Formulation and Optimization of Diclofenac Sodium Loaded Ethylcellulose Nanoparticles

Abstract Design of experiment (DoE) is a useful time and cost-effective tool for analyzing the effect of independent variables on the formulation characteristics. The aim of this study is to evaluate the effect of the process variables on the characteristics involved in the preparation of Diclofenac Sodium (DC) loaded ethylcellulose (EC) nanoparticles (NP) using Central Composite Design (CCD). NP were prepared by W/O/W emulsion solvent evaporation method. Three factors were investigated (DC/EC mass ratio, PVA concentration, homogenization speed) in order to optimize the entrapment efficiency (EE) and the particle size of NP. The optimal formulation was characterized by Fourier Transform Infrared (FTIR), Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), and in vitro release. Optimized formulation showed an EE of 49.09 % and an average particle size of 226.83 nm with a polydispersity index of 0.271. No drug-polymer interaction was observed in FTIR and DSC analysis. SEM images showed that the particles are spherical and uniform. The in vitro release study showed a sustained release nature, 53.98 % of the encapsulated drug has been released over 24hours period. This study demonstrated that statistical experimental design methodology can optimize the formulation and the process variables to achieve favorable responses.

Formulação, análise físico-química e microbiológica de cimentos endodônticos bioativos / Formulation, physicochemical and microbiological analysis of bioactive endodontic cements

Os cimentos endodônticos bioativos apresentam inúmeras aplicações clínicas, devido as suas propriedades biológicas, como a bioatividade; alta capacidade de vedação; ação antimicrobiana; liberação de íons cálcio, além de apresentar resposta inflamatória reduzida ou ausente. Baseada nesses benefícios, a presente pesquisa objetivou desenvolver e caracterizar cimentos endodônticos bioativos de baixo custo e efetividade antimicrobiana para uso na endodontia. Para isso, foram preparadas algumas formulações contendo cimentos finos, escória moída e celulose. Esses cimentos testes foram comparados com o MTA branco reparador da Angelus®. Sendo então divididos em quatro grupos: Grupo 1 (cimento fino cinza com escória moída cinza - MZVI e celulose); Grupo 2 (cimento branco cinza, escória moída branca - MPW e celulose); Grupo 3 (cimento fino branco e celulose) e Grupo 4 (MTA branco, Angelus ­ controle positivo). As amostras de cada grupo foram submetidas às análises de Difração de Raio-X (DRX), Análise Termogravimétrica (TG), Termogravimetria Derivada (DTG), Microscopia Eletrônica de Varredura (MEV), Potencial hidrogeniônico (pH), Picnometria, Espectroscopia de Infravermelho com Transformada de Fourier (FTIR) e Potencial Antibacteriano contra Enterococcus faecalis por meio do teste de difusão em ágar. Os testes estatísticos foram realizados utilizando o SPSS. As diferenças entre os grupos foram verificadas por meio do teste ANOVA com post hoc de Tukey, estatística descritiva e análises gráficas. Após a avaliação dos dados podese observar, principalmente, a presença de hidróxido de cálcio, silicato dicálcico, silicato tricálcico, aluminato tricálcico e carbonato de cálcio. Além disso, os cimentos apresentaram pH alcalino, ação antimicrobiana contra Enterococcus faecalis e na análise do MEV foi possível observar partículas de dimensões irregulares com uma distribuição heterogênea na matriz polimérica, contrastando com a homogeneidade apresentada pelo MTA. Porém, nas demais características, os cimentos apresentaram, de forma geral, grande semelhança com o MTA branco da Angelus, com maior destaque para o grupo 2. Assim, pode-se concluir que é possível formular cimentos bioativos, reutilizando escórias e mantendo as propriedades físico-químicas e antimicrobiana presentes no MTA (AU).

Bioactive endodontic cements have numerous clinical applications due to their biological properties, such as bioactivity; high sealing capacity; antimicrobial action; realease of calcium ions, also having a reduced or no inflammatory response. Based on these benefits, the present research aimed to develop and characterize low cost bioactive endodontic cements and antimicrobial effectiveness for endodontic use. For this, some formulations containing fine cements, ground slag and cellulose were prepared. These test cements were compared with Angelus® repairing white MTA. It was then divided into four groups: Group 1 (gray fine cement with gray ground slag - MZVI and cellulose); Group 2 (white gray cement, white ground slag - MPW and cellulose); Group 3 (white fine cement and cellulose) and Group 4 (white MTA, Angelus ­ positive control). The samples from each group were subjected to X-Ray Diffraction (XRD), Thermogravimetric Analysis (TGA), Derived Thermogravimetry (DTG), Scanning Electron Microscopy (SEM), Hydrogen Potential (pH), Picnometry, Infrared Spectroscopy with Fourier Transform (FTIR) and Antibacterial Potential against Enterococcus faecalis through the agar diffusion test. Statistical tests were performed using SPSS. Differences between groups were verified using the ANOVA test with Tukey's post hoc, descriptive statistics and graphical analyses. After evaluating the data, it was possible to observe, mainly, the presence of calcium hydroxide, dicalcium silicate, tricalcium silicate, tricalcium aluminate and calcium carbonate. In addition, the cements showed alkaline pH, antimicrobial action against Enterococcus faecalis and in the SEM analysis it was possible to observe particles of irregular dimensions with a heterogeneous distribution in the polymer matrix, contrasting with the homogeneity presented by MTA. However, in the other characteristics, the cements showed, in general, great similarity with the white MTA from Angelus, with greater emphasis on group 2. Thus, it can be concluded that it is possible to formulate bioactive cements, reusing slag and maintaining the MTA physicochemical and antimicrobial properties (AU).

