外文翻译-搅拌性能比较单轴和双轴搅拌机

外文翻译-搅拌性能比较单轴和双轴搅拌机 附录: 外文资料与中文翻译 外文资料: Comparing mixing performance of uniaxial and biaxial bin blenders Amit Mehrotra and Fernando J. Muzzio Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ, 08855, United States Received 17 February 2009; revised 30 May 2009; accepted 14 June 2009. Available online 27 June 2009. Abstract The dynamics involved in powder mixing remains a topic of interest for many researchers; however the theory still remains underdeveloped. Most of the mixers are still designed and scaled up on empirical basis. In many industries, including pharmaceutical, the majority of blending is performed using ―tumbling mixers‖. Tumbling mixers are hollow containers which are partially loaded with materials and rotated for some number of revolutions. Some common examples include horizontal drum mixers, v- blenders, double cone blenders and bin blenders. In all these mixers while homogenization in the direction of rotation is fast, mediated by a convective mixing process, mixing in the horizontal (axial) direction, driven by a dispersive process, is often much slower. In this paper, we experimentally investigate a new tumbling mixer that rotates with respect to two axes: a horizontal axis (tumbling motion), and a central symmetry axis (spinning motion). A detailed study is conducted on mixing performance of powders and the effect of critical fundamental parameters including blender geometry, speed, fill level, presence of baffles, loading pattern, and axis of rotation. In this work Acetaminophen is used as the active pharmaceutical ingredient and the formulation contains commonly used excipients such as Avicel and Lactose. The mixing efficiency is characterized by extracting samples after pre-determined number of revolutions, and analyzing them using Near Infrared Spectroscopy to determine compositional 1 distribution. Results show the importance of process variables including the axis of rotation on homogeneity of powder blends. Graphical abstract The dynamics involved in powder mixing remains a topic of interest for many researchers; however the theory still remains underdeveloped. Most of the mixers are still designed and scaled up on empirical basis. In many industries, including pharmaceutical, the majority of blending is performed using ―tumbling mixers‖. In all these mixers while homogenization in the direction of rotation is fast, mediated by a convective mixing process, mixing in the horizontal (axial) direction, driven by a dispersive process, is often much slower. In this paper, we experimentally investigate a new tumbling mixer that rotates with respect to two axes: a horizontal axis (tumbling motion), and a central symmetry axis (spinning motion). Keywords:Powder mixing ; Cohesion; Blender ; Mixer; Relative standard deviation; NIR; Acetaminophen Article Outline 1. Introduction 2. Materials and methods 2.1. Near infrared spectroscopy 2.2. Bin blenders used in this study: uni-axial blender (Blender 1), bi-axial blender (Blender 2) 2.3. Experimental method 3. Results 4. Conclusion References 2 1. Introduction Particle blending is a required step in a variety of applications spanning the ceramic, food, glass, metallurgical, polymers, and pharmaceuticals industries. Despite the long history of dry solids mixing (or perhaps because of it), comparatively little is known of the mechanisms involved [1], [2] and [3]. A common type of batch industrial mixer is the tumbling blender, where grains flow by a combination of gravity and vessel rotation. Although the tumbling blender is a very common device, mixing and segregation mechanisms in these devices are not fully understood and the design of blending equipment is largely based on empirical methods. Tumblers are the most common batch mixers in industry, and also find use in myriad of application as dryers, kilns, coaters, mills and granulators [4], [5], [6], [7] and [8]. While