Fluidized Bed Spray Research Articles

Particle coating growth behaviors in a spray fluidized bed based on Gas-Liquid-Solid Quasi-Three-phase DEM numerical simulation

Wet granulation processes are widely used in chemical, food, pharmaceutical, and various other industrial processes. During the process of particle coating growth, particle fluidization state and liquid characteristics have an impact on the layer's thickness and homogeneity. In this study, discrete element, liquid bridge, and droplet motion models were combined to investigate the impact of injection gas velocity, droplet diameter and injection liquid viscosity on the particle growth ratio and coating thickness distribution, and the particle growth mechanism was investigated. The particle growth area, which is the area where the number of coated particles exceeds 0, was significantly expanded by decreasing the droplet diameter and increasing the gas velocity at appropriate ranges. The frequency of droplet and particle collisions increased, and average relative liquid content decreased with increasing particle growth area. By accelerating the injection of gas and reducing the viscosity of the injected liquid, the fluidization condition of the particles, which primarily affected the particle cycle frequency, could be enhanced. The improvement of particle growth area and particle cycle frequency allowed more particles to participate in growth and improved the quality of the grown particles. The proportion of small particles dramatically grew while the proportion of large particles reduced. The standard deviation of particle diameter decreased, and particle growth became more uniform.

Agglomeration of Spray-Dried Milk Powder in a Spray Fluidized Bed: A Morphological Modeling

The type of solid substrate plays a critical role in determining the kinetics of the spray fluidized bed (SFB) agglomeration process. In the case of porous (also soft) primary particles (PPs), droplet aging is due to imbibition and drying. The surface properties of the substrate also change due to imbibition. The focus of the present work is to simulate the agglomeration of the spray-dried milk powder using the Monte Carlo (MC) method coupled with a drying-imbibition model. In order to extract the morphology of the formed agglomerates, an aggregation model is employed. Further, this aggregation model is employed to predict the number of positions on the PPs (later agglomerates) for droplet deposition; previously, the ‘concept of positions’ was used. The transient growth of different milk powders (whole and skim) is depicted using the enhanced MC model. The enhancement in the droplet deposition model had a prominent influence on the overall kinetics of agglomeration. As expected, this enhanced MC model predicted that the agglomeration rate of skim milk powder is higher than that of whole milk powder.

Influence of cycle time distribution on coating uniformity of particles in a spray fluidized bed by using CFD-DEM simulations

Cycle Time Distribution (CTD) plays a critical role for determining uniformity of particle coating in spray fluidized beds. However, the CTD is influenced by both geometrical structure and operating conditions of fluidized bed. In this study, a spray fluidized bed of coating process is simulated by a comprehensive Computational Fluid Dynamics-Discrete Element Model (CFD-DEM). To achieve different behaviors of CTD, some modifications are designed on a pseudo-2D internally circulating fluidized bed, which traditionally composes of a high-velocity upward bed and low-velocity downward bed. These modifications include making the air distributor slope and/or laying a baffle in the downward bed. First, the CTD and evolution of particle size distribution under different bed structures are compared. The CTD directly influences the coating uniformity. By making the particles flowing along a parallel direction in the downward bed through the geometrical modifications, the CTD becomes narrower and the coating uniformity is significantly improved. Second, under the optimized bed structure, the influence of operating conditions on the coating uniformity is studied. Properly increasing the fluidization gas velocity and the fluidization gas temperature and reducing the liquid spray rate can improve the coating uniformity.

Toward Targeted Invasive Predator Control: Developing pH-Responsive Subcutaneous Implants for Native Mammals

Introduced predators are a significant threat to global biodiversity and are responsible for most of all modern bird, reptile, and mammal extinctions. In Australia, the introduced feral cat (Felis catus) kills 459 million mammals annually and leaves many species facing extinction. Attempted reintroductions of threatened mammal species often fail due to the persistence of intractable feral cats─termed “problem individuals”─and the swift depredation of the reintroduced population. Biomaterial implants could hold the key to targeting problem individuals. Herein, we report the development of the population-protecting implant, a subcutaneous implant for native mammals. The implant is intended to be inert within the subcutaneous environment for the life of the native mammal and to release a toxic payload in the gastric environment of a feral cat when ingested during a predation event. By toxifying and causing the death of the feral cat, the problem individual is eliminated, and the remaining population of native mammals is protected from further predation. To achieve this, an innovative reverse enteric coating was developed for use as a biomaterial, which exhibited a previously unreported level of pH selectivity for solubility at gastric pH. Large batches of implants were manufactured via fluidized-bed spray coating with a uniform reverse enteric coating and low intrabatch variability. Implants with a 300 μm coating afforded significant stability and retention of the payload at subcutaneous pH in vitro, with rapid release of the payload observed at gastric pH. In addition, implants exhibited favorable stability in vivo in rats, with no observed difference in biocompatibility compared to conventional radio-frequency identification microchips. This work demonstrates a proof of concept of an innovative type of implant and serves as the basis for its future development and translation into the field.

Morphological descriptors of agglomerates produced in continuously operated spray fluidized beds

This work presents the results of a systematic investigation of structural and morphological descriptors of agglomerates produced in continuously operated fluidized bed spray agglomeration. Experiments with glass beads as primary particles and a water-based HPMC mixture as top sprayed binder solution were carried out within a cylindrical fluidized bed of pilot plant scale. Characterization of all agglomerates was performed by X-ray micro-computed tomography. Investigated descriptors include number of primary particles, radius of gyration, coordination number and angle distribution as well as porosity and fractal properties. Utilizing these descriptors, a comparison regarding morphology of agglomerates produced in batch and continuous operation under similar process conditions and process times is drawn.

A Fast and Improved Tunable Aggregation Model for Stochastic Simulation of Spray Fluidized Bed Agglomeration

Agglomeration in spray fluidized bed (SFB) is a particle growth process that improves powder properties in the chemical, pharmaceutical, and food industries. In order to analyze the underlying mechanisms behind the generation of SFB agglomerates, modeling of the growth process is essential. Morphology plays an imperative role in understanding product behavior. In the present work, the sequential tunable algorithm developed in previous studies to generate monodisperse SFB agglomerates is improved and extended to polydisperse primary particles. The improved algorithm can completely retain the given input fractal properties (fractal dimension and prefactor) for polydisperse agglomerates (with normally distributed radii of primary particles having a standard deviation of 10% from the mean value). Other morphological properties strongly agreed with the experimental SFB agglomerates. Furthermore, this tunable aggregation model is integrated into the Monte Carlo (MC) simulation. The kinetics of the overall agglomeration at various operating conditions, like binder concentration and inlet fluidized gas temperature, are investigated. The present model accurately predicts the morphological descriptors of SFB agglomerates and the overall kinetics under various operating parameters.

Monte Carlo modeling of spray agglomeration in a cylindrical fluidized bed: From batch-wise to continuous processes

Monte Carlo method is a stochastic approach that can simulate different micro-mechanisms occurring in spray fluidized bed (SFB) agglomeration. As no model covered the simulation of continuous SFB agglomeration process existing before, an event-driven constant volume Monte Carlo model is proposed. By adding particle feed and discharge events that take place periodically, the Monte Carlo model is extended to simulate continuous SFB agglomeration process. In these events, new particles are fed, and individuals are randomly selected and removed according to the feed rate and the change in bed mass. The experimental results show that the decrease of feed rate or bed mass increases the particle size. The comparison of experimental and simulation results shows that the continuous Monte Carlo model can predict the evolution of the particle size distribution with collision frequency prefactor 0.05 and breakage probability 0.17%. The development of bed mass in experiments can be reproduced in the simulations.

