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Effect of Tablet Deflectors in the Draft Tube of Fluidized/Spouted Bed Coaters Ganeshkumar Subramanian,† Richard Turton,*,‡ Suhas Shelukar,§ and Luke Flemmer| Department of Chemical Engineering, West Virginia University, Morgantown, West Virginia 26506, Merck Research Laboratories, West Point, Pennsylvania 19486-0004, and Peltec, Inc., Morgantown, West Virginia 26505
The control of tablet-to-tablet variation that occurs during batch coating operations is important in the pharmaceutical industry. This is particularly true when the coating substance contains an active ingredient (drug). The current work focused on evaluating the effect of tablet deflectors in the spray zone on the variation of coating material received by individual tablets as they pass through the spray. Digital video imaging was used to show how these deflectors changed the solids’ velocity and voidage profiles near the spray nozzle. A series of coating experiments was conducted to establish how such deflectors affected the coating variation per tablet per pass and the overall variation in coating received per tablet in a batch coating process. For the optimum deflector considered in this work, the relative standard deviation of coating mass was reduced from 11.3% without any deflector to 6.7%. Introduction The coating of tablets in the pharmaceutical industry has traditionally been accomplished using rotating perforated pans.1,2 These devices offer advantages over other coating devices (fluidized beds and tangential spray coaters) such as simplicity of operation, ability to clean the nozzle during coating, and ability to provide a low mechanical stress environment for the tablets. However, this equipment generally leads to higher tablet-to-tablet variability and longer batch processing times because of poor heat and mass transfer. When the variability between the amount of coating received by tablets in the same batch or between batches must be very small, as is the case with the “precision coating” of active ingredients onto tablets, then the fluidized/ spouted bed with a draft tube (“Wurster”) insert may be the preferred coating method.3 The theory describing the tablet-to-tablet variation occurring during batch and continuous operations has been developed previously.4-6 This theory, under the basic assumption that the tablets circulate independently of each other, states that the coating variability can be quantified by knowing the circulation time distribution of the solids through the spray zone and the distribution of coating material received per tablet per pass through the spray. When particles or tablets with a wide size distribution are coated in fluidized beds, the tablet-to-tablet variability occurring in batch coating operations has been shown to be a strong function of the tablet size (“diameter”).7,8 However, for the coating of a batch of identical tablets for relatively short periods of time, over which the relative mass gain of the tablets is small (say 30 min) for batch operations using equipment where gross dead spots have been eliminated, the major contributor to the coating mass variability is the variation of the coating mass received per tablet per pass through the spray. This suggests that reducing the variation in coating mass received per tablet per pass may noticeably improve the overall coating performance. It is postulated that the local overwetting of tablets that pass close to the spray nozzle can be reduced significantly by placing deflectors at the bottom of the draft tube that guide tablets away from the nozzle. In this study, the effect of placing tablet deflectors in the vicinity of the spray nozzle on the local tabletvelocity and -voidage profiles is quantified using digital video imaging techniques. In addition, the effect of these deflectors on the variability of the amount of coating received per tablet per pass and on the variability of the amount of coating received per tablet during the entire coating operation is investigated. Materials and Methods Fluidized-Bed and Tablet Deflectors. The semicircular fluidized-bed coating apparatus is shown in Figure 1 and has been used in previous studies.11,12 There have been many studies carried out in semicircular beds.13-18 From these and other studies, it has been shown that voidage and velocity measurements from semicircular fluidized and spouted beds are qualitatively the same as full (circular) beds. If measurements are taken at a distance of several millimeters inside the bed, then the effect of the wall is significantly reduced. Voidage measurements taken under these conditions are slightly lower than those obtained for circular beds using optical probes, but the voidage profiles in both beds are very similar.17,18 The velocity measurements are more significantly affected, with velocities being approximately 30% lower in the semicircular beds. However, as with the voidage data, the velocity profiles in both types of beds are similar in
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Figure 2. Diagram of gas distribution plate and tablet deflectors: (A) basic deflector; (B) modified deflectors 1-3; (C) modified deflector 4 (“optimum” deflector).
