Nanoparticle-coated organic-inorganic microparticles: experimental design and gastrointestinal tolerance evaluation

The influences of the spray-drying parameters and the type of nanoparticles (nanocapsules or nanospheres) on the characteristics of nanoparticle-coated diclofenac-loaded microparticles were investigated by using a factorial design 3². Gastrointestinal tolerance following oral administration in rats was evaluated. Formulations were selected considering the best yields, the best encapsulation efficiencies and the lowest water contents, presenting surfaces completely coated by nanostructures and a decrease in the surface areas in relation to the uncoated core. In vitro drug release demonstrated the influence of the nanoparticle-coating on the dissolution profiles of diclofenac. Nanocapsule-coated microparticles presented a protective effect on the gastrointestinal mucosa.

Evaluation of the influence of base and alkyl bromide on synthesis of pyrazinoic acid esters through fatorial design

Pyrazinoic acid esters have been synthesized as prodrugs of pyrazinoic acid. In the literature, its preparation is reported through the reaction of pyrazinoyl chloride with alcohols and the reaction with DCC/DMAP. In this work, it is reported a 2² factorial design to evaluate the preparation of these esters through the substitution of alkyl bromides with carboxylate anion. The controlled factors were alkyl chain length of bromides (ethyl and hexyl) and the used base (triethylamine and DBU). Results revealed that the used base used has significant effect on yield, and alkyl bromide used has neither significant influence, nor its interaction effect with base.

Use of experimental design in the optimisation of a solid phase preconcentration system for Cobalt determination by GFAAS

In this work is proposed a solid phase preconcentration system of Co2+ ions and its posterior determination by GFAAS in which fractional factorial design and response surface methodology (RSM) were used for optimization of the variables associated with preconcentration system performance. The method is based on cobalt extraction as a complex Co2+-PAN (1:2) in a mini-column of polyurethane foam (PUF) impregnated with 1-(2-pyridylazo)-naphthol (PAN) followed by elution with HCl solution and its determination by GFAAS. The chemical and flow variables studied were pH, buffer concentration, eluent concentration and preconcentration and elution flow rates. Results obtained from fractional factorial design 2(5-1) showed that only the variables pH, buffer concentration and interaction (pH X buffer concentration) based on analysis of variance (ANOVA) were statistically significant at 95% confidence level. Under optimised conditions, the method provided an enrichment factor of 11.6 fold with limit of detection and quantification of 38 and 130 ng L-1, respectively, and linear range varying from 0.13 to 10 µg L-1. The precision (n = 9) assessed by relative standard deviation (RSD) was respectively 5.18 and 2.87% for 0.3 and 3.0 µg L-1 cobalt concentrations.

Statistical isomorphism of three-level factional factorial designs

From a statistician's standpoint, the interesting kind of isomorphism for fractional factorial designs depends on the statistical application. Combinatorially isomorphic fractional factorial designs may have different statistical properties when factors are quantitative. This idea is illustrated by using Latin squares of order 3 to obtain fractions of the 3(3) factorial. design in 18 runs.

Some theory for constructing minimum aberration fractional factorial designs

Minimum aberration is the most established criterion for selecting a regular fractional factorial design of maximum resolution. Minimum aberration designs for n runs and n/2 less than or equal to m < n factors have previously been constructed using the novel idea of complementary designs. In this paper, an alternative method of construction is developed by relating the wordlength pattern of designs to the so-called 'confounding between experimental runs'. This allows minimum aberration designs to be constructed for n runs and 5n/16 less than or equal to m less than or equal to n/2 factors as well as for n/2 less than or equal to m < n.

Use of Experimental Design for the Optimization of the Production of New Secondary Metabolites by Two Penicillium Species

A fractional factorial design approach has been used to enhance secondary metabolite production by two Penicillium strains. The method was initially used to improve the production of bioactive extracts as a whole and subsequently to optimize the production of particular bioactive metabolites. Enhancements of over 500% in secondary metabolite production were observed for both P. oxalicum and P. citrinum. Two new alkaloids, citrinalins A (5) and B (6), were isolated and identified from P. citrinum cultures optimized for production of minor metabolites.

Design/Evaluation of A Methodology For Performance Optimization Of Indexable Carbide Inserts

In this project, two broad facets in the design of a methodology for performance optimization of indexable carbide inserts were examined. They were physical destructive testing and software simulation.For the physical testing, statistical research techniques were used for the design of the methodology. A five step method which began with Problem definition, through System identification, Statistical model formation, Data collection and Statistical analyses and results was indepthly elaborated upon. Set-up and execution of an experiment with a compression machine together with roadblocks and possible solution to curb road blocks to quality data collection were examined. 2k factorial design was illustrated and recommended for process improvement. Instances of first-order and second-order response surface analyses were encountered. In the case of curvature, test for curvature significance with center point analysis was recommended. Process optimization with method of steepest ascent and central composite design or process robustness studies of response surface analyses were also recommended.For the simulation test, AdvantEdge program was identified as the most used software for tool development. Challenges to the efficient application of this software were identified and possible solutions proposed. In conclusion, software simulation and physical testing were recommended to meet the objective of the project.

