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1、Comparing mixing performance of uniaxial and biaxial bin blenders Amit Mehrotra, Fernando J. Muzzio Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ, 08855, United States a b s t r a c ta r t i c l ei n f o Article history: Received 17 February 2009 Received in

2、revised form 30 May 2009 Accepted 14 June 2009 Available online 27 June 2009 Keywords: Powder mixing Cohesion Blender Mixer Relative standard deviation NIR Acetaminophen The dynamics involved in powder mixing remains a topic of interest for many researchers; however the theory still remains underdev

3、eloped. 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

4、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 dispers

5、ive 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 effec

6、t of critical fundamental parameters including blender geometry, speed, fi ll level, presence of baffl es, 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 Lactos

7、e. The mixing effi ciency is characterized by extracting samples after pre-determined number of revolutions, and analyzing them using Near Infrared Spectroscopy to determine compositional distribution. Results show the importance of process variables including the axis of rotation on homogeneity of

8、powder blends. 2009 Elsevier B.V. All rights reserved. 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

9、), comparatively little is known of the mechanisms involved 13. A common type of batch industrial mixer is the tumbling blender, where grains fl ow bya combination of gravity and vessel rotation. Although the tumbling blender is a very common device, mixing and segregation mechanisms in these device

10、s 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 fi nd use in myriad of application as dryers, kilns, coaters, mills and granulators 48. While free-fl owing materials in rotating dru

11、ms have been extensively studied 9,10, cohesive granular fl ows in these systems are still not completely understood. Little is known about the effect of fundamental param- eters such as blender geometry, speed, fi ll level, presence of baffl es, loading pattern and axis of rotation on mixing perfor

12、mance 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

13、 (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 symmetryaxis (spinning motion). We examine the effects of fi ll level,

14、 mixing time, loading pattern and axis of rotation on the mixing performance of a free-fl owing matrix of Fast Flo lactose and Avicel 102, containing a moderately cohesive API, micronized Acetaminophen. We use extensive sampling to character- ize mixing by tracking the evolution of Acetaminophen hom

15、ogeneity 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. 2. Materials and methods The materials used in the study are listed

16、 in Table 1, along with their size and morphology. Acetaminophen is blended with com- monly 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

17、and Lactose are commonly used pharmaceutical Powder Technology 196 (2009) 17 Corresponding author. Tel.: +1 732 445 3357; fax: +1 732 445 2581. E-mail address: (F.J. Muzzio). 0032-5910/$ see front matter 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.powtec.2009.06.008 C

18、ontents lists available at ScienceDirect Powder Technology journal homepage: 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 quantifi ed

19、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 Av

20、icel 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 analy

21、sis. 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 11162482 nm in the refl ectance mode. Partial least square (PLS) re

22、gression 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. 2.2. Binblendersusedinthisstudy:uni-axialblender(Blender1),b

23、i-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 baffl es, which are mounted on

24、a removable lid. In this study all the experiments are conducted without the use of baffl es. 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 determin

25、e 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 tothe central axis of symmetry is geared tobe halfof thatof therateofrotationaroundthe horizontal axis. 2.3. Experimental method Two types of

26、 initial powder loading used in the experiments: top bottom loading and sideloading, which are schematically repre- sented in Fig. 3. To avoid agglomeration, the API, acetaminophen, was delumped prior to loading it into the blender by passing it through a 35mesh screen. In order tocharacterize mixin

27、gperformance, 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. Approxi

28、- mately 7 samples are taken from each thief stab, and a total of fi ve stabs are used at each sampling time, as shown in Fig. 4 so a total of 35 samples are taken at each sampling point. The experimental plan used in this study is as follows: Fill level: blender 160% Fill level: blender 260%, 70%,

29、80% Loading pattern: blender 1 sideside loading, topbottom loading Loading pattern: blender 2 sideside loading, topbottom loading Speed: blender 115 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 27.5, 15, 30, 60, 120 revol

30、utions 3. Results The homogeneity index used is the RSD, where C is the concentration of each individual sample, C _ is the average concentra- tion of all samples and n is the total number of samples obtained at a given sampling time. RSD = S C ; where S = ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi

31、 ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffiffi ffi ffi ffi ffiffi ffiffi ffiffi ffiffi n P C2 P C2 n n 1 s We examine the effect of fi ll level on mixing performance. Previously there have been studies on the effect of fi ll level in the Bohle bin blender, Gallay bin blender and V-blender a

32、nd double cone blender 1113. 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 fi ll levels. To avoid repetition, studies for fi ll level are not conducted for bin blender 1. Results av

33、ailable from a previous study using MgSt as a tracer showed that mixing in a uni-axial blender slowed down quite dramatically as the fi ll level exceeded 70%. Moreover, results for acetaminophen can be assumed to be similar to those obtained in previous work by Muzzio et al. 11,13, for a single axis

34、 rectangular bin blender 11, which have shown that even after few hundred revolutions homo- geneity achieved with a 80% fi ll level is very poor as compared to 60% fi ll level. To examine the effect of fi ll level in a dual axis blender, experi- ments were performed in blender 2 with the top-bottom

