Utility of Multivariate Analysis in Modeling the Effects of Raw Material Properties and Operating Parameters on Granule and Ribbon Properties Prepared in Roller Compaction

This article aimed to model the effects of raw material properties and roller compactor operating parameters (OPs) on the properties of roller compacted ribbons and granules with the aid of principal component analysis (PCA) and partial least squares (PLS) projection. A database of raw material properties was established through extensive physical and mechanical characterization of several microcrystalline cellulose (MCC) and lactose grades and their blends. A design of experiment (DoE) was used for ribbon production. PLS models constructed with only OP-modeled roller compaction (RC) responded poorly. Inclusion of raw material properties markedly improved the goodness of fit (R²?=?.897) and model predictability (Q²?=?0.72).     

On-line dissolution determination of Baicalin in solid dispersion based on near infrared spectroscopy and circulation dissolution system

Drug on-line circulation dissolution system with near infrared spectrophotometer for dissolution determination was reported in this paper and subsequently partial least squares (PLS) calibration model was established for concentration prediction of Baicalin in solid dispersion. When the main factor number in PLS calibration model was 6, the correlation coefficients of PLS calibration samples and prediction ones were all 0.9999 and the relative standard deviations were 0.69% and 1.10%, respectively, which showed good robustness and predictability. Combining drug circulation dissolution system with the PLS calibration model, dissolution of Baicalin in raw material drug and solid dispersion were obtained at different times. The results indicated that the dissolution property of Baicalin in solid dispersion (especially at the early time) had been significantly improved. The accumulated dissolution of Baicalin in the solid dispersion at 45 min reached nearly 40%, increasing by 15% compared with raw material drug (about 25%). The aforementioned PLS model associated with drug circulation dissolution system provided a simple, accurate and on-line support for dissolution determination of drug, especially at the early time of rapid dissolution.     

Multivariate methods in the development of a new tablet formulation: excipient mixtures and principal properties

A tablet formulation for direct compression has previously been studied using multivariate design. An optimization study of one of the most important tablet properties, disintegration time, revealed that excipients with Principal Properties (PP's) that were predicted as suitable by the model were not represented within the studied material. The feasibility of using mixtures of excipients in the multivariate approach to tablet formulation to solve this problem has been investigated in the present study. By mixing different excipients of the same excipient class, it should be possible to obtain mixtures with the predicted PP's, which in turn should give a formulation with the desired properties. In order to investigate the utility of this approach, separate mixture designs were applied to both binders and fillers (diluents). As reported here, the Partial Least Squares Projections to Latent Structures (PLS) model developed in the previously published screening study has been validated in the sense that the interesting region of the PP space identified in it has been shown to contain excipients, pure or mixed, that give the formulation suitable properties. Formulations with suitable properties were found with the mixture experiments. The local models also offer several alternatives for the composition of the formulation that yield the desired disintegration time.     

The use of LS–PLS for improved understanding, monitoring and prediction of cheese processing

In this paper we demonstrate both a design strategy and a set of analysis techniques for a designed experiment from an industrial process (cheese making) with multivariate responses (sensory data). The design strategy uses two-level factorial design for the factors that can be controlled, and blocking on the raw material to cover other non-designed variation in the raw material. We measure both the raw materials and on several points during the process with FT-IR spectroscopy. The methods of analysis complement each other to give more understanding and better modelling. The 50–50 MANOVA method provides multivariate analysis of variance to test for significance of effects for the design variables. Ordinary PLS2 analysis gives an overview of the data and generates hypotheses about relations. Finally, the orthogonal LS–PLS method is extended to multivariate responses and used to identify the source of the observed block effect and to build models that can be used for statistical process control at several points in the process. In these models, the information at one point is corrected for information that has already been described elsewhere.     