Optimization of an amperometric biosensor for the detection of hepatitis C virus using fractional factorial designs

Fractional factorial design and factorial with center point design were applied to the development of an amperometric biosensor for the detection of the hepatitis C virus. Biomolecules were immobilized by adsorption on graphite electrodes modified with siloxane-poly(propyleneoxide) hybrid matrix prepared using the sol-gel method. Several parameters were optimized, such as the streptavidin concentration at 0.01 mg mL(-1) and 1.0% bovine serum albumin, the incubation time of the electrodes in the complementary DNA solution for 30 minutes and a 1: 1500 dilution of the avidin-peroxidase conjugate, among others. The application of chemometric studies has been efficient, since the best conditions have been established with a restricted number of experiments, indicating the influence of different factors on the system.

Optimum design of experiments for statistical inference

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

UV filters in water samples: Experimental design on the SPE optimization followed by GC-MS/MS analysis

Esse estudo descreve o desenvolvimento e otimização de um método de extração em fase solida (SPE) para análise dos filtros ultravioletas (UV): benzofenona-3 (BP-3), etilhexil salicilato (ES), etilhexil metoxinamato (EHMC) e octocrileno (OC) em matrizes ambientais. Um planejamento fatorial fracionário (PFF) 25-1 foi empregado na avaliação das variáveis significativas do método de extração. As condições experimentais otimizadas da avaliação estatística foram: capacidade do cartucho de 500 mL, eluente acetato de etila, metanol como solvente de lavagem (10% em água, v/v) and volume do eluente de 3 × 2 mL e pH 3. Os parâmetros analíticos avaliados foram satisfatõrios, apresentando linearidade de 100 a 4000 ng L -1, recuperaç ões para os quatro níveis de fortificação (Limite de Quantificação do Método, 200, 1000 e 2000 ng L-1) entre 62 e 107% com desvio padrão relativo menor que 14%. Os limites de quantificação foram encontrados na faixa de ng L-1, variando entre 10 e 100 ng L-1. O método proposto foi aplicado para a determinação dos quatro filtros UV em amostras de águas naturais. This study describes the development and optimization of a solid-phase extraction (SPE) method for analysis of ultraviolet (UV) filters, benzophenone-3 (BP-3), ethylhexyl methoxycinnamate (EHMC), ethylhexyl salicylate (ES) and octocrylene (OC), in environmental matrices. A 25-1 fractional factorial design (FFD) was used to evaluate the significant variables for the extraction method. The optimized experimental conditions determined from the statistical evaluation were: breakthrough volume of 500 mL, eluent of ethyl acetate, wash solvent of methanol (10% in water, v/v), eluent volume of 3 × 2 mL and pH 3. The evaluated analytical parameters were satisfactory for the analytes and showed linearity between 100 and 4000 ng L-1, recoveries for four fortification levels (Method Quantification Limit, 200, 1000 and 2000 ng L-1) were between 62 and 107% with relative standard deviations less than 14%. Limits of quantification were in the ng L-1 range and were between 10 and 100 ng L-1. The proposed method was used to analyze four UV filters in natural water samples. ©2013 Sociedade Brasileira de Química.

Optimization of in situ derivatization SPME by experimental design for GC-MS multi-residue analysis of pharmaceutical drugs in wastewater

This paper presents the development of a procedure, which enables the analysis of nine pharmaceutical drugs in wastewater using gas chromatography-mass spectrometry (GC-MS) associated with solid-phase microextraction (SPME) for the sample preparation. Experimental design was applied to optimize the in situ derivatization and the SPME extraction conditions. Ethyl chloroformate (ECF) was employed as derivatizing agent and polydimethylsiloxane-divinylbenzene (PDMS-DVB) as the SPME fiber coating. A fractional factorial design was used to evaluate the main factors for the in situ derivatization and SPME extraction. Thereafter, a Doehlert matrix design was applied to find out the best experimental conditions. The method presented a linear range from 0.5 to 10 mu g/L, and the intraday and interday precision were lower than 16%. Applicability of the method was verified from real influent and effluent samples of a wastewater treatment plant, as well as from samples of an industry wastewater and a river.

Influence of temperature, light and nutrients on the growth rates of the macroalga Gracilaria domingensis in synthetic seawater using experimental design

In the present study, the daily relative growth rates (DRGR, in percent per day) of the red macroalga Gracilaria domingensis in synthetic seawater was investigated for the combined influence of five factors, i.e., light (L), temperature (T), nitrate (N), phosphate (P), and molybdate (M), using a statistical design method. The ranges of the experimental cultivation conditions were T, 18-26A degrees C; L, 74-162 mu mol photons m(-2) s(-1); N, 40-80 mu mol L-1; P, 8-16 mu mol L-1; and M, 1-5 nmol L-1. The optimal conditions, which resulted in a maximum growth rate of a parts per thousand yen6.4% d(-1) from 7 to 10 days of cultivation, were determined by analysis of variance (ANOVA) multivariate factorial analysis (with a 2(5) full factorial design) to be L, 74 mu mol photons m(-2) s(-1); T, 26A degrees C; N, 80 mu mol L-1; P, 8 mu mol L-1; and M, 1 nmol L-1. In additional, these growth rate values are close to the growth rate values in natural medium (von Stosch medium), i.e., 6.5-7.0% d(-1). The results analyzed by the ANOVA indicate that the factors N and T are highly significant linear terms, X (L), (alpha = 0.05). On the other hand, the only significant quadratic term (X (Q)) was that for L. Statistically significant interactions between two different factors were found between T vs. L and N vs. T. Finally, a two-way (linear/quadratic interaction) model provided a quite reasonable correlation between the experimental and predicted DRGR values (R (adjusted) (2) = 0.9540).

Spray Congealing of Pharmaceuticals: Study on Production of Solid Dispersions Using Box-Behnken Design

This work aimed at evaluating the spray congealing method for the production of microparticles of carbamazepine combined with a polyoxylglyceride carrier. In addition, the influence of the spray congealing conditions on the improvement of drug solubility was investigated using a three-factor, three-level Box-Behnken design. The factors studied were the cooling air flow rate, atomizing pressure, and molten dispersion feed rate. Dependent variables were the yield, solubility, encapsulation efficiency, particle size, water activity, and flow properties. Statistical analysis showed that only the yield was affected by the factors studied. The characteristics of the microparticles were evaluated using X-ray powder diffraction, scanning electron microscopy, differential scanning calorimetry, and hot-stage microscopy. The results showed a spherical morphology and changes in the crystalline state of the drug. The microparticles were obtained with good yields and encapsulation efficiencies, which ranged from 50 to 80% and 99.5 to 112%, respectively. The average size of the microparticles ranged from 17.7 to 39.4 mu m, the water activities were always below 0.5, and flowability was good to moderate. Both the solubility and dissolution rate of carbamazepine from the spray congealed microparticles were remarkably improved. The carbamazepine solubility showed a threefold increase and dissolution profile showed a twofold increase after 60 min compared to the raw drug. The Box-Behnken fractional factorial design proved to be a powerful tool to identify the best conditions for the manufacture of solid dispersion microparticles by spray congealing.

Design of nest access grids and perches in front of the nests: Influence on the behavior of laying hens.

In aviary systems for laying hens, it is important to provide suitable nest access platforms in front of the nests, allowing hens to reach and explore each of the nests easily. This access platform is needed to achieve good nest acceptance by the hens and thereby prevent mislaid eggs. In the present experiment, the behavior of hens using 2 different nest access platforms, a plastic grid and 2 wooden perches, was examined. Furthermore, the nests were placed on both sides of the aviary rack (corridor side and outdoor side), either integrated into the aviary rack itself (integrated nest; IN) or placed on the walls of the pens (wall nest; WN), resulting in a 2 × 2 factorial design Four thousand five hundred white laying hens were housed in 20 test pens. The eggs in the nests and mislaid eggs were collected daily, and the behavior of hens on the nest accesses was filmed during wk 25 and 26, using focal observation and scan sampling methods. More balancing, body contact, and agonistic interactions were expected for nests with perches, whereas more walking and nest inspections were expected for nests with grids. There were more mislaid eggs and balancing found in pens equipped with nests with wooden perches. More agonistic interactions and balancing, less standing, and a longer duration of nest inspection were found with the WN compared with the IN. Interactions between platform design and position of the nests were found for duration of nest visits, body contact, and walking, with the highest amount for WN equipped with plastic grids. Nests on the corridor side were favored by the hens. Nest-related behaviors, such as nest inspection, standing, and walking, decreased over time as did the number of hens on the nest accesses, whereas sitting increased. These results indicate that the hens had more difficulties in gripping the perches as designed. The lower number of hens on the nest access platforms in front of IN may be due to a better distribution around nests and tier changes within the aviary rack. Based on these results, grids rather than perches provide for improved nesting behavior.

Factorial designs: an overview with applications to orthodontic clinical trials.

Factorial designs for clinical trials are often encountered in medical, dental, and orthodontic research. Factorial designs assess two or more interventions simultaneously and the main advantage of this design is its efficiency in terms of sample size as more than one intervention may be assessed on the same participants. However, the factorial design is efficient only under the assumption of no interaction (no effect modification) between the treatments under investigation and, therefore, this should be considered at the design stage. Conversely, the factorial study design may also be used for the purpose of detecting an interaction between two interventions if the study is powered accordingly. However, a factorial design powered to detect an interaction has no advantage in terms of the required sample size compared to a multi-arm parallel trial for assessing more than one intervention. It is the purpose of this article to highlight the methodological issues that should be considered when planning, analysing, and reporting the simplest form of this design, which is the 2 × 2 factorial design. An example from the field of orthodontics using two parameters (bracket type and wire type) on maxillary incisor torque loss will be utilized in order to explain the design requirements, the advantages and disadvantages of this design, and its application in orthodontic research.