The influence of the particle's size on the setting reaction of sol-gel derived calcium silicate particles / A influência do tamanho de partícula na reação de presa de cimentos de silicate de cálcio produzidos por sol-gel

Introduction: This study aims to analyze the influence of particles size of sol-gel derived calcium silicate particles in the setting reaction of bioactive endodontic cements. Materials and Methods: Sol-gel derived calcium silicate particles were synthesized and sieved to separate the particles in different sizes: CS400, CS200, and CS100. A commercial MTA (Control) was used as control. The particle size and the specific surface area were assessed by laser diffraction and nitrogen adsorption. The cements were prepared with water as the liquid for the reaction. The setting time was conducted according to ISO 6876, and the setting kinetics was analyzed by Fourier trans-formed infrared spectroscopy (FTIR) at different time points between 120s to 72h. Results: The particle size varied from 9.45µm (CS400 ) to 31.01 (Control). The higher specific surface area valuer reached 15.14g/cm2 in the CS400. The smallest particle sizes, the higher specific surface area, and the lowest setting time were found for CS400 (p < 0.05). Control presented the highest setting time (p < 0.05). The FTIR analyses showed the differences in materials structure over time, with faster hydration and crystallization for CS400. The setting kinetics was slower for Control even when compared to a sol-gel derived group with similar particle size. Conclusion:The route of synthesis and the particle size influences the setting reaction of calcium silicate-based cements. The reduction of particle size for sol-gel derived calcium silicates lead to the acceleration of the setting reaction of the produced bioactive endodontic cement.

Introdução: Este estudo tem como objetivo analisar a influência do tamanho de partículas de silicato de cálcio derivadas de sol-gel na reação de presa de cimentos endodônticos bioativos. Materiais e Métodos: Partículas de silicato de cálcio derivadas de sol-gel foram sintetizadas e peneiradas para separar as partículas em diferentes tamanhos: CS400, CS200 e CS100. Um MTA comercial (Controle) foi usado como controle. O tamanho das partículas e a área superficial específica foram avaliados por difração a laser e adsorção de nitrogênio. Os cimentos foram preparados com água como líquido para a reação. O tempo de presa foi conduzido de acordo com a ISO 6876, e a cinética de presa foi analisada por espectroscopia de infravermelho transformada de Fourier (FTIR) em diferentes pontos de tempo entre 120s a 72h. Resultados: O tamanho de partícula variou entre 9,45µm (CS400) e 31,01 (Controle). A maior área de superfície foi encontrada nas partículas do grupo CS400 (15.14g/cm2). Os menores tamanhos de partícula, a maior área de superfície específica e o menor tempo de presa foram encontrados para CS400 (p < 0,05). O Control apresentou o maior tempo de presa (p < 0,05). As análises de FTIR mostraram as diferenças na estrutura dos materiais ao longo do tempo, com hidratação e cristalização mais rápidas para CS400. A cinética de presa foi mais lenta para Control mesmo quando comparado a um grupo derivado de sol-gel com tamanho de partícula semelhante. Conclusão: A rota de síntese e o tamanho das partículas influenciam a reação de endurecimento dos cimentos à base de silicato de cálcio. A redução do tamanho de partícula para silicatos de cálcio derivados de sol-gel leva à aceleração da reação de pega do cimento endodôntico bioativo produzido.

Desenvolvimento e caracterização de dispersões sólidas de efavirenz / Development and characterization of efavirenz solid dispersions