free-flowing materials in rotating drums have been extensively studied [9] and [10], cohesive granular flows in these systems are still not completely understood. Little is known about the effect of fundamental parameters such as blender geometry, speed, fill level, presence of baffles, loading pattern and axis of rotation on mixing performance of cohesive powders or the scaling requirements of the devices. However, conventional tumblers, rotating around a horizontal axis, all share an important characteristic: while homogenization in the direction of rotation is fast, mediated by a convective mixing process, mixing in the horizontal (axial) direction, driven by a dispersive process, is often much slower. In this paper, we experimentally investigate a new tumbling mixer that rotates with respect to two axes: a horizontal axis (tumbling motion), and a central symmetry axis (spinning motion). We examine the effects of fill level, mixing time, loading pattern and axis of rotation on the mixing performance of a free-flowing matrix of Fast Flo lactose and Avicel 102, containing a moderately cohesive API, micronized Acetaminophen. We use extensive sampling to characterize mixing by tracking the evolution of Acetaminophen homogeneity using a Near Infrared spectroscopy detection method. After materials and methods are described in Section 2, results are presented in Section 3, followed by conclusions and recommendations, which are presented in Section 4. 3 2. Materials and methods The materials used in the study are listed in Table 1, along with their size and morphology. Acetaminophen is blended with commonly used excipients and is used as a tracer to evaluate the degree of homogeneity achieved as a function of number of revolutions. Acetaminophen is one of the drugs most widely used in mixing studies, and Avicel and Lactose are commonly used pharmaceutical excipients. In the interest of brevity their SEM images are not included in this paper, but can be found in ―Handbook of Pharmaceutical excipients‖. 2.1. Near infrared spectroscopy Acetaminophen homogeneity was quantified using near infrared spectroscopy. A calibration curve was constructed for a powder mixture containing (in average) 35% avicel PH 102, 62% lactose and 3% acetaminophen. Near infrared (NIR) spectroscopy can be a useful tool to characterize acetaminophen. Samples are prepared by keeping the ratio of Avicel to lactose randomized in order to minimize effects of imperfect blending of excipients during the actual experiments on the accuracy of the results. The Rapid Content Analyzer instrument manufactured by FOSS NIR Systems (Silver Spring, MD) and Vision software (version 2.1) is used for the analysis. The samples are prepared by weighing 1 g of mixture into separate optical scintillation vials; (Kimble Glass Inc. Vineland, NJ) using a balance with an accuracy of ? 0.01 mg. Near-IR spectra are collected by scanning in the range 1116–2482 nm in the reflectance mode. Partial least square (PLS) regression is used in calibration model development using the second derivative mathematical pretreatment to minimize the particle size effects. As shown in Fig. 1, excellent agreement is achieved between the calibrated and predicted values. 4 Fig. 1. Fig. 1. Near Infrared (NIR) spectroscopy validation curve. The equation used to predict acetaminophen concentration is validated by testing samples with known amounts of acetaminophen concentration. The y axis represents the concentration calculated from the equation and the x axis represents the actual concentration. Thus a perfectly straight line at 45? would represent the best calibration model. Each point on the graph represents a single sample. The concentration of acetaminophen examined here ranges from 0 to 8%. 