纳米氧化铝/有机氟复合乳液的组装及其拒水拒油性

采用自制的不同微观形态的纳米氧化铝与有机单体通过原位聚合制备出纳米氧化铝/有机氟聚合物复合乳液。纳米氧化铝在聚合前经过偶联剂改性,使其表面结合上活性基团以利于与有机单体聚合。采用多种分析手段对改性前后纳米材料以及所制备的复合乳液的微观结构及形态进行了表征,并对复合乳液整理后的涤纶织物进行了拒水拒油性测试。实验结果表明:偶联剂KH-570改性后的纳米氧化铝在有机单体以及合成的复合乳液中具有极好的分散稳定性,以珊瑚状氧化铝为原材料制备的复合乳液整理后织物拒水拒油性强于球状纳米氧化铝,而且与市售有机氟乳液相比,该复合乳液具有用量少、焙烘温度低、功能持久性强等优点。      

The influence of API concentration on the roller compaction process: modeling and prediction of the post compacted ribbon,granule and tablet properties using multivariate data analysis

Objective: While previous research has demonstrated roller compaction operating parameters strongly influence the properties of the final product, a greater emphasis might be placed on the raw material attributes of the formulation. There were two main objectives to this study. First, to assess the effects of different process variables on the properties of the obtained ribbons and downstream granules produced from the rolled compacted ribbons. Second, was to establish if models obtained with formulations of one active pharmaceutical ingredient (API) could predict the properties of similar formulations in terms of the excipients used, but with a different API.

Materials and methods: Tolmetin and acetaminophen, chosen for their different compaction properties, were roller compacted on Fitzpatrick roller compactor using the same formulation. Models created using tolmetin and tested using acetaminophen. The physical properties of the blends, ribbon, granule and tablet were characterized. Multivariate analysis using partial least squares was used to analyze all data.

Results: Multivariate models showed that the operating parameters and raw material attributes were essential in the prediction of ribbon porosity and post-milled particle size. The post compacted ribbon and granule attributes also significantly contributed to the prediction of the tablet tensile strength.

Conclusions: Models derived using tolmetin could reasonably predict the ribbon porosity of a second API. After further processing, the post-milled ribbon and granules properties, rather than the physical attributes of the formulation were needed to predict downstream tablet properties. An understanding of the percolation threshold of the formulation significantly improved the predictive ability of the models.     

有机硅-聚氨酯-环氧树脂三元共聚物的合成及表面性能研究

以甲苯-2,4-二异氰酸酯(TDI)、聚醚二元醇为主要原料制得-NCO封端的预聚体,并按一定比例和环氧树脂E-51混合均匀;另用3-氨丙基三乙氧基硅烷(硅烷偶联剂550)、八甲基环四硅氧烷(D4)合成一系列分子量不同的氨丙基聚硅氧烷,利用多元胺作固化剂,合成一系列氨丙基聚硅氧烷改性聚氨酯/环氧共聚物。测试了材料的力学性能、表面接触角、吸水率,同时对材料进行了表面电子能谱(ESCA)分析。结果表明:氨丙基聚硅氧烷-聚氨酯-环氧三元共聚物具有良好的拉伸强度、疏水性能以及较低的表面张力。     

Densification, crystallization, and electrical properties of lead zirconate titanate glass-ceramics

Piezoelectric glass-ceramics in the lead zirconate titanato-lead silicate system were developed. SiO(2) was required for glass formability, and excess PbO allowed low temperature processing. The amounts of those constituents were limited by the optimization of the piezoelectric properties. Only a small region of compositions in this system yielded the desired combination of glass formability, crystallization and densification behavior, and resulting piezoelectric properties. Selected compositions were melted and roller quenched to form glass ribbon, then milled into glass powder. Pressed glass powder densified to closed porosity at 850 degrees C with piezoelectric d(33 ) and g(33) coefficients of 26 pC/N and 33x10(-3 ) Vm/N. The low temperature sintering behavior of these ferroelectric glass-ceramics provides the possibility of incorporating a piezoelectric material as a sensor or actuator in thick film circuits or low-fire multilayer packages.     

A chemometric analysis for evaluation of early-stage cartilage degradation by infrared fiber-optic probe spectroscopy

In vivo identification of early-stage cartilage degradation could positively impact disease progression in osteoarthritis, but to date remains a challenge. The primary goal of this study was to develop an infrared fiber-optic probe (IFOP) chemometric method using partial least squares (PLS1) to objectively determine the degree of cartilage degradation. Arthritic human tibial plateaus (N = 61) were obtained during knee replacement surgery and analyzed by IFOP. IFOP data were collected from multiple regions of each specimen and the cartilage graded according to the Collins Visual Grading Scale of 0, 1, 2, or 3. These grades correspond to cartilage morphology that displayed normal, swelling or softening, superficially slight fibrillation, and deeper fibrillation or serious fibrillation, respectively. The model focused on detecting early cartilage degradation and therefore utilized data from grades 0, 1, and 2. The best PLS1 calibration utilized the spectral range 1733-984 cm(-1), and independent validation of the model utilizing 206 spectra to create a model and 105 independent test spectra resulted in a correlation between the predicted and actual Collins grade of R2 = 0.8228 with a standard error of prediction of 0.258 with a PLS1 rank of 15 PLS factors. A preliminary PLS1 calibration that utilized a cross-validation technique to investigate the possibility of correlation with histological tissue grade (33 spectra from 18 tissues) resulted in R2 = 0.8408 using only eight PLS factors, a very encouraging outcome. Thus, the groundwork for use of IFOP-based chemometric determination of early cartilage degradation has been established.     