A baixa solubilidade aquosa dos insumos farmacêuticos ativos (IFA) é um grande desafio no desenvolvimento de formulações farmacêuticas, pois pode resultar em biodisponibilidade insuficiente e variável. Diversas estratégias de modificação do estado sólido dos compostos ativos, têm sido propostas para incrementar a solubilidade de fármacos pouco solúveis em água. Dentre as estratégias abordadas a ispersão sólida (DS) é uma das formas mais promissoras de aumentar a solubilidade, dissolução e a biodisponibilidade de IFAs com baixa solubilidade aquosa. O efavirenz (EFV) é um inibidor não nucleosídeo da transcriptase reversa (NNRTI) e um dos componentes da terapia antirretroviral de alta atividade (HAART), sendo parte da primeira linha de tratamento de infecções do vírus HIV tipo 1. O antirretroviral está classificado como pertencente à classe II do SCB, e exibe baixa solubilidade aquosa (solubilidade menor que 10 µg/mL) e alta permeabilidade com absorção dependente da taxa de dissolução, resultando em biodisponibilidade oral baixa e variável. A administração de fármacos pouco solúveis na forma de DS é um método atraente para aumentar a biodisponibilidade in vivo. Neste estudo, um método de triagem rápida por evaporação de solvente foi empregado para preparar DS de EFV, variando-se proporções em misturas compostas pelos carreadores, polivinilpirrolidona K-28/32 (PVP K-28/32), copovidona (CoPVP), hidroxipropilmetilcelulose ftalato (HPMCP-50, HPMCP-55 e HPMCP-55s), poloxâmero 188 (P188) e poloxâmero 407 (P407). A solubilidade das DS foi avaliada por meio do método do equilíbrio (shake-flask), onde selecionou-se os polímeros P188 e P407 que conduziram a uma elevada capacidade de saturação em meio aquoso, superior a 1.000 vezes ao fármaco puro. As propriedades físico-químicas e do estado sólido das amostras foram avaliadas por meio de calorimetria exploratória diferencial (DSC); termogravimetria (TG); espectroscopia do infravermelho com transformada de Fourier (FTIR), difratometria de raios X pelo método do pó (DRXP) e ensaios de dissolução com emprego do aparato IV USP. Os resultados de DRXP demonstraram que os carreadores P188 e P407 foram capazes de estabilizar o EFV na forma amorfa nas DS, fato esse evidenciado pela ausência de picos característicos do antirretroviral

he low aqueous solubility of the active pharmaceutical ingredient (API) is a major challenge in the development of pharmaceutical formulations as it may result in insufficient and variable bioavailability. Several strategies for modifying the solid-state of the active compounds have been proposed to increase solubility of drugs that are poorly soluble in water. Among the strategies approaches, solid dispersion (SD) is one of the most promising ways to increase solubility, dissolution and bioavailability of APIs with low aqueous solubility. Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) and one of the components of highly active antiretroviral therapy (HAART), being part of the first line of treatment of type 1 HIV virus infections. The antiretroviral is classified as belonging to BCS class II, and exhibits low aqueous solubility (solubility less than 10 µg / mL) and high permeability with dissolution ratedependent absorption, resulting in low and variable oral bioavailability. Drug delivery of poorly aqueous soluble drugs in form SD is an appealing method to increase in vivo bioavailability. In this study, a fast screening method of solvent evaporation method was used to prepare EFV SD, varying the proportions in mixtures composed by the carriers polyvinylpyrrolidone K-28/32 (PVP K-28/32), copovidone (CoPVP), hydroxypropylmethylcellulose phthalate (HPMCP-50, HPMCP-55 e HPMCP-55s), poloxamer 188 (P188) e poloxamer 407 (P407). The solubility of the samples was evaluated by the method of equilibrium (shake-flask), wherein the polymers P188 and P407 were selected due to the capacity to promote high saturation in aqueous medium, 1,000 times superior to the pure drug. The physicochemical and solid-state properties of the samples were evaluated by differential scanning calorimetry (DSC); thermogravimetry (TG); Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRPD) and dissolution assays using the IV USP apparatus. The results of XRPD demonstrated that the carriers P188 and P407 were able to stabilize the EFV in amorphous form in the SD, a fact evidenced by the absence of characteristic peaks of the antiretroviral

Caracterizações física e química de cimentos experimentais autoadesivos à base de cálcio / Physical and chemical characterizations of calcium-based self-adhesive experimental cements

Objetivo: Avaliar a Resistência de União (RU), Grau de Conversão (GC), Liberação de Cálcio (LC), Resistência Flexural (RF), Módulo de Elasticidade (ME) e Viscosidade (VS) de cimentos experimentais à base de cálcio autocondicionantes e autoadesivos. Três cimentos experimentais: A (CONTROLE) ­ sem fonte de cálcio, B (HIDROCAL) ­ com hidróxido de cálcio, C (CLORECAL) ­ com cloreto de cálcio foram sintetizados e avaliados juntamente a um cimento comercial D (ULTRAPLUS) (Ultra-Blend Plus®). Metodologia: Para a RU, foi utilizado o teste de cisalhamento, cujas amostras (1,3mm de diâmetro com 2mm de altura) foram aderidas à dentina bovina (n=10) e tensionadas em máquina de ensaios (1 mm/min) até́ ocorrer o deslocamento. Para o GC (n=3), foi utilizada a Espectroscopia Infravermelha com transformada de Fourier (FTIR). Na determinação da LC (n=3) foram utilizadas amostras circulares (1,0 mm x 0,4 mm) e a leitura foi realizada através de um espectrofotômetro de absorção atômica nos tempos de 3h, 24h e 72h. Para RF/ME (n=10), amostras em formato de barra (7mm x 2mm x 1mm) foram confeccionadas e avaliadas por meio de uma Máquina de Ensaios Universal no teste de flexão de três pontos. Para a VS (n=30), a variação da taxa de deformação foi determinada por um reômetro rotacional de cilindros concêntricos. Os dados foram analisados por ANOVA 1 e 2 fatores seguido pelo pós teste de tukey (p<0,05). Resultados: Para RU todos os materiais experimentais apresentaram valores estatisticamente maiores que o comercial (p<0,01). Para o GC os cimentos CONTROLE e HIDROCAL apresentaram valores estatisticamente maiores que os demais (p<0,01). Frente à LC o CLORECAL e ULTRAPLUS apresentaram valores estatisticamente superiores após 72h (p<0,01). O ULTRAPLUS apresentou estatisticamente a maior RF e o menor ME (p<0,05). Os cimentos HIDROCAL e CLORECAL apresentaram valores de VS estatisticamente superiores aos demais (p<0,01). Conclusão: De maneira geral, o cimento experimental à base de cloreto de cálcio mostrou-se mais promissor (AU).

