Fluidized Bed Granulator.

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Granulation
Granulation is one of the most important unit operations in the production of pharmaceutical oral dosage forms. However, there are many different technologies each having different strengths and weaknesses. Granulation is often required to improve the flow of powder mixtures and mechanical properties of tablets. Granules are usually obtained by adding liquids binder or solvent solutions. Larger quantities of granulating liquid produce a narrower particle size range and coarser and harder granules, i.e. the proportion of fine granulate particles decreases. The optimal quantity of liquid needed to get a given particle size should be known in order to keep a batch-to-batch variations to a minimum. Wet granulation is used to improve flow, compressibility, bio-availability, homogeneity, electrostatic properties, and stability of solid dosage forms. The particle size of granulate is determined by the quantity and feeding rate of granulating liquid. Wet granulation is used to improve flow, compressibility, bio-availability, and homogeneity of low dose blends, electrostatic properties of powders, and stability of dosage forms. Granulator process solutions involve smaller particles adhering to each other in order to grow larger particles or agglomerates. Particle size is critical in a granulator process solution because if the particles are too large or too small they do not have the product characteristics important to produce light powders into high density free-flowing granulates. There are many variables in controlling a granulator process, ranging from feed rate of the granulator liquid to the resonance time of the granulator chamber. All of these parameters affect the particle size in different ways. With an on-line sensor, the particle size is measured instantaneously and continuously in real time helping to monitor and control the granulator process.

Granulation methods:
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Fluid Bed Top Spray Granulation

The fluid bed granulation process also known as agglomeration involves suspending particulates in an air stream and spraying a liquid from the top down onto the fluidized bed. Particles in the path of the spray get slightly wetted and become tacky. The tacky particles collide with other particles and adhere to them to form a granule. Granulation can be performed using fluid beds fitted with spray nozzles. It is possible to have completely closed material handling by a closed linking with upstream and downstream equipment. Also, fully automatic cleaning in fluid beds using stainless steel filters now compares favorably with what is possible in a single pot. There are two different modes of fluid bed granulating: Dry Stage: In Dry stage granulation, the particles only require a slight wetting to become tacky and stick to each other. The granulating solution is applied at a rate less than or equal to the evaporation rate. Thus the particles remain "dry" through the entire process. Wet Stage: In Wet stage granulation, the particles require significant wetting before they become tacky enough to stick to each other. The granulating solution is applied at a rate higher than the evaporation rate until the particles build up enough moisture to granulate. The characteristics of the particles when wet and the type of granulating solution being used will determine which mode of granulating is most appropriate. While Dry stage is more common, Wet stage granulating allows for denser products.

Fluid Bed Granulation, Drying, and Coating

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Purpose designed for cGMP processing of fine powders, pellets, granules, crystals and tablets.

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Fluid Bed Processor for Granulation, Coating, Pelletization, and Solution Layering

Fluid bed drying

The product to be dried is fluidized by passing hot air through it. The process achieves fast heat transfer making it very efficient, yet gentle on the product. Capacity: from 50g to several ton/batch or several ton/hr.

History and description of batch fluid bed processors

Batch fluid bed processing has been used in the pharmaceutical industry for the past 30 years. Figure 1 shows the components of a typical fluid bed processor. The technology was originally developed specifically for rapid drying. Over the years, fluid bed processing has come into routine use for other applications such as granulation, agglomeration, air suspension coating, rotary pelletization, and powder and solution layering, but the principle of the fluid bed processor has not changed.

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Figure 1: Typical Components of a Fluid Bed Processor for Granulation, Coating, Pelletization, and Solution Layering

A fluidized bed is a bed of solid particles with a stream of air or gas passing upward through the particles at a rate great enough to set them in motion. As the air travels through the particle bed, it imparts unique properties to the bed. For example, the bed behaves as a liquid. It is possible to propagate wave motion, which creates the potential for improved mixing. In a bubbling fluidized bed, no temperature gradient exists within the mass of the fluidized particles. This isothermal property results from the intense particle activity in the system. Thus, the fluid bed can be used to dry the wet product, agglomerate particles, improve flow properties, instantize the product, or produce coated particles for controlled release or taste masking. Modular systems designed to carry out multiple processes in which only a container change is necessary to change the type of unit operation being performed have been developed by all the manufacturers of fluid bed processors. Although the basic process of the fluid bed has not changed much, the versatility of fluid bed processing has evolved over the past 30 years in response to the demands of the pharmaceutical industry, the guidance of regulatory agencies, and competitive innovation on the part of equipment manufacturers.

