 1ppm of gluten content. After mixing rice flour (RF) with water at the ratio of 1:1.3, the decreased of apparent viscosities was found. Result showed that wheat flour based batter (WFBB) had higher wet pick-up (51.97%) than unblended RFBB (29.05-44.82%). However, the wet pick-up value was improved upon mixing three types of RF at various ratios. The RFBB formulas which contained high amount of dry-milled RD31 flour were more lightness and redness than others. These results suggested that the combination of RD6:KDML105:RD31 at the ratio of 16.7:16.7:66.7 provided the desirable RFBB as it contained similar AAC to WFBB. In addition, the coated chicken nugget with this sample tended to retain moisture content in both crust and core regions, and reduce oil content due to better oil resistance of RF than wheat flour.

Assessment of some attributes of unripe cooking banana (Cardaba Musa ABB), pigeon pea (Cajanus cajan) and orange fleshed sweet potato (Ipomoea batatas) flour blends for use as complementary feeding

This study assessed the nutrient composition, physicochemical, functional and sensory properties of flour blends prepared from cooking banana, pigeon pea and orange fleshed sweet potato flour blends for use as complementary food. Fourteen blends were generated using the simplex centroid mixture design. All data obtained were subjected to analysis of variance and the mean values were separated using Duncan’s Multiple Range Test. The protein, crude fibre, crude fat, ash and carbohydrate of the blends were significantly (p≤0.05) different with values ranging from 10.60-21.65%, 0.36-1.24%, 1.2-1.43%, 0.77 – 2.25% and 65.86 -75.36%, respectively. There was no significant (p≤0.05) difference in the moisture content, total carotenoid content and pH value of the blends. The L* value (40.77 to 45.25) showed no significant (p≤0.05) difference while the redness (a*) and yellowness (b*) value were significantly (p≤0.05) different with values ranging from 2.32 – 4.59 and 11.88 – 15.88 respectively. There was a significant (p≤0.05) difference in the bulk density (0.73 – 0.78 g/ml), water absorption capacity (122.05-178.10%), swelling power (6.21 – 8.48%) and solubility (3.77-7.30%) values. Gruels obtained from the flour blends had sensory scores of above 6.00 (on a 9-point Hedonic scale), signifying high acceptability for all the sensory attributes evaluated.

Biologically active compounds from white and black mustard grains: An optimization study for recovery and identification of phenolic antioxidants

This work aimed to determine the best solvent mixture for extraction of antioxidant compounds from two varieties of mustard grains (white - Sinapsis alba and black - Brassica nigra) using a simplex centroid mixture design. For this, the experiments were performed using pure, binary or ternary solvent mixtures containing water, acetone and methanol. All extracts were analyzed for total phenolic compounds (TPC), DPPH- and ABTS-radical scavenging activities. The binary mixture of water and acetone, in equal proportions, was the best solvent combination to obtain an extract with higher TPC content and antioxidant properties. The extraction of antioxidant compounds with water/acetone resulted in increases of 23-folds for TPC, 48-folds for ABTS and 25-folds for DPPH compared to pure acetone. For black mustard, the extract obtained with this solvent combination was 19-, 31- and 27-folds higher than that produced with pure acetone for TPC, ABTS and DPPH, respectively. Additionally, the bioactive compounds from the mustard extracts were identified by UHPLC-MS/MS, as follows: 3,4-di-hydroxybenzoic acid, ferulic acid and sinapic acid in white mustard and 3,4-di-hydroxybenzoic acid, ferulic acid, sinapic acid and rutin in black mustard. This work reported for the first time an optimization study for recovery of phenolic compounds from mustard grains in order to obtain extracts with better antioxidant properties.

Optimization of Emulsifier and Stabilizer Concentrations in a Model Peanut-Based Beverage System: A Mixture Design Approach.

Colloidal stability as well as physicochemical and rheological properties are among the critical determinants of the sensory quality of beverages. The present study investigated the effects of lecithin, xanthan gum, propylene glycol alginate, and their combinations on the colloidal stability and physicochemical/rheological properties of a model peanut-based beverage. A simplex centroid mixture design was applied, and the visual stability, centrifuge stability, physicochemical properties (soluble solids, pH, water activity, color), and rheological parameters (flow behavior and viscosity) of the samples were determined. All the evaluated parameters were significantly affected (p < 0.05) by the type and quantity of emulsifier or stabilizer used. At the 0.5% total usage level, the optimum stabilizer and emulsifier combination was that of 66% xanthan gum and 34% lecithin. A further increase of lecithin in the mixture caused a decrease in the colloidal stability of the sample. Irrespective of emulsifier and stabilizer type and quantity, all samples exhibited shear-thinning flow behavior, with samples containing xanthan gum being more pseudoplastic than the others. The prediction model for the visual stability index found in this study may be used by the industry to formulate similar beverages for better colloidal stability.

Evaluation of Functional and Pasting Properties of Blends of High Quality Cassava, Defatted Tigernut and Chicken Feet Composite Flour

Annually, the chicken processing industries generate significant quantities of chicken feet which are often discarded because they are undervalued and underutilized. However, this study was done to add value to chicken feet by evaluating the functional and pasting properties of high quality cassava-defatted tigernut-chicken feet composite blend. Tigernut seeds and chicken feet were processed into flour respectively. Simplex centroid mixture design was used to generate fourteen (14) blends based on the HQCF (70-90%), CFF (5-45%) and DTNF (5-45%). Standard laboratory procedures were used to determine the functional properties (swelling power (SP), water absorption capacity (WAC), oil absorption capacity (OAC), bulk density (BD), least gelation concentration (LGC) and pasting properties of the blends. Results showed significant differences (P<0.05) in the functional properties of composite flour in terms of swelling power, water absorption capacity (WAC), oil absorption capacity (OAC), bulk density (BD) and least gelation concentration (LGC) ranging from 3.83-5.72 (g/g), 90.43-110.40 (%), 87.86-107.23 (%), 0.51-0.75 (g/ml), and 2.00-10.00 (%w/v) respectively. The pasting profile (peak viscosity, trough, breakdown viscosity, final viscosity, setback viscosity, peak time and peak temperature) of the high quality cassava-defatted tigernut-chicken feet flour blends had significant differences (P<0.05) with values ranging from 76.50-434(RVU), 52.17 – 157.09 (RVU), 20.33 -262.96 (RVU), 76.71-215.13 (RVU), 24.55-59.25 (RVU), 4.17-4.90 (Min) and 94.28-95.88(0C). As CFF and DTNF inclusion increased, the peak, trough, breakdown, final and setback viscosities decreased. This study revealed that chicken feet flour could be a good food ingredient in food formulations such as short crust pastries, sauces, weaning foods and gravies to reduce their paste thickness.

Preformulation studies of finasteride to design matrix systems for topical delivery

A preformulation study with finasteride (FIN) was conducted to enable the development of a topical matrix system to treat androgenic alopecia. The compatibility of the drug with hidroxypropyl-β-cyclodextrin (HPβCD) and the hydrophilic polymers Klucel EXF (KLU) and Soluplus (SOL) were evaluated according to a simplex centroid mixture design. An extensive analytical arsenal was used to encompass the stability of the drug in the different mixtures. The selected excipients showed to have intense thermal interaction with FIN, which was dependent on the composition of the sample, shifting FIN melting peak to reduced temperatures along with the decrease of its associated enthalpy. The mixture design allowed measuring the interactions between components, showing that KLU enhanced the ability of the drug to form inclusion complexes with HPβCD, while SOL exhibited the opposite effect. The stability of samples was preserved even after a thermal treatment used to simulate pharmaceutical processing. Indeed, no drug content decaying was observed, which corroborates the chemical stability of the systems as indicated by thermogravimetry, chromatographic, morphological and spectroscopic assays. The original crystalline phase of the drug (orthorhombic form I) did not change after the heating treatment of the samples, demonstrating its physical stability. Thus, these series of experiments may guide the development of delivery systems for topical use of FIN, showing which combinations and proportions of components can lead to better results in terms of stability and drug delivery.

Inhibitory effect of mixture herbs/spices on formation of heterocyclic amines and mutagenic activity of grilled beef

ABSTRACTNatural antioxidants in spices and herbs have attracted considerable attention as potential inhibitors against the formation of mutagenic heterocyclic amines (HCAs) in heat-processed meat. In this study, the inhibitory activity of four spices/herbs and their mixtures on HCAs formation in grilled beef were examined. A simplex centroid mixture design with four components comprising turmeric, curry leaf, torch ginger and lemon grass in 19 different proportions were applied on beef samples before grilling at 240 ºC for 10 min. The HCAs were extracted from the samples using solid phase extraction (SPE) method and analysed using Liquid chromatography mass spectrometry LC-MS/MS. All spices/herbs in single or mixture forms were found to reduce total HCA concentrations in marinated grilled beef ranging from 21.2% for beef marinated with curry leaf to 94.7% for the combination of turmeric and lemon grass (50:50 w/w). At the optimum marinade formula (turmeric: lemon grass 52.4%: 47.6%), concentration of 2-amino-3-methylimidazo[4,5-f]quinolone (IQ), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), Harman, Norharman and AαC were 2.2, 1.4, 0.5, 2.8 and 1.2 ng/g, respectively. The results of the mutagenic activity demonstrated that this optimised marinade formula significantly (p < 0.05) diminished mutagenicity of marinated grilled beef in bacterial Ames test.