Objective: To evaluate the Bond Strength (BS), Degree of Conversion (DC), Calcium Release (CR), Flexural Strength (FS), Elastic Modulus (EM) and Viscosity (VS) of experimentally calcium based cements self-etching and self-adhesive. Three experimental cements: A (CONTROL), B (HYDROCAL), C (CLORECAL) were synthesized and evaluated with a commercial cement D (ULTRAPLUS) (Ultra-Blend Plus®- South Jordan, Utah, USA). Methodology: For the BS, the shear test was used, whose samples 1.3mm in diameter and 2mm in height) were adhered to the bovine dentin (n=10) and tensioned in a testing machine (1mm/min) until occurring the displacement. For the DC (n=3), Infrared Spectroscopy with Fourier transform (FTIR) was used. In determining the CR (n = 3) circular samples (1.0mmx0.4 mm) were used and the reading was performed through an atomic absorption spectrophotometer at 3h, 24h and 72h. For FS/ ME (n= 0), bar-shaped samples (7mmx 2mmx1mm) were made and evaluated using a Universal Testing Machine in the three-point flexion test. For VS (n = 30), the variation in the strain rate was determined by a rotational concentric cylinder rheometer. Results: For BS, all experimental materials showed statistically higher values than the commercial material (p <0.01). For the DC, the CONTROL and HIDROCAL cements showed statistically higher values than the others (p <0.01). In relation to CR, CLORECAL and ULTRAPLUS showed statistically higher values after 72 hours (p <0.01). ULTRAPLUS showed statistically the highest FS and the lowest EM (p <0.05). The HIDROCAL and CLORECAL cements showed VS values statistically higher than the others (p <0.01) Conclusion: In general, the experimental cement based on calcium chloride proved to be more promising (AU).

Characterization and identification of ascorbyl methylsilanol pectinate for cosmetic formulations application

The ascorbyl methylsilanol pectinate (AMP) presents the same functional properties of ascorbic acid (AA). Besides antioxidant and depigmentant activity, the AMP presents silanol in its chemical structure. The aim of this work was to characterize and indentify the AMP alone and in cosmetic formulations. The following techniques were employed: Fourier Transform Infrared Spectrophotometry, particle size distributions, in vitro antioxidant activity with 2.2-diphenyl-1-picrylhydrazyl (DPPH) and Oxigen Radical Absorbance Capacity Assay and High Performace Liquid Chromatography (HPLC) (developed and validated method) for the active ingredient; Microscopy, HPLC and Normal Stability Assay (NSA) for the emulsions. Particle size distributions results showed that the average size of AMP was 1.0 µm and polydispersity index was 0.1. In DPPH assay AA and AMP were statistically the same. The value of ORAC obtained for AMP was 0.74 and for AA in the literature was 0.95. In the NSA the formulations were stable in conditions of 5.0 and 45.0 ± 2.0 ºC for 90 days. Adequate stability at ambient temperature out of reach of light was also observed. Thus, this works presented an acceptable method for quantification of AMP alone and in cosmetic formulations. AMP was an adequate choice for the incorporation in emulsions with antioxidant efficacy.

Rapid identification of microbial contaminants in pharmaceutical products using a PCA/LDA-based FTIR-ATR method

Microbiological quality of pharmaceuticals is fundamental in ensuring efficacy and safety of medicines. Conventional methods for microbial identification in non-sterile drugs are widely used; however they can be time-consuming and laborious. The aim of this paper was to develop a chemometric-based rapid microbiological method (RMM) for identifying contaminants in pharmaceutical products using Fourier transform infrared with attenuated total reflectance spectrometry (FTIR-ATR). Principal components analysis (PCA) and linear discriminant analysis (LDA) were used to obtain a predictive model capable of distinguishing Bacillus subtilis (ATCC 6633), Candida albicans (ATCC 10231), Enterococcus faecium (ATCC 8459), Escherichia coli (ATCC 8739), Micrococcus luteus (ATCC 10240), Pseudomonas aeruginosa (ATCC 9027), Salmonella typhimurium (ATCC 14028), Staphylococcus aureus (ATCC 6538), and Staphylococcus epidermidis (ATCC 12228) microbial growth. FTIR-ATR spectra provide data on proteins, DNA/RNA, lipids, and carbohydrates constitution of microbial growth. Microbial identification provided by PCA/LDA based on FTIR-ATR method were compatible with those obtained using traditional microbiological methods. The chemometric-based FTIR-ATR method for rapid identification of microbial contaminants in pharmaceutical products was validated by assessing the sensitivity (93.5%), specificity (83.3%), and limit of detection (17-23 CFU/mL of sample). Therefore, we propose that FTIR-ATR spectroscopy may be used for rapid identification of microbial contaminants in pharmaceutical products and taking into account the samples studied