Figure 1. Schematic diagram of semicircular fluidized-bed coating equipment.
shape. Because the purpose of this work is to establish the effect of tablet deflectors on the voidage and velocity patterns in fluidized/spouted coating equipment, the results of visualization studies in the semicircular equipment were suitable for that purpose. The coating equipment illustrated in Figure 1 is made primarily of Plexiglas with a 0.0635-m-thick clear glass front face. The main bed has an inside diameter of 22.9 cm that expands to 31.5 cm at the top of the bed. The dimensions of the draft tube insert are shown in Figure 1. The position of the draft tube can be moved up or down, thus allowing control of the gap (hgap) between the bottom of the insert and the perforated distributor plate. Air is fed to the unit from a blower via an orifice meter that was calibrated against a wet turbine-type meter. The air then passes through a 10-kW heater and a manual control valve and finally enters the plenum section of the bed beneath the distributor plate. A coating solution
can be pumped through the custom-built semicircular, dual-fluid nozzle using a peristaltic pump. This liquid is atomized in the nozzle using house air available at 3.1-4.5 bar (30-50 psig). The gas distributor and the design of the tablet deflectors are shown in Figure 2. The gas distributor consists of a drilled stainless steel plate. The section of the distributor that lies beneath the draft tube contains a total of 136 0.25-cm-diameter holes drilled in concentric semicircles with an approximate triangular pitch. The section of the distributor that lies in the outer annular area contains many hundreds of 0.10-cm-diameter holes drilled on an approximately triangular pitch in concentric semicircles. The ratio of the open area between the inner and outer sections is 0.83. The basic shape of the tablet deflectors used in this work is illustrated in Figure 2A. Several variations on this shape were also investigated; these modifications consisted of placing thin semicircular sections of tubing at different distances from the center of the deflector, as shown in Figure 2B. The location of the tubes on the modified deflectors is given in the table in Figure 2B. Based on the results of both the digital imaging and the coating experiments, an optimized design was then tested, and this is shown in Figure 2C. The important difference between the optimized design and the modified designs shown in Figure 2B is that, in the optimized design, the deflector has been shaped to give a smooth transition to the optimum top diameter, thus eliminat-
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Figure 4. Diagram illustrating the sequence and timing of events occurring during the measurement of tablet velocities.
Figure 3. Two-camera setup used in the video imaging of tablet movement through the draft tube.
ing the abrupt change in diameter caused by the semicircular sections of tubing in the designs shown in Figure 2B. Velocity and Voidage Measurements. Both the voidage and velocity of tablets in the draft tube region of the bed were obtained by capturing digital images of the tablets 0.2 cm inside the front surface of the semicircular bed. The experimental setup is shown in Figure 3. The images for velocity measurements were obtained using two CCD cameras (Sony XC 75 CE CCD, Sony Inc.) equipped with Ultrak TV lenses (50 mm and aperture f 1.3) with 8-mm extension rings. The cameras were focused a short distance (0.2 cm) inside the flat front face of the bed. For the conditions used in this work, the maximum tablet velocity was around 2.5 m/s. To evaluate the tablet velocity accurately, successive tablet images within the field of view (FOV) of the camera had to be captured. For the work performed here, the FOV was 2 cm by 2 cm and successive fields of data were required to be captured at no greater than 5 ms apart. This rate of capture is not possible using the standard RS-170 framing rate of 33.33 ms (30 Hz). Instead of using a high-speed camera, the method adopted in this work was to use two synchronized CCD cameras to capture images of the same area of the bed at times of between 1 and 5 ms apart. The timing events were controlled by customized software, and the user sets the time lag. The setup for the cameras is shown in Figure 3. It is important that the cameras be arranged in a steep isosceles triangle in order to minimize parallax effects. The greater the angle at the apex, θ, the greater is the difference between the images from the two cameras. Once the cameras were setup, the customized software was used to calibrate the two images from the camera in order to minimize these errors. The timing sequence for the two cameras is shown in Figure 4. To obtain data when the bed was running, a “grab” event was initiated that caused both cameras to obtain images at the preselected time lag.
Figure 5. Image of tablets used in this work.
