Perfect powder mixtures

The ordered mixing of both crystal violet and salicylic acid in microfine form with a coarse sucrose powder results in perfect (or almost perfect) mixtures. Such mixtures have zero standard deviation for concentration of minor ingredient between samples, due to the mixing operation. The homogeneity of perfect mixtures can be defined using Buslik's concept of homogeneity. It is useful to differentiate between absolute homogeneity and relative homogeneity. Absolutely homogeneous systems have zero standard deviation above a limiting sample size. Relatively homogeneous systems have a gradually decreasing standard deviation with increasing sample size. Relative homogeneity of a system is inversely proportional to the sample weight at a fixed standard deviation. Absolute homogeneity is inversely proportional to the sample weight at which there is a discontinuity between the standard deviation of the unmixed system and a standard deviation of zero.     

Pattern recognition for characterization of pharmaceutical powders

A large part of pharmaceutical manufacturing involves the use of particulate materials. It is well known that both particle size and shape affect the physical characteristics of tablets. An image processing and analysis algorithm based on the invariant image moment technique was developed in this work to determine the particle shape by comparing features (moments) extracted from templates to those extracted from each of the objects in the image. First it determines the particle shape (rectangle, circle, etc.) and then calculates its specific dimensions (diameter, aspect ratio).The statistical validation of the vision system obtained a repeatability of 0.0012 in and 0.5% relative standard deviation and accuracy within 0.1 to 0.9% of the average value considered as true value. Also the pattern recognition technique indicated high precision and accuracy for images containing particles with some level of contact between them. The shape recognition of microcrystalline cellulose (MCC) indicated that particles of equant and acicular shape as defined by USP are predominant. The results suggest that image processing and analysis would be a suitable tool for pharmaceutical process analytical technologies (PAT) and process optimization.     

Discrimination limit between mean gray values for the prediction of powder concentrations

Powder mixing is one of the most impacting steps in the handling of pharmaceutical powders for tablet production due to its strong effect in the properties and potency of the tablets. The monitoring of this process to detect the required mixing end point so that adequate properties and potency on the tablets are achieved requires continuous analysis of the powder concentration. However, its complex dynamics requires fast and accurate methods to determine the concentrations.Image analysis has already been shown to be suitable for this application. The objectives of this work were to further demonstrate its applicability to bright as well as dark powders, to determine the discrimination limit of the used vision system between powder's Mean Gray Values (MGV) in mixtures, and to develop a mathematical model to accurately predict calibration curves with minimum adjustable parameters. The study was emphasized for bright powders in the region of MGV between 255 and 140 and for dark powders in the region between 139 and 0. Mixtures of powders with difference in density greater than 0.3 g/cm³ showed considerably deviation in the prediction of concentrations. The discrimination limit between MGV attained was between 21 and 17 for both bright and dark powders. Below this range, unacceptable residuals larger than 8% w/w were obtained.     

REFRACTIVE INDEX OF SUPERCRITICAL CO 2 -ETHANOL SOLVENTS

In-line analysis of refractive index is required for efficient design and monitoring of supercritical fluid extraction and precipitation processes. In the present work, a robust method has been developed based on measurements of laser beam deviation using an interferometer and image processing system. Data on refractive index of CO 2 -ethanol mixtures were obtained at pressures between 70 and 200 bar and temperatures between 308 and 363 K, for continuous flow of premixed solvents and, in addition, for equilibrium gas phase below the mixture critical pressure. The refractive index of a mixture is a linear function of ethanol mole fraction and can adequately describe mixing and phase behavior in the vessel. For pure CO 2 , refractive index was determined as a function of pressure and density and its Lorentz-Lorenz functions determined.     

Assessing the homogeneity of an ordered mixture

The sample standard deviation of the content of minor component in a number of samples is the most widely used method of assessing the homogeneity of an ordered mix. A number of investigators have used thief probes to withdraw samples from a mixture. This study has demonstrated that the use of a thief can result in non-representative samples being removed from a mixer in which the mixture has undergone ordered unit segregation. Since this sampling technique has been widely used, some doubt must exist about the magnitude of values quoted in the literature for the sample standard deviation of ordered mixtures.It has been shown that producing an ordered mixture at 0 or 84% relative humidity results in significantly less segregation of the carrier particles. This finding has application as a simple method of minimizing ordered unit segregation during a mixing operation.     

Real-time monitoring of drug concentration in a continuous powder mixing process using NIR spectroscopy

A non-destructive NIR spectroscopic method was used to acquire on-line spectra of a continuous mixing process, and evaluate the performance of this novel system. Partial least squares (PLS) calibration models were developed and used for real-time determination of active ingredient concentration on the blends produced with a continuous mixer. The NIR method was developed for concentrations ranging from 0 to 15% (w/w) of acetaminophen (APAP), the active pharmaceutical ingredient used in the experiments. The calibration model's overall accuracy was 0.41% (w/w), and estimated through the root mean square error of cross validation (RMSECV) for samples predicted using leave-class-out cross validation. In this cross validation, each concentration was defined as a class, and when a sample of a specific concentration was predicted all samples of that concentration were left out of the calibration model. The precision of the calibration model was also estimated at various concentration levels, to facilitate the differentiation between the variation in drug concentration due to the analytical method's measurement uncertainty and the variation in the drug distribution throughout the powder blend. The results obtained are very promising since in three of the five powder mixes, the variation in the drug concentration in the powder blends was similar to that of the analytical method indicating a high degree of blend homogeneity     

Nano-mixing of dipyridamole drug and excipient nanoparticles by sonication in liquid CO2

Nanoparticles (about 200 nm thick and 600–12000 nm long flakes) of dipyridamole, a poorly water-soluble anti-thrombosis drug, are produced by supercritical antisolvent solvent with enhanced mass transfer method. Applicability of sonication in liquid CO₂ for mixing of drug and excipient nanoparticles is demonstrated for several binary mixtures of drug and excipient. The drug particles are mixed with three different excipients: silica nanoparticles, lactose microparticles, and polyvinylpyrrolidone nanoparticles. To intimately mix at nanoscale, macro mixtures of dipyridamole and excipient particles are sonicated in liquid carbon dioxide. The effects of ultrasonic energy, amplitude, and component weight ratio are studied for the binary mixtures. Characterization of mixing is done using several methods. Scanning electron microscopy is used as a primary method for microscopic analysis. Two macroscopic effects, drug dissolution and blend homogeneity (relative standard deviation), are used to characterize mixing quality of drug/lactose mixture. Results of drug dissolution and blend homogeneity show effectiveness of the proposed mixing method for fine size particles. Material handling properties of drug/silica and lactose/silica mixtures were examined. Upon mixing, the handling properties are significantly improved as measured by compressibility index and Hausner ratio. Liquid CO₂ offers an environmentally benign media for mixing. In addition, the mixture obtained does not contain any residual solvent as compared to the sonication in organic liquids. Upon depressurization, CO₂ is easily removed from the mixture providing a facile recovery of the product.     

Repeatability and intermediate precision of a mass concentration calibration system

Many aerosol instruments require calibration to make accurate measurements. A centrifugal particle mass analyzer (CPMA) and aerosol electrometer can be used to calibrate aerosol instruments that measure mass concentration. To understand the sources of uncertainty in the calibration method, two CPMA-electrometer systems were tested to measure the repeatability and intermediate precision of the system, where the repeatability is the standard deviation of several measurements using the same system over a short period of time, and the intermediate precision is the standard deviation of several measurements using different instruments with different calibrations over a long period of time. It was found that the repeatability of the CPMA and the aerosol electrometer were both 0.8%, while the intermediate precision was 1.3% and 2.2%, respectively. The intermediate precision of the aerosol electrometers determined here compares well with a broader study by national metrology institutes which determined an intermediate precision of ～1.7%. By propagation of uncertainty, it is expected that a CPMA-electrometer system would have repeatability of 1.1% and an intermediate precision of ～2.1%. This compares favorably to thermal-optical analysis methods which aim to measure black carbon mass concentrations for instrument calibration, which have a repeatability in the range of 8.5–20% and reproducibility in the range of 20–26% for elemental carbon. Thus, the CPMA-electrometer method may be a good alternative to existing instrument calibration procedures.

Copyright © 2019 American Association for Aerosol Research     

基于Eyring绝对速率理论的流体混合物黏度推算

为了建立起一个统一的、可同时应用于纯质与混合物高压黏度计算的绝对速率理论模型,基于此前已有的纯质黏度模型,提出了相应的混合法则,将其扩展至对混合流体的计算当中。为验证模型精度,首先选取了27种纯质流体,通过拟合其黏度数据得到模型参数。随后,对27种二元混合物以及3种三元混合物的黏度进行了计算。其中,对于二元混合物,仍需要引入额外的二元交互参数,可通过拟合混合体系黏度数据得到。结果表明,该黏度模型对所选纯质、二元混合物和三元混合物的黏度均有着较高的计算精度,其相对偏差的平均绝对值分别为1.54%、2.35%和3.86%,最大偏差为8.62%、12.9%和19.7%。最后,将本文模型与自由体积模型进行了比较,其对高黏度和互缔合流体的计算精度均高于后者。     

Precision and accuracy in the color specification of virgin olive oils from the bromthymol blue method

Twenty experienced observers with nondefective color vision judged 27 virgin olive oil samples within an acceptable color range, using the bromthymol blue (BTB) method, under controlled observation conditions (daylight source with a correlated color temperature of 6500 K, and standard gray back-ground). On the average, 44.8% of the observers agreed in their selections of the BTB standard solution matching a given oil sample, and this percentage increased to 88.2% considering ±one step in the two dimensions (pH and concentration) of the BTB scale. On the average, the lowest color difference between oil samples and available BTB solutions was 6.6 Commission Internationale de l'éclairage 1976-(L^*a^*b^*) (CIELAB) units, but this color difference was approximately two times greater for the color difference between oil samples and BTB solutions selected by our observers. The colors of the BTB standard solutions in the CIELAB space are not uniformly distributed, and thus one step in pH or concentration is equivalent to CIELAB color differences varying in a wide range (1.7–13.5 and 1.7–26.3 CIELAB units, respectively). From these values, indicating low precision, accuracy, and uniformity, some suggestions are made for future improvements of the current BTB method.     

Experimental study of the mixing kinetics of binary pharmaceutical powder mixtures in a laboratory hoop mixer

As increasingly commented by the literature during the last 5 years, estimating the homogeneity of a powder mixture and following powder mixing processes is not a simple task. In this paper, we present the development and statistical validation of a sampling methodology for defining the number of samples required to provide a reasonable estimation of the homogeneity attained in a laboratory scale tumbler mixer. This method is then used to follow the mixing kinetics of a dilute binary powder mixture in a hoop mixer. Special attention is paid to the statistical meaning of the values obtained and the influence of the physical characteristics such as particle size and shape. The role of the particle shape of the majority powder is particularly emphasised and it is quantitatively demonstrated that spherical particles are harder to mix and more ready to segregate than particles with irregular shapes. The different mixing mechanisms at play are identified; the practical limits of use of such tumbler mixers with pharmaceutical powders are discussed.     

粉末压片-X荧光法测定无机包膜钛白粉主含量

采用粉末压片法制样,建立了无机包膜钛白粉中主含量TiO₂的X射线荧光光谱分析方法。选用了一组工业无机包膜钛白粉产品作为标准样品,以化学滴定法对标准样品的含量进行分析测定作为标准样品值,并采用经验α系数法以及康普顿散射线内标法对基体效应进行校正并建立了分析曲线,讨论了测量条件及分析方法。精密度和准确度实验表明,本方法相对标准偏差（RSD）为0.14%,准确度可靠。     

Analysis of solvents mixtures employing rank annihilation factor analysis on near infrared spectral data from sequential addition of analyte

Determination of the analyte concentration in the presence of unknown interfering species is the goal in chemometrics techniques such as rank annihilation factor analysis (RAFA). In this work, using a hard model for sequential addition of analyte to an unknown mixture and a RAFA based approach, concentration of one component in a mixture of organic solvents was determined. Application of hard models causes a unique result from RAFA. The considered analyte was added sequentially to the unknown mixture in a number of steps and a near-infrared (NIR) spectrum was measured in each step. The required information for performing the analysis is the pure spectrum of the analyte (the desired solvent) and density (g mL^− 1) of mixtures obtained from each step of addition. Acceptable results from analysis of simulated data and binary mixture of toluene and cyclohexene, as a synthetic sample, were obtained. Effect of extent of spectral overlap, noise and initial mass fraction of analyte on accuracy and precision of the obtained results were investigated. Quantification of toluene in Gasoline, as a real sample with unknown composition, was successfully performed by the proposed method.     