Shape differences among symmetrically shaped skeletal growth patterns in a panoramic view: a Fourier analysis

Abstract The objective of this study was to apply elliptic Fourier analysis (EFA) to find shape differences among skeletal growth patterns in both radiographic and tomographic panoramic views, controlling for asymmetry. Lateral and panoramic images were obtained from 350 patients. After screening patients with asymmetric linear and angular values and natural asymmetric hemimandibular shape, 240 patients were included in the study: 48 with tomographic information and 192 with radiographic information. The images were classified according to the mandibular plane angle and the ANB angle. Mandibular contours were digitized on the panoramic images and EFA was performed with 20 harmonics, filtering rotation, translation and size properties. As there were no differences between radiographic and tomographic panoramic mandibular contours and normal distribution was found in all groups, MANOVA was conducted to determine differences using a Hotelling's p-values with Bonferroni correction and an XY graph tool was applied to visualize these differences graphically. A 95% confidence level was used. Significative differences were found among hypodivergent, normodivergent, and hyperdivergent patterns in Class I, II, and III (p < 0.05), located mainly in the symphyseal region. The results of this study suggest that EFA is a useful tool to mathematically analyze mandibular contours and their morphological differences given by facial biotypes. This method could improve the precision of the mandibular prediction models.

Registro de emisiones otoacústicas transientes basado en microcontroladores de alto rendimiento / Transient Otoacoustic Emissions Register based on High Performance Microcontrollers

La hipoacusia tiene una incidencia notable entre los recién nacidos. Una intervención temprana durante el período de maduración auditiva permite minimizar los efectos en el desarrollo intelectual del infante. Se propone el desarrollo de un Registrador de Emisiones Otoacústicas Transientes como parte de un sistema de cribado neonatal basado en microcontroladores de alto rendimiento. La prueba consiste en aplicar periódicamente un estímulo tipo chasquido para obtener la respuesta coclear. Se promedian las señales adquiridas y se aplica la Transformada Rápida de Fourier. El espectro obtenido es dividido en bandas de media octava para analizar la correlación y la relación señal-ruido. Si estos parámetros son mayores que los umbrales de referencia en la mayoría de las bandas, se considera al paciente apto para el desarrollo normal. El firmware fue implementado sobre el procesador STM32F405 y evaluado con el simulador Baby Isao; obteniéndose una sensibilidad del 87.5 por ciento y una especificidad del 93.75 por ciento(AU)

Hearing loss is highly incident among newborns. Early intervention during the period of auditory maturation allows adequate levels of intellectual development to be achieved. The development of a Transient Otoacoustic Emissions Recorder is proposed as part of a neonatal screening system based on high-performance microcontrollers. The test consists of periodically applying a click stimulus to obtain the cochlear response. The acquired signals are averaged and the Fast Fourier Transform is applied. The spectrum obtained is divided into half-octave bands to assess the correlation as well as the signal-noise ratio. If these parameters are greater than the reference thresholds in most of the bands, the patient is considered suitable for normal cognitive development. The firmware was implemented on the STM32F405 processor and evaluated with the Baby Isao simulator; obtaining a sensitivity of 87.5 percent and a specificity of 93.75 percent(AU)

Determination of Electrocution Using Fourier Transform Infrared Microspectroscopy and Machine Learning Algorithm / 法医学杂志

Objective To analyze the differences among electrical damage, burns and abrasions in pig skin using Fourier transform infrared microspectroscopy （FTIR-MSP） combined with machine learning algorithm, to construct three kinds of skin injury determination models and select characteristic markers of electric injuries, in order to provide a new method for skin electric mark identification. Methods Models of electrical damage, burns and abrasions in pig skin were established. Morphological changes of different injuries were examined using traditional HE staining. The FTIR-MSP was used to detect the epidermal cell spectrum. Principal component method and partial least squares method were used to analyze the injury classification. Linear discriminant and support vector machine were used to construct the classification model, and factor loading was used to select the characteristic markers. Results Compared with the control group, the epidermal cells of the electrical damage group, burn group and abrasion group showed polarization, which was more obvious in the electrical damage group and burn group. Different types of damage was distinguished by principal component and partial least squares method. Linear discriminant and support vector machine models could effectively diagnose different damages. The absorption peaks at 2 923 cm-1, 2 854 cm-1, 1 623 cm-1, and 1 535 cm-1 showed significant differences in different injury groups. The peak intensity of electrical injury's 2 923 cm-1 absorption peak was the highest. Conclusion FTIR-MSP combined with machine learning algorithm provides a new technique to diagnose skin electrical damage and identification electrocution.