Influence of polydispersity and breakage on stochastic simulations of spray fluidized bed agglomeration

Monte Carlo (MC) model is a stochastic and discrete method to enhance the understating of spray fluidized bed (SFB) agglomeration in the field of food, chemical and pharmaceutical industry. Previous studies focused on agglomerates composed of monodisperse primary particles. Size dispersity of primary particles is, though, an important aspect to fully assess the morphological features of an agglomerate. In the current work, a polydisperse tunable aggregation model is therefore developed. The radius of gyration, porosity, surface area and agglomeration rate increase with primary particle dispersity. Furthermore, the breakage of already formed agglomerates is introduced in the MC model. The influence of breakage decreases the overall growth rate and the arithmetic mean diameter of the particle size distribution by around 11%. The overall growth rate and the diameter of agglomerates with a similar number of primary particles increase with decreasing temperature of fluidization gas and increasing mass fraction of binder.

Preparation and in vitro/in vivo evaluation of a clonidine hydrochloride drug–resin suspension as a sustained-release formulation

Objective The purpose of the present study was to prepare a clonidine hydrochloride (CH) sustained-release suspension. Methods The processes involved in the drug formulation included drug loading, impregnating, and suspension preparation. Clonidine hydrochloride drug–resin complexes (CH-DRC) were prepared using the bath method and the CH-DRC impregnated before the microencapsulation process. Based on the bottom spray fluidized bed coating method, the CH microencapsulated drug–resin complexes (CH-MC) were also prepared using Surelease® (the suspension of ethyl cellulose aqueous dispersion) as the coating material. The effects of coating (process/formulation) on the in vitro release of coating microcapsule were evaluated via single factor investigation and orthogonal design optimization. The CH-MC with optimized formulation was further dispersed in a suitable medium to obtain a sustained-release suspension. Rats were given commercial CH ordinary tablets and the CH sustained-release suspension via intragastric administration. The plasma concentration–time curve and related pharmacokinetic parameters were investigated using the non-compartment model. Results The T max of the CH sustained-release suspension was delayed from 2 h to 5 h compared with the CH ordinary tablets. Similarly, the C max was reduced from 32.138 µg·mL−1 to 18.150 µg·mL−1 with the concentration–time curve being more gentle compared with the commercially CH ordinary tablets. After oral administration, the relative bioavailability of CH sustained-release suspension (AUC0–24 of 137.703 µg·h·mL−1) to its CH ordinary tablets (AUC0–24 of 123.337 µg·h·mL−1) was 111.65%. Conclusions The findings showed that the CH sustained-release suspension for oral administration was successfully formulated.

The Reaction Extraction Combining Crystallization for Growth of Sodium Chloride in a Spray Fluidized Bed Crystallizer

At present, the crystal size of sodium chloride prepared by a traditional crystallization process (such as stirred crystallization) is inhomogeneous, and it has a great quantity of fine grains in crystallizer. This work presents a novel approach for the growth of sodium chloride from supersaturated solutions by reaction-extractive crystallization in a spray fluidized bed crystallizer (SFBC), in which sodium sulfate solution is transformed into potassium chloride and sulphuric acid based on a reactive extraction-crystallization process using triisooctylamine (TOL) in n-octanol as the extraction system. This paper mainly studies the effect of operating conditions (e.g., circulation flow rate, velocity ratio of oil and aqueous phases, crystallization temperature, hydraulic residence time, and feed velocity) on the crystal size distribution (CSD) during the crystallization process of sodium chloride in a SFBC. Experimental results show that the optimum conditions are 1.0362 m/s as the best circulation flow rate, 9.5 : 8.5 as the best velocity ratio of oil and aqueous phases, 313 K as the best temperature, 4320 s as residence time, and 8 mL.min−1 as the best feed velocity. Meanwhile, the proposed extraction kinetic model about extraction rates is developed and validated against data from the SFBC. And it proves that the reactive extraction system is controlled by diffusion and chemical reaction. Analysis of the extraction kinetic model and comparison with experiments reveal that the extraction kinetic model results are in well agreement with experiments. Furthermore, the uniform and large crystals can be obtained in a spray fluidized bed crystallizer without special concentration since extraction and crystallization are carried out in the same equipment. In addition, all of the sodium chloride products prepared under the optimal conditions in SFBC show a better CSD performance than the stirred crystallization. This research demonstrates that this process enables controlling the crystal size in a rather wide range, thus further underlining the potential of this technique for applications in the crystallization industry.