The center of a given tablet was then located in each field from the two cameras using a computer-generated crosshair. The horizontal and vertical distances between the successive images were computed and recorded. These data were then converted into magnitude and direction using the appropriate time lag. To obtain a map of tablet velocities in the draft tube, the front face of the bed was divided into 70 2 cm by 2 cm square grids, and repeated measurements were made for each square. Voidage measurements were obtained in a given region of interest of the bed using a single CCD camera mounted perpendicular to the flat front face of the bed. A shutter speed of 0.1 ms was used in order to obtain crisp, blur-free images. The software counted the number of tablets in the FOV automatically. To convert the number count to a voidage, the depth of field (DOF) of the camera and lens system had to be found. The DOF was obtained by calibration19 and using this value with the known volume of tablets in a given volume of bed, the local void volume in the bed was calculated. This process was repeated on the same 2 cm by 2 cm grid as that used for the velocity measurements to give a map of the voidage profile in the draft tube. Tablets and Coating Materials. All of the experimental runs were carried out using placebo tablets that were 8.05 mm in diameter and 4.2 mm in thickness, with an average tablet volume of 0.170 cm3 and an average tablet weight of 0.205 g. These placebo tablets (Merck & Co., Inc.) were made by compressing a mixture of Avicel PH101 and magnesium stearate and pan
Ind. Eng. Chem. Res., Vol. 42, No. 12, 2003 2473 Table 1. Operating Conditions for the Continuous-Coating Runs variable fluidizing air flow rate coating liquid flow rate total volume of the coating liquid temperature of air run time
value
comments
m3/s
weight of the bed material
0.066 10 mL/min 550 mL of Aquacoat + 50 mL of distilled water 45 °C 60 min of coating time + 10 min of drying time 3.675 kg
weight of the blue dye
2.7 g
atomizing air pressure
35 psi
Table 2. Operating Conditions for the Pulse Test Runs variable
value
fluidizing air flow rate coating liquid flow rate total volume of the coating liquid temperature of air total time of coating weight of the bed material weight of the blue dye used in the pulse atomizing air pressure bed air temperature volume of the pulse duration of the pulse
0.066 m3/s 10 mL/min 100 mL 45 °C 10 min 3.675 kg 2.7 g 35 psi 45 °C ∼1.5 mL 8-10 s
coating with an aqueous solution of (hydroxypropyl)methylcellulose (HPMC) and (hydroxypropyl)cellulose. These tablets were used as the starting material for this work, and their shape is illustrated in Figure 5. Two types of experiments were performed in the current work. For the continuous coating experiments, the conditions used are given in Table 1. In these experiments, the coating took place over a 60-min period and then the coated tablets were dried for an additional 10 min in the bed using the same flow of fluidizing air. The results from these tests were used to determine the distribution of coating material on the batch of tablets and also the coating efficiency. The object of the current work is to minimize the spread of the coating distribution while maintaining the coating efficiency. After the drying period had finished, the batch of tablets was removed from the bed and a random sample of 100 tablets was taken from the batch. Each tablet was then dissolved in 10 mL of distilled water, the solution was then filtered, and an additional 5 mL of water was used to wash any remaining dye from the filter paper. The resulting 15 mL of liquid, containing the blue dye, was poured into a cuvette and allowed to stand overnight. The concentration of the blue dye was determined by measuring the absorbance at a wavelength of 629 nm using a Lambda 2 UV/vis spectrophotometer (PerkinElmer Corp., Norwalk, CT). The mass of blue dye per tablet, which is proportional to the total mass of coating per tablet, was then calculated. Another series of coating experiments was also performed. In these experiments, a pulse of blue dye was introduced into the coating mixture for a period equal to the average circulation time of tablets in the bed (approximately 8-10 s). The purpose of the pulse tests was to evaluate the distribution of coating material received per particle per pass through the spray. As with the results from the continuous-coating tests, a narrow coating-per-pass distribution is desirable. The conditions used for these pulse tests are given in Table 2. The pulse tests consisted of starting a coating run using the same conditions and materials as those given
Aquacoat is an ethylcellulose aqueous dispersion containing 30% solids supplied by FMC Corp., Newark, DE
Avicel PH101 and magnesium stearate tablets coated with HPMC, Merck & Co., West Point, PA FD&C Blue Dye No. 1, Warner-Jenkinson Co., St. Louis, MO Table 3. Experimental Matrix for Experiments To Determine the Velocity and Voidage Profiles in the Bed deflector type gas modified gap distributor flow height deflector no expt plate (m3/s) 1b deflector (m) deflectora 1 2 3 4 5 6 7 8
Ac A A A A A Bd A
0.0649 0.0684 0.0686 0.0695 0.0684 0.0707 0.0684 0.0766
0.027 0.027 0.027 0.074 0.074 0.074 0.074 0.074
Y Y Y Y Y Y Y Y
a ,bFor
descriptions of deflectors, refer to parts a and b of Figure 2, respectively. c Open areas for the portion of the distributor under the draft tube/area outside draft tube ) 0.83. d Open areas for the portion of the distributor under the draft tube/area outside draft tube ) 0.92.
