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Fluid Bed Granulation, Drying, and Coating Print Send link
Home / GEA Pharma Systems / cGMP Products / Fluid-Bed Drying Systems
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Related Pages
 GEA Pharma
Systems Lighthouse
Probe™ Technology
Airflow in Batch Fluid-
Bed Processing by
Dilip M. Parikh:
reprinted from
Pharmaceutical
Technology, March
1991.
Fluid-Bed Processing
in the 1990s by Dilip
M. Parikh: reprinted
from Pharmaceutical
Technology
Supplement, October
1996

Fluid Bed Processor for

Granulation, Coating, Pelletization,
and Solution Layering
Fluid bed drying

Gentle, rapid drying of powders and particles

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.
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.

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 prevalent in the industry
before the 1970s. Late in that decade, 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 Figure 3 Current
within the building. Figure 2 Fluid Bed
Design of a
This also meant that Processor with the Old
typical Fluid Bed
the pressure-relief Design
Processor
duct, doors, 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 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, 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; 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 multiple-
column 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 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 Niro 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 material-handling
requirements, and reduces the footprint of the machines.

Summary: Over the past 30 years, fluid bed technology has progressed
from a process to dry a product quickly to a more sophisticated
technology that can be used for granulation, drying, particle coating, and
pelletization. The improvement in the technology is driven by the
pharmaceutical industry and the manufacturers of the equipment.
Changes in the pharmaceutical industry require an efficient
manufacturing operation, and continuing enhancements in fluid bed
technology can certainly assist in that effort.
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