Top-spray Fluidized Bed Research Articles

Influence of multi-factor interactions on particle growth during top-spray fluidized bed agglomeration

Considering the strong dependence of agglomerate characteristics on various operating parameters, this study employs the control variable methodology (CVM) and response surface methodology (RSM) to investigate the influence of multi-factor interactions on particle growth during top-spray fluidized bed agglomeration. First, CVM is conducted to assess the effects of individual operating parameters on the agglomerate properties, such as mean particle size, relative width, and sphericity. Then, the interactive relationship between these input variables and the quality attributes of the process is investigated using RSM. The results show that the mean particle size increases with the increase of binder viscosity and spray rate, while it decreases with the increase of fluidization gas velocity and inlet gas temperature. The relative width of the particle size distribution increases with the spray rate, binder viscosity, and fluidization gas velocity, and hardly changes with the inlet gas temperature. The mean particle size is more sensitive to the binder spray rate at a lower level of fluidization gas velocity or a higher level of inlet gas temperature. The fluidization gas velocity corresponding to the maximum D50 changes when the binder viscosity and binder spray rate are at different levels.

Assessment of the coating quality in a top-spray fluidized bed coater: An experimental study

The effects of multiple factors on the coating process in a top-spray fluidized bed coater were systematically investigated. The intra-particle coating variability could be assessed by the SEM measurement. Fluidizing gas temperature (0.5–0.9, normalized by the boiling point of water), injection velocity (0.115–0.397 m/s) and concentration (2.1–5.2 wt%) of the coating liquids, atomizing pressure (1.0–3.0 bar) and nozzle height (378 and 470 mm) were found to impact particle agglomeration, coating efficiency and thickness dramatically. Their impact trends and mechanisms were analyzed in detail. The effect of the particle size (0.22–1.26 mm) on particle agglomeration behavior was highlighted. Critical injection velocities and the corresponding agglomeration ratios were experimentally determined. Finally, it was established that there were no universal optimum conditions for the spray coating process, and they can be experimentally determined according to the attributes of interest.

Development of a time-dependent oral colon delivery system of anaerobic Odoribacter splanchnicus for bacteriotherapy

Odoribacter (O.) splanchnicus is an anaerobic member of the human intestinal microbiota. Its decrease in abundance has been associated with inflammatory bowel disease (IBD), non-alcoholic fatty liver, and cystic fibrosis. Considering the anti-inflammatory properties of O. splanchnicus and its possible use for IBD, intestinal isolate O. splanchnicus 57 was here formulated for oral colonic release based on a time-dependent strategy. Freeze-drying protocol was determined to ensure O. splanchnicus 57 viability during the process. Disintegrating tablets, containing the freeze-dried O. splanchnicus 57, were manufactured by direct compression and coated by powder-layering technique with hydroxypropyl methylcellulose (Methocel™ E50) in a tangential-spray fluid bed. Eudragit® L was then applied by spray-coating in a top-spray fluid bed. Double-coated tablets were tested for release, showing gastric resistance properties and, as desired, lag phases of reproducible duration prior to release in phosphate buffer pH 6.8. The cell viability and anti-inflammatory activity of the strain were assessed after the main manufacturing steps. While freeze-drying did not affect bacterial viability, the tableting and coating processes were more stressful. Nonetheless, O. splanchnicus 57 cells survived manufacturing and the final formulations had 106-107 CFU/g of viable cells. The strain kept its anti-inflammatory properties after tableting and coating, reducing Escherichia coli lipopolysaccharide-induced interleukin-8 cytokine release from HT-29 cells. Overall, O. splanchnicus 57 strain was formulated successfully for oral colon delivery, opening new ways to formulate pure cultures of single anaerobic strains or mixtures for oral delivery.

Characterization of a Commercial Whey Protein Hydrolysate and Its Use as a Binding Agent in the Whey Protein Isolate Agglomeration Process.

