C H A P T E R

35
Development, Optimization, and Scale-Up of
Process Parameters: Wurster Coating
D. Jones1,† and E. Godek2
1
Glatt Air Techniques Inc., Ramsey, NJ, United States 2OWI-Consulting, Inc., Coatesville, PA, United States

35.1 INTRODUCTION The spray pattern is generally a solid cone of droplets,

with a spray angle ranging from approximately
In 1959, Dr Dale Wurster, then at the University of 30 50 degree (Fig. 35.3). The so-called “coating zone,”
Wisconsin, introduced an air suspension coating tech- which is formed is a narrow ellipse, and varies in vol-
nique now known as the Wurster system. The Wurster ume depending on the size of the substrate being
process enjoys widespread use in the pharmaceutical sprayed and the pattern density in the partition.
industry for layering and film-coating of particles and The diagram in Fig. 35.4 illustrates the regions of flow
pellets, as well as the emerging controlled-release tablet in the Wurster process. The region outside of the partition
dosage forms. Product containers typically range in size is referred to as the down bed. The configuration of the
from 3.5v (100 500-g batch sizes) to 55v (up to approxi- orifice plate in this area depends on the size and density
mately 1100 kg). The Wurster process is used commer- of the material to be processed. The purpose of the airflow
cially for coating particles from less than 100 µm to in the down bed region is to keep the substrate in near-
tablets, and for layering to produce core materials. weightless suspension, irrespective of its distance to either
the wall of the product container or the partition. The
goal is to have it travel rapidly downward (to minimize
35.2 BASIC DESIGN cycling time), and then be drawn horizontally toward,
and ultimately into the gap at the base of the partition. In
The basic design components of a commercially avail- general, larger substrates, like tablets, require significantly
able Wurster system are shown in Figs. 35.1 and 35.2. more air to produce this condition than smaller sub-
The coating chamber is typically slightly conical, and strates, like pellets or fine particles. The orifice plate must
houses a cylindrical partition (open on both ends) that is be selected accordingly (no single down-bed plate can
approximately half the diameter of the bottom of the achieve good fluidization properties for all substrates). As
coating chamber (in up to 18v Wurster coaters). At the mentioned previously, the material flow inside of the par-
base of the chamber is an orifice plate that is divided tition is controlled by the up-bed or partition plate. In
into two regions. The open area of the plate under the general, this plate is considerably more permeable than
partition is very permeable. This permits a high volume the down-bed plate. In pilot- and production-scale
and velocity of air to pneumatically transport the sub- Wurster systems, the up-bed plates are removable so that
strate vertically through the partition. As they accelerate one or the other may be changed to fine-tune the behavior
upward, particles pass a spray nozzle that is mounted in in these individual regions (see Fig. 35.5).
the center of this up-bed orifice plate. The nozzle is A second key process variable in Wurster coating is
referred to as a two-fluid or binary type, where liquid is the height that the partition sits above the orifice plate,
delivered to the nozzle port at low pressure and is which controls the rate of substrate flow horizontally
atomized by air at a preselected pressure and volume.
†
Deceased.

Developing Solid Oral Dosage Forms

DOI: http://dx.doi.org/10.1016/B978-0-12-802447-8.00035-2 997 © 2017 Elsevier Inc. All rights reserved.
998 35. DEVELOPMENT, OPTIMIZATION, AND SCALE-UP OF PROCESS PARAMETERS: WURSTER COATING

FIGURE 35.1 Glatt model GPCG-60 fluid-bed processor fitted FIGURE 35.3 Spray nozzle and spray pattern (using water).
with an 18v HS Wurster insert. Source: Photograph courtesy from Glatt
Air Techniques, Inc.

FIGURE 35.2 18v HS Wurster coater—inside view showing spray

nozzle, HS nozzle surround, and partition. Source: Photograph courtesy
from Glatt Air Techniques, Inc. FIGURE 35.4 Diagram of the HS Wurster process.

into the coating zone. Typically, the smaller the parti- essentially enhance deceleration in the air space rather
cles to be coated, the smaller the gap will be. When the than by high velocity impact against machine compo-
Wurster coating chamber is assembled properly, the nents in the filter housing. By contrast, tablets do not
resulting flow pattern should be relatively smooth and need much expansion height, and in fact, attrition may
rapid in the down bed, and very dense and homoge- be a severe problem if they travel too high into the
neous in the up-bed (or partition) region. expansion area. The orifice plate and partition height
The substrate exits the partition at a high rate of should be optimized so that the tablets travel upward
speed, requiring a region to decelerate. Above the prod- only a very short distance out of the partition before
uct container is the expansion area (or freeboard, in tra- beginning their descent. As a result, a mesh bonnet can
ditional fluidized bed terms), which is typically conical be used in the expansion chamber, just above the prod-
to allow for decreasing air and particle velocity. uct container, to keep the tablets from colliding with
Wurster machines designed for pellets and small parti- the expansion chamber. The coarse mesh is intended to
cles employ elongated expansion chambers to allow the fines from the cores or some spray-dried

