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 (R(2) = .897) and model predictability (Q(2) = 0.72).     

Development of a design space and predictive statistical model for capsule filling of low-fill-weight inhalation products

The objectives of this study were to develop a predictive statistical model for low-fill-weight capsule filling of inhalation products with dosator nozzles via the quality by design (QbD) approach and based on that to create refined models that include quadratic terms for significant parameters. Various controllable process parameters and uncontrolled material attributes of 12 powders were initially screened using a linear model with partial least square (PLS) regression to determine their effect on the critical quality attributes (CQA; fill weight and weight variability). After identifying critical material attributes (CMAs) and critical process parameters (CPPs) that influenced the CQA, model refinement was performed to study if interactions or quadratic terms influence the model. Based on the assessment of the effects of the CPPs and CMAs on fill weight and weight variability for low-fill-weight inhalation products, we developed an excellent linear predictive model for fill weight (R^2?=?0.96, Q^2?=?0.96 for powders with good flow properties and R^2?=?0.94, Q^2?=?0.93 for cohesive powders) and a model that provides a good approximation of the fill weight variability for each powder group. We validated the model, established a design space for the performance of different types of inhalation grade lactose on low-fill weight capsule filling and successfully used the CMAs and CPPs to predict fill weight of powders that were not included in the development set.     

Properties of zirconia-toughened mullite ceramics improved by B2O3 additive

Zirconia-toughened mullite (ZTM) ceramics has been prepared by using an electrically fused mullite as a raw material and its mechanical properties and microstructure as a function of impurities in the raw material were studied. These impurities led to a decrease in the mechanical properties of ZTM ceramics by changing the properties of the glassy phase in the ceramics, especially at high temperature. The mechanical properties of the ceramics were improved by adding B2O3, and the toughness at room temperature increased from 4.4 MPa m^1/2 to 5.9 MPa m^1/2 while that at 800°C increased from 2.9 MPa m^1/2 to 4.4 MPa m^1/2. The toughness of the ceramics on the addition of B2O3 at room temperature was increased by 34% and that at 800°C by 52%. The influence of the impurities on the ZTM ceramics and the improvement of the ceramic properties by the addition of B2O3 were studied and their mechanisms were discussed. This revised version was published online in November 2006 with corrections to the Cover Date.     

Influence of spoliation in poly(2-hydroxy ethyl methacrylate) soft contact lens on its free volume and optical transparency

The calcification in poly(2-hydroxy ethyl methacrylate) contact lens was investigated using positron annihilation spectroscopy (PLS). The two poly(2-hydroxy ethyl methacrylate) (PHEMA) lenses of different companies were calcified employing a simple mechanism of calcification in abiotic aqueous solutions. The calcium deposit was analyzed using energy dispersive X-ray spectroscopy (EDS). Calcified lenses showed decrease in ortho-positronium (o-Ps) lifetime and free volume hole size of the lens material suggesting diffusion of Ca²⁺ into these cavities. The change in optical property viz. refractive index of these calcified lenses were measured and correlated with positron results. To find a better correlation, a series of worn spoilt PHEMA lenses of the same power with mainly calcium deposits, were similarly characterized using PLS and refractive index. These results correlate well with the free volume of the material. For hydrophilic lenses this correlation is reported for the first time.     

Near-infrared spectroscopic analysis of the breaking force of extended-release matrix tablets prepared by roller-compaction: influence of plasticizer levels and sintering temperature

The aim of this study was to investigate the feasibility of near-infrared (NIR) spectroscopy for the determination of the influence of sintering temperature and plasticizer levels on the breaking force of extended-release matrix tablets prepared via roller-compaction. Six formulations using theophylline as a model drug, Eudragit® RL PO or Eudragit® RS PO as a matrix former and three levels of TEC (triethyl citrate) as a plasticizer were prepared. The powder blend was roller compacted using a fixed roll-gap of 1.5?mm, feed screw speed to roller speed ratio of 5:1 and roll pressure of 4?MPa. The granules, after removing fines, were compacted into tablets on a Stokes B2 rotary tablet press at a compression force of 7?kN. The tablets were thermally treated at different temperatures (Room Temperature, 50, 75 and 100?°C) for 5?h. These tablets were scanned in reflectance mode in the wavelength range of 400–2500?nm and were evaluated for breaking force. Tablet breaking force significantly increased with increasing plasticizer levels and with increases in the sintering temperature. An increase in tablet hardness produced an upward shift (increase in absorbance) in the NIR spectra. The principle component analysis (PCA) of the spectra was able to distinguish samples with different plasticizer levels and sintering temperatures. In addition, a 9-factor partial least squares (PLS) regression model for tablets containing Eudragit® RL PO had an r² of 0.9797, a standard error of calibration of 0.6255 and a standard error of cross validation (SECV) of 0.7594. Similar analysis of tablets containing Eudragit® RS PO showed an r² of 0.9831, a standard error of calibration of 0.9711 and an SECV of 1.192.     

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.     

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.     

Tuning the Structural and Optoelectronic Properties of Cs2AgBiBr6 Double-Perovskite Single Crystals through Alkali-Metal Substitution

Lead-free double perovskites have great potential as stable and nontoxic optoelectronic materials. Recently, Cs₂AgBiBr₆ has emerged as a promising material, with suboptimal photon-to-charge carrier conversion efficiency, yet well suited for high-energy photon-detection applications. Here, the optoelectronic and structural properties of pure Cs₂AgBiBr₆ and alkali-metal-substituted (Cs_1−xY_x)₂AgBiBr₆ (Y: Rb⁺, K⁺, Na⁺; x = 0.02) single crystals are investigated. Strikingly, alkali-substitution entails a tunability to the material system in its response to X-rays and structural properties that is most strongly revealed in Rb-substituted compounds whose X-ray sensitivity outperforms other double-perovskite-based devices reported. While the fundamental nature and magnitude of the bandgap remains unchanged, the alkali-substituted materials exhibit a threefold boost in their fundamental carrier recombination lifetime at room temperature. Moreover, an enhanced electron–acoustic phonon scattering is found compared to Cs₂AgBiBr₆. The study thus paves the way for employing cation substitution to tune the properties of double perovskites toward a new material platform for optoelectronics.     

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.     

Comparative binder efficiency modeling of dry granulation binders using roller compaction

Roller compaction parameters’ impact on granules and tableting properties of coprocessed Avicel^® DG [ADG], a physical mixture of the two components at the same composition present in ADG [PADCP], and microcrystalline cellulose and Kollidon^® VA-64 Fine physical mixture [KVA64] was quantified by analysis of variance (ANOVA) and multivariate methods. Roller force, roller gap, and roller speed levels were selected for evaluation. A 3³ full-factorial experimental design with three center points for roller force, roller gap, and roller speed was used. The response parameters studied were granule-to-fines (GF) ratio, compressibility index (CI), tablet thickness (TT), tablet friability (TF), tablet breaking force (TBF) and disintegration time (DT). A model acetaminophen tablet formulation was roller granulated and tableted at 10?kg scale. Principal component analysis of ADG and PADCP formulations were separated from KVA64 formulations, indicating different granule and tableting properties were binder dependent. This difference in binder performance was also confirmed by ANOVA. The ANOVA also showed that there were no statistical performance differences between coprocessed ADG and its comparable physical blend with the exception of TT. Principal component regression (PCR) analyses of ADG and PADCP revealed that these excipients exhibited a statistically significant negative effect on granules-to-fine (GF) ratio, TT, TBF, and DT. KVA64 demonstrated a positive effect on these parameters. The KVA64 physical mixture demonstrated an overall better performance and binding capability. This study strongly suggests that there is no performance advantage of coprocessed Avicel^® DG when compared to a physical mixture of the two components at the same composition.     

Multivariate Methods in the Development of a New Tablet Formulation: Excipient Mixtures and Principal Properties

ABSTRACT

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.     

Transport Properties under Magnetic Field and J c (H) Peak Effect on Single-Crystal Bi-2212 Whiskers

In this study, 50 nm–18 mm in length superconducting single-crystal Bi-2212 whiskers have been fabricated using glass-ceramic BSCCO material. The microstructure, transport and magnetic properties were characterized by XRD, SEM-EDX, R–T, I–V and M–H analysis. Highly c-axis oriented single-crystal whiskers were produced without any grain boundaries in any crystallographic direction. T _c and T _zero were obtained to be 94.8 K and 92.8 K, respectively, and decreased with increasing the magnetic field. Magnetic properties, M–H curves of the whiskers, were investigated at 3 different constant temperatures up to 5 T. Symmetric hysteresis loops for all temperature and field cases were obtained and maximum J _c ^mag value was calculated to be 4.58×10⁶ A cm⁻² at 10 K for 0 T but dropped to 1.61×10⁶ A cm⁻² at 30 K for 0 T. Transport critical current density, J _c ^trans, of the whiskers in low magnetic field (between 0 and 270 Oe) and in a wide temperature region (5–75 K) was investigated. It was obtained that initially J _c ^trans increased with increasing the magnetic field but then started to decrease with further increase on the magnetic field at all temperature values. We have investigated this problem in terms of the Bulk pinning model, the Geometrical barrier model and the Bean–Livingston surface barrier model. We have noticed that all these models were not fitted well to our data. However, we have modified the Bean–Livingstone model by adding a new parameter. It was found that this modified formula fitted well to the data obtained in this work and can give successful explanations to the other results obtained by other groups.     

Electrical Properties and Ferromagnetism in (Ga,Cr)As

MBE-grown (Ga,Cr)As has interesting electric and magnetic properties. Ga_1–x Cr _x As with x = 0.1 exhibits short-range ferromagnetic behavior at low temperatures. This is manifest in several anomalous properties: magnetization does not scale with B/T; fitting M(B) requires a model of distributed magnetic cluster or polarons; and inverse susceptibility is nonliner in T (non-Curie–Weiss) at low fields. At room temperature, the conductivity is activated and Hall measurements yield a hole concentration of 10²⁰ cm^–3, indicating that chromium acts as an acceptor similar to Mn in GaAs. For decreasing temperature, the conductivity decreases by eight orders of magnitude and follows exp(1/T ^1/2).     

Microscopic and Macroscopic Magnetic Properties of the MgAl x Cr x Fe2 − 2x O4 Spinel Ferrite System

To determine the influence of the substitution of Al³⁺ and Cr³⁺ for Fe³⁺ in MgFe₂O₄ ferrites on the structural and magnetic properties, the MgAl _x Cr _x Fe_{2 – 2x} O₄ (x = 0.0–0.8) spinel systems were studied by using the X-ray diffraction analysis, magnetization in strong fields, magnetic susceptibility in weakly variable electric fields, and Mössbauer spectroscopy. Unlike previous investigations, it was discovered that a half of Al³⁺ occupies tetragonal positions. The system forms a noncollinear spin structure and a central paramagnetic doublet is superimposed over the magnetic sextet in the Mössbauer spectrum (0.5 > x > 0.2). The dependence of the magnetic susceptibility on temperature reveals the normal ferromagnetic properties of the material.     

纳米二氧化钛抗菌热收缩膜的制备与性能研究

目的 比较不同质量分数二氧化钛(TiO₂)对抗菌热收缩膜的物理性能和抗菌效果。方法 以线性低密度聚乙烯、乙烯–醋酸乙烯酯共聚物、聚偏二氯乙烯为原料,采用共挤压法制备纳米TiO₂质量分数分别为0%、2%、3%、4%的抗菌热收缩膜,并对其性能进行研究。结果 纳米TiO₂颗粒在抗菌热收缩膜表面均匀分布,添加纳米TiO₂对热收缩膜的厚度和不透明度没有显著影响(P>0.05)。随着纳米TiO₂添加量的增加,纳米TiO₂抗菌热收缩膜的断裂伸长率和拉伸强度呈先升高后下降趋势。当纳米TiO₂质量分数为3%时,断裂伸长率和拉伸强度分别达到最大值238.48%和55.64MPa。添加纳米TiO₂对热收缩膜的氧气透过量和水蒸气透过量没有影响(P>0.05)。纳米TiO₂抗菌热收缩膜对假单胞菌MN10、肉杆菌VE51、乳球菌VE58和乳杆菌VMR17表现出优异的抗菌性能,随着TiO₂     

On-line predictions of the aspen fibre and birch bark content in unbleached hardwood pulp, using NIR spectroscopy and multivariate data analysis

An on-line fibre-based near-infrared (NIR) spectrometric analyser was adapted for on-site process analysis at an integrated paperboard mill. The analyser uses multivariate techniques for the quantitative predication of the aspen fibre (aspen) and the birch bark contents of sheets of unbleached hardwood pulp. The NIR analyser is a prototype constructed from standard NIR components. The spectroscopic data was processed by using principal component analysis (PCA) and partial least square (PLS) regression. Three sample sets were collected from three experimental designs, each composed of known pulp contents of birch, aspen and birch bark. Sets 1 and 2 were used for model calibration and set 3 was used to validate the models. The PLS model that produced the best predictions gave an error of prediction (RMSEP) of 13% for aspen and less than 2% for birch bark. Eight components resulted in an R²X of 99.3%, R²Y of 99.6%, and Q² of 95.3%. For additional validation of aspen, three unbleached hardwood samples from the mill's production were calculated to lie between − 7% and + 6%, regarding to the PLS model. When vessel cells were counted under a light microscope a value for the aspen content of 4.7% was obtained. The predictive models evaluated were suitable for quality assessments rather than quantitative determination.     

Static Response of Geometrically Nonlinear Laminated Composite Plates Having Uncertain Material Properties

The effect of uncertainty in material properties on the transverse bending of laminated composite plate is investigated. The transverse shear and large rotations have been included in the system equation in the framework of higher order shear deformation theory. The analysis uses Green–Lagrange nonlinear strain displacement equations to model geometric nonlinearity. The stochastic finite element analysis is performed using a direct iteration approach to handle deterministic geometric nonlinearity and perturbation approach to handle the randomness in the material properties. Mean and variance of the transverse deflection have been obtained by employing a C⁰ isoparametric nonlinear finite element model.     

Preparation of high-T c superconducting film in the system of Bi-Sr-Ca-Cu-O from sol-gel process and its properties

High-T _c superconducting Bi₂Sr₂CaCu₂O_x films withT _c ^off =80 K were prepared by the dipping method of sol-gel processing using inorganic salts. The influence of the preparation conditions on the superconducting properties of the derived material is reviewed. Bi, Sr, Ca and Cu nitrates were used as raw materials. Glycerol was used as solvent. The thickness of films made by the dip method was about 0.5 m. The films were crystallized by heat-treatment at 830°C for 10 min.T _c ^off of films was 80 K andJ _c at 77 K was more than 8 kA cm^–2. Synthesis of high-T _c superconducting films was very easy and the crystallization of films was possible with a relatively low heat-treatment temperature.     

Flow Properties of Awned and De-Awned Paddy Grains Through a Horizontal Hopper Orifice

In a modern rice mill, de-awning is an important process before husking operation to eliminate awns of the paddy grains for easy conveying in the elevators, chutes, and hopper orifices. This experiment was conducted to study the effects of independent variables of de-awning percentage, orifice cross-sectional area and paddy grains moisture content on the flowing rate (FR) and variations of flowing rate (VFR) of paddy grains through a horizontal hopper orifice. A local paddy variety, namely, Hashemi, which is characterized by long awns was used as a raw material in the test. The results indicated that flow rate (FR) and variations on flow rate (VFR) significantly (p < 0.01) affected by the de-awning percentage, orifice cross-sectional area and paddy moisture content. FR increased from 45.00 to 87.57 g s^?1 and VFR decreased from 54.93 to 21.49%, as de-awning increased from 14.67 to 84.93%. FR increased as the orifice cross-sectional area increased from 12.08 to 34.81 cm²; however, higher VFR was obtained at lower orifice cross-sectional area. For the awned (87% of the grains had originally awns) and de-awned paddy (82% of the grains were de-awned), FR decreased as the paddy moisture content increased from 8.67 to 15.06%wb; while VFR increased at higher grain moisture content.     

Tableting Properties of Experimental and Commercially Available Lactose Granulations for Direct Compression

Abstract

Lactose granulations (125-250 μm) were prepared from two different β-lactose monohydrate powders and one roller dried B-lactose powder respectively, by wet granulation with only water as a binder. As an effect of the granulation process, the flow properties improved, but the compactibility decreased. Moreover, the lubricant sensitivity of the granule fractions was higher than found for the starting materials. The compactibility of the granule fractions was found to be dependent on the type of lactose, the surface area of the starting powder and the granule bulk density. For lubricated lactose granulations, the lubricant sensitivity, expressed as Lubricant Sensitivity Ratio (LSR), increased with an increase of bulk density. The β-lactose content of roller-dried β-lactose is hardly affected by the granulation process, which explains the good compactibility of the granule fractions prepared from this type of lactose. On the other hand, anhydrous α-lactose present in the roller-dried β-lactose starting material is converted into α-lactose monohydrate during the granulation process, which improves tablet disintegration.

The compaction properties of commercially available lactose granulations have been compared with those of the experimental granulations and with a free flowing sieved α-lactose monohydrate. As an effect of the higher powder surface area and the relatively low bulk density, Tablettose^R has a better compactibility than α-lactose monohydrate 100 Mesh. The excellent compactibility of another commercially available lactose granulation, Pharmatose^K DCL 15, was attributed to the presence of more β-lactose, providing strong intergra-nular cohesion.