环己酮肟重排反应混合物中游离肟的测定

建立了环己酮肟重排反应混合物中游离肟含量的测定方法。研究了重氮化 -偶联反应机理、条件及试剂选择、用量 ,探讨了溴化钾对提高反应速率的作用。该方法灵敏度高、准确性好 ,在最佳实验条件下 ,测定环己酮肟的最小检测限为 0 1mg/L ,变异系数 <1% ,加标回收率为 95 %～ 99%。     

Low cholesterol egg powder. Nutritive and quality characteristics of the product

The purpose of this study is to obtain a low cholesterol egg powder for the preparation of different foods for persons whose egg consumption is restricted. Egg white and yolk mixtures prepared in different proportions were dehydrated; the following dried mixtures were obtained: A (1:1), B (2:1) and C (3:1) of egg white:yolk respectively. These mixtures were evaluated using the following parameters: proximal analysis, microbiological assay and protein quality evaluation. Physical characteristics of the powder and the sensorial tests of foods prepared with these mixtures were carried out. The fat and the cholesterol content in the mixture C were decreased by 40% and 20% respectively. The microbiological tests showed that the three mixtures were safe for human consumption. The PER of sample A (whole egg) was 3.65 and for the mixture C 3:1 egg white:yolk was 3.05. The PER of the 50:50 protein mixtures eggs white and yolk: with corn lime treated flour (HMN) were higher than that of the casein standard. The sensorial tests of the foods prepared with all the mixtures were acceptable.     

Effect of powder treatment on injection moulded zirconia ceramics

Agglomerated fine zirconia powder was exposed to dry and wet ball milling and to wet mixing. The subject of study was the effect of powder treatment on the disintegration of agglomerated particles, on the rheological properties of thermoplastic ceramic mixtures, and on the properties of sintered yttria-stabilized tetragonal zirconia polytrystalline ceramics (Y-TZP). Test specimens in the shape of bars and discs were produced by injection moulding of ceramic mixtures containing 52.5 and 49 vol% of powder. The powder treatment was found to yield improved rheological properties of ceramic mixtures and improved mechanical properties of sintered specimens in the case of 52.5 vol% of powder in the ceramic mixture. However, the same or even better mechanical properties of sintered components were found when the loading of ceramic mixture was reduced to 49 vol% of powder and non-treated powder was used.     

Effect of operating conditions and design parameters in a continuous powder mixer

An experimental investigation was carried out to study the mixing performance and flow behavior in a continuous powder mixer for a typical pharmaceutical mixture. Blender performance, characterized by the relative standard deviation (RSD) of composition of blend samples taken at the blender discharge and by the variance reduction ratio (VRR) of the blender, was measured as a function of impeller rotation rate, flow rate and blade configuration. The flow behavior in the continuous mixer was characterized using the residence time distribution (RTD) and powder hold-up measurements. To quantify the strain applied to the powder in the blender, the number of blade passes experienced by the powder in the blender was calculated using the residence time measurements. The relationship between different experimental parameters and mean residence time and mean centered variance was examined. The mixing performance was largely dominated by the material properties of the mixture, which had a larger effect than the ingredient flow rate variability contributed by the feeders. Holdup was strongly dependent on impeller rotation rate; as impeller rotation rate increased, holdup (and therefore, residence time) decreased sharply. As a result, intermediate rotation rates showed the best mixing performance. Blade configuration affected performance as well; blade patterns where some of the blades push the powder backwards improved the mixing performance.     

45%精异丙甲草胺微囊悬浮剂高效液相色谱分析

建立高效液相色谱法分离测定45%精异丙甲草胺微囊悬浮剂中有效成分。采用CHIRALPAK AY-H手性柱和紫外可变波长检测器,以正己烷+无水乙醇为流动相,测定试样中精异丙甲草胺的质量分数。方法的标准偏差为0.21,变异系数为0.46%,平均回收率为99.71%。该方法操作简便,分离效果好,精密度与准确度高。     

一种运动检测算法在无人机视频遥感上的应用

提出了一种基于灰度投影与位平面匹配的图像全局运动估计算法，并将其应用于无人机图像稳定系统中．算法采用灰度投影获取全局运动，用网格检测和灰度切分图精确匹配的方法获取更准确的运动数据．由于算法中使用自适应性的灰度切分层选择和基于灰度投影的运动估计缩小搜索区域，使算法效率在空间复杂度和时间复杂度上得到提高，具有较好的实时性和对影像的适应性．