Desenvolvimento e otimização de sistemas conservantes empregando os conceitos de Qualidade por Design (QbD) e Tecnologia Analítica de Processos (PAT) / Development and optimization of preservative systems using Quality by Design (QbD) and Process Analytical Technology (PAT) concepts

Recentemente, produtos farmacêuticos e cosméticos com concentrações mínimas de parabenos e outros conservantes ganharam e apelo comercial e de segurança, devido à controvérsia sobre a segurança dos conservantes. No entanto, o uso de conservantes é essencial para garantir a conservação microbiana de produtos cosméticos e farmacêuticos durante o seu uso. Neste trabalho, desenvolveu-se um método quimiométrico de espectroscopia no infravermelho com Fourier transform near-infrared (FTIR) para prever a eficácia de sistemas conservantes em produtos farmacêuticos e cosméticos tópicos usando os conceitos de Quality by design (QbD) e Process Analytical Technology (PAT). A abordagem de QbD foi usada para determinar a eficácia antimicrobiana frente aos microrganismos: Candida albicans (ATCC 10231), Escherichia coli (ATCC 8739) e Staphylococcus aureus (ATCC 6538), em funções das concentrações de parabenos, e determinar a região de Design Space, empregando o delineamento de compóstio central (CCD) Todas as 15 formulações preparadas foram analisadas utilizando um espectrofotômetro (FTIR) equipado com aparato de Attenuated Total Reflectance (ATR). Os modelos de regressão por Partial Least Squares (PLS) para predição dos "slopes" das curvas de morte microbiana em função dos espectros ATR/FTIR foram bem ajustados, com R2 e R2-predição de 0,9937 e 0,8921, 0,9947 e 0,8783, e 0,9957 e 0,9222 para Candida albicans (ATCC 10231), Escherichia coli (ATCC 8739) e Staphylococcus aureus (ATCC 6538), respectivamente. O método FTIR proposto aplicado em uma abordagem de PAT foi capaz de prever a eficácia do sistema conservante em tempo reduzido. Este método de predição de silício permitirá um controle lote-a-lote da eficácia do sistema conservante de produtos farmacêuticos e cosméticos

Recently, pharmaceuticals and cosmetics with minimal concentrations of parabens and other preservatives have gained and commercial and safety appeal due to controversy over the safety of preservatives. However, the use of preservatives is essential to ensure the microbial conservation of cosmetic and pharmaceutical products during use. In this work, a chemometric method of infrared spectroscopy with Fourier transform (FTIR) was developed to predict the effectiveness of preservative systems in pharmaceutical products and topical cosmetics using the concepts of Quality by design (QbD) and Process Analytical Technology (PAT). The QbD approach was used to determine antimicrobial efficacy against candida albicans (ATCC 10231), Escherichia coli (ATCC 8739) and Staphylococcus aureus (ATCC) microorganisms 6538), in functions of paraben concentrations, and determine the Design Space region, employing the design of central composite (CCD). All 15 prepared formulations were analyzed using a spectrophotometer (FTIR) equipped with Attenuated Total Reflectance (ATR). The Partial Least Squares (PLS) regression models for the prediction of the slopes of microbial death curves as a function of ATR /FTIR spectra were well adjusted, with R2 and R2-prediction 0.9937 and 0.8921, 0.9947 and 0.8783, and 0.9957 and 0.9222 for Candida albicans (ATCC 10231), Escherichia coli (ATCC 8739) and Staphylococcus aureus (ATCC 6538)respectively. The proposed FTIR method applied in a PAT approach was able to predict the effectiveness of the preservative system in reduced time. This method in silico prediction will allow a batch-to-lot control of the effectiveness of the preservative system of pharmaceuticals and cosmetics

Attenuated total reflection Fourier transform infrared as a primary screening method for cancer in canine serum

Preparation and Characterization of Nanocomposite Scaffolds (Collagen/β-TCP/SrO) for Bone Tissue Engineering

BACKGROUND: Nowadays, production of nanocomposite scaffolds based on natural biopolymer, bioceramic, and metal ions is a growing field of research due to the potential for bone tissue engineering applications. METHODS: In this study, a nanocomposite scaffold for bone tissue engineering was successfully prepared using collagen (COL), beta-tricalcium phosphate (β-TCP) and strontium oxide (SrO). A composition of β-TCP (4.9 g) was prepared by doping with SrO (0.05 g). Biocompatible porous nanocomposite scaffolds were prepared by freeze-drying in different formulations [COL, COL/β-TCP (1:2 w/w), and COL/β-TCP-Sr (1:2 w/w)] to be used as a provisional matrix or scaffold for bone tissue engineering. The nanoparticles were characterized by X-ray diffraction, Fourier transforms infrared spectroscopy and energy dispersive spectroscopy. Moreover, the prepared scaffolds were characterized by physicochemical properties, such as porosity, swelling ratio, biodegradation, mechanical properties, and biomineralization. RESULTS: All the scaffolds had a microporous structure with high porosity (~ 95–99%) and appropriate pore size (100–200 µm). COL/β-TCP-Sr scaffolds had the compressive modulus (213.44 ± 0.47 kPa) higher than that of COL/β-TCP (33.14 ± 1.77 kPa). In vitro cytocompatibility, cell attachment and alkaline phosphatase (ALP) activity studies performed using rat bone marrow mesenchymal stem cells. Addition of β-TCP-Sr to collagen scaffolds increased ALP activity by 1.33–1.79 and 2.92–4.57 folds after 7 and 14 days of culture, respectively. CONCLUSION: In summary, it was found that the incorporation of Sr into the collagen-β-TCP scaffolds has a great potential for bone tissue engineering applications.

Optimal template selecting combined with non-liner template matching for Doppler fetal heart rate extraction / 生物医学工程学杂志

The ultrasound Doppler fetal heart rate measurement is the gold standard of fetal heart rate counting. However, the existing fetal heart rate extraction algorithms are not designed specifically to suppress the high maternal interference during the second stage of labor, and false detection occurrences are common during labor. With this background, a method combining time-frequency frame template library optimal selecting and non-linear template matching is proposed. The method contributes a template library, and the optimal template can be selected to match the signal frame. After the short-time Fourier transform of the signal, the difference between the signal and the template is optimized by leaky rectified linear unit (LReLU) function frame by frame. The heart rate was calculated from the peak of the matching curve and the heart rate was calculated. By comparing the proposed method with the autocorrelation method, the results show that the detection accuracy of the proposed method is improved by 20% on average, and the non-linear template matching of 23% samples is at least 50% higher than the autocorrelation method. This paper designs the algorithm by analyzing the characteristics of the interference and signal mixing. We hope that this paper will provide a new idea for fetal heart rate extraction which not only focuses on the original signal.

Alendronate-Anionic Clay Nanohybrid for Enhanced Osteogenic Proliferation and Differentiation

BACKGROUND: Alendronate (AL), a drug for inhibiting osteoclast-mediated bone-resorption, was intercalated into an inorganic drug delivery nanovehicle, layered double hydroxide (LDH), to form a new nanohybrid, AL-LDH, with 1:1 heterostructure along the crystallographic C-axis. Based on the intercalation reaction strategy, the present AL-LDH drug delivery system (DDS) was realized with an enhanced drug efficacy of AL, which was confirmed by the improved proliferation and osteogenic differentiation of osteoblast-like cells (MG63). METHODS: The AL-LDH nanohybrid was synthesized by conventional ion-exchange reaction and characterized by powder X-ray diffraction (PXRD), high-resolution transmission electron microscopy (HR-TEM), and Fourier transform infrared (FT-IR) spectroscopy. Additionally, in vitro efficacy tests, such as cell proliferation and alkaline phosphatase (ALP) activity, were analyzed. RESULTS: The AL was successfully intercalated into LDH via ion-exchange reaction, and thus prepared AL-LDH DDS was X-ray single phasic and chemically well defined. The accumulated AL content in MG63 cells treated with the AL-LDH DDS nanoparticles was determined to be 10.6-fold higher than that within those treated with the intact AL after incubation for 1 hour, suggesting that intercellular permeation of AL was facilitated thanks to the hybridization with drug delivery vehicle, LDH. Furthermore, both in vitro proliferation level and ALP activity of MG63 treated with the present hybrid drug, AL-LDH, were found to be much more enhanced than those treated with the intact AL. This is surely due to the fact that LDH could deliver AL drug very efficiently, although LDH itself does not show any effect on proliferation and osteogenic differentiation of MG63 cells. CONCLUSION: The present AL-LDH could be considered as a promising DDS for improving efficacy of AL.

Efficient QRS complex detection algorithm based on Fast Fourier Transform

An ECG signal, generally filled with noise, when de-noised, enables a physician to effectively determine and predict the condition and health of the heart. This paper aims to address the issue of denoising a noisy ECG signal using the Fast Fourier Transform based bandpass filter. Multi-stage adaptive peak detection is then applied to identify the R-peak in the QRS complex of the ECG signal. The result of test simulations using the MIT/BIH Arrhythmia database shows high sensitivity and positive predictivity (PP) of 99.98 and 99.96% respectively, confirming the accuracy and reliability of proposed algorithm for detecting R-peaks in the ECG signal.

Classification of radiographic lung pattern based on texture analysis and machine learning

This study evaluated the feasibility of using texture analysis and machine learning to distinguish radiographic lung patterns. A total of 1200 regions of interest (ROIs) including four specific lung patterns (normal, alveolar, bronchial, and unstructured interstitial) were obtained from 512 thoracic radiographs of 252 dogs and 65 cats. Forty-four texture parameters based on eight methods of texture analysis (first-order statistics, spatial gray-level-dependence matrices, gray-level-difference statistics, gray-level run length image statistics, neighborhood gray-tone difference matrices, fractal dimension texture analysis, Fourier power spectrum, and Law's texture energy measures) were used to extract textural features from the ROIs. The texture parameters of each lung pattern were compared and used for training and testing of artificial neural networks. Classification performance was evaluated by calculating accuracy and the area under the receiver operating characteristic curve (AUC). Forty texture parameters showed significant differences between the lung patterns. The accuracy of lung pattern classification was 99.1% in the training dataset and 91.9% in the testing dataset. The AUCs were above 0.98 in the training set and above 0.92 in the testing dataset. Texture analysis and machine learning algorithms may potentially facilitate the evaluation of medical images.