in Table 1, except that no blue dye was added to the coating solution. After approximately 10 min from the start of spraying, a concentrated pulse of coating fluid containing 2.7 g of FD&C Blue Dye No. 1 was introduced into the coating line. The duration of this pulse was chosen to closely match the average circulation time of the tablets in the equipment. Therefore, on average, every tablet was exposed to this spray of intense blue dye only once. After the pulse was injected, the coating solution was stopped, the bed material was dried for a short period, and the batch of tablets was removed from the bed. Again, 100 tablets were randomly selected from the batch, and each tablet was dissolved in 2 mL of distilled water and filtered, and then the filter paper was rinsed with an additional 1 mL of water. The 3 mL of solution containing the blue dye was then allowed to stand overnight and analyzed for dye content using the spectrophotometer. Results and Discussion Velocity and Voidage Profiles. The experimental design matrix used in this work is given in Table 3. There are three main factors considered in the experimental design: fluidizing gas velocity, gap height, and design of the tablet deflector. A fourth factor, the configuration of the gas distributor plate, was also tested, and details are given elsewhere.19 The dependent variables in this experimental study were the voidage and velocity profiles in the draft tube. Tests were repeated for several of the conditions given in Table 3, and the measured profiles were found to agree. However, because it was difficult to quantify the voidage and velocity profiles through a single set of parameters, a full statistical analysis was not performed. Rather, the
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Figure 6. Comparison of voidage and velocity profiles obtained at the same conditions of gas flow, tablet inventory, gas distributor plate, and without a tablet deflector using a low gap height (2.7 cm, experiment 3) and a high gap height (7.4 cm, experiment 6).
consequences of the presence and shape of the particle deflectors on the profiles were determined over the range of operation given in Table 3. Because of limitations of the blower and the large tablet size, the air flow rates could only be varied over the narrow range shown in Table 3. However, there is a significant effect due to air velocity even for the range of values tested here. The variable with the greatest effect on the profiles within the bed is the gap height, hgap. Voidage and velocity profiles for experiments 3 and 6, which differ in operating conditions by only the gap
height, are shown in Figure 6. It can be seen that the effect of increasing the gap height is to increase the tablet velocities and to make the voidage more uniform across the draft tube. The net result is a higher flux of solids through the draft tube. From Figure 6, it is also evident that there is a considerable amount of solids near the spray nozzle. As these solids pass through the spray zone, they will receive significant coating and will tend to shelter tablets farther away from the spray. In the ideal case, all tablets would receive the same amount of coating each time they passed through the
Ind. Eng. Chem. Res., Vol. 42, No. 12, 2003 2475 Table 4. Summary of the Results of Continuous-Coating Experiments with Tablet Deflectors
deflector type no deflector modified deflector 1 modified deflector 2 modified deflector 3 modified deflector 4 (“optimum” deflector)
Figure 7. Comparison of voidage profiles under similar operating conditions using different tablet deflectors [no deflector, experiment 6; deflector (Figure 2A), experiment 4; modified deflector 1 (Figure 2B), experiment 5].