羟基磷灰石-钛酸钡仿人骨复合材料的制备及其性能

以HA粉和BT粉为原料,用烧结工艺制备羟基磷灰石-钛酸钡(HA-BT)仿人骨复合材料,使用D/max2200PCX光衍射仪、S4800场发射扫描电镜及其附带的X射线能谱仪、STA449F3同步热分析仪、1036PC万能材料试验机、LC2735准静态压电系数测量仪和ZJD-C型介电常数测试仪对其表征,研究BT含量和烧结温...     

核-壳纳米Ag@ZrO_2复合材料的制备及其抑菌性能

首先,采用溶胶-凝胶法以锆酸四丁酯为原料制备了直径约为230nm单分散性ZrO_2亚微球;然后,以ZrO_2为前体,加入少量AgNO3,用物理方法将Sn2+离子吸附在ZrO_2表面,Ag+被还原成Ag0负载在ZrO_2表面合成Ag@ZrO_2晶种,加入甲醛合成核-壳纳米Ag@ZrO_2复合材料;最后用TEM、XRD和UV-Vis对制备的ZrO_2和Ag@ZrO_2进行表征,并研究其对金黄色葡萄球菌(S.aureus)和大肠杆菌(E.coli)的抑菌性能。结果表明:当Ag浓度为0.6mg/mL时,Ag@ZrO_2对S.aureus和E.coli的抑菌率分别为95.5%和99.0%。因此,Ag@ZrO_2作为理想的抗菌材料可以应用于日常生活和医疗实践中。     

聚醚改性有机硅表面活性剂的制备及其有机硅乳液的性能

以含氢硅油(PHMS)、烯丙基聚醚(PE)为原料,氯铂酸-异丙醇为催化剂制备聚醚改性有机硅(PMS)表面活性剂;考察了其对不同黏度二甲基硅油(PDMS)的乳化性能;并利用红外光谱、全自动界面张力仪等对其进行表征.通过正交试验确定合成的较佳条件为:m(PE)/m(PHMS)＝1、90℃反应5h、催化剂用量(Pt)2.0×10-3%,该条件下PHMS的反应转化率高达93.5%.PMS的临界胶束浓度(CMC)为8.5×10-6mol/L,表面张力γCMC为29.5mN/m,对二甲基硅油具有优良的乳化作用.所制有机硅乳液(SAF)对十二烷基磺酸钠起泡体系具有良好的消抑泡性能,且在10～90℃温度范围、酸碱条件下,均可持续保持消抑泡活性.     

Simultaneous square wave voltammetric determination of 2-mercaptobenzothiazole and 2-mercaptobenzoxazole by partial least squares method in water samples

A rapid sensitive and versatile method for simultaneous determination of 2-mercaptobenzothiazole (MBT) and 2-mercaptobezoxazole (MBO) based on the square wave voltammetric (SWV) using mercury drop electrode (SMDE) has been presented. A three-electrode system containing SMDE working electrode, Pt auxiliary electrode and Ag/AgCl reference electrode was used throughout. The linear calibration graphs are in the concentration range of 7-40 microg mL(-1) and the equations are: (Deltai)=1.372CMBT-9.112 (r=0.9982) and (Deltai)=0.246CMBO-1.736 (r=0.9985) for MBT and MBO, respectively. Partial least squares regression (PLS) was applied to resolve the seriously overlapped voltammograms without any pre-separation step. The five level partial factorial design was used as calibration design method and the cross-validation method was used to select the number of significant factor for PLS model building. Five significant PLS components are used for MBT and MBO. A set of synthetic sample mixtures were used to validate the propose method. The root-mean-square errors of predictions (RMSEPs) and percent of relative prediction errors (RPEs) are 0.841 and 0.777 microg mL(-1) and +/-3.58 and +/-3.74% for MBT and MBO, respectively. The developed method was then applied to the analysis of these two compounds in different water samples with satisfactory results.     