The first objective of this study was to characterize the chemical properties of three lots of whey protein hydrolysate (WPH) obtained from a commercial manufacturer. The degree of hydrolysis (DH) of WPH was between 13.82 and 15.35%, and was not significantly (p > 0.05) different between the batches. From MALDI-TOF, 10 to 13 different peptides were observed in the range of 2.5–5 kDa and 5–8 kDa, respectively. The second objective of the study was to evaluate the effectiveness of WPH as a binder in whey protein isolate (WPI) wet agglomeration. For this purpose, a 3 × 3 × 2 factorial design was conducted with pre-wet mass (60, 100, and 140 g), WPH concentration (15, 20, and 25%), and flow rate (4.0 and 5.6 mL·min−1) as independent variables. WPI agglomeration was carried out in a top-spray fluid bed granulator (Midi-Glatt, Binzen, Germany). Agglomerated WPI samples were stored at 25 °C and analyzed for moisture content (MC), water activity, relative dissolution index (RDI), and emulsifying capacity. Pre-wet mass, flow rate, and the WPH concentration had a significant (p < 0.05) effect on the MC. Moreover, all interactions among the main effects had also a significant (p < 0.05) effect on MC. High MC and water activity were observed for the treatments with a higher pre-wet volume and higher flow rate, which also resulted in clumping of the powders. The treatment with the 60 g pre-wet mass, 20% WPH concentration, and 5.6 mL·min−1 flow rate combination had the highest RDI among all the samples. In conclusion, WPH can be used as a potential alternative to soy lecithin in WPI wet agglomeration.

Modelling of urea aggregation efficiency via particle tracking velocimetry in fluidized bed granulation

This work presents a predictive model to estimate the particle size distribution (PSD) and aggregation efficiency of wet granulation of urea in top spray fluidized bed. To elucidate the model solution, the experimental granulation process of urea particles was performed. Urea particles with an average size of 250 µm, were charged and fluidized at the granulator by spraying a binder solution. Urea granule samples were withdrawn at different granulation time, and the respective particle size distributions were characterized using the sieving method. An empirical model for aggregation rate constant has been developed based on the experimental data at various operating conditions and used in population balance model to estimate the PSD. Furthermore, the model has been extended to determine aggregation efficiency using particle tracking velocimetry method (PTV). The developed model could be employed to estimate the urea granulation performance and kinetics in fluidized bed for design and scale-up purpose.

CFD–DEM–PBM coupled model development and validation of a 3D top-spray fluidized bed wet granulation process

In pharmaceutical manufacturing, fluidized bed granulation is one of the common processing options available to achieve better flowability of powders through size enlargement of primary particles. In fact over the last 50 years, various fluidized bed operations including freezing, drying, impregnation, coating, etc. have become a common place in the chemical processing industry due to the high level of contacts between fluids and solids attainable in a fluid bed system. These complex interactions between the fluid and particles also mean that simulating fluidized beds are still a challenging endeavor. Generally, Computational Fluid Dynamics (CFD) packages are employed to model the pressure drops in fluids; however, the presence of high concentration of solids and the complexity of granulation behavior require more advanced particle models than are available with CFD software. As a result, coupled frameworks that utilize the strength of particulate simulations such as Discrete Element Method (DEM) and bulk granulation modeling such as Population Balance Model (PBM) in conjunction with CFD information are the next steps to developing practical fluid bed granulation models.This paper aims to provide a comprehensive description of the development and validation of a coupled CFD–DEM–PBM framework for a fluidized bed wet granulation operation. A two-way coupled CFD–DEM model is developed for a 3-dimensional, lab-scale, top spray fluid bed granulator to study the effects of process parameters such as inlet air flow rate and inlet air temperature on the particle flow dynamics and the residence time in the spray zone. A one-way transfer of data from CFD–DEM to PBM is then applied to relate the effects of particle-fluid interactions to granulation behavior occurring within the fluidized bed system. Mechanistic rate expressions were developed in the PBM to create links between CFD–DEM results and PBM rate kernels which can express the effect of critical process parameters (CPPs) such as air flow rate, inlet air temperature, binder spray rate, etc. to experimentally measured critical quality attributes (CQAs) including granule size distribution and liquid content values. From comparison with experimental results, the framework presented shows good accuracy at capturing the dynamics of the system. The presented framework demonstrates a practical process model development methodology by efficiently coupling multi-phase simulation techniques which can be used for effective process design, development and scale-up purposes.

Two-compartment modeling and dynamics of top-sprayed fluidized bed granulator

• Compartmental approach is used to model and simulate a top sprayed fluidized bed granulator. • The dynamic behavior is analysed by varying the process conditions and parameters. • Finite volume scheme is modified to solve the proposed mathematical model. • New analytical solutions are derived for the verification of model. • Constant volume Monte Carlo is developed for the proposed model and used for the validation. A top Spray Fluidized Bed Granulator (SFBG) is being modeled and analyzed with the help of population balance equation (PBE) and analytical as well as numerical results. The mathematical model for SFBG is derived using the concept of compartment modeling. The granulator is divided into two compartments, a wet compartment in which aggregation is the dominant process, and a dry compartment that is dominated by breakage. A new discretization is given to solve the model which is based on the idea of conserving the important properties of the system. The numerical results of the moments derived by the new discretization are validated against the developed exact results for different combinations of the aggregation and breakage kernels. The model is also tested for physical tractable kernel and the numerical results are authenticated with the results of constant volume Monte Carlo. The two-compartment model is shown to behave dynamically in a distinctly different manner to the simpler one-compartment model. The most critical parameter is the exchange flow between the compartments. When the characteristic time for this flow is low relative to the rates of aggregation and breakage, the effect of breakage is amplified disproportionally relative to breakage, and whereas the single-compartment granulator always reaches steady state between the rates of aggregation and breakage, the two-compartment model may, under some conditions, lead to continuously decreasing size under the dominance of breakage.

An application of deep learning to detect process upset during pharmaceutical manufacturing using passive acoustic emissions

The multivariate nature of a fluidized bed system creates process complexity that increases the risk of production upset. This research explores the use of passive acoustic emissions monitoring paired with an artificial neural network to detect fluidized bed distributor plate blockage. In many cases, early process failure detection can allow for immediate intervention, thus lowering operation costs. Blockages were simulated by actively covering portions of a top-spray fluidized bed distributor plate. Piezoelectric microphones were placed within the fluidized bed exhaust and attached externally to the vessel wall. Several time and frequency domain feature vectors were extracted from the monitoring data using the open source pyAudioAnalysis library in Python. Through deep learning, the artificial neural network used these feature vectors to train against each distributor plate blockage condition. The deep learning model was then evaluated using k-fold cross validation. The findings were very positive and successfully demonstrated an application of deep learning to detect process upset.

Inline acoustic monitoring to determine fluidized bed performance during pharmaceutical coating

Fluidized beds are used by pharmaceutical manufacturers for multi-particulate drug coating. They provide effective mass and heat transfer; however, unit optimization can be difficult due to the multivariate nature of a fluidized bed system. This research explores the use of passive acoustic emissions monitoring as a method to improve temperature management during pellet coating. A piezoelectric microphone was placed inside the exhaust of a conical top spray fluidized bed. Spherical 1000 μm pellets were coated while recording acoustic emissions. Fluidization air temperature was adjusted between trials as a controlled variable to determine if pellet drying rate could be extracted from the data. During each trial, pellets became damp as the coating solution was applied. Drying stages were used to remove moisture whereby pellet fluidization continued without spraying. The moving standard deviation of the acoustic emissions increased by approximately 40 mV during each 2-min coating stage. The emissions then decreased during drying. This decrease was at a rate proportional to pellet drying independently measured at each controlled temperature. The overall coating-drying emissions profile was similar for trials using either sugar or Acryl-EZE® coating solutions. Passive acoustic emissions monitoring is non-invasive and provides reliable coating and drying information during fluidized bed operation.

Association of PLGA Microspheres to Carrier Pellets by Fluid Bed Coating: A Novel Approach towards Improving the Flowability of Microparticles.

Micro- and nanoparticles have been vastly studied due to their biopharmaceutical advantages. However, these particles generally display very weak packing and poor mechanical properties. Hereby, a new methodology is proposed to associate poorly flowing particles to macrostructures targeting the improvement of flowability and redispersibility of the particles. Cecropia glaziovii-loaded PLGA microspheres (4.59 ± 0.04 μm) were associated with carrier pellets by film coating in a top-spray fluid bed equipment. Optimal conditions were determined employing a IV-Optimal factorial design and RGB image analysis as 1% (w/v) Kollicoat® Protect as coating polymer (2:1 weight ratio of coating suspension to carrier pellets), containing 5 mg/mL microspheres (loading of 28.07 ± 1.01 mg/g). The method led to an improvement of the overall flowability. No relevant molecular interactions between PLGA microspheres and polymers were found. Microspheres detached rapidly from the surface of the pellets, without agglomeration, when exposed to hydrodynamic forces. In vitro release profiles, prior to and after fluid bed coating, showed no relevant changes in drug release rate and extent. The methodology developed is suitable for further applications when an improvement on the flow properties and redispersibility of the product is desired. We showed an easy-to-implement methodology that can be executed without significant increase in costs.

A process optimization strategy of a pulsed-spray fluidized bed granulation process based on predictive three-stage population balance model

In this work, a three-stage population balance model (TSPBM) was developed for a pulsed top-spray fluidized bed granulation (FBG) process. The batch top-spray FBG process was divided into three stages based on the analysis of granule properties evolution and different granulation mechanisms were considered in each stage of the TSPBM. In each stage, population balance model (PBM) describes the evolution of granule size distribution (GSD), and partial least square (PLS) regressions describes the relationship between the operating variables and kernel parameters in PBM. By fitting coefficients of PLS regressions using experimental data, the developed TSPBM establishes a predictive relationship between the manipulated binder spray parameters of pulsed frequency, binder flow rate and atomization pressure and granule critical quality attributes (CQAs). A model-based multi-stage optimization strategy was proposed to improve the granule quality of the pulsed-spray FBG. The optimization strategy reduced the process error caused by mismatch between developed model and actual system. In the optimization strategy, volume average granule diameter is only measured online at the end of each stage. Based on the online measurement, the optimization strategy adjusts process operating variables to remedy any drift between measured and predicted GSD. Validation experiments and simulation tests were carried out to validate the effectiveness of the proposed TSPBM and optimization strategy. The developed TSPBM is shown to accurately predict experimental GSD and shows high accuracy comparing to the one-stage PBM. The proposed optimization strategy can improve the prediction capability by >50% compared to an offline optimization.

Using response surface methodology to optimize the operating parameters in a top-spray fluidized bed coating system

The fluidized bed coating system is a conventional process of particles coating in various industries. In this work, an experimental investigation was conducted using Response Surface Methodology (RSM) to optimize the coating mass of particles in a top-spray fluidized bed coating. The design of experiments (DOEs) is a useful tool for controlling and optimization of products in industry. Thus, DOE was conducted using MINITAB software, version 16. This process used a sodium silicate solution for coating the sodium percarbonate particles. The effect of the fluidization air flow rate, atomization air flow rate and liquid flow rate on the coating mass in the top-spray fluidized bed coating was investigated. The experimental results indicated that the coating mass of particles is directly proportional to the liquid flow rate of the coating solution and inversely proportional to the air flow rate. It was demonstrated that the flow rate of the coating solution had the greatest influence on the coating efficiency.

Influence of top spray fluidized bed agglomeration conditions on the reconstitution property and structure modification of skim yoghurt powder

Spray dried yoghurt powder (Control) has small particle size (57 µm) that cause high cohesiveness forces between particles. Wetting time of control yoghurt powder takes more than 1 hr by forming lump on the surface of water. Smaller particle size cause higher contact surface area per unit mass of powder that limits flowability of yoghurt powder. Yoghurt powder turned into instant form due to particle size enlargement by applying agglomeration process. In addition, agglomerates showed lower bulk, tapped, and particle densities and excellent flowability. Effects of inlet air temperature (50–80 °C), atomizing pressure (0.5–1.5 bars) and sprayed water amounts (50–80 g) were investigated in this study. Response surface methodology was used to find the best conditions in view of high quality reconstitution properties of yoghurt powder. The best process conditions were determined as 62.5 °C inlet temperature, 0.9 bar atomizing pressure and 68 g sprayed water amount. Practical applications Optimization of top sprayed fluid bed agglomeration process parameters has not yet been studied for dairy powders. By using optimization process, effects of agglomeration process parameters (inlet air temperature, amount of binder, and atomization pressure) on quality parameters of yoghurt powder were revealed. Improvement of yoghurt powder reconstitution properties will be the first study in the literature. These studies provide an insight for further studies about top spraying bed agglomeration process.