III. DESIGN, DEVELOPMENT AND SCALE-UP OF FORMULATION AND MANUFACTURING PROCESS

 35.3 HS WURSTER CONSIDERATIONS 999

FIGURE 35.5 Up- and down-bed orifice plates for an 18v

HS Wurster coater. Source: Photograph courtesy from Glatt Air FIGURE 35.6 Spray nozzle and pattern shown with its nozzle
Techniques, Inc. surround (patented). Source: Courtesy from Glatt Air Techniques, Inc.

coating to exit the process area, avoiding incorporation

in the layers of film. A conventional Wurster machine is Ramsey, NJ, and involves the use of a proprietary
typically not used extensively for tablet coating because device to influence the behavior of the substrate in
of the comparatively high stress to which the tablets proximity to the coating zone. Unfortunately, the liquid
may be exposed. However, it is recommended when spray-application rate is not controlled by the drying
the film quality (minimal defects) or active component capacity of the fluidization air, but by the nature of the
distribution uniformity are very important, especially coating material (tackiness) or by the region immedi-
for modified-release tablets. The films applied by ately surrounding the spray nozzle (the first area of
Wurster systems are high quality due to the concurrent focus is this region). In all Wurster inserts, the high
spray and high-drying efficiency of this air suspension velocity of air rushing through the partition relative to
process. There have been modifications to the Wurster the lower velocity in the down bed creates suction at
process specifically for tablet coating. These include the partition gap according to Bernoulli’s Principle. As
spray nozzle surrounds, partition geometry, and air- a consequence, particles entering the partition through
flow adjustability at the interface between the wall of the gap have a horizontal component to their flow.
the product container and the down-bed orifice plate Some travel toward the spray nozzle instead of simply
(to be described in more detail later in this chapter). making the transition from horizontal to vertical flow.
Pellets and small particles are layered or coated exten- The atomizing air has a very high velocity (it is likely
sively via the Wurster process using water, organic sol- supersonic), and creates another area where Bernoulli’s
vents, or even by spraying molten materials. All fluidized- Principle applies, which draws the substrate to the base
bed techniques are known for high rates of heat and mass of the developing spray pattern. In a standard Wurster
transfer, and the Wurster process is very effective in this machine, the nozzle is elevated above the orifice plate
regard. Highly water-soluble materials can be coated at a position just below the confluence of fluidizing
using water-based applications without concern for core substrate particles. A portion of the developing up-bed
penetration. Droplets applied to the surface spread to stream of product can pass the nozzle tip, either closely
form a continuous film or layer, and then quickly give up or at a further distance. The zone directly above the
their moisture to the warm, dry air. After a thin film has nozzle tip is where the coating liquid and the atomiz-
been applied, spray rates can be increased because the sol- ing air mix, and droplets begin to form. Particles that
uble core has been isolated. Films applied with volatile are very close to this zone tend to be strongly over-
organic solvents are also high in quality because the wetted, and if they contact other particles, agglomer-
formed droplets impinge on the substrate very quickly, ates are formed. To control what could otherwise be
minimizing the potential for spray drying of the film. severe agglomeration, a typical response is to reduce
the spray rate. This leaves a large amount of the drying
capacity unused. Other commonly used agglomeration
35.3 HS WURSTER CONSIDERATIONS control techniques include raising the inlet (and prod-
uct) temperature to increase the drying rate or raising
HS Wurster technology, shown in Figs. 35.4 and the atomizing air pressure to shrink droplet size—
35.6, is a product of Glatt Air Techniques, Inc., in options which are in conflict with producing high-

III. DESIGN, DEVELOPMENT AND SCALE-UP OF FORMULATION AND MANUFACTURING PROCESS

1000 35. DEVELOPMENT, OPTIMIZATION, AND SCALE-UP OF PROCESS PARAMETERS: WURSTER COATING

quality films. Even using these corrective measures, a

quantity of agglomeration in traditional Wurster sys-
tems is almost inevitable.
The HS modification for the Wurster process was
conceived to keep particles away from the spray nozzle
until the spray pattern is fully developed. As a result,
more of the excess drying capacity can be used, and the
application rate increased substantially (more than dou-
bled in many pilot-scale experiments). Agglomeration is
also substantially diminished or eliminated because the
particles are kept away from the wettest portion of the
pattern (Fig. 35.6). An additional benefit is that the high-
atomizing air velocities necessary to produce very small
droplets for coating of particles smaller than 100 µm
may be useable without pulverizing the substrate. The
velocity of this air diminishes dramatically with dis-
tance from the nozzle, and even a few centimeters are
significant. Therefore, keeping the product away from FIGURE 35.7 Cross-section showing boundary layer between
the nozzle tip allows the atomization air velocity to coating and core material (2003 magnification).
decrease significantly before contacting the substrate,
reducing the likelihood of attrition, especially during
the early stages of coating.
Coating of substrates smaller than 100 µm has been
achieved more frequently using the HS Wurster coater.
Success depends on many factors, both process- and
product-related. Product considerations, such as flow
properties of the substrate (generally poor in this size
range, which must be improved), as well as the liquid,
which must be amenable to atomizing to droplets well
below 10 µm, must be addressed. The tremendous sur-
face area of such fine particles also requires very high
coating quantities, and consequently, a low potency of
the final-coated product (often less than 50%).