Principle Of Fluidization
The principle of operation of fluidized systems are based on the fact that if a gas is allowed to flow through a bed of particulate solids at velocity greater than the settling velocity of the particles and less than the terminal velocity for pneumatic conveying and equal to the minimum velocity of fluidization (V mf ), the solids get partially suspended in the stream of upward moving gas. The gas stream negates the gravitational pull due to weight of particles to enable the suspended state of the solid. 22

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The resultant mixture of solids and gas behave like a liquid and thus rightly solids are called Fluidized. The solid particles are continually caught up in eddies and fall back in a random boiling motion so that each fluidized particle is surrounded by the gas stream for efficient drying or granulation or coating purpose. In the process of fluidization there occurs an intense mixing between the solids or gas resulting in uniform condition of temperature, composition and particle size distribution throughout the bed. Theory Of Fluidization Phenomenon of Fluidization Stages of fluidization:- The stages of fluidization is mostly based on the fluid velocity passing through the particle bed. According to Ridgeway and Quinn the stages of fluidization can be summarized as follows. 1) Static bed 2) Expanded bed 3) Mobile bed 4) Bubble formation 5) Pneumatic transport Role of Fluidization velocity A mass of finely divided solids is transformed into a fluidized bed by lifting action of gas passing through it. Thus three stages can be identified in the process of fluidizing a bed of solids basing on the velocity of gas flow through it. They include 1) Fixed bed or Static Bed 2) Expanded bed or particulate fluidization.

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3) Mobilized bed

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1) When a fluid is pumped upward through a bed of fine solid particles at a very low flow rate the fluid percolates through the void spaces (pores) without disturbing the bed. This is known as a fixed bed process .(9) 2) If the upward flow rate is very large the bed mobilizes pneumatically and may be swept out of the process vessel. This is known as Mobilized bed process .(9) 3) At an intermediate flow rate the bed expands. This is known as an expanded bed (9) . 4) After mobile bed formation if velocity is further increased the bed expands considerably with increase in voidage and bubble formation (1) occurs. 5) If further increase in velocity of air occurs, eventually the lifting force of passing air blows particle out of the bed altogether leading to Pneumatic transport .(1) In the fixed bed the particles are in direct contact with each other, supporting each others weight. In the expanded bed the particles have a mean free distance between particles and the particles are supported by the drag force of the fluid. The expanded bed has the properties of a fluid and is also called a fluidized bed. As shown in Figure below, the velocity of the fluid through the bed opposite to the direction of gravity determines whether the bed is fixed, expanded, or is swept out. This led to the development of the concept of minimum fluidization velocity (V mf ) at which the bed just begins to fluidize. Thus the primary concern is to measure and optimize the V mf for efficient fluidization.

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(a) Slow flow rate (b) Intermediate flow rate (c) High flow rate Fixed bed Fluidized bed Mobilized bed

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Instrumentation And Operation Instrumentation

Figure- Fluid bed granulator

1. Inlet air filter 2. Condenser 3. Humidifier 4. Inlet air Heater 5. HEPA filter 6. Inlet air 7. Inlet air plenum

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8. Gas distributor plate 9. Product container 10. Conical expansion zone 11. Filter housing 12. Product filter 13. Outlet air 14. HEPA filter 15. Fan 16. Spray gun

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Operation
A suction fan mounted at the top portion generates the airflow necessary for fluidization of powders. The air used for fluidization is heated to the desired temperature by an air heater. The liquid granulating agent is pumped from its container & sprayed as a fine mist through a spray head onto the fluidized powder. The wetted particles undergo agglomeration through particle contacts. After appropriate agglomeration is achieved, the spray operation is discontinued and the material is dried and discharged from unit.

Principle Of Granulation
The powder is fluidized by the hot air in fluid bed granulator. The binding liquid such as solution, suspension is sprayed on the fluidized powder to build liquid bridges among them to form agglomerates. The liquid bridge that serve to hold the particle together in two ways (1) by surface tension at the air liquid interface (2) by hydrostatic suction. 22

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The liquid bridges are dried by the hot fluid air to stick the powder together. While the liquid sprayed continuously, the particles grow bigger to a desire granule size. The process is carried out continuously. Finally it forms ideal, uniform and porous granules.

Types Of Fluidized Bed Granulator 1) Top Spray Fluid Bed Granulator

The recrystallization and hardening binder technology are generally carried out in the top spray granulator. In this equipment spray nozzle located at the top the

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base of the product container is equipped with a fine mesh retention screen to allow small particle size. Spray nozzle to permit positioning above the static bed in the lengthened expansion chamber. The granulator is operated by fluidizing the bed of powder & spraying the granulating solution at the controlled rate. Proper agglomeration achieved, the liquid spray is cut off and the material allows drying to the desired moisture content.

2) Rotating Disk Fluid Bed Granulator With Dryer Option

Layering technology carried out by rotating disk granulator and coater. The technique have been extended to coating operation and combined with an expansion chamber to form the rotating disk granulator & coater fluid bed device. The rotating disk can be moved up or down to create a variable slit opening between the outer perimeter of the disk and the side wall of the container. This allows independent control of air velocity over air volume, air is drawn into the product container through the slit under negative pressure. At the same time the disk rotate at varying speed & product move under centrifugal force to the outer positions where it is lifted by the fluidizing air stream into the expansion chamber. As the material fall to the center of the rotating disk and repeat the processes. This fluidization pattern also described as a spiraling helix or rope like pattern around the inside the rotor chamber. The motion of fluidization of the particle controlled by the forces like fluidization, centrifugal force and gravity. Spray nozzle immerged in the bed of fluidization and spray applied in tangential fashion with respect to the particle flow. Pallet production by the layering technique, in this process started with seed material (smaller as diameter 250 mm). The solution or suspension of the drug and binder can be applied to the seed material in several layers. Drugs can apply as a dry powder fed into the bed at a controlled rate. So that bed expands both horizontal and vertical, layers up to 1000% at starting weight can be applied. The 22

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resulting pellets formed are uniform and subsequently coated for controlled release.

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In the layering technique dry powder can be fed into the wet bed resulting in the build up the layers of the powder on to the particle substrate. At the end of the coating process the liquid spray is cut off and the material in the product chamber is dried by increasing the fluidizing air volume and temperature.

Advances in Hardware
Components that make up a fluid bed processor have not changed substantially. However, the shape of the fluid bed in the early days was quite different from the design offered by most manufacturers today. Figure 2 shows the shorter design that was Figure 3 Current prevalent in the industry before Figure 2 Fluid Bed Processor with Design of a typical the Old Design the 1970s. Late in that decade, Fluid Bed Processor several factors changed the design of fluid bed processors. FDA introduced GMP guidelines in the United States; controlled-release products that required uniform particle coating were developed; and as machinery manufacturers developed modular fluid bed units, pharmaceutical manufacturers began to carry out agglomerating, coating, pelletization, and tablet coating in the processor. These changes required taller processing unitl. Figure 3 shows a current design of typical fluid bed processor.

Ten-bar design
Fluid bed processing involves fine dust and dry process air, which can cause an explosion triggered by a static charge. Such an explosion creates a momentary overpressure in the processor. Until late in the 1970s, the typical fluid bed processor was capable of withstanding only 2 bar overpressure. A 2-bar unit required a pressure-relief duct to vent the over-pressure in case of an explosion. The processor had to protrude through the roof or be installed near the outside wall of the facility to minimize the length of the pressure-relief duct. The processor required doors equipped with gaskets, posing a cleaning problem. It was thought that a machine capable of withstanding higher pressure was very expensive to make. However, 10-bar, pilot-size units were introduced by some manufacturers in the late 1970s. A 10-bar unit does not require a pressure-relief duct and thus can be installed anywhere within the building. This also meant that the pressure-relief duct, doors, 22

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door gaskets, and cleaning problems due to doors and gaskets were eliminated. In the 1990s one can obtain a production unit with a 10-bar shock resistance.

Air-handling unit
For a fluid bed processor used in manufacturing, process air is generally drawn from the outside of the building. The conditioning of this air to a constant humidity and dew point is now considered essential. The drying capacity of the air depends on its temperature, humidity, and volume. Because of the globalization of the pharmaceutical industry, fluid bed processes must be able to be transferred from one location to another anywhere in the world. To ensure the consistency of the process conditions and thus the product produced, it is important that the quality of the process air be consistent and re-producible. The recent trend is to have an air-handling unit that can produce air of consistent quality with the desired dew point throughout the year.

Distributor design
The process air brought into the fluid bed processor must be distributed so that the product is uniformly fluidized. This was formerly achieved by means of perforated stainless steel plates with an open area of 4 - 30%. But because the fluid bed process deals with fine powder, a fine screen of 60-325 mesh had to be used in conjunction with the perforated plate. This arrangement was satisfactory from the process point of view. However, cleaning the sandwich construction was difficult.

Figure 5 GILL PLATE Air Distributor

The assurance of proper cleaning was always questioned, and screen ripping was common. In 1990, a new design of the air distributor called the overlap GILL PLATE was introduced. Figure 5 shows the newer design of the air distributors. The basic concept of this design, the GILL PLATE, is widely used in the continuous fluid bed dryer. The design was modified to address the batch fluid bed process requirements. The NON-SIFTING GILL PLATE has the same 22

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capability of distributing air as the previous design. However, unlike the previously used sandwich-type air distributor, the overlap GILL PLATE is easier to clean and, in fact, can be cleaned in place. These NON-SIFTING GILL PLATE air distributors are usually suitable for a unit in which the container is stationary and product discharge is by gravity or pneumatic means.

Process filters
Filters retain the product in the processor. The early design was a single filter bag with a number of socks attached to the filter frame, which, in turn, was attached to an air piston, used to mechanically shake the filter bag during processing. In the single-stroke shaker, filter shaking is accompanied by a loss of fluidization. This creates an intermittent process. In the coating process, the loss of fluidization could cause agglomeration. To provide continuous fluidization of the product, a split filter bag with two separate filter-shaking pistons was introduced in the 1980s. Cleaning of these filter bags was a concern throughout the industry. To prevent cross-contamination between products, pharmaceutical manufacturers used separate filters for each product. The washing of these bags was cumbersome. The bags were made of polypropylene, polyester, or nylon. Because filter bags are generally hand sewn and have numerous seams, they can tear upon repeated use. If the tear happens during processing, product can be lost. Moreover, filter bag handling and cleaning poses a problem of operator safety when a potent compound is processed. To partially address these issues, manufacturers of fluid bed equipment introduced cartridge filters. The cartridge is cleaned by pulses of air during the operation, with no interruption of fluidization. Inclined and vertical designs have emerged. It is claimed that the inclined cartridge allows easy access and can be taken in or out of the processor by placing it in a plastic bag. These cartridges are made up of Gore-Tex laminated polyester felt material and can be cleaned manually or ultrasonically. However, processing potent compounds required a clean-in-place system. A pleated stainless steel cartridge made of three layers of wire screen was introduced in 1991. These cartridges were made of stainless steel because other construction materials were not capable of withstanding the repeated cleaning required during product changeovers. The introduction of stainless steel cartridges for the first time provided the opportunity for cleaning in place of a fluid bed processor.

Clean-in-place design
Cleaning of process equipment used for different products has been discussed extensively in the literature. Formerly, to clean fluid bed processing equipment, the filter bags and the air distributor with sandwiched construction had to be removed from the unit and disassembled, The cleaning required 8 - 10 hours, 22

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and the assurance of cleaning was sometimes operator-dependent. In 1993 a patent was granted for a true clean-in-place (CIP) system. The introduction of overlap GILL PLATE air distributors and stainless steel filter cartridges provided the possibility of cleaning all the components of the fluid bed in place. Because this system can be automated, cleaning can be performed without operator intervention. This automation makes it easy to validate the cleaning procedure. By providing a tank washer for the processor, strategically placed cleaning nozzles, and a cartridge-filter cleaning system, the fluid bed can be cleaned in place. The unique cartridge-cleaning system involves cartridges that can be raised and lowered during the cleaning cycle, a spray nozzle at the top of the cartridge, and annular nozzles around the cartridge tower base. The pleats of the cartridge get cleaned as the cartridges are moved up and down and the force of the spray rotates the cartridges. At the same time, the nozzle at the top of the cartridge tower sprays liquid through the cartridge filter media and backflushes the cartridge. The lower plenum and overlap gill air distributor is cleaned by a nozzle placed in the lower plenum. The cleaning regimen is determined in the early stages of cleaning method development and programmed to provide consistency in cleaning.

Process Advances
The fluid bed process was originally used for the drying of pharmaceutical granulations. However, over the years, agglomeration and air-suspension coating have been introduced. Researchers have discussed the incorporation of microwave technology in the laboratory fluid bed processor. A rapid drying is claimed to be the advantage of this system. There is no commercial installation of this development to date. Fluid bed processes using organic solvent require an inert gas, such as nitrogen, to replace the air as the medium of fluidization and a solvent recovery system to condense out the sol-vent and recycle the gas. In 1989, a vacuum fluid bed system was presented by Luy et al. A fluidized bed was generated and sustained under vacuum, thereby eliminating the use of inert gas. The developers claim several advantages for this sys-tem, such as considerable emission reduction, increased recovery rate of the solvent, and an application for oxygen-sensitive materials. Introduction of a rotor module for the fluid bed by various manufacturers has made possible the production of pellets of a broad size distribution, along with the layering of a drug sub-stance (powder, solution, or suspension) on an inert substrate. Coating of particles and pellets has been carried out in the fluid bed for the last 30 years using air suspension techniques. The Wurster process is the most popular method for coating particles. However, the technology has certain disadvantages, such as nozzle inaccessibility, prolonged process time, and a mini-mum volume requirement. In 1995, the PRECISION COATER ( Patented ), incorporating a modified air suspension technique, was introduced by Niro (Aeromatic-Fielder Division, Columbia, MD; 22

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19). It was designed to allow easy removal of the nozzles for cleaning, faster process time because of a patented particle accelerator, good utilization of thermal and kinetic energies, and scalability from a single-column to a multiplecolumn setup. A trend in the pharmaceutical industry is to use the fluid bed processor to mask the taste of bitter particles by granulating them with melted waxes or coating them with powdered wax. The end point of a fluid bed drying or granulating process has customarily been determined by monitoring the temperature of the exhaust gas stream. The reproducibility of the process is determined by a combination of bed temperature, exhaust air temperature, and drying time. During drying, the product passes through three distinct temperature phases. At the beginning of the process, the material heats up from the ambient temperature to approximately the wet-bulb temperature of the air in the dryer. This temperature is maintained until the product moisture content is reduced to a critical level. When the surface water is no longer present, the product temperature rises further. The termination of the drying process is thus determined by plotting drying curves and by performing experiments. Efforts to measure product moisture as it changes during agglomeration or drying have been made by using infrared moisture measurement . The unit discussed by these authors operates in the near infrared region using five wavelengths. The unit does need to be calibrated every time a new product is to be processed.

Figure 9 PLC Based Control Screen

Automation and Controls: Fluid bed processing requires accurate and reliable control of all the process parameters. Earlier designs of process control systems used pneumatic controls, which provided safe operation in hazardous areas but relied on operator actions to achieve repeatable product quality and accurate data acquisition. Current designs use programmable logic controllers (PLCs) and personal computers to achieve sophisticated control and data acquisition. Access to all user-configured data is protected by security levels, with passwords permitting individuals access only to selected functions. Figure 9 shows the typical PLC-based control screen. For further information about our control systems and how we address FDA's Process Analytical Technology initiative (PAT), please access the Real Time Process Determination (RTPD) page. Real Time Process Determination is a comprehensive software solution that tracks process conditions. It acts as your 22

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most experienced operator and provides concise advice on how to run the process. It is an integrated suite of programs that work along with a GEA Pharma Systems fluid bed processor control system. This includes a program that runs during a fluid bed process and a program for the post batch analysis of the data collected. The most important sensors for control of the drying process are sensors for inlet and exhaust air temperature and an airflow sensor located in the air transport system. Other important parameters that must be sensed for agglomeration and coating are product temperature, atomizing air pressure, air dew point or humidity, and spray rate of the binder solution. Less critical variables are filter and product-bed pressure drop and filter cleaning frequency. All of these sensors provide constant feedback of the information to the operator and the control system. The signals are stored electronically and recalled as a batch re-port, either as a printout or an electronic batch report. With this ability to recall data analysis, a greater insight can be gained into the process. A high-shear mixer can be placed in line with a fluid bed processor. After the mixture is granulated in a high-shear mixer, the dense material is transported to the fluid bed dryer to dry. These two unit operations and the transfer between them can be controlled by a single controller. Such a system optimizes containment, minimizes materialhandling requirements, and reduces the footprint of the machines Understanding Fluidized-Bed Granulation This study demonstrates the beneficial use of a spatial-filter velocimetry particle-size analyzer during granulation.

Common Problem In Fluid Bed Granulation

1) Excessive fine - In sufficient quantity of binder - High fluidized velocity or air flow - Weak binder or low concentration of spraying liquid - Inlet temperature too high - Binder spray rate is too low - High atomization air pressure - Fine droplet size of the binder. 22

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2) Excessive coarse granulation - Binder spray rate too high - Inlet air temperature too low - Low fluidization velocity or air flow - Stronger binder or higher concentration of spraying liquid. - Nozzle position too low 3) Final moisture inconsistency Improper fluidization - Temperature probe out of calibration - Humidity of outside air 4) Poor fluidization - Air velocity is low - Processor fan does not have adequate pressure drop - Air distributor not cleaned properly - Too much product in the product container - Incorrect air distribution plate - Exhaust filter porosity to small - Exhaust is blocked 5) Finished product non uniformity - Insufficient filter shaking - Product homogeneity before granulation is not adequate - Lumps in raw materials - Spraying time is insufficient

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6) Low yield - Filter bag is not shaked at the end of the process - Material stick to the expansion chambers as a result of static charge - Wrong porosity exhaust filter - Air distributor with coarser screen opening

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In the system, a granulating solution or solvent is sprayed into or onto the bed of suspended particles. The rate of addition of binder or solvent, conc. of binder, spray rate, distance between spray nozzle & fluid bed, temperature of air, volume & moisture content of the air all play important role in the quality & performance of the final product In general fluid bed granulation yields less dense particles than conventional methods.

Advantages, Disadvantages And Applications Of Fluidized Bed Systems

Advantages
1. Liquid like behavior, easy to control 2. Rapid mixing, uniform temperature and concentrations. 3. Resists rapid temperature changes, hence responds slowly to changes in operating conditions and avoids temperature runaway with exothermic reactions. 4. Applicable for large or small scale operations. 5. Heat and mass transfer rates are high, requiring smaller surfaces. 6. Continuous operation. 7. Ease of process control due to stable conditions.

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Fluidized Bed Granulator. Disadvantages

1. Bubbling beds of fine particles are difficult to predict and are less efficient. 2. Particle comminution (breakup) is common. 3. Pipe and vessel walls erode due to collisions by particles. 4. Non-uniform flow patterns (difficult to predict).

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5. Size and type of particles, which can be handled by this technique, are limited. 6. Due to the complexity of fluidized bed behavior, there are often difficulties in attempting to scale-up from smaller scale to industrial units.

Applications
Degree of application decides importance of process. Fluid bed systems are widely applied in non- pharmaceutical fields in comparison to their use in pharmaceutical fields as there are numerous apparatus, process and product parameters that affect the quality of final pharmaceutical product. Also in pharmaceutical field each formulation presents its own individual development problems that had led to fluidized systems not reaching its full potential in pharmaceutical production: 1. Fluidized bed dryers are used in drying of various materials such as powders, tablets, granules, coals, fertilizers, plastic materials. 2. This process is being used in granulation of pharmaceutical powders. 3. Fluidized bed coaters are used widely for coating of powders, granules, tablets, pellets, beads held in suspension by column of air. 4. The three types (Top spray, Bottom spray, Tangential spray) are mainly used for aqueous or organic solvent-based polymer film coatings. 5. Top-spray fluidized bed coating is used for taste masking, enteric release and barrier films on particles/tablets. Bottom spray coating is used for

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sustained release and enteric release and Tangential spray coating is used for SR and enteric coating products.

References http://www.pharmainfo.net/free-books/fluidized-bed-systemsreview
(.http://www.niroinc.com/pharma_systems/fluid_bed_drying.asp)

1. S.M. Iveson, et al., Powder Technol. 117 (12), 339 (2001). 2. T. Naervanen, et al., AAPS PharmSciTech 9 (1), 282287 (2008). 3. S. Watano, Powder Technol. 117 (12), 163172 (2001). 4. S. Watano and K. Miyanami, Powder Technol. 83 (1), 5560 (1995). 5. S. Watano et al., Chem. Pharm. Bull. 48 (8), 11541159 (2000). Citation: When referring to this article, please cite it as "A. Burggraeve, T. Van Den Kerkhof, M. Hellings, J.P. Remon, C. Vervaet, T. De Beer, "Understanding Fluidized-Bed Granulation," Pharmaceutical Technology 35 (8) 63-67(2011). (http://pharmtech.findpharma.com/pharmtech/IT/Understanding-Fluidized-BedGranulation/ArticleStandard/Article/detail/734124) ( http://www.pharmaceuticalmachinery.in/granulation.htm) (.http://www.niroinc.com/pharma_systems/fluid_bed_drying.asp)

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BY
BAKHT AMIR AMIR NAWAZ SYED YAQOOB SHAH MUHAMMAD ASIF IHSAN ALI 12-07-12 12-07-16 12-07-30 12-07-37 12-07-39

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