spray zone. For this case, the amount of coating deposited on each tablet would then depend only on the number of times the tablet passed through the spray zone. Therefore, to minimize the variation in the coating received per tablet per pass, it would seem logical to try to divert tablets away from the source of the spray, which in turn would tend to improve the uniformity of spray deposition on the tablets. To this end, the tablet deflectors shown in Figure 2 were developed. Referring to Table 3, a comparison of the voidage profiles obtained
sample standard sample RSDtotal, % coating deviation, mean, Xtotal Stotal/Xtotal efficiency Stotal 0.0136 0.0077 0.0106 0.0132 0.0093
0.121 0.114 0.103 0.137 0.139
0.113 0.068 0.103 0.096 0.067
83 82 80 89 89
in experiments 1-3 and 4-6 may be used to estimate qualitatively the effect that the different deflectors have on the local voidage in the spray region. The results of these comparisons are very similar, and only the results for the larger gap height (hgap ) 7.4 cm) are shown in Figure 7. From this figure, it can be seen that the effect of adding the tablet deflectors is to reduce the tablet density in the area immediately around the tip of the spray nozzle, while “pushing” solids to the side of the draft tube. This effect is much more pronounced for modified deflector 1 (experiment 5) as compared to the deflector without the modification (experiment 4). The effect of the tablet deflectors was further investigated by performing a series of continuous-coating runs to evaluate the effect of the tablet deflectors on mass coating variability within each batch. Continuous-Coating Experiments. Following the test procedure for continuous-coating runs presented in Table 1, the effect of each of the tablet deflectors given in Figure 2 was investigated. The results of these experiments are summarized in Table 4, and the distributions are shown in Figure 8. The parameter RSD (relative standard deviation) is an estimate of the coefficient of variation (CV) of the distribution of coating on the batch of tablets and hence is a measure of the spread of the distribution around the mean value. The goal of this work is to minimize the RSD and, therefore, the optimum tablet deflector is the one giving the lowest RSD or the narrowest coating distribution. From these results, it is clear that modified deflector 4 has the lowest RSD, which is marginally lower than that of modified deflector 1. In addition, this deflector also has the highest coating efficiency and appeared to produce the lowest dusting and tablet breakage. Pulse-Coating Experiments. To quantify further the role played by the tablet deflectors on the coating mass variability, a comparison between the case using the “optimum” deflector (modified deflector 4) and that with no deflector was made utilizing pulse-coating tests. These tests were conducted following the procedures outlined in Table 2. The results are summarized in Table 5, and the coating mass distributions are shown in Figure 9. From these results, it can be seen that the RSD for the optimum deflector is significantly lower than that for the case without a deflector, which is consistent with the results from the continuous-coating tests. Comparison with Theory According to previous work,4,5,10 the batch coating of tablets may be described by a renewal process. Thus, the CV of the coating distribution for a batch run can be related to the CV of the cycle time distribution and
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Figure 8. Comparison of coating mass distributions for continuous-coating operations under similar coating conditions using different tablet deflectors: (A) no deflector; (B) modified deflector 1; (C) modified deflector 2; (D) modified deflector 3; (E) modified deflector 4 (“optimum” deflector). Table 5. Summary of the Results for Pulse-Coating Tests statistical data
no deflector
modified deflector 4
standard deviation of distribution, S mean of distribution, X h RSD ) S/X h
0.101 µg/tablet
0.090 µg/tablet
0.0811 µg/tablet 1.245
0.105 µg/tablet 0.858
the CV of the distribution of mass per tablet per pass by the following expression:
σtotal2 µtotal
σpass2 µct σct2 µct ) + 2 µ 2 Trun µ 2 Trun pass
(1)
ct
where σ is the standard deviation, µ is the mean, Trun is the total time for coating, “total” refers to the distribution of total mass deposited during a batch coating operation, “pass” refers to the distribution of mass received per tablet per pass through the spray zone, and “ct” refers to the cycle time distribution for tablets passing through the spray zone. Shelukar et al.,3 in a cylindrical coating apparatus of size similar to that used in this work, used a magnetically tagged tracer
tablet to estimate the cycle time distribution of tablets and a pulse technique to measure the coating per pass distribution. By comparing the relative magnitude of the terms on the right-hand side of eq 1, they concluded that the major cause of variation was due to the coating mass per pass distribution that accounted for between 76 and 86% of the total variation. However, their data showed that the terms on right-hand side of eq 1 were higher than those on the left-hand side by as much as 60%. Cheng and Turton9 did not measure the coating per pass distribution independently but calculated it from the difference between the CV of the cycle time distribution and the CV of the overall coating distribution using eq 1. They concluded that an even greater fraction of the total variation could be attributed to the coating mass per pass distribution for the coating of 1-mm sucrose beads. From the above results, it is clear that the CV of the coating per pass distribution plays a much more significant role on the overall coating distribution than does the CV of the cycle time distribution. Therefore, as a first approximation, it is reasonable to ignore the second term on the right-hand side of eq 1, and the
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these effects will tend to underestimate the predicted RSD using renewal theory. The results of the current work indicate that an improved method to measure the coating-per-pass distribution needs to be found in order to verify the predictions of renewal theory to this type of coating process. Conclusions
Figure 9. Comparison of coating mass distributions for pulsecoating tests under similar coating conditions using different tablet deflectors: (A) no deflector; (B) modified deflector 4 (“optimum” deflector). Table 6. Comparison of the Results from Equation 2 left-hand side of eq 2 no deflector
0.113
modified deflector 4 (“optimum” deflector)
0.067
right-hand side of eq 2
% error
1.245x(8)/(50)(60) 43% ) 0.0643 0.858x(10)/(50)(60) 26% ) 0.0495
results of the pulse tests and continuous-coating runs for the case with no deflector and the case with the modified deflector 4 can be compared using eq 2:
x
σtotal σpass ≈ µtotal µpass
µct Trun
The use of tablet deflectors in fluidized-bed equipment for the batch coating of tablets was shown to increase the uniformity of the coating mass distribution. Both tablet velocity and voidage profiles in the draft tube insert of the equipment were measured using video imaging techniques. The major effect of the tablet deflectors was to increase the voidage in the vicinity of the spray zone and hence reduce the local wetting phenomenon that is known to occur close to the spray source. A total of four deflectors were used, and in each case the RSD of the mass coating distribution was reduced compared to coating without a deflector at similar conditions. The optimum deflector used showed a decrease in RSD of over 40% and an increase in coating efficiency of 6%. A series of pulse tests were conducted that showed a considerable reduction in the RSD of the coating per tablet per pass distribution for the optimum deflector. Results for the pulse- and continuous-coating runs were compared and found to agree quite well with the predictions of coating renewal theory. Finally, it was found that although the trends between the RSD of the overall (continuous) coating distributions and the coating-per-pass distribution were in good agreement, a comparison of absolute values of these terms using renewal theory showed significant error. To address this anomaly, experiments to determine the evolution of the coating distribution with time are underway. Acknowledgment
(2)
The total run time, Trun, for the continuous-coating runs was the same for both experiments, while the average cycle time, µct, for the runs with no deflector and modified deflector 4 were 8 and 10 s, respectively. The left-hand side of eq 2 can be estimated from the results of the continuous-coating runs given in Table 4, and the remaining terms on the right-hand side can be estimated from the pulse test results given in Table 5. The results from substituting experimental values into eq 2 are given in Table 6. The results in Table 6 show that the error between the left- and right-hand sides of eq 2 is between 26 and 43%, with the term on the right-hand side underestimating the overall RSD. When the contribution of the cycle time distribution in eq 1 is ignored, two types of errors will be introduced. The first is simply due to omitting the second term. As explained previously, this, in itself, is not expected to cause a large error because the cycle time will be fairly narrow and on average for the tests described here a tablet makes approximately 300 passes through the spray during the continuouscoating operation. However, another consequence of the cycle time distribution is that when performing the pulse tests, not all of the tablets will pass through the spray just once. This may have the effect of narrowing the measured coating-per-pass distribution. Both of
The authors acknowledge Merck & Co. for providing financial support and for supplying the placebo tablets and also FMC for supplying the Aquacoat ECD. R.T. also takes this opportunity to thank Professor Levenspiel for his guidance and inspiration over the last 20 years. It has truly been a pleasure and honor to interact with and be mentored by such a gifted individual. Nomenclature CV ) coefficient of variation hgap ) height of the gap between the distributor plate and the bottom of the draft tube (mm) RSD ) relative standard deviation ) standard deviation/ mean S ) sample standard deviation T ) time (s) X h ) sample mean Greek Letters µ ) population mean σ ) population standard deviation Subscripts ct ) cycle time pass ) per pass MD-4 ) modified deflector number 4 ND ) no deflector run ) time of coating run total ) total for batch coating operation
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Literature Cited (1) Ansel, H. C.; Popovich, N. G. Pharmaceutical Dosage Forms and Drug Delivery Systems, 5th ed.; Lea and Febiger: Philadelphia, PA, 1990. (2) Kadam, K. L. Granulation Technology for Bioproducts; CRC Press: Boca Raton, FL, 1990. (3) Shelukar, S.; Ho, J.; Zega, J.; Roland, E.; Yeh, N.; Quiram, D.; Nole, A.; Katdare, A.; Reynolds, S. Identification and Characterization of Factors Controlling Tables Coating Uniformity in a Wurster Coating Process. Powder Technol. 2000, 110, 29. (4) Mann, U. Analysis of Spouted-Bed Coating and Granulation. 1. Batch Operation. Ind. Eng. Chem. Process Des. Dev. 1983, 22, 288. (5) Mann, U.; Crosby, E. J.; Rubinovitch, M. Number of Cycles Distribution in Circulating Systems. Chem. Eng. Sci. 1974, 29, 761. (6) Mann, U. Coating of Particulate Solids by Air Suspension. Ph.D. Dissertation, University of Wisconsin, Madison, WI, 1974. (7) Iley, W. J. Effect of Particle Size and Porosity on Particle Film Coatings. Powder Technol. 1991, 65, 441-445. (8) Sudsakorn, K.; Turton, R. Non-Uniformity of Coating on a Size Distribution of Particles in a Fluidized Bed Coater. Powder Technol. 2000, 110, 37. (9) Cheng, X. X.; Turton, R. The Prediction of Variability Occurring in Fluidized Bed Coating Equipment. Part 1: The Measurement of Particle Circulation Rates in a Bottom Spray Fluidized Bed Coater. Pharm. Dev. Technol. 2000, 5 (3), 311. (10) Cheng, X. X.; Turton, R. The Prediction of Variability Occurring in Fluidized Bed Coating Equipment. Part 2: The Role of Nonuniform Particle Coverage as Particles Pass through the Spray Zone. Pharm. Dev. Technol. 2000, 5 (3), 323. (11) Saadevandi, B. A.; Turton, R. The Application of Computer-Based Imaging to the Measurements of Particle and
Voidage Profiles in a Fluidized Bed. Powder Technol. 1998, 98, 183. (12) Saadevandi, B. A. The Use of Imaging Techniques to Study the Hydrodynamics of Particle Motion in a Fluidized Bed Coating Device in the Region of Liquid Spray. Ph.D. Dissertation, West Virginia University, Morgantown, WV, 1996. (13) Randelman, R.; Benkrid, A.; Caram, H. S. Investigation of Solid Flow Pattern Measurements in Fluidized Bed. AIChE Symp. Ser. 1983, 83 (255), 23. (14) Rovero, G.; Piccinini, N.; Lupo, A. Solids Velocities in Full and Half-Sectional Spouted Beds. Entropie 1985, 124, 13. (15) Day, J. Y.; Morgan, M. H.; Littman, H. Measurements of Spout Voidage Distributions, Particle Velocity, and Particle Circulation Rates in Spouted Beds of Course ParticlessII. Experimental Verification. Chem. Eng. Sci. 1987, 42, 1461 (16) Bankrid, A.; Caram, H. S. Solids Flow in the Annular Region of a Spouted Bed. AIChE J. 1989, 35, 1328. (17) He, Y. L.; Qin, S. Z.; Lim, C. J.; Grace, J. R. Particle Velocity Profiles and Solids Flow Patterns in Spouted Beds. Can. J. Chem. Eng. 1994, 72, 229. (18) He, Y. L.; Qin, S. Z.; Lim, C. J.; Grace, J. R. Measurements of Voidage Profiles in Spouted Beds. Can. J. Chem. Eng. 1994, 72, 229. (19) Subramanian, G. Video Imaging of the Flow Patterns of Tablets in a Semicircular Laboratories Fluidized Bed. M.S. Thesis, Department of Chemical Engineering, West Virginia University, Morgantown, WV, May 2000.
Received for review August 2, 2002 Revised manuscript received November 25, 2002 Accepted November 26, 2002 IE020577K