Adulterants interference on Fourier Transform Infrared analysis of raw milk / Interferência de adulterantes na análise do leite cru por espectroscopia pela transformada de Fourier

O objetivo deste trabalho foi analisar as leituras de composição do leite cru por meio de espectrofotometria FTIR, utilizando-se curva de regressão PLS, bem como as contagens de células somáticas e bacteriana total por citometria de fluxo, após adição de amido e sacarose. O leite cru foi adulterado com três concentrações de amido e sacarose (0,1%, 0,5% e 1%), colocado em frascos contendo bronopol ou azidiol, os quais foram armazenados em duas temperaturas (7±2°C e 25±2°C ). As análises foram realizadas após zero, três, 24, 48, 72 e 168 horas de armazenamento. O modelo de regressão linear múltipla foi utilizado para análise estatística. A adição de amido e sacarose resultou em mudança significativa (P<0,05) para todas as variáveis dependentes. O leite adulterado com amido resultou em aumento nas leituras de gordura, proteína, lactose, sólidos totais (ST), sólidos não gordurosos (SNG), CCS e CBT e em diminuição das leituras de caseína, do nitrogênio ureico do leite (NUL) e do ponto de congelamento. O leite adulterado com sacarose resultou no aumento das leituras da lactose, ST, SNG e NUL, enquanto as leituras de proteína, caseína, ponto de congelamento e CCS diminuíram. Este trabalho evidencia a importância do monitoramento de adulterantes reconstituintes no leite por afetarem os resultados analíticos da qualidade do leite, obtidos por métodos eletrônicos.(AU)

Simultaneous monitoring of motion ECG of two subjects using Bluetooth Piconet and baseline drift

Uninterrupted monitoring of multiple subjects is required for mass causality events, in hospital environment or for sports by medical technicians or physicians. Movement of subjects under monitoring requires such system to be wireless, sometimes demands multiple transmitters and a receiver as a base station and monitored parameter must not be corrupted by any noise before further diagnosis. A Bluetooth Piconet network is visualized, where each subject carries a Bluetooth transmitter module that acquires vital sign continuously and relays to Bluetooth enabled device where, further signal processing is done. In this paper, a wireless network is realized to capture ECG of two subjects performing different activities like cycling, jogging, staircase climbing at 100 Hz frequency using prototyped Bluetooth module. The paper demonstrates removal of baseline drift using Fast Fourier Transform and Inverse Fast Fourier Transform and removal of high frequency noise using moving average and S-Golay algorithm. Experimental results highlight the efficacy of the proposed work to monitor any vital sign parameters of multiple subjects simultaneously. The importance of removing baseline drift before high frequency noise removal is shown using experimental results. It is possible to use Bluetooth Piconet frame work to capture ECG simultaneously for more than two subjects. For the applications where there will be larger body movement, baseline drift removal is a major concern and hence along with wireless transmission issues, baseline drift removal before high frequency noise removal is necessary for further feature extraction.

Hydroxyapatite Nanorod-Modified Sand Blasted Titanium Disk for Endosseous Dental Implant Applications

BACKGROUND: Sand blasted titanium (Ti) is commonly used in designing endosseous dental implants due to its biocompatibility and ability to form bonds with bone tissues. However, titanium implants do not induce strong interactions with teeth bones. To increase strong interactions between Ti disk implants and teeth bones, the L-glutamic acid grafted hydroxyapatite nanorods (nHA) were immobilized on albumin modified Ti disk implants (Ti-Alb). METHODS: For modification of Ti disk implants by nHA, the L-glutamic acid grafted nHA was synthesized and then immobilized on albumin modified Ti disk implants. Fourier transformed infrared spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscope; energy dispersive spectroscopy and confocal laser scanning microscopy were used to confirm the modification of Ti disk implants. The bioactivity of nHA-modified Ti disk implants was evaluated by seeding MC3T3-E1 cells on Ti-nHA implants. RESULTS: Characterization techniques have confirmed the successful modification of Ti disk implants by L-glutamic acid grafted nHA. The nHA-modified Ti disk implants have shown enhanced adhesion, proliferation and cytotoxicity of MC3T3-E1 cells in comparison to pristine Ti implants. CONCLUSION: The modification of Ti implants by L-glutamic acid grafted nHA has produced highly osteogenic Ti disk plants in comparison to pristine Ti disk implants due to the formation of bioactive surfaces by hydroxyapatite nano rods on Ti disk implants. Ti-nHA disk implants showed enhanced adhesion, proliferation, and MC3T3-E1 cells viability in comparison to pristine Ti disk implants. Thus nHA might be to be useful to enhance the osseointegration of Ti implants with teeth bones.