Evaluation of the compaction properties of a solid dispersion of indomethacin with crospovidone by tableting process analyzer

A powder solid dispersion system (SD) of indomethacin (IM) with crospovidone (CrosPVP) possesses good fluidity and can be used for tablet formulation. Tablets of SD can be prepared by direct compression and have adequate hardness and a small variation in weight. Forces during the tableting process were measured with a tableting process analyzer (TabAll) equipped with a single-punch. The pressure transmission ratio (PTR) from the upper to the lower punch and the die wall force (DWF) were examined during the tableting process. Ejection force (EF) and scraper pressure (SP) were measured for determining the capping and sticking properties during the tableting process. Adding 1% magnesium stearate (MS) to the SD resulted in high PTR and DWF values and a low EF value. PTR and DWF values increased and EF value decreased when MS and microcrystalline cellulose (MCC) were added to the SD. A thousand tablets could be manufactured without problems such as sticking or capping when 1% MS and 50% MCC were added to the SD containing 25% IM.     

Theoretical analysis of tablet hardness prediction using chemoinformetric near-infrared spectroscopy.

In order to clarify the theoretical basis of the variability in the measurement of tablet hardness by compression pressure, NIR spectroscopic methods were used to predict tablet hardness of the formulations. Tablets (200 mg, 8 mm in diameter) consisting of berberine chloride, lactose, and potato starch were formed at various compression pressures (59, 78, 98, 127, 195 MPa). The hardness and the distribution of micropores were measured. The reflectance NIR spectra of various compressed tablets were used as a calibration set to establish a calibration model to predict tablet hardness by principal component regression (PCR) analysis. The distribution of micropores was shifted to a smaller pore size with increasing compression pressure. The total pore volume of tablets decreased as the compression pressure increased. The hardness increased as the compression pressure increased. The hardness could be predicted using a calibration model consisting of 7 principal components (PCs) obtained by PCR. The relationship between the predicted and the actual hardness values exhibited a straight line, an R(2) of 0.925. In order to understand the theoretical analysis (scientific background) of calibration models used to evaluate tablet hardness, the standard error of cross validation (SEV) values, the loading vectors of each PC and the regression vector were investigated. The result obtained with the calibration models for hardness suggested that the regression vector might involve physical and chemical factors. In contrast, the porosity could be predicted using a calibration model composed of 2 PCs. The relationship between the predicted and the actual total pore volume showed a straight line with R(2) = 0.801. The regression vector of the total pore volume might be due to physical factors.     

Negative velocity dependence of friction for poly(2‐Acrylamido‐2‐methyl propanesulfonic acid) hydrogel sliding against a glass surface in the low‐velocity region

The frictional behavior of poly(2‐acrylamido‐2‐methylpropanesulfonic acid) (PAMPS) hydrogel sliding against a glass substrate in water over a wide sliding velocity (v) region has been investigated. The results showed that the frictional behavior of PAMPS gel conformed to a hydrodynamic lubrication mechanism only at relatively high sliding velocities. At low sliding velocities, a “negative” velocity dependence of friction was observed, which we believe not to be attributable to the experimental friction‐measuring mode used. This wider and weak mixed region at low sliding velocities is in contrast to the extremely narrow mixed region in the case of solid friction with a lubricant. The area of the PAMPS hydrogel surface subject to shearing decreased with increasing sliding velocity, and this would seem to be responsible for the weakly negative dependence of friction on velocity. In addition, the friction was found to increase with increasing the compressive modulus (E) of the gels attributing to the shearing exerted on the gel surface, in which the shear stress increased with E. The hydration layer between the sliding surfaces also contributes to the friction and weakens the dependence of friction on E to some extent. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2014 , 52, 765–772     

The growth of shear bands in polystyrene

Shear-band growth velocities have been determined as a function of stress and temperature in polystyrene. The results demonstrate that shear bands can propagate under isothermal conditions; an adiabatic temperature rise at the shear band tip is not necessary for continued localization and growth of the band. The velocity is stress activated with a shear activation volume of 4600 ų and thermally activated with an activation enthalpy of 2.8 eV. Comparison of these values of the activation parameters with those for bulk shear flow in polystyrene indicates that the shear band propagation is controlled by the plastic strain rate of the glassy polymer immediately ahead of the tip of the band. Argon's molecular kink model of the elemental deformation process is consistent with measured values of the activation parameters whereas Bowden and Raha's dislocation model is not. The shear bands grow at an angle of ca. 38° to the axis of compression, and if the direction of compression is altered, the shear bands will change direction so as to maintain the 38° angle. Current explanations can not quantitatively account for the large deviation of the shear bands from the 45° plane of maximum shear stress.     

Influence of physical parameters and lubricants on the compaction properties of granulated and non-granulated cross-linked high amylose starch

Cross-linked high amylose starch (CLA) is a pharmaceutical excipient used in direct compression for the preparation of controlled release tablets and implants. In this work the compression properties of CLA in bulk and granulated forms (without binder) were evaluated for the first time. Tablets were prepared on an instrumented single punch machine. The flow properties and the compression characteristics (compressibility, densification behavior, work of compression) of the materials as well as the mechanical strength of the finished compacts (compactibility) were systematically examined. Wet granulation was found to improve the flowability and the compressibility of CLA but concomitantly reduced its compactibility. It was demonstrated that CLA was a plastically deforming material with a plasticity index and a yield pressure value comparable to those of pregelatinized starch. The compactibility of granulated CLA was independent of particle size in the range of 75 to 500 microm, but slightly decreased when the percentage of the fine particles (<75 microm) in the bulk powder was increased. Water and colloidal silicone dioxide facilitated the consolidation of CLA, while magnesium stearate had an opposite effect on the tablet crushing force.     

Effect of surface mobility on the particle sliding along a bubble or a solid sphere

The sliding velocity of glass beads on a spherical surface, made either of an air bubble or of a glass sphere held stationary, is measured to investigate the effect of surface mobility on the particle sliding velocity. The sliding process is recorded with a digital camera and analyzed frame by frame. The sliding glass bead was found to accelerate with increasing angular position on the collector's surface. It reaches a maximum velocity at an angular position of about 100 degrees and then, under certain conditions, the glass bead leaves the surface of the collector. The sliding velocity of the glass bead depends strongly on the surface mobility of a bubble, decreasing with decreasing surface mobility. By a mobile surface we mean one which cannot set up resistive forces to an applied stress on the surface. The sliding velocity on a rigid surface, such as a glass sphere, is much lower than that on a mobile bubble surface. The sliding velocity can be described through a modified Stokes equation. A numerical factor in the modified Stokes equation is determined by fitting the experimental data and is found to increase with decreasing surface mobility. Hydrophobic glass beads sliding on a hydrophobic glass sphere were found to stick at the point of impact without sliding if the initial angular position of the impact is less than some specific angle, which is defined as the critical sticking angle. The sticking of the glass beads can be attributed to the capillary contracting force created by the formation of a cavity due to spontaneous receding of the nonwetting liquid from the contact zone. The relationship between the critical sticking angle and the particle size is established based on the Yushchenko [J. Colloid Interface Sci. 96 (1983) 307] analysis.     

快扫描傅立叶变换红外光声光谱对SBS/PET双层复合材料的研究

采用快扫描傅立叶变换红外光声光谱研究了苯乙烯-丁二烯-苯乙烯嵌段共聚物/聚对苯二甲酸乙二醇酯 (SBS/PET)双层复合材料.以碳黑膜作参比,氦气作吹扫气体,分辨率设定为8 cm-1,通过调节干涉仪动镜速率,获得了不同实验条件下的红外光声光谱图.比较了相同和不同速率时单一样品以及样品间的光谱变化.对3种不同表层厚度的样品,在同一动镜速率下,表层SBS越薄,其光谱信息越小,通过对特征吸收峰强度的对比,有效比较了其样品表层的厚度.随着动镜速率的逐渐增大,表层光谱特征被相对加强,同时底层光谱特征相对减弱.研究表明,采用快扫描红外光声光谱,在不破坏、不接触双层样品的情况下,通过改变动镜速率即可对表层和底层材料进行分析,并对表层SBS膜厚度进行区分.     

Transition processes from the lamellar to the onion state with increasing temperature under shear flow in a nonionic surfactant/water system studied by Rheo-SAXS

In a previous paper, we reported for the first time the lamellar-to-onion transition with increasing temperature at around 67 °C under a constant shear rate (0.3-10 s(-1)) in a nonionic surfactant C(16)E(7)/water system. In this study, the first temperature-shear rate diagram has been constructed in a wider range of shear rate (0.05-30 s(-1)) than in our previous study based on the temperature dependence of the shear stress at constant shear rate. The results suggest that the critical temperature above which the transition begins does not depend on the shear rate very much, although it takes a very shallow minimum. Then we have performed simultaneous measurements of small-angle X-ray scattering/shear stress (rheo-SAXS) with a stepwise increase in temperature of 0.1 K per 15 min at a constant shear rate of 3 s(-1) near the transition temperature. When the temperature exceeds 67 °C, just before the increase in the shear stress, the intensity of the Bragg peak for the velocity gradient direction (approximately proportional to the number of lamellae with their normal along this direction) is suddenly increased. As the temperature increases by 0.2 K, the shear stress begins to increase. At the same time, the peak intensity in the velocity gradient direction rapidly decreases and instead the intensity in the neutral direction increases. As the temperature increases further, the intensities in both the neutral and gradient directions decrease whereas the intensity in the flow direction increases, corresponding to the formation of onions. We have also performed rheo-SAXS experiments with a stepwise increase in shear rate at 72 °C. The sequence of the change in the intensity in each direction is almost the same in the temperature scan experiments at constant shear rate, suggesting that the transition mechanisms along these two paths are similar. The abrupt enhancement of the lamellar orientation with the layer normal along the velocity gradient direction just before the transition is the first finding and strongly supports the coherent buckling mechanism in the lamellar-to-onion transition proposed by Zilman and Granek (Zilman, A. G.; Granek, R. Eur. Phys. J. B 1999, 11, 593).     

Nano-scale superhydrophobicity: suppression of protein adsorption and promotion of flow-induced detachment

Wall adsorption is a common problem in microfluidic devices, particularly when proteins are used. Here we show how superhydrophobic surfaces can be used to reduce protein adsorption and to promote desorption. Hydrophobic surfaces, both smooth and having high surface roughness of varying length scales (to generate superhydrophobicity), were incubated in protein solution. The samples were then exposed to flow shear in a device designed to simulate a microfluidic environment. Results show that a similar amount of protein adsorbed onto smooth and nanometer-scale rough surfaces, although a greater amount was found to adsorb onto superhydrophobic surfaces with micrometer scale roughness. Exposure to flow shear removed a considerably larger proportion of adsorbed protein from the superhydrophobic surfaces than from the smooth ones, with almost all of the protein being removed from some nanoscale surfaces. This type of surface may therefore be useful in environments, such as microfluidics, where protein sticking is a problem and fluid flow is present. Possible mechanisms that explain the behaviour are discussed, including decreased contact between protein and surface and greater shear stress due to interfacial slip between the superhydrophobic surface and the liquid.     

粉末压片-X-射线荧光光谱法分析砂岩型铀矿制样中粘结剂用量的探讨

由于砂岩型铀矿的成矿特性,样品粉末的内聚力小,采用直接压片法有时难以成型,样片表面常见裂纹,上机测量易碎裂。混合压片法适应性强,制样成功率高,但常见的问题是样品经粘结剂稀释会影响元素的检出限及结果的准确性。本文对粉末压片-X射线荧光光谱法测定砂岩型铀矿地质样品时,前期制样中添加粘结剂的比例进行了研究。试验按照不同比例在铀矿石标准物质GBW04101、GBW04102中添加粘结剂,在扫描电镜下观察到随着粘结剂用量的增加样片表面的光滑度及致密度都呈上升趋势,在X-射线荧光光谱仪上对主量元素进行测定后发现X射线强度在粘结剂添加量大于0.2 g时明显下降,经与GBW04101、GBW04102标准值进行对比后优选出粘结剂与样品的最佳比例为1：20,在此比例下制成的样片光滑平整,不易碎裂,用粉末压片-X射线荧光光谱法进行测定,标准物质测定结果的相对误差为0.56%～6.76 %,相对标准偏差(RSD,n=12)为0.013 %～7.68 %,均达到了《地质矿产实验室测试质量管理规范》DZ/T 0130-2006的要求。本文为粉末压片-X射线荧光光谱法分析砂岩型铀矿地质样品提供了可靠的实验参考依据。     

A novel method for predicting disintegration time in the mouth of rapidly disintegrating tablet by compaction analysis using TabAll

A tableting process analyzer (TabAll) was used to predict disintegration time in the mouth of rapidly disintegrating tablet. Analyzer profiles recorded upper punch displacement and die wall force encountered during tablet processing. Changes in the mixing ratio of spherical sugar granules and microcrystalline cellulose or lactose affected upper punch displacement and die wall force profiles. Analysis of the compaction process revealed a strong association between disintegration time in the mouth and stationary time, relaxation time of upper punch displacement, and relaxation time of die wall force; disintegration time in the mouth decreased as the three parameters increased. Thus, analysis of the compaction process is useful for predicting disintegration time in the mouth of rapidly disintegrating tablet, which can assist the formulation of new rapidly disintegrating tablets.     

Some electrophysical properties of polyphthalocyanines under the action of high pressure and shear deformation

The effect of high pressure or the combined action of high pressure and shear deformation on the conductivity G and capacitance C of metal-free polyphthalocyanines (PPhCs), differing in macromolecular size, order, and degree of crosslinking, has been studied. It has been found that both G and C increase with compression. A similar phenomenon is observed under the combined action of high pressure and shear deformation on PPhC, but in this case the critical pressure needed for change in G is lower than that observed in uniaxial compression experiments. Spectroscopic investigations show that the effects of pressure and deformation on the electrophysical properties of samples under load is not connected with changes in the chemical structure of PPhC, but appear to be due to the change in the average distance between the regions of continuous conjugation. The sizes of such regions may be increased by preliminary thermal treatment.     

Athermal simulation of plastic deformation in amorphous solids at constant pressure

An algorithm is introduced for the molecular simulation of constant-pressure plastic deformation in amorphous solids at zero temperature. This allows to directly study the volume changes associated with plastic deformation (dilatancy) in glassy solids. In particular, the dilatancy of polymer glasses is an important aspect of their mechanical behavior. The new method is closely related to Berendsen's barostat, which is widely used for molecular dynamics simulations at constant pressure. The new algorithm is applied to plane strain compression of a binary Lennard-Jones glass. Conditions of constant volume lead to an increase of pressure with strain, and to a concommitant increase in shear stress. At constant (zero) pressure, by contrast, the shear stress remains constant up to the largest strains investigated (ε = 1), while the system density decreases linearly with strain. The linearity of this decrease suggests that each elementary shear relaxation event brings about an increase in volume which is proportional to the amount of shear. In contrast to the stress–strain behavior, the strain-induced structural relaxation, as measured by the self-part of the intermediate structure factor, was found to be the same in both cases. This suggests that the energy barriers that must be overcome for their nucleation continually grow in the case of constant-volume deformation, but remain the same if the deformation is carried out at constant pressure. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 2057–2065, 2004     

Tabletting of solid dispersion particles consisting of indomethacin and porous silica particles

We attempted to make the rapidly dissolving tablet (Tab) containing solid dispersion particles (SD) with indomethacin (IMC) and porous silica (Sylysia350) as carrier prepared by using spray-drying technique. Rapidly dissolving tablet was formulated with mannitol as a diluent and low substituted hydroxypropylcellulose (L-HPC) or partly pre-gelatinized starch (PCS) as a disintegrant. The percent dissolved from Tab (SD) was higher than that of tablet containing physical mixture (PM) at 20 min. Nearly 100% of drug in Tab (SD) was dissolved within 60 min, while the drug dissolution of Tab (PM) was not completed at the same time period. In addition, the tensile strength of Tab (SD) was much higher than that of Tab (PM). Adding L-HPC in Tab (SD) (Tab (SD-L-HPC)), the percent dissolved from Tab (SD-L-HPC) at 5 min became much higher than that from Tab (SD). The dissolution profile of IMC from Tab (SD-L-HPC) was almost the same irrespective of the compression pressure, while the tensile strength of tablet increased with increasing the compression pressure. In comparing the compaction property of these tablets by observing the ratio of residual die wall pressure (RDP) to maximum die wall pressure (MDP) (RDP/MDP), it was found that addition of L-HPC in the tablet formulation improved compactibility. In case that PCS was formulated as disintegrant, Tab (SD-PCS), similar improvement in the dissolution profile and tensile strength was observed, though the dissolution rate of IMC from Tab (SD-PCS) was slightly lower than that from Tab (SD-L-HPC) irrespective of the compression pressure.     

沥青基球状活性炭担载尿素用于NO2的低温选择性催化还原行为研究

将作为还原剂的尿素担载于沥青基球状活性炭(PSAC)上研究了NO₂的低温选择性催化还原(SCR)反应。结果表明,PSAC上尿素担载量的提高可以增大NO₂与尿素的反应几率;当尿素担载量由8%提高到30%时,SCR反应脱硝活性显著提高,脱硝时间相应延长。在30~90℃,升高反应温度会减小NO₂在PSAC表面的吸附量,从而导致NO_x的脱除量减小。增加反应气氛中NO₂和O₂的浓度均有利于脱硝活性的提高,但当O₂进料浓度大于9%时,继续增加O₂进料浓度对脱硝活性的改善作用变得微弱。降低空速有利于提高脱硝活性和延长脱硝时间。当反应温度为30℃、空速为2000h^-1、NO₂和O₂的进料浓度分别为0.05%和21%时,尿素担载量为8%的PSAC可在49h内实现85%以上的NO_x转化率。     

Hemodynamics and Wall Shear Stress of Blood Vessels in Aortic Coarctation with Computational Fluid Dynamics Simulation

The purpose of this study was to identify the characteristics of blood flow in aortic coarctation based on stenotic shape structure, stenosis rate, and the distribution of the wall load delivered into the blood vessels and to predict the impact on aneurysm formation and rupture of blood vessels by using a computational fluid dynamics modeling method. It was applied on the blood flow in abdominal aortic blood vessels in which stenosis occurred by using the commercial finite element software ADINA on fluid-solid interactions. The results of modeling, with an increasing stenosis rate and Reynolds number, showed the pressure drop was increased and the velocity was greatly changed. When the stenosis rate was the same, the pressure drop and the velocity change were larger in the stenosis with a symmetric structure than in the stenosis with an asymmetric one. Maximal changes in wall shear stress were observed in the area before stenosis and minimal changes were shown in stenosis areas. The minimal shear stress occurred at different locations depending on the stenosis shape models. With an increasing stenosis rate and Reynolds number, the maximal wall shear stress was increased and the minimal wall shear stress was decreased. Through such studies, it is thought that the characteristics of blood flow in the abdominal aorta where a stenosis is formed will be helpful in understanding the mechanism of growth of atherosclerosis and the occurrence and rupture of the abdominal aortic flow.     

The effects of combined pressure–temperature on mechanical behavior of polypropylene

The effects of combined pressure and temperature on the mechanical behavior of polypropylene have been studied. Tests were conducted in tension and compression superimposed on various hydrostatic pressures up to 7 kbar at temperatures of 20, 50, and 75°C. The experimental data have been analyzed in view of molecular and continuum approaches. It has been observed that the Young's modulus and the yield strength in both tension and compression increased significantly with increasing pressure at all temperatures studied. However, the rate of increase of the Young's modulus undergoes abrupt change about the glass-transition pressure (P_g). The P_g is linearly dependent on the test temperature and the pressure coefficient of the T_g is estimated, from P_g versus temperature relations, to be about 18°C/kbar for the polypropylene samples of this study. Pressure dependence of the yield stress is described by a generalized Eyring theory incorporating pressure effects and two flow mechanisms, the α- and the β-relaxation processes. The theory predicts a bilinear dependence of the yield stress of polypropylene on hydrostatic pressure as observed in the tests. The paper also described a method of healing stress whitening in polypropylene by a combination of shear stress and hydrostatic pressure.     

Rheology of polymer brush under oscillatory shear flow studied by nonequilibrium Monte Carlo simulation

The rheological behaviors of polymer brush under oscillatory shear flow were investigated by nonequilibrium Monte Carlo simulation. The grafted chain under oscillatory shear flow exhibited a waggling behavior like a flower, and the segments were found to have different oscillatory phases along the chain contour. Stress tensor was further obtained based on the statistics of sampled configuration distribution functions. The simulation reproduced the abrupt increase of the first normal stress difference N(1) with the flow velocity over a critical value, as observed in the experiment of Klein et al. [Nature (London) 352, 143 (1991)]. However, our simulation did not reproduce the brush thickening with shear velocity increased, which was suggested to be responsible for the abrupt increase of N(1) in the above-mentioned paper. This simulation demonstrates that the increase of normal stress might be an inherent behavior of polymer brush due to chain deformation under flow.     

Formulation design of an oral, fast-disintegrating dosage form containing taste-masked particles of famotidine

A fast-disintegrating dosage form has been developed as a user-friendly formulation that disintegrates in the mouth immediately. Patients can take it without water like a liquid formulation. In this study famotidine taste-masking technology was applied to the new fast-disintegrating tablet in an attempt to produce a novel, taste-masked, fast-disintegrating tablet. Partial granulation was found to be an effective and practical way to address content uniformity, however, oral disintegration time tended to become longer as content uniformity improved. The disintegration time was improved considerably by controlling ambient humidity during the compression process (>50% RH). Furthermore, since the new fast-disintegrating technology made it possible to use low compression force, there was no change in the structure or dissolution rate of the taste-masked particles after compression. Therefore, this system can produce a taste-masked fast-disintegrating tablet with satisfactory attributes.     

CFD simulations of net-type turbulence promoters in a narrow channel

The most common spacers or turbulence promoters for membrane processes are net-like materials which enhance mass transfer as well as provide passage for feed solutions. The enhanced membrane performance of spacer-filled channels is determined by the fluid flow patterns induced by the spacer filaments. Insight into the effect of spacer characteristics can be obtained by computational fluid dynamics. In this research, the commercial finite volume package FLUENT was used to visualise the flow pattern in a rectangular membrane channel. Three transverse filament arrangements were simulated. The results show that both high shear stress regions and eddies are present in the channel due to the spacer cylinders. The mass transfer enhancement on the wall/membrane surface is directly related to the high shear stress value, velocity fluctuation, and eddy formation. The peak shear stress and velocity fluctuation are repeated after each spacer cylinder, while the eddies are generally found before and after each cylinder. The CFD simulation also suggests that reducing the transverse filament distance will reduce the distance between shear stress peaks and consequently introduce larger shear stress regions near the wall region and increase the number of eddies, which will benefit membrane mass transfer. However, the penalty for this is that energy losses will also be significantly increased. The selection of optimum spacer geometry design involves a trade-off between these competing effects.