Population balance modeling of volume and time dependent spray fluidized bed aggregation kernel using Monte Carlo simulation results

This paper seeks to extend the work of Hussain et al. (A new framework for population balance modeling of spray fluidized bed agglomeration, Particuology 19 (2015) 141–154) to develop a detailed one-dimensional population balance modeling (PBM) of the spatially homogeneous spray fluidized bed aggregation (SFBA) process. A new mathematical model of the volume and time dependent aggregation kernel is developed based on process specific microscopic mechanisms. In addition, the population balance equations of other important process related parameters (total number of available droplets and size distribution of wet particles) are presented. The developed PBM contains a new mathematical model which estimates the death rate of binder droplets due to the drying mechanism. For the verification of the developed PBM, a constant number Monte Carlo (MC) algorithm is used, which simulates important micro-mechanisms of the SFBA process (droplet addition, droplet drying, volume dependent particle collisions, aggregation, and rebound). The MC algorithm is capable of analyzing the effects of each microscopic event on the aggregation behavior. Volume dependency in particle collisions is used, while mimicking the SFBA process in the MC simulation algorithm. Furthermore, the volume and time dependent probability of successful wet position collisions is successfully extracted using the MC simulations and then transferred to the development of the PBM. Finally, the accuracy of the proposed PBM is verified by comparing its results against the predictions of the MC simulations.

Influence of operating parameters on process behavior and product quality in continuous spray fluidized bed agglomeration

The present work investigates continuous spray fluidized bed agglomeration with internal separation using glass primary particles and sprayed solution of cellulosic binder. Different fluidization and thermal parameters were investigated with respect to their influences on process behavior and product quality. Product quality is characterized with respect to particle size, sphericity and porosity. Trends between operation parameters and product characteristics are established, especially in view of the drying potential of the fluidization gas. In addition to the successful identification of the parameter influences, this study has detected general relationships between drying potential and agglomerate porosity, as well as between agglomerate size and porosity.

Ultrathin coating of particles in fluidized bed using submicron droplet aerosol

In this work, we demonstrate that particles can be coated in a fluidized bed with coating solution provided by a novel aerosol generator. Aerosol droplets are smaller than 1μm in volume-based diameter, hence they are very much smaller than droplets in conventional spray fluidized bed processes (around 40μm). A proof-of-principle experiment with 30% aqueous coating solution of sodium benzoate and γ-Al2O3 core particles in 150mm fluidized bed fed with droplet aerosol supplied from the chamber side is presented. To simultaneously coat and dry the particles, inlet of fluidization air was at 50°C. Moreover, Monte Carlo simulations of coating with small aerosol and large spray droplets were conducted. Due to dramatically smaller building blocks, ultrathin particle coating of high-resolution (very small layer thickness) can be attained with the new aerosol process, with the potential of even going nanoscale. Full coverage of particles is reached substantially faster than in the conventional process, so that material demand is much lower and sensitive materials can be processed in short residence time. Solids yield of around 30% was much higher than expected, that is considered to be technically viable and may be enhanced by the recycling of entrained solids or better equipment design.

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.

A tunable aggregation model incorporated in Monte Carlo simulations of spray fluidized bed agglomeration

Constant volume Monte Carlo (CVMC) model is a discrete and stochastic approach to enhance the understanding of spray fluidized bed (SFB) agglomeration. Previous CVMC model used a simplified approach, considering the formed agglomerates as characteristic spheres with porosity as a function of their fractal properties. This means that other morphological descriptors such as coordination number could not be assessed. In the present work, a tunable aggregation model is developed to reconstruct the SFB agglomerates consisting of monodisperse spherical primary particles by a particle-cluster algorithm using a novel approach of tuning the fractal dimension at a given prefactor (= 1). Various morphological descriptors obtained from this aggregation model are validated using experimental data. Furthermore, this aggregation model is incorporated into the CVMC framework to evaluate both, the morphological descriptors and formation kinetics of SFB agglomerates produced under different process conditions (inlet fluidized gas temperature and binder content).

Estimation of the dominant size enlargement mechanism in spray fluidized bed processes

AbstractThis work deals with estimating the dominant size enlargement mechanism in spray fluidized beds. A new process model is presented, which consists of population balances and a heat‐ and mass‐transfer model. New methods to incorporate the wet surface fraction and the Stokes criterion are proposed, which allow for the probability of wet collisions and the probability of successful wet collisions to be calculated. The product of these parameters, the probability of successful collisions, is linked to the dominant size enlargement mechanism. Simulation studies were performed to investigate the influence of inlet gas temperature, viscosity, droplet size, and contact angle on the probability of successful collisions. Further simulation results based on experiments available in literature suggest that exceeding a probability of successful collisions of 0.001 is sufficient for agglomeration to become dominant. Otherwise, layering will be the dominant size enlargement mechanism. Finally, regime maps of layering and agglomeration are constructed.

Influence of process variables on spray agglomeration process in a continuously operated horizontal fluidized bed

Experiments on continuously operated spray fluidized bed agglomeration are presented in this work. The process is conducted with glass beads and water-based binder hydroxypropylmethylcellulose (HPMC). By varying the process parameters, the results show that by the decrease of air temperature or feed rate and by the increase of binder concentration, larger particles can be achieved. Larger particle size also results in higher bed mass and more fluctuations in the process. Besides parameters variations, different internal and outlet weir configurations are used. Tracers are used in the experiments to characterize the particle residence time distribution. The separation effect can be decreased and the particle residence time can be optimized by the installation of internal weirs and lower height of outlet weir. The results show that the jets from the spray nozzles are increasing the motion and mixing of particles significantly.

Optimization and characterization of novel sustained release supermicro-pellet based dry suspensions that load dexibuprofen

Traditional dosage forms of dexibuprofen extremely limit their clinical applications because of the bitter taste and the frequent drug administration caused by the relatively short half-life of the drug. This study aims to design novel sustained release (SR) supermicro-pellet based dry suspensions that load dexibuprofen, and also optimize the formulations in terms of morphology, release rate, flowability, and physicochemical stability of dosage forms. Drug-loaded pellets were prepared by using a bottom spray fluid bed coating technique using microcrystalline cellulose supermicro-pellets as the core and PVP K30 or Poloxamer 188 as the binder. The drug-loaded pellets were further coated with Kollicoat SR 30D to form SR pellets. The optimal SR dry suspensions are composed of SR pellets, diluent granules, and suspending agents. PVP K30- and Poloxamer 188-based SR pellets release the drug molecules in a SR manner over 8 h and show a high release profile for Poloxamer 188-based pellets. The drug release profile is not affected by the rotation speed of the paddle but shows a distinct pH-responsive behavior. The physical property of dexibuprofen has been changed during the preparation process. The SR dry suspensions (F5, with high amount of xanthan gum in suspending agents and low amount of poloxamer 188 in diluent granules) show high physical stability with the sedimentation rate of 0.8 (Hu/H) within 5 min and good flowability with the angle of repose (θ) at 27°. Low content variations were observed with a value of A+1.80SD ≤ 15, and no significant change was found in the drug content under high humidity and strong light. In conclusion, novel SR supermicro-pellet based dry suspensions have been successfully prepared, and the optimal formulation shows excellent SR, good flowability, content uniformity, and physicochemical stability.

Stochastic model to simulate spray fluidized bed agglomeration: a morphological approach

Constant volume Monte Carlo (CVMC) method is a stochastic method used to describe the agglomerate growth during spray fluidized bed agglomeration (SFBA). The methodology overcomes the difficulties of expressing and solving multivariate population balance equations (PBE). It enables to account for micro-scale events and processes involved in the agglomeration process, especially for binder addition and drying. Previous CVMC models assume that all agglomerates have the same porosity. This simplistic assumption is replaced in the present paper by given fractal dimension, which means that porosity can change with agglomerate size and process conditions. Evaluation of measured morphological descriptors and the agglomeration rates shows that this leads to more realistic results.

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.