2.2. Bin blenders used in this study: uni-axial blender (Blender 1), bi-axial blender (Blender 2) Due to its widespread use, a cylindrical blender 1 with a capacity of 30 L is chosen as a reference blender in the study. As shown in Fig. 2, this blender has a circular cross section and tapers at the bottom. It can be used with or without baffles, which are mounted on a removable lid. In this study all the experiments are conducted without the use of baffles. Mixing performance in this device is used to provide a base-line for evaluating the mixing performance of a newly developed blender 2 with a capacity of 40 L, which is also cylindrical, in order to determine the effect of dual axis of rotation on mixing performance. The blender shown in Fig. 2(b) has two axis of rotation. The spinning rate of precession relative to the central axis of symmetry is geared to be half of that of the rate of rotation around the horizontal axis. 5 Fig. 2. Fig. 2. Pictorial representation of (a) bin blender 1 and (b) bin blender 2 showing the corresponding axis of rotation. 2.3. Experimental method Two types of initial powder loading used in the experiments: bottom loading and side–loading, which are schematically top– represented in Fig. 3. To avoid agglomeration, the API, acetaminophen, was delumped prior to loading it into the blender by passing it through a 35 mesh screen. In order to characterize mixing performance, a groove sampler was used to extract samples from the blenders at 7.5, 15, 30, 60, 120 revolutions. The thief was carefully inserted in the bin, and a core was extracted at each point of insertion (each ―stab‖) minimizing perturbation to the powder bed remaining in the blender. Approximately 7 samples are taken from each thief stab, and a total of five stabs are used at each sampling time, as shown in Fig. 4 so a total of 35 samples are taken at each sampling point. Fig. 3. Fig. 3. Schematic of the loading pattern used in the study. In top–bottom loading, Avicel is loaded first into the blender followed by Lactose on top of it and finally Acetaminophen is uniformly sieved over. In side–side loading avicel is placed at the bottom and then Acetaminophen is only sieved only in half part of the blender and is sandwiched between lactose and Avicel. Fig. 4. 6 Fig. 4. (a) Thief sampler (b) top view of the sampling position scheme. The experimental plan used in this study is as follows: • Fill level: blender 1–60% • Fill level: blender 2–60%, 70%, 80% • Loading pattern: blender 1 — side–side loading, top–bottom loading • Loading pattern: blender 2 — side–side loading, top–bottom loading • Speed: blender 1–15 rpm, 20 rpm, 25 rpm • Speed: blender 2 — rotational/spinning:15/7.5 rpm, 20/10 rpm, 30/15 rpm • Sampling time: blender 1, blender 2–7.5, 15, 30, 60, 120 revolutions 3. Results The homogeneity index used is the RSD, where C is the concentration of each individual sample, C_? is the average concentration of all samples and n is the total number of samples obtained at a given sampling time. We examine the effect of fill level on mixing performance. Previously there have been studies on the effect of fill level in the Bohle bin blender, Gallay bin blender and V- blender and double cone blender [11], [12] and [13]. All the aforementioned blenders have only one axis of rotation, therefore the objective of this study is to examine how dual axis impact mixing performances at high fill levels. To avoid repetition, studies for fill level are not conducted for bin blender 1. Results available from a previous study using MgSt as a tracer showed that mixing in a uni-axial blender slowed down quite dramatically as the fill level exceeded 70%. Moreover, results for acetaminophen can be assumed to be similar to those obtained in previous work by Muzzio et al. [11] and [13], for a single axis rectangular bin blender [11], which have shown that even after few hundred revolutions homogeneity achieved with a 80% fill level is very poor as compared to 60% fill level. To examine the effect of fill level in a dual axis blender, experiments