Effect on the partial least-squares prediction of yarn properties combining raman and infrared measurements and applying wavelength selection

The combination of Raman and infrared spectroscopy on the one hand and wavelength selection on the other hand is used to improve the partial least-squares (PLS) prediction of seven selected yarn properties. These properties are important for on-line quality control during production. From 71 yarn samples, the Raman and infrared spectra are measured and reference methods are used to determine the selected properties. Making separate PLS models for all yarn properties using the Raman and infrared spectra, prior to wavelength selection, reveals that Raman spectroscopy outperforms infrared spectroscopy. If wavelength selection is applied, the PLS prediction error decreases and the correlation coefficient increases for all properties. However, a substantial wavelength selection effect is present for the infrared spectra compared to the Raman spectra. For the infrared spectra, wavelength selection results in PLS prediction errors comparable with the prediction performance of the Raman spectra prior to wavelength selection. Concatenating the Raman and infrared spectra does not enhance the PLS prediction performance, not even after wavelength selection. It is concluded that an infrared spectrometer, combined with a wavelength selection procedure, can be used if no (suitable) Raman instrument is available.     

若干功能材料性能优化建模方法研究

通过对稀土荧光粉，ＶＰＴＣ材料，镍氢电池阴极材料的优化建模计算，研究和比较了线性ＰＬＣ方法，加非线性项的ＰＬＣ方法和加非线性项的ＰＬ－ＳＡＮＮ方法建模的效果。结果表明：当材料，性能和影响性能的因子间非线性较为严重时，加非线性项的ＰＬＳ－ＡＮＮ方法建模的效果较好，其预测结果和实测结果相当符合。     

拟薄水铝石包覆氧化石墨烯改性环氧树脂-氰酸酯复合材料的微观表征及力学性能

以物理法石墨烯为原料,采用改进的Hummers法制备了氧化石墨烯(GO),通过溶胶-凝胶法在氧化石墨烯表面生长拟薄水铝石(AlOOH)纳米颗粒,得到拟薄水铝石包覆氧化石墨烯(GO@AlOOH),以环氧树脂(E51)和双酚A型氰酸酯(BCE)为原料,GO@AlOOH作为增强体,制备GO@AlOOH/E51-BCE复合材料。采用红外光谱和X射线表征GO@AlOOH,结果表明:AlOOH和GO存在着相互作用,且其表面含有羟基活性基团。复合材料的SEM结果显示:GO@AlOOH的加入使得树脂断裂面明显改变,性能得到提升。当掺杂量为0.6wt%时,复合材料的弯曲强度、弯曲模量以及冲击强度达到最大,分别为158.23 MPa、2.37 GPa和46.96 kJ/m2。该复合材料具有优异的力学性能,具有一定的发展潜力。      

A novel approach for development of a multivariate calibration model using a Doehlert experimental design: Application for prediction of key gasoline properties by Near-infrared Spectroscopy

Alternative methods for quality control in the petroleum industry have been obtained using Near-infrared Spectroscopy (NIRS) combined with multivariate techniques such as PLS (Partial Least-Square). The process of development and refinement of PLS models usually follows a nonsystematic and univariate procedure. The Standard Error of Cross Validation (SECV), the Standard Error of Prediction (SEP) and the determination coefficient (r²_regr.) are usually the only guides used in pursuit of the best model. In the present work, a novel approach was proposed using a Doehlert experimental design with three input variables (wavenumber range, preprocessing technique and regression/validation technique) varied at 5, 7 and 3 levels, respectively. Besides SECV, SEP and r²_regr., some additional response variables, such as the slope, r² and p_value from the external validation, as well as the number of PLS factors, were simultaneously assessed to find the optimum conditions for PLS modeling. The optimum setting for each input variable was simultaneously defined through a multivariate approach using a desirability function. With the proposed approach, the main and interaction effects could also be investigated. The methodology was successfully applied to obtain PLS models to monitor the gasoline quality through the process of product loading in trucks. To prevent product contamination or adulteration, fast prediction of key properties was obtained from FT-NIR spectra within the 7300-3900 cm^− 1 region with SECV in the range 0.04-0.63% w/w for composition (Aromatics, Saturates, Olefins and Benzene) and 0.0008 for Relative Density 20/4 °C. Each optimized PLS model was obtained with less than 40 modeling runs, demonstrating the efficiency of the proposed approach.     

Effects of roller burnishing process parameters on surface roughness of A356/5%SiC composite using response surface methodology

In this study,a simple roller burnishing tool was made to operate burnishing processes on A356/5%SiC metal matrix composite fabricated by electromagnetic stir casting under different parameters.The effects of burnishing speed,burnishing force and number of burnishing passes on the surface roughness and tribological properties were measured.Scanning electron microscopy(SEM) graphs of the machined surface with PCD(insert-10) tool and roller burnished surface with tungsten carbide(WC) roller were taken into consideration to observe the surface finish of metal matrix composites.The mechanical properties(tensile strength,hardness,ductility) of A356/5%SiC metal matrix composites were studied for both unburnished samples and burnished samples.The results revealed that the roller burnished samples of A356/5%SiC led to the improvement in tensile strength,hardness and ductility.In order to find out the effects of roller burnishing process parameters on the surface roughness of A35675%SiC metal matrix composite,response surface methodology(RSM)(Box-Behnken design) was used and a prediction model was developed relevant to average surface roughness using experimental data.In the range of process parameters,the result shows that roller burnishing speed increases,and surface roughness decreases,but on the other hand roller burnishing force and number of passes increase,and surface roughness increases.Optimum values of burnishing speed(1.5 m/s),burnishing force(50 N) and number of passes(2)during roller burnishing of A356/5%SiC metal matrix composite to minimize the surface roughness(predicted1.232 urn) have been found out.There was only 5.03%error in the experimental and modeled results of surface roughness.     

Investigation of electrolyte measurement in diluted whole blood using spectroscopic and chemometric methods

The feasibility of using near-infrared (NIR) spectroscopy in combination with partial least-squares (PLS) regression was explored to measure electrolyte concentration in whole blood samples. Spectra were collected from diluted blood samples containing randomized, clinically relevant concentrations of Na+, K+, and Ca2+. Sodium was also studied in lysed blood. Reference measurements were made from the same samples using a standard clinical chemistry instrument. Partial least squares (PLS) was used to develop calibration models for each ion with acceptable results (Na+, R2 = 0.86, CVSEP = 9.5 mmol/L; K+, R2 = 0.54, CVSEP = 1.4 mmol/L; Ca2+, R2 = 0.56, CVSEP = 0.18 mmol/L). Slightly improved results were obtained using a narrower wavelength region (470-925 nm) where hemoglobin, but not water, absorbed indicating that ionic interaction with hemoglobin is as effective as water in causing measurable spectral variation. Good models were also achieved for sodium in lysed blood, illustrating that cell swelling, which is correlated with sodium concentration, is not required for calibration model development.     

Assessment of granulation technologies for an API with poor physical properties

Granulation technologies are widely used in solid oral dosage forms to improve the physical properties during manufacture. Wet, dry, and melt granulation techniques were assessed for Compound A, a BCS class II compound. Characterization techniques were used to quantify physical property limitations inherent for Compound A including hygroscopicity, low solubility and bulk density, and poor powder flowability. High shear aqueous wet granulation induced an undesirable water mediated phase transition of the solid form. A formulation and process for dry granulation by roller compaction was developed and scaled to 10 kg batch size. Roll force, and roll gap parameters were assessed. Porosity of compacted ribbons was analyzed by mercury intrusion porosimetry, and particle size distributions of milled ribbons by sieve analysis. A roll force of 15 kN/cm produced granules with higher density and improved flow properties compared to the pre-blend. Fines content (<75 µm) decreased from approximately 90% pre-granulation to 26% post-granulation. Cohesive properties of Compound A limited drug loading (API:excipient ratio) in roller compaction to 0.6:1 or less. Hot melt granulation by extrusion assessed with four polymers. A vast improvement in drug loading of 4:1 was achieved via melt processes using low molecular weight thermo-binders (glyceryl behenate and Polyethylene glycol 4000). Granules produced by melt processing contained less fines compared to wet and dry granulation. Both roller compaction and melt extrusion are viable granulation process alternatives for scale up to overcome the physical property limitations of Compound A.