Novel method for improving the water dispersibility and flowability of fine green tea powder using a fluidized bed granulator

To develop new green tea beverages and dietary supplements in powder form, the surface of green tea powder (GTP) was modified by spraying a hydrophilic polymer Soluplus® (Sol) solution using a top-spray fluidized bed granulator. This enhanced the water dispersibility and powder flowability of the GTP. Spraying with levels of 0.5%–9% Sol polymers improved the flow properties but significant agglomeration occurred in products coated with 3%–9% Sol, but not in those coated with 0.5% and 1% Sol. This suggested that low levels of coating solution inhibited agglomeration. The highest level of water dispersibility and improved flowability with no agglomeration were exhibited by GTP with 1% Sol coating. Overall, surface modification with hydrophilic polymer can improve the flow properties, dispersibility and other properties of GTP. This method might also be useful for developing other novel food ingredient powders.

DEM-CFD investigation of particle residence time distribution in top-spray fluidised bed granulation

Numerical simulations in process engineering become more and more to a powerful tool in process optimisation and for improvement of process understanding. For multiphase flows, like fluidised bed granulation as a three phase system, the dynamics can be described by the coupled approach between the Discrete Element Method (DEM) for the solid and liquid phase with Computation Fluid Dynamics (CFD) for the gas phase. A key challenge in this simulation approach is given by the huge number of single particles in the original system. In order to run a three-phase top-spray fluidised bed by the coupled DEM-CFD in reasonable time scales, a scaling approach based on similarity models has been applied. Within the top-spray fluidised bed particle and droplet motions are investigated in a two-compartment approach, considering a spray and a drying zone. It can be shown that different particle crossing lengths and particle velocities through the spray zone lead to a particle residence time distribution with crucial impact on particle wetting and thus growth behaviour. In addition top-sprayed droplets are respected to obtain droplet existing time distributions and therefrom overspray ratios. Concluding from the results different particle wetting procedures in the spray zone are identified and discussed.

Investigation of wetting and drying process in a gas-solid fluidized bed by electrical capacitance tomography and pressure measurement

Top-spray configurations are widely used in pharmaceutical fluidized beds for particle coating and granulation. The process is complex due to the change of particle moisture as well as particle density. It is important to investigate the flow hydrodynamics in the process. In this paper, electrical capacitance tomography (ECT) combined with pressure transducers are used to investigate the flow hydrodynamics of gas-solids flow in a top-spray fluidized bed for wetting and drying. The flow characteristics investigated include bubble size, dominant frequency and standard deviation. Discrete wavelet transforms (DWT) and Fast Fourier Transform (FFT) are used to analyze the capacitance and pressure signals. The effects of key process parameters, including superficial velocity, particle size and spraying conduction on the flow hydrodynamics, are analyzed. The result indicates that both the material moisture and particle size influence the minimum fluidized velocity and bubble characteristics during the wetting and drying process. The result also indicates that the moisture content of particles and superficial fluidization velocity are two main factors, which determine the bubble characteristics in the top-spray process. The bubble size presents a complex trend, which is influenced by the spray pressure. The fluctuation frequency of bubbles presents a different trend in the wetting and drying stage.

Performance Evaluation of Top-Spray Fluidized Bed Coating for Healthy Coated Rice Production

Coating with top-spray fluidized bed at inappropriate operating condition not only provides low product quality but also leads to low coating efficiency and improper energy consumption. The objective of this study was therefore to study the effects of superficial air velocity (Vf), atomization air pressure (Ap), and recycled exhaust air (Ra) on the performance of top-spray fluidized bed coating (TSFBC) in terms of product quality, coating efficiency (CE), and energy consumption for producing turmeric extract coated rice (TECR). The experimental results showed that the operation of TSFBC without Ra provided the final moisture content (MC) of TECR lower than 12 % (wet basis (w.b.)) for all Vf’s and Ap’s. The lowering final MC of TECR below 11.8 % (w.b.) led to the fissure of all TECR kernels. The Ra with 80 % could significantly reduce the number of fissured kernels and the energy consumption of electric heater by 41.7–46.5 %. The operation of TSFBC at low Vf, i.e., 2 m/s, resulted in high number of uncoated white rice kernels (UCWR) for all Ap’s and Ra. When the Vf was increased to 2.5 or 3 m/s, the number of UCWR was significantly reduced and the value of CE was higher than that at 2 m/s. At such both velocities, the Ap and Ra insignificantly affected the CE but the Ra slightly affected the number of UCWR.

Fluid bed film coating of fine ibuprofen particles

Fine pharmaceutical powders pose significant challenge in fluid bed (FB) film coating due to their high cohesion. Ibuprofen powders, considered as model Geldart group C powders with Sauter mean diameters of 41μm (coarse) and 22μm (micronized), could not be fluidized due to severe agglomeration, solid-bridging, and poor flowability. Dry coating, applied as a pre-processing method that coats nano-silica on the surface of ibuprofen, enabled sufficiently improved flow, hence fluidization via reduced cohesion. Resulting coarse and micronized ibuprofen powders were successfully polymer film coated in a top spray fluidized bed. As a major novelty, apart from pre-processing through 20nm silica surface coating that enabled fluidization, agglomeration during FB processing was minimized by introducing 180nm colloidal silica particles that were pH stabilized in polymer spraying suspension using NaOH. In contrast, lack of or poorly stabilized colloidal particles led to significant agglomeration. Spray rate and fluidization velocity were both investigated to understand their effect on agglomeration of the coarse ibuprofen powders. Increased spray rate led to increased agglomeration due to the overly wet conditions, while increased fluidization velocities unexpectedly led to increased agglomeration resulting from electrostatic charging. To simplify the experimental design, a simple scaling relationship was introduced to estimate the coating conditions for the micronized ibuprofen powders based on the processing conditions of the coarse ibuprofen powders. This relationship, based on the minimum fluidization velocity, led to comparable agglomeration levels for powders with Sauter mean diameters of 21 and 42μm. To the author's knowledge these are the first successful results where micronized pharmaceutical powders were polymer coated in a traditional top spray fluidized bed.

Quality attributes and anthocyanin content of rice coated by purple-corn cob extract as affected by coating conditions

We investigated the optimal conditions for coating rice with the water extract of purple-corn cob (PCC) using a top-spray fluidized bed coating method with variations of inlet air temperature of 50, 60 and 70°C and spraying time of 5, 10 and 15min. The results showed that increasing the inlet air temperature significantly reduced the final MC. Fissured coated rice increased with increasing temperature and spraying time. The percentage of head rice yield was not affected by inlet temperature, while it tended to decrease with longer spraying time except at 15min. In addition, longer spraying time resulted in higher values of chroma implying a larger amount of coating solution. We also found that increasing the temperature decreased the total phenolic, total flavonoids and total anthocyanins contents as well as their antioxidant activities as determined by DPPH and FRAP assays. In contrast, those values were increased when the spraying time increased. The same trend was found for anthocyanin composition. Based on the optimization criteria with the highest desirability of 0.702, we recommend an inlet air temperature of 50°C and spraying time of about 15min to obtain the minimum fissure and maximum coating material.

Passive acoustic emissions monitoring of the coating of pellets in a fluidized bed—A feasibility analysis

Pharmaceutical pellets are small spherical particles that contain the active ingredient or drug. They are often film coated and packed into capsules as a multiple unit dosage form to provide modified drug release. Conventional methods used to evaluate pharmaceutical film coatings require invasive sampling and off-line testing, which are time consuming, disruptive to the process and often non-representative of the pellet bed indicating the need for developing more reliable monitoring methods. Passive acoustic emissions measurements have shown potential as a monitoring tool due to the non-invasive nature and real-time means of collecting process information. The goal of this study was to assess passive acoustic emission monitoring of the coating of pellets in a fluidized bed. Microphones were attached to the exterior of a top spray fluidized bed reflecting local fluidization conditions and information on nozzle performance. Decreased fluidization conditions were identified from acoustic emissions acquired at the interface of the liquid spray and fluidized pellet bed, influencing the distribution of the coating spray throughout the bed and drying of the film coat around the pellet core. Acoustic emissions acquired from the exhaust of an air outlet at the top of the column showed potential application for the detection of nozzle clogging. Continued research regarding the development of passive acoustic emissions monitoring would provide important information about fluidized bed coating of pellets and potentially improve process control for the determination of an optimum coating end-point.