35、loading pattern for a rotational speed of 15 rpm and with spinning speed of 7.5rpm.Thefi lllevelsexaminedare60%,70% and80%respectivelyand 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 f

36、or non-agglomerating materials, the curves Table 1 Materials studied in this paper. NameSize and morphologyVendor, City, State Fast-Flo Lactose100 , sphericalForemost farms, Newark, NJ Avicel PH 102 Microcrystalline cellulose 90 , needle-likeFMC, Rothschild, WI Acetaminophen40 , needle-likeMallinckr

37、odt, St Louis, MO 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

38、 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%. 2A. Mehrotra, F.J. Muzzio / Powder Technology 196 (2009) 17

39、 Fig. 2. Pictorial representation of (a) bin blender 1 and (b) bin blender 2 showing the corresponding axis of rotation. Fig. 3. Schematicoftheloadingpatternusedinthestudy.Intopbottomloading,Avicelisloadedfi rstintotheblenderfollowedbyLactoseontopofitandfi nallyAcetaminophenisuniformly sieved over.

40、In sideside 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. (a) Thief sampler (b) top view of the sampling position scheme. Fig. 5. Mixing curves for different fi ll levels in blender

41、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. 3A. Mehrotra, F.J. Muzzio / Powder Technology 196 (2009) 17 show a rapidly decaying region. The slope of the cur

42、ves in this region, in semi-logarithmic coordinates, is used to defi ne 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. Similar to previous studies with other tumbling blenders we ob- serv

43、ethat blending performance is adverselyaffected byincreasing fi ll levels. As shown in Fig. 5, the curve for 80% fi ll performs more poorly than those for 60% and 70% fi ll; as fi ll level increases, RSD curves decay more slowly, signifying a slower mixing process. However, the effect is not as pron

44、ounced as in other bin blenders and after about only 100 revolutions, the same plateau (the same asymptotic blend homo- geneity) is achieved for all three fi ll 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 wi

45、th dual rotation axis. Experiments were conducted for both blenders with top-bottom and side-side loading. Experiments were performed at 60% fi ll level and the rotation speeds considered for blender 1 are 15 rpm, 20 rpm and 25 rpm respectively. As shown in Figs. 6 and 7, whenplotted as a function o

46、f blender revolutions, there is not much of an effect of rotation speed on the homogeneity index (RSD) of acetaminophen at 60% fi ll level. It is observed that mixing perfor- manceat 20 rpmand25 rpmis slightly better than at 15 rpm,however the differences in the performance of the blender under diff

47、erent speeds are probably too small to be signifi cant. RSD curves decay with the same slope, indicating similar mixing rates. In the study reported here, the fi ll level is only 60%, and all the rotational speeds are enough to achieve homogenization. The aforementioned studies were con- ducted at 8

48、5% fi ll level. For such a high fi ll 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 homogeniza- tion. Moreover, the fl ow properties of MgSt are known to be strongly different than those of most materi

49、als, and are known to have a deep Fig. 6. Mixing curves for top-bottom loading experiments with 60% fi ll 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. Fig. 7. Mixingc

50、urvesforsidesideloadingexperimentswith60%fi lllevel.RSDisplottedasafunctionofnumberofrevolutions.Dottedlinescorrespondtoexperimentsintheblender1, while solid lines represent data points from the blender 2. 4A. Mehrotra, F.J. Muzzio / Powder Technology 196 (2009) 17 impact on the fl ow properties of

51、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. Subsequently, experiments were performed using the blender 2 at three r

52、otation speeds: 15 rpm, 20 rpm and 30 rpm, and as explained before, the corresponding spinning speeds were 7.5 rpm, 10 rpm and 15rpm.Filllevelconsideredfor both side-side andtop-bottomloading was 60%. Again, it was observed that varying rotation and spinning speeds didnot makemuchdifferenceinmixingr

53、ate.As showninFigs.6and7, 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 level

54、s of asymptotic homogeneity), but no signifi cant 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 fi ll level was kept a

55、s 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 symmetryaxis) on mixing performance. As shown in Fig. 6,

56、 the mixing curves for the blender 2 lie below those for the blender 1 for each rotation rate, indicating faster mixing. Note that the fi nal RSD asymptote reached for both blenders is also different, with the blender 2 showing a lower asymptote (better fi nal mixed state, presumably due to a lesser

57、 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 confi rmed that spinning a

58、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 madebetweenthe two loading patterns for both blenders. Again, to achie

59、ve a fair comparison, all experiments are performed at 15 rpm and 60% fi ll level. As evident in Fig. 8, in both Fig. 8. Comparisonbetweenthemixingcurvesof theblender2andtheblender1fortopbottomandsidesideloadingpattern.Dottedlinescorrespondtoexperimentsintheblender1, while solid lines represent data points from the blender 2. Experiments are performed at 15 rpm with 60% fi ll level. Fig. 9. A typical mixing plot, with RSD plotted against number of revolutions. The two solid lines emphasize on the two distinctive mixing regimes. 5A. Mehrotra, F.J. Muzzio / Powder Techno