were performed in blender 2 with the top-bottom loading pattern for a rotational speed of 15 rpm and with spinning speed of 7.5 rpm. The fill levels examined are 60%, 70% and 80% 7 respectively and samples are taken after 7.5, 15, 30, 60, 120 revolutions. Typical results are shown in Fig. 5, which shows the RSD vs. number of blender revolutions. As expected for non-agglomerating materials, the curves show a rapidly decaying region. The slope of the curves in this region, in semi-logarithmic coordinates, is used to define the mixing rate. The curves then level off to a plateau that indicates the maximum degree of homogeneity that is achievable in the blender for a give material. Fig. 5. Fig. 5. Mixing curves for different fill levels in blender 2. The RSD of acetaminophen is plotted as a function of number of revolutions. The loading pattern in top-bottom and the blender rotational speed is 15 rpm with spinning speed of 7.5 rpm. Similar to previous studies with other tumbling blenders we observe that blending performance is adversely affected by increasing fill levels. As shown in Fig. 5, the curve for 80% fill performs more poorly than those for 60% and 70% fill; as fill level increases, RSD curves decay more slowly, signifying a slower mixing process. However, the effect is not as pronounced as in other bin blenders and after about only 100 revolutions, the same plateau (the same asymptotic blend homogeneity) is achieved for all three fill levels. Next, the effect of rotational speed is investigated in the blender 1 with one axis of rotation and is compared to the blender 2 with dual rotation axis. Experiments were conducted for both blenders with top-bottom and side-side loading. Experiments were performed at 60% fill level and the rotation speeds considered for blender 1 are 15 rpm, 20 rpm and 25 rpm respectively. As shown in Fig. 6 and Fig. 7, when plotted as a function of blender revolutions, there is not 8 much of an effect of rotation speed on the homogeneity index (RSD) of acetaminophen at 60% fill level. It is observed that mixing performance at 20 rpm and 25 rpm is slightly better than at 15 rpm, however the differences in the performance of the blender under different speeds are probably too small to be significant. RSD curves decay with the same slope, indicating similar mixing rates. In the study reported here, the fill level is only 60%, and all the rotational speeds are enough to achieve homogenization. The aforementioned studies were conducted at 85% fill level. For such a high fill level, at low speeds, a stagnant core is known to occur at the center of many blenders, requiring higher shear stress per unit volume to achieve homogenization. Moreover, the flow properties of MgSt are known to be strongly different than those of most materials, and are known to have a deep impact on the flow properties of the mixture as a whole. Furthermore, MgSt is famously known to be a shear sensitive material. Thus an expectation that lubricated and unlubricated blends would show similar behavior with respect to shear is probably unwarranted. Fig. 6. Fig. 6. Mixing curves for top-bottom loading experiments with 60% fill level. RSD is plotted as a function of number of revolutions. Dotted lines correspond to experiments in the blender 1, while solid lines represent data points from the blender 2. 9 Fig. 7. Fig. 7. curves for side–side loading experiments with 60% fill level. RSD is plotted as a function of number of revolutions. Dotted lines correspond to experiments in the while solid lines represent data points from the 2. Subsequently, experiments were performed using the blender 2 at three rotation speeds: 15 rpm, 20 rpm and 30 rpm, and as explained before, the corresponding spinning speeds were 7.5 rpm, 10 rpm and 15 rpm. Fill level considered for both side-side and top-bottom loading was 60%. Again, it was observed that varying rotation and spinning speeds did not make much difference in mixing rate. As shown in Fig. 6 and Fig. 7, mixing curves for blender 2 vary only slightly with rotation speed. For the top-bottom loading pattern it appears that mixing improves slightly when rotation speed is increased (the plateau is slightly lower for higher rotation speeds, indicating an improvement in the levels of asymptotic homogeneity), but no significant changes with speed are observed in side-side loading pattern. The blending performance of both blenders is compared at different rotation speeds for both side-side and top-bottom loading patterns. To make a fair comparison, the fill level was kept as 60% for both blenders, a condition for which both blenders achieve effective mixing at long enough times. Due to geometric similarity of the two blenders, this comparison help evaluate the effect of spin (rotation with respect to the central symmetry axis) on mixing performance. As shown in Fig. 6, the mixing curves for the blender 2 lie below those for the blender 1 for each rotation rate, indicating faster mixing. Note that the final RSD asymptote 10 reached for both blenders is also different, with the blender 2 showing a lower asymptote (better final mixed state, presumably due to a lesser effect of the slow mixing mode in the horizontal direction) than blender 1. Similar results were obtained for the side-side loading pattern, as displayed in Fig. 7. The RSD curves for the blender 1 for all the three rotation rates lie above the blender 2. It is therefore confirmed that spinning a blender in direction perpendicular to the rotation axis helps in enhancing mixture homogeneity; however, for the materials examined here, the rotation rate does not have much effect on mixing performance. Finally, a comparison is made between the two loading patterns for both blenders. Again, to achieve a fair comparison, all experiments are performed at 15 rpm and 60% fill level. As evident in Fig. 8, in both blenders top–bottom loading gives a more rapid decay of the side RSD, indicating faster homogenization as compared to side– loading pattern. However, for both loading modes, blender 2 achieves faster homogenization. Fig. 8. Fig. 8. Comparison between the mixing curves of the blender 2 and the blender 1 for top–bottom and side–side loading pattern. Dotted lines correspond to experiments in the blender 1, while solid lines represent data points from the blender 2. Experiments are performed at 15 rpm with 60% fill level. As reported in previous studies, all the RSD curves in this paper exhibit a common trend with respect to time, characterized by an initial period of rapid homogenization due to convective mixing, followed by a period of much slower homogenization typically controlled by dispersion or shear. This trend is shown schematically in Fig. 9. The first regime is a fast exponential decay and the second one 11 is a slow exponential asymptote to a limiting plateau. The first part represents a rapid reduction in heterogeneity driven by the bulk flow (convection); the slope of the RSD curve, in semi-logarithmic coordinates, is the convective mixing rate. The second part is driven by individual particle motion (dispersion) or by the slow erosion of API agglomerates due to shear. Fig. 9. Fig. 9. A typical mixing plot, with RSD plotted against number of revolutions. The two solid lines emphasize on the two distinctive mixing regimes. When only one mixing mechanism is present (a situation that can be achieved by careful control of the initial loading pattern), a simple mass-transfer model, represented in Eq. (1) can be used, as in past studies [14], to capture the evolution of the RSD in powder systems. In this model, an exponential curve decaying towards a plateau is fitted to the mixing curves, where σ is the standard deviation, σ? the final standard deviation, A is an integration constant, λ signifies the mixing rate constant, and N is the number of revolutions. This model predicts that the experimental variance will decay exponentially with time as it approaches the random mixture state. In order to characterize numerically the ― mixing rate,‖ λ has to be computed for each blending experiment. )σ?σ?=Ae?λN The values for parameters A and λ are calculated by minimizing the sum of squares of errors between the data and an exponential function. The value of final standard deviation (σ?) is taken as the lowest value of the variance achieved in the mixing studies. The values for λ are computed for blending experiments with different percentage fill, and loading pattern and the results are plotted in Fig. 10 and Fig. 11. As shown in Fig. 10, the mixing rate constant decreases with 12 increase in percentage fill level. A broader comparison with two other bin blenders is provided in Fig. 11, which displays the mixing rate for the blender 2, for the blender 1 with and without baffles, and for a commercially available rectangular blender. The figure also illustrates the effect of loading pattern on these four bin blenders, all of them rotated at 20 rpm. It is evident that blender 2 with dual axis of rotation has the highest mixing rate constant of the entire group. For all blenders used in this study, there is also an effect of loading pattern on mixing; it was found that top–bottom loading pattern gives better mixing performance than side-side loading. Fig. 10 Fig. 10. Mixing performance was evaluated at three different fill levels for blender 2. Experiments were performed at 60%, 70% and 80% fill levels at 15 rpm with top–bottom loading. Mixing rate constant (λ) values is plotted as a function of fill level and found to increase with decrease in fill level. Fig. 11 Fig. 11. Mixing performance of bin blenders along with loading pattern are compared at 20 rpm with 60% fill level. Mixing rate constant (λ) values plotted for different loading patterns in bin blenders with and without baffle and as shown above, blender 2 13 givers a better mixing performance as compared to blender 1. There is also a pronounced effect of loading pattern, and regardless of the blender used, top–bottom loading always gives a better performance compared to side–side. 4. Conclusion The effects of fill level, mixing time, loading pattern and axis of rotation on the mixing performance of a free-flowing matrix of Fast Flo lactose and Avicel 102, containing a moderately cohesive API, micronized Acetaminophen was examined. Blending performance was found to be adversely affected at increasing fill levels. Top–bottom loading pattern was shown to lead to better mixing rformance than side-side loading pattern. It was also confirmed pe that spinning a blender in direction perpendicular to the rotation axis helps in enhancing mixture homogeneity. A mathematical mixing model was utilized to compare mixing rates at different fill levels, blender types and loading pattern. It was shown that mixing rates were enhanced at low fill levels, top-bottom loading patterns, and for blender with dual axis of rotation. References [1] B.H. Kaye, Powder Mixing: Chapman & Hall. [2] K. Sommer, Statistics of mixedness with unequal particle sizes, Journal of Powder and Bulk Technology 3 (4) (1979), pp. 10–14. View Record in Scopus | Cited By in Scopus (1) [3] Fernando J. Muzzio, Troy Shinbrot and Benjamin J. Glasser, Powder technology in the pharmaceutical industry: the need to catch up fast, Powder Technology 124 (2002), pp. 1–7. Article | PDF (277 K) | View Record in Scopus | Cited By in Scopus (39) [4] C. 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Abstract | Article | PDF (290 K) | View Record in Scopus | Cited By in Scopus (13) [13] Osama S. Sudah, D. Coffin-Beach and F.J. Muzzio, Quantitative characterization of mixing of free-flowing granular material in tote ( bin)-blenders, Powder Technology 126 (2002), pp. 191–200. Article | PDF (432 K) | View Record in Scopus | Cited By in Scopus (29) [14] P.E. Arraita, Nhat-hang Duong, F.J. Muzzio, P. Godbole and S. Reynolds, A study of the mixing and segregation mechanisms in the Bohle Tote blender via DEM simulations, Powder Technology 164 (2006), pp. 50–57. 15 中文翻译: 搅拌性能比较单轴和双轴搅拌机 阿米特Mehrotra和费尔南多j的Muzzio 化工系与生化工程，罗格斯大学，皮斯卡塔韦，新泽西州，08855，美国 收到2009年2月17日; 修订09年5月30日; 接受09年6月14日。 可在线2009年6月27日。 摘要 所涉及的粉末混合动力仍然是许多研究者感兴趣的话 题 快递公司问题件快递公司问题件货款处理关于圆的周长面积重点题型关于解方程组的题及答案关于南海问题 ，但是仍然落后的理论。该混频器大多仍 设计 领导形象设计圆作业设计ao工艺污水处理厂设计附属工程施工组织设计清扫机器人结构设计 ，规模化的实证基础上。在许多行业，包括医药，大多数的混合是使用“翻滚混频器“。滚筒搅拌机是部分加载的材料和一些圈数旋转中空容器。一些常见的例子包括水平滚筒搅拌机，V型混合机，双锥混合机和bin搅拌机。在所有这些混频器而在同质化是快速旋转方向，由对流混合过程介导的，在水平(轴向)方向色散过程驱动，混合，往往是慢得多。在本论文中，我们探讨一种新的翻滚实验搅拌机，关于两个轴旋转:一个(翻滚动作)水平轴，中心对称轴(旋转运动)。进行详细研究的粉末混合性能和关键参数的影响，包括搅拌器的基本几何形状，速度，补平，挡板的存在，加载模式和旋转轴。在这项工作中对乙酰氨基酚用作活性药物成分和配方包含如常用Avicel和乳糖辅料。混合效率的特点，通过提取后，预先确定样 16 品的转数来分析和近红外光谱技术，以确定成分的分布。结果显示过程变量包括粉末混合均匀性的旋转轴的重要性。 图形抽象 所涉及的粉末混合动力仍然是许多研究者感兴趣的话题，但是仍然落后的理论。该混频器大多仍设计，规模化的实证基础上。在许多行业，包括医药，大多数的混合是使用“翻滚混频器“。在所有这些混频器而在同质化是快速旋转方向，由对流混合过程介导的，在水平(轴向)方向色散过程驱动，混合，往往是慢得多。在本论文中，我们探讨一种新的翻滚实验搅拌机，关于两个轴旋转:一个(翻滚动作)水平轴，中心对称轴(旋转运动)。 关键词:粉末混合;凝聚力;搅拌机，混合机，相对 标准 excel标准偏差excel标准偏差函数exl标准差函数国标检验抽样标准表免费下载红头文件格式标准下载 偏差;近红外;对乙酰氨基酚 17 文章概要 1.简介 2.材料和方法 2.1.近红外光谱 2.2.滨本研究使用搅拌器:单轴搅拌机(果汁机1)， 双向轴向搅拌机(搅拌机2) 2.3.实验方法 3.结果 4.结论 参考文献 18 1.简介 粒子混合是在多种应用的必要步骤，横跨陶瓷，食品，玻璃，冶金，聚合物，医药等行业。尽管历史悠久，混合干燥固体(或因为它可能)比较小，是已知的机制，涉及[1]，[2]和[3]。阿批工业搅拌机常见的类型是翻滚的搅拌机，其中谷物由重力和旋转组合船只流量。虽然翻滚搅拌这些设备是在一个非常常见的设备，混合和分离的机制尚未完全了解，对于混合设备的设计主要是实证方法的基础。玻璃杯是最常见的一批工业搅拌机，并在应用中找到无数用烘干机，窑炉，镀膜机，研磨机和粉碎机[4] [5] [6] [7] [8]。虽然在旋转鼓自由流动的材料已被广泛地研究这些系统[9]和[10]，凝聚力颗粒流仍然没有完全理解。知之甚少的基本几何参数，如搅拌机，速度的影响，补平，在场的挡板，装上的凝聚力粉末或设备的比例要求，混合性能模式和旋转轴。 然而，传统的酒杯，围绕水平轴旋转，都有一个重要的特点:而在同质化是快速旋转方向，由对流混合过程介导的，在水平(轴向)方向色散过程驱动，混合，是往往慢得多。 在本论文中，我们探讨一种新的翻滚实验搅拌机，关于两个轴旋转:一个(翻滚动作)水平轴，中心对称轴(旋转运动)。我们研究的填充水平的影响，搅拌时间，装上了一个快速弗洛乳糖自由流动矩阵和Avicel 102混合性能模式和旋转轴，含中等凝聚力的API，微粉扑热息痛。我们使用广泛的特点，通过跟踪取样对乙酰氨基酚的同质性进化利用近红外光谱检测方法搅拌。材料和方法后，在第2部分所述，结果显示在第3，结论和建议，这些建议随后在第四节的。 19 2.材料和方法 在研究中所用的材料列于表1，以及它们的大小和形态。对乙酰氨基酚是常用的辅料混合，并作为示踪剂来 评价 LEC评价法下载LEC评价法下载评价量规免费下载学院评价表文档下载学院评价表文档下载 作为一种转数实现的功能同质化程度。对乙酰氨基酚是最广泛的混合研究使用的药物之一，Avicel和乳糖常用药用辅料。在简洁利益的扫描电镜图像不包括在本文件，但可以在“药用辅料手册”中找到 2.1 近红外光谱 对乙酰氨基酚同质性量化使用近红外光谱。校准曲线构建了一个含有粉末混合物(平均)35,avicel102 PH值，62,和3,乳糖对乙酰氨基酚。近红外(NIR)光谱技术可以成为一个有用的工具来描述对乙酰氨基酚。样品准备通过保留Avicel乳糖的比例随机为了尽量减少辅料的混合效果不完善在对实际实验结果的准确性。内容分析仪器的快速近红外系统由开放源码软件(银春，MD)和Vision软件(版本2.1)制造的用于分析。制备出的样品重量为单独的光闪烁瓶1克的混合物;(金布尔玻璃公司瓦恩兰，新泽西州)使用具有精度为?0.01毫克平衡。近红外光谱范围内收集1116年至2482年，在反射模式纳米扫描。偏最小二乘(PLS)回归校正模型用于开发采用二阶导数的数学预处理，以减少颗粒尺寸效应。如图所示。 1，优良的 协议 离婚协议模板下载合伙人协议 下载渠道分销协议免费下载敬业协议下载授课协议下载 是实现之间的校准和预测值。 20 图.1 图.1 近红外(NIR)光谱验证曲线。对乙酰氨基酚的浓度来预测方程式测试验证了对乙酰氨基酚的浓度与已知金额样本。 y轴表示从公式计算浓度和X轴代表实际浓度。因此，一个完美的45度直线将代表最佳校正模型。图上的每个点代表一个样本。对乙酰氨基酚的浓度在这里检查范围从0到8,。 2.2.滨本研究使用搅拌器:单轴搅拌机(果汁机1)，双向轴向搅拌机(搅拌机2) 由于它的广泛使用，圆柱搅拌机有30升水容量的1为一个学习参考搅拌机。如图所示。 2，该搅拌器具有圆形横截面的底部和蜡烛。它可用于有或无挡板，这是一个可移动的盖子上。在这项研究中所有的实验进行的，没有使用的挡板。在这个混合使用设备的性能评价提供了一个新开发的搅拌器240 L，这也是圆柱形的，为了一个容量混合性能基线，以确定旋转双轴混合性能的影响。如图所示的搅拌器。 2(二)有两个旋转轴。进动相对于中轴对称旋转速度是面向的是水平轴的旋转速度的一半。 图2. 21 图2.图形表示(a)对滨搅拌器1和(二)滨搅拌器2显示相应的旋转轴。 2.3 实验方法 顶底侧装装，这是示意图图表示:两种粉在初步实验中使用的负荷类型。 3。为了避免结块，空气污染指数，对乙酰氨基酚，是delumped之前加载到搅拌机通过一个由35目筛它。为了表征混合性能，一槽取样器是用来提取7.5，15，30，60，120革命从搅拌机样本。小偷被仔细地插在垃圾桶，一个核心是在每个插入点(每一个“刺“)尽量减少扰动粉搅拌床其余提取。大约有7个样本是从每个贼刺，并刺伤共有五个在每个采样时间，如图所示，使用。 4因此，一共有35个样本采取每个采样点。 图3 图3.示意图在研究中使用的装载模式。在顶底加载，Avicel装入乳糖随后在顶部，这样，最终对乙酰氨基酚是均匀筛在果汁第一。在并排侧面装载avicel被放置在底部，然后对乙酰氨基酚是唯一过筛只在一半的搅拌器组成部分，是乳糖和Avicel之间夹。 图4. 图4.(一)取样器(b)俯视计划的取样位置.. 实验计划在本研究中使用如下: •填写级别:搅拌机1-60, •填写级别:搅拌机2-60,，70,，80, 22 •加载模式:搅拌机1 - 侧方加载，顶底加载 •加载模式:搅拌机2 -侧侧加载，顶底加载 •速度:搅拌机1-15转，20转，25转 •速度:搅拌器2 -旋转/旋转:15/7.5转速，转速20/10，30/15转 •采样时间:搅拌机1，搅拌机2-7.5，15，30，60，120革命 3(结果同质化的指标是区域市政总署，其中C是每个人的样品浓度，C_?是所有样品平均浓度和N是在给定时间采样所得样品总数。 我们研究了填料混合性能水平的影响。此前曾有关于填写博勒斌搅拌器水平的影响研究，Gallay斌搅拌器和V-搅拌器及双锥形搅拌机[11]，[12]和[13]。所有上述搅拌机只有一个旋转轴，因此本研究的目的是研究如何影响双轴搅拌在高填充量演出。为了避免重复，为补平研究没有就斌果汁机1。结果从以前的使用作示踪剂MgSt研究表明，在现有单轴搅拌机混合相当显着放缓作为填充水平超出70,。此外，对乙酰氨基酚的结果可以被假定为类似以前的工作得到了Muzzio等人。 [11]和[13]对于一个轴，矩形槽搅拌机[11]，这表明，即使在几百革命与填充量达到80,的同质性非常差相比，60,的填充水平。 为了探讨填充量在双轴搅拌机的影响，实验进行的顶底加载模式为15 rpm的旋转速度和旋转速度为7.5转速在搅拌器2。检查的填充量为60,，70,和80,分别抽取样本后，7.5，15，30，60，120革命。典型的结果显示在图。 5，它显示了区署主场迎战转数 23 的搅拌器。至于非烧结材料的预期，迅速衰减曲线显示区域。对这一地区的曲线在半对数坐标，坡度，是用来定义混合率。水平的变化曲线，然后开了一个高原，表示最大程度的同质性是在果汁实现了送料。 图 5 图 5.在搅拌机混合2不同填充量曲线。对乙酰氨基酚RSD是由于对转数的函数曲线。在顶底搅拌转速和负荷模式157.5转速旋转速度rpm。 与其他类似翻滚搅拌机以往的研究我们观察到混合性能的不利影响，增加填充量。如图所示。 5，80,的填充曲线表现超过60,和70,填补这些不足，用作填充量的增加，相对标准偏差曲线衰减更慢，标志着一个较慢的混合过程。然而，效果明显不如在其他斌搅拌机和革命后，大约只有100，同样的高原(相同的渐近混合均匀性)是对所有三种填充量达到。 接下来，旋转速度的影响进行了研究，在搅拌机1一个旋转轴，并与具有双旋转轴搅拌机2。实验进行与顶底和边侧加载两个搅拌机。实验是在60,的填充水平和旋转速度为1考虑的15搅拌器转速，转速20 rpm和25分别。如图所示。 6和图。 7，当作为一个搅拌器革命绘制功能，没有太多的在60,的旋转速度均匀性指数对乙酰氨基酚(区署)的填充水平。据观察，在20 rpm和25 rpm的搅拌性能略低于15转好，但根据不同速度在搅拌器的性能差异 24 可能是太小，无法显着。相对标准偏差曲线具有相同斜率衰减，表明类似的混合率。在这项研究报告在这里，填充量仅为60,，所有的旋转速度足以实现同质化。上述研究是在85,的填充水平。对于这样的高填充量，在低转速，停滞不前的核心是众所周知的发生在许多搅拌机中心，要求更高的每单位体积的剪应力，实现同质化。此外，MgSt的流动性是已知的最强烈比材料的不同，已知有一对整个混合物的流动性深刻的影响。此外，MgSt是出了名称为是一个剪切敏感材料。因此，如果期望润滑和无润滑融合方面将显示剪类似的行为可能是不必要的。 图 6 图 6.60,的顶底加载实验混合曲线补平。 RSD是由于对转数的函数曲线。虚线对应于实验，果汁机1，而实线代表从搅拌两个数据点。 图7 图7.侧方加载实验混合曲线与60,的填充水平。 RSD是由于对转数的函数曲线。虚线对应于实验，果汁机1，而实线代表从搅拌两 25 个数据点。 随后，实验采用在三个转速搅拌器2:15转，20转和30转，并作为解释过，相应的纺丝速度为750转，10转和15转。填充水平两侧端和顶底加载审议的60,。 同样，有人认为，不同的旋转速度和旋转并没有太大的差别的混合率。如图所示。 6和图。 7，混合为Blender 2只略有变化曲线的旋转速度。对于顶底加载模式看来，混合时略有提高转速增加(高原是高转速略有下降，表明在渐近均匀性水平的提高)，但速度没有显着变化是在侧面观察端加载模式。 这两个搅拌机混合性能比较在两个侧端和顶底装载方式不同的旋转速度。为了公平的比较，填充量维持于60既搅拌机，其中一个条件都实现有效的搅拌机在足够长的时间搅拌,。由于这两个搅拌机几何相似，这种比较帮助评估自旋效应混合性能(相对于中央的对称轴旋转)。如图所示。 6，搅拌2下面的旋转速度为每1的谎言搅拌机混合曲线，表明快混合。请注意，最后两个区署渐进达成的搅拌机也不同，以搅拌器呈现出较低的渐进比果汁机1(更好的最终混合状态，大概是由于一个缓慢的混合模式在水平方向较小的影响)2。 类似的结果，得到了方方装载模式，如下图显示。 7。相对标准偏差曲线所有三个旋转速度高于果汁2躺果汁机1。因此，确认在垂直方向旋转的旋转轴搅拌机混合均匀性提高有帮助;但是，对于研究材料，旋转速度并没有多大影响的混合性能。 最后，提出了比较两者之间的装载方式为搅拌机。同样，要实现公平的比较，所有的实验演出，在15 rpm和60,的填充水平。图中可以明显看出。 8，在这两个搅拌机顶底加载给出了一个相对 26 标准偏差更迅速衰减，表明更快的同质化相比，边侧加载模式。但是，对于两个加载方式，搅拌机2实现更快的同质化。 图8 图8.比较2的混合搅拌器曲线和对顶底和边侧加载模式果汁机1。虚线对应于实验，果汁机1，而实线代表从搅拌两个数据点。实验中我们以60,的填充量在15rpm。 正如在以前的研究报告，所有区署曲线本文表现出对时间的共同趋势，由初期的快速同质化，由于对流混合的特点，由一个典型的慢得多的均质剪切分散或控制的时期之后。这种趋势是示意如图所示。 9。第一个政权是一个快速的指数衰减，第二个是一个缓慢的指数渐近到一个极限的高原。第一部分是一个由大量流动(对流)驱动的异质性迅速减少，在区署曲线的斜率在半对数坐标，是对流混合率。第二部分是由单个粒子的运动(分散)或结块的空气污染指数因剪切缓慢侵蚀。 图9 图9.一个典型的混合，RSD为阴谋，策划反对转数。这两个实线着重在两个不同的混合制度。 27 当只有一个混合机制存在(一种可以由最初装载模式实现严格控制的情况)，一个简单的传质模型，方程表示。 (1)可以使用，在过去的研究为[14]，以捕捉到区署在粉料系统的演化。在此模型中，以指数衰减曲线走向高原是安装在混合曲线，其中σ是标准差，σ?最终标准差，A为积分常数，λ标志着混合速率常数，n是多少的革命。该模型预测，实验变异会随时间呈指数衰减，因为它接近随机混合的状态。为了表征数字的“混合率，“λ要为每一个混合实验计算。 ?λNσ?σ=Ae为参数A，λ值的计算方法是尽量减少数据之间的误差? 和指数函数的平方和。最终的标准偏差(σ?)值是作为在混合变异的研究方面取得的最低值。为λ的值计算了不同比例混合的实验与填充和加载模式，结果在图绘制。 10和图。11。如图所示。 10，混合率不断下降的百分比增加填充量。与另外两个斌搅拌机中提供了更广泛的比较图。 11，这显示了2个混合搅拌速率和无挡板的搅拌1日，和市售的长方形的搅拌器。这数字也说明了这四个斌装上搅拌机格局的影响，他们都在20 rpm的旋转。很明显，搅拌器与旋转轴2双具有最高的混合率整个集团不变。在本研究中使用的所有搅拌机，还有一个装上混合模式的影响，它被发现，顶底加载模式提供更好的混合比侧方加载性能。 图10 图10.混合性能进行了评估在三个搅拌器2个不同的填充量。实验 28 是在60,，70,和80,填充量在15顶底负荷转。搅拌速率常数(λ)值绘制为填充量增加的功能，发现在填充水平的下降。 图11 图11.混合搅拌机性能的bin随着加载模式进行了比较，60,在20转补平。搅拌速率常数(λ)值绘制不同装载方式在bin搅拌机和无挡板，如上图所示，搅拌机2度外一个更好的混合性能相比，果汁机1。还有一个明显的效果装载模式，以及所使用的搅拌器不分，顶底加载总是给人一种更好的性能相比，副作用的一面。 29 4.结论 中的填充水平，搅拌时间，效果装上了一个快速弗洛乳糖自由流动矩阵和Avicel102混合性能模式和旋转轴，含中等凝聚力的API，对乙酰氨基酚微粒进行了检查。交融的表现被认为是不利的影响在增加填充量。顶底加载模式被证明是导致优于侧方加载模式的混合性能。另据证实，在垂直方向旋转的旋转轴搅拌机混合均匀性提高有帮助。一个数学模型，利用混合比较不同填充量，搅拌器的类型和装载模式混合率。结果表明，混合率提高在低填充量，顶底装载方式，并与旋转双轴搅拌机。 30 参考文献 [1] B.H.凯，粉搅拌:查普曼和霍尔。 [2]光索默，统计的mixedness不等粒径，期刊粉体和散装技术3(4)(1979年)，页10-14。查看图书馆论坛记录|万方图书馆论坛(1) [3]费尔南多j的Muzzio，特洛伊Shinbrot，并在制药行业的粉体技术本杰明j的格拉瑟:必须急起直追，，粉末技术124(2002)，页1-7。文章| PDF文件(277金)|浏览图书馆论坛记录|万方图书馆论坛(39) [4]三丹尼斯等。一种表面更新与应用中的药片，粉末技术130(2003)，第174-180旋转鼓涂层模型。文章| PDF文件(216金)|浏览图书馆论坛记录|万方图书馆论坛(17) [5] G.R.伍德尔和JM蒙罗，粒子运动与融合的回转窑，粉末技术76(1997)，第241-24页。 [6] P.J.T.米尔斯等。粘结剂的粘度对颗粒集聚效应在低剪切混合机/凝聚，粉末技术113(2000)，页140-147。文章| PDF文件(529金)|浏览图书馆论坛记录|万方图书馆论坛(32) [7] R.J.斯珀林，学者楼戴维森和D.M.斯科特，对在旋转窑和盘造粒机，化学工程科学55(2000)，第2303至2313年颗粒物质不流问题。文章| PDF文件(459金)|浏览图书馆论坛记录|万方图书馆论坛(13) [8]河特顿和X.X.城，规模为固体颗粒，片剂，粉末技术150(2005)，第78-85喷涂进程的设立。文章| PDF文件(360金)|浏览图书馆论坛记录|万方图书馆论坛(17) [9] D.V. 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