35.4 COATING AND PROCESS

CHARACTERISTICS FIGURE 35.8 Cross-section of drug-layered, film-coated pellet
(1203 magnification).

The coating liquid is sprayed in the direction of

motion of the fluidizing particles. In general, the fluidi- 35.5 PROCESSING EXAMPLES
zation is orderly, with very rapid, dilute-phase pneu-
matic transport in the up bed, and relatively smooth The Wurster process is used commercially for coat-
and rapid transport in the down-bed region (outside of ing and layering (high solids build up onto a type of
the partition). Droplet travel distance is minimized core material). Substrates include particles smaller
because the liquid is sprayed into a well-organized than 100 µm, crystals, granules, pellets, and tablets. As
pattern of substrate moving relatively close to the noz- mentioned previously, films may be applied using
zle. In this manner, droplets reach the substrate prior water-based solutions, aqueous dispersions, or organic
to any appreciable evaporation. By retaining their low solvents.
viscosity they are able to spread on contact, and the The first example of a material layered and coated
resultant films are excellent, even when using organic using the Wurster process is shown in cross-section in
solvents as an application medium. The drying effi- Fig. 35.8. The starting material is a very small, nonpa-
ciency of the fluidized-bed also minimizes the poten- reil sugar seed, and it is layered to a high potency
tial for core penetration, and the sample shown in using a suspension of drug in a dilute-binder solution.
Fig. 35.7 clearly shows a well-defined boundary layer Release of the drug is controlled by a film subse-
between the substrate and the coating material; in this quently applied. All three components are clearly
case a film applied using an aqueous dispersion. identifiable.

III. DESIGN, DEVELOPMENT AND SCALE-UP OF FORMULATION AND MANUFACTURING PROCESS

 35.5 PROCESSING EXAMPLES 1001
The example shown in Fig. 35.9 is a tablet, film- particles may be filled into capsules or compressed into
coated (for sustained release) and layered with an tablets to be delivered. Although the product must be
additional dose of active material prior to drilling with processed at low temperatures, core penetration was not
a laser. Immersed in liquid, drug solute exits the laser a problem due to the process parameters used and the
hole in this type of dosage form. The Wurster process drying capability of the Wurster process.
was selected for this product due to its abilities in film Often the economics of coating very small particles
and drug distribution uniformity. dictate whether a product ever reaches the market-
The product in Fig. 35.10 is coated with a moisture place. When coated in a standard Wurster system, the
barrier. The substrate contains a significant quantity drug particles shown in Fig. 35.12 proved too costly to
of material smaller than 5 µm. Agglomeration of fine produce. However, when the HS components were fit-
particles does occur, as seen in the scanning electron ted to the pilot-scale 18v Wurster machine, the process
micrograph (SEM). However, the average particle size time was reduced by more than 50%, and the product
of the finished product is still less than 50 µm. The film is now commercially produced. The SEM shows very
is applied from a volatile organic solvent solution, good morphological properties for the core, in that the
and is typically very tacky, hence the agglomeration particles are nearly spherical, and are not porous. In
“crater” where another particle has detached. laboratory trials, this substrate was found to be very
A water-soluble core, coated with a soft, heat-sensitive robust—attrition of the cores early in the coating pro-
polymer system is shown in Fig. 35.11. The cross-section cess (before they were sufficiently coated to have
shows the deformable nature of the film, and these improved surface strength) was essentially nonexistent.

FIGURE 35.9 Cross-section of a tablet coated using the Wurster FIGURE 35.11 Water-soluble crystal coated for sustained release
process (1503 magnification). (1003 magnification).

FIGURE 35.10 Very fine particles coated with a moisture barrier FIGURE 35.12 Drug core particles coated for taste masking,
using the HS Wurster process (10003 magnification). incorporation into oral suspension (2503 magnification).

III. DESIGN, DEVELOPMENT AND SCALE-UP OF FORMULATION AND MANUFACTURING PROCESS

1002 35. DEVELOPMENT, OPTIMIZATION, AND SCALE-UP OF PROCESS PARAMETERS: WURSTER COATING

35.6 PROCESS VARIABLES 35.6.2 Fluidization pattern

Irrespective of the amount of substrate in the
35.6.1 Batch size
Wurster insert, the fluidization pattern is controlled by
The working capacity for a Wurster insert of a partic- the orifice plate configuration, the partition height, and
ular size is generally defined as the volