Effect of Binder Concentration and Method of Addition on Granule Growth in a High Intensity Mixer

Abstract

A model system consisting of microcrystalline cellulose and povidone was used to study the effect of binder concentration and method of addition on granule growth in a high intensity mixer. The methods of binder addition include blending the dry binder with the excipient prior to granulating with water and granulation of the excipient with an aqueous solution of the binder. When the binder was dry-mixed with excipient prior to wetting, a good correlation was obtained between granule size and binder level. The growth of granules prepared by this method also appears to be related to the mechanical “resistance” encountered by the mixing blade during wet massing. In general, granules prepared by the addition of aqueous binder solutions are smaller than granules prepared with corresponding concentrations of dry binder and demonstrate a lesser degree of granule growth with respect to increasing binder level. For the wet addition method, the mechanical resistance was found to be essentially constant with respect to binder level.     

Granulations in a Fluidized-Bed: Effect of Binders and Their Concentrations on Granule Growth and Modeling the Relationship Between Granule Size and Binder Concentration

Lactose and mixture of lactose and microcrystalline cellulose (1:1) were granulated in a fluid-bed equipment using PVP, acacia and gelatin as binders. The effect of these binders, their concentrations, and volume of granulation liquid on granule growth and granule sue distribution was studied. It has been shown that individual binder and binder concentration affect granule growth and growth mechanism. Also, the volume of granulation liquid and part dissolution of excipients being granulated contribute significantly to the granule size and size distribution. On the basis of granule growth data, a mathematical relationship which relates granule size as a function of binder concentration is proposed. Granule growth constant for the binders is computed from the granule size against binder concentration data. The constant describes granule growth pattern, and is termed as binder coefficient, β. The numerical value of binder coefficient, which varies with the binder, indicates relative activity and effectiveness of each individual binder. A relationship between the binder coefficients is also established. This is shown to predict granule sue for a binder relative to another binder for the desired concentration. The validity and the applicability of the proposed relationship was tested on the data obtained during present investigations as well as on data reported by other authors.     

Effect of Primary Particle Size on Granule Growth and Endpoint Determination in High Shear Granulators

ABSTRACT

Three different grades of lactose monohydrate having widely differing mean particle sizes, yet similar tap densities, were granulated using a 25L instrumented Fielder mixer. The size distribution, porosity, and pore saturation of the wet granules were determined using a combination of “frozen granule” sieve analysis, mercury pycnometry, and oven drying. The granulating system was found to operate at quasi-steady-state, as granule growth ceased afler liquid addition was terminated. The resultant granule size distributions were strongly dependent on lactose grade. with coarser grades yielding larger granules for identical process conditions. In contrast. the magnitude of the power curves decreased with increasing primary particle size. Both of these observations are consistent with the fact that both the capillary and viscous interparticle fluid forces, which are believed to provide the main interparticle bonding forces in the wet mass, are inversely proportional to particle size.     

Effect of Impeller and Chopper Design on Granulation in a High Speed Mixer

Abstract

Effects of impeller and chopper design upon granule growth are investigated by granulation of dicalcium phosphate in a Fielder PMAT 25 laboratory high speed mixer. It is shown that the effects of the impeller design with respect to the blade inclination and impeller rotation speed can be described in terms of the volume swept out by the impeller. A high swept volume causes high densification of the agglomerates and narrow granule size distributions. Chopper size and rotation speed have no effect upon the granule size distribution. It is suggested that the primary function of the chopper is to disturb the uniform flow pattern of the mass. Effects of deposition of moist mass on the wall of the bowl on granule growth are demonstrated, and suggestions for reducing the deposition are given.     

Use of a Motor Load Analyzer to Monitor the Granulation Process in a High Intensity Mixer

A motor load analyzer instrumented to a high intensity mixer was examined for its ability to monitor the granulation process with varying formulation and processing parameters. A lactose/microcrystalline cellulose blend with povidone as the binder was used as the test system.

The motor load analyzer was able to note chopper operation and liquid addition methods. However, it could not differentiate between povidone addition as an aqueous solution or as part of the lactose microcrystalline cellulose blend, followed by massing with water. The compression characteristics of the granulations depended upon chopper usage, and povidone and liquid amounts, and their methods of addition.     

Use of a Motor Load Analyzer to Monitor the Granulation Process in a High Intensity Mixer

Abstract

A motor load analyzer instrumented to a high intensity mixer was examined for its ability to monitor the granulation process with varying formulation and processing parameters. A lactose/microcrystalline cellulose blend with povidone as the binder was used as the test system.

The motor load analyzer was able to note chopper operation and liquid addition methods. However, it could not differentiate between povidone addition as an aqueous solution or as part of the lactose microcrystalline cellulose blend, followed by massing with water. The compression characteristics of the granulations depended upon chopper usage, and povidone and liquid amounts, and their methods of addition.     

Effect of Impeller and Chopper Design on Granulation in a High Speed Mixer

Effects of impeller and chopper design upon granule growth are investigated by granulation of dicalcium phosphate in a Fielder PMAT 25 laboratory high speed mixer. It is shown that the effects of the impeller design with respect to the blade inclination and impeller rotation speed can be described in terms of the volume swept out by the impeller. A high swept volume causes high densification of the agglomerates and narrow granule size distributions. Chopper size and rotation speed have no effect upon the granule size distribution. It is suggested that the primary function of the chopper is to disturb the uniform flow pattern of the mass. Effects of deposition of moist mass on the wall of the bowl on granule growth are demonstrated, and suggestions for reducing the deposition are given.     

Wet Granulation in a Small Scale High Shear Mixer

Abstract

Wet granulation of lactose and corn starch in a 10 litre high shear mixer was examined. The effect of the amount of water added, granulation time and impeller speed on five properties of the granules was investigated by a response surface design.

It was shown that moisture level as a major effect on geometric mean diameter and flow rate of the granules. The impeller speed markedly influences the geometric mean diameter, geometric standard deviation, compactability index and percentage of granules smaller than 1250 μm. Finally the granulation time has an evident influence on compactability index.

Theoretical optimum conditions were obtained for the five response variables and are comparable with the experimental results.     

Wet Granulation in a Small Scale High Shear Mixer

Wet granulation of lactose and corn starch in a 10 litre high shear mixer was examined. The effect of the amount of water added, granulation time and impeller speed on five properties of the granules was investigated by a response surface design.

It was shown that moisture level as a major effect on geometric mean diameter and flow rate of the granules. The impeller speed markedly influences the geometric mean diameter, geometric standard deviation, compactability index and percentage of granules smaller than 1250 μm. Finally the granulation time has an evident influence on compactability index.

Theoretical optimum conditions were obtained for the five response variables and are comparable with the experimental results.     

Optimization of Granulates in a High Shear Mixer by Mixture Design

Abstract

Optimization of wet granulation in a 10 litre high shear mixer was examined by mixture design. Lactose, corn starch and cellulose microcrystalline were used as eccipients of the granules. Mixing ratios of these eccipients were selected as formulation factors. In addition, the impeller speed and granulation time was employed as independent process variables. A two-phase experimental strategy was drawn up: one phase for the percentages of the three eccipients and the other phase for the determination of the influence of process variable on geometric mean diameter. The percentages were studied using a Scheffè simplex-centroid design, and the other phase was examined using a Doehlert experimental matrix.     

Effect of Bi2O3 Addition on the Single-Crystal BiSrCaCuO Whisker Growth

Bi-2212 superconducting whiskers have been fabricated by annealing a melt-quenched precursor using suitable heat-treatment cycles for Bi_3+x Sr₂Ca₂Cu₃O_8+?? where x=1 and 2. Approximately 1?C3 mm long whiskers were fabricated for x=1 and x=2 and their physical, electrical and magnetic properties were investigated. Crystallization activation energies of the materials were calculated according to Kissinger and Augis?CBennet method using the DTA data. Microstructural changes from glass to heat-treated glass-ceramic materials at different temperatures were investigated with SEM, EDX and XRD analyses. It was observed that the structure of the whiskers has high c-axis oriented single-crystalline Bi-2212 phase. The whiskers fabricated for x=1 and 2 showed very smooth surface without cracks and dislocations. T _c of the whiskers for x=1 and 2 were obtained to be 83.2 K and 79.8 K respectively. The change of magnetization with applied magnetic fields (M?CH) was investigated at three different temperatures, 10, 20 and 40 K, and J _c?mag was determined using the Bean model.     

高能超声在颗粒/金属熔体体系中的声学效应

讨论并分析了600℃的SiCp/ZA27熔体中超声的作用机理和有效作用范围.研究结果表明:在实验所用超声处理条件下(20kHz,1kW),ZA27合金熔体中声空化效应引发的熔体局部高压最大可达105MPa,局部高温可达1.77×104K;声流在熔体体系各个部位的作用强度不同,要获得优质的复合材料就必须在工艺上保证熔体的各个部位均能受到超声的有效作用.高能超声之所以能够制备出颗粒均匀分布、界面结合良好的SiCp/ZA27复合材料是高能超声在金属熔体中产生的声空化与声流共同作用的结果.     

热泵热水器中浓度和pH对不锈钢表面污垢生长的影响

热泵热水器中制冷剂与水换热而将其加热至60℃,结垢严重。为抑制污垢,分别在0.5和1.0mmol/lCaCO3溶液中,通过静态反应法使污垢在不锈钢表面生长,分别用称重法和SEM获得不同浸入时间的结垢重量和污垢的微观形貌。结果表明：相同条件时ss304表面比ss316更易结垢且前者易形成文石而后者易形成方解石;Ca2+浓度较高使本体溶液均相成核率和表面异相成核率均增大而产生更多晶核,但单个晶体尺寸减少、结垢重量降低且不影响晶型种类比例;pH升高不仅使本体溶液中均相成核率和表面异相成核率均增加,且均相成核率增加更多,导致结垢量降低,并促进方解石的形成。换热器表面析晶污垢形成的主要机理是难溶盐分子先在溶液内形成污垢颗粒,而后沉积到表面上,而不仅通过在表面的反应和吸附而直接形成。     

低浓度氮气对单晶金刚石生长质量的影响

利用微波等离子体化学气相沉积法在CH₄/H₂ 反应气体中引入不同低浓度氮气条件下, 研究氮气对单晶金刚石生长质量的影响。利用发射光谱、拉曼光谱以及扫描电子显微镜对单晶金刚石质量进行表征。结果表明:随着气源中氮气浓度的增加, 单晶金刚石增长速率随之增加, 表面多晶缺陷得到抑制, 且Raman光谱法测得一阶特征拉曼峰随着氮气浓度的提高而向高波数移动, 呈现出压应力, 整体质量变差。经过退火过程之后, 引入氮原子的单晶金刚石生长拉应力得到释放, 样品呈现出拉应力。     

Influence of Liquid Bonding Strength on Power Consumption During Granulation in a High Shear Mixer

Abstract

A comparison between the effects of different binders on power consumption and -granule growth by granulation in a Fielder PMAT 25 high shear mixer demonstrates that the power consumption is influenced by the intra-granular porosity and the surface tension of the binder solution. It is suggested that the effects are due to a correlation between the power consumption and the strength of mobile liquid bondings in the moist agglomerates. It is shown that the power consumption reflects the change of the intragranular porosity for a particular granulation process with dicalcium phosphate.     

Instrumentation of a Vertical High Shear Mixer with a Motor Slip Monitoring Device

The main impeller shaft of a vertical high shear mixer was instrumented with a device which measures motor slip and displays its output in percent horsepower. Response was proportional to mixer load. A warm-up period was required to minimize variability in output. High speed impeller operation showed more consistency in response than low speed impeller operation. During the granulation process of the different test systems, a typical response profile showed a change in percent horsepower as the binder solution was added followed by a plateauing at about the proposed optimum mixing time. Additional studies to correlate this observation with granulation physical and compression characteristics are necessary     

Instrumentation of a Vertical High Shear Mixer with a Motor Slip Monitoring Device

Abstract

The main impeller shaft of a vertical high shear mixer was instrumented with a device which measures motor slip and displays its output in percent horsepower. Response was proportional to mixer load. A warm-up period was required to minimize variability in output. High speed impeller operation showed more consistency in response than low speed impeller operation. During the granulation process of the different test systems, a typical response profile showed a change in percent horsepower as the binder solution was added followed by a plateauing at about the proposed optimum mixing time. Additional studies to correlate this observation with granulation physical and compression characteristics are necessary     

包装内 CO2 含量对冷却肉特征微生物生长的影响

将来自冷却猪肉的混合菌种接种于液体培养基中,采用不同 CO2 含量气调包装后,于 5 ℃下贮藏。 采用相应的选择性培养基测定其中假单胞菌属、肠杆菌科及乳酸菌 3 种特征微生物的生长规律,同时测定了菌落总数的变化。 结果表明:兼性厌氧型微生物乳酸菌对气调包装内 CO2 含量变化不敏感;气调包装内 CO2 对需氧微生物肠杆菌科微生物和假单胞菌属的最大比生长速(μmax )存在抑制作用,CO2 含量越大,抑制作用越强;样品中菌落总数的变化也受到 CO2 含量的影响,高浓度 CO2 会抑制菌落总数的增长速率;CO2 含量的变化对肠杆菌科和假单胞菌属生长速率及菌落总数的增长速率的影响,可以通过一个 2 参数平方根方程进行很好地描述。     

Granulation in a Fluidized Bed II Effect of Binder Amount on the Final Granules

There are many parameters affecting the properties of the final granules prepared in a fluidized bed. In this study one of the product parameters, quantity of the binder, has been studied for its effect on the final granule size, size distribution and friability

Determination of granule size change as a function of binder quantity leaded us to study the growth mechanisms during fluidized bed granulation. Two mechanisms are suggested;

1) Snowballing of primary granules (nuclei)

2) Agglomeration of primary granules

It has been shown that there is a critical amount of binder at which the formation of the primary granules comes to an end if more binder is added to the system. Then granule growth occurs by agglomeration of the primary granules. The physical properties of the granules formed before and after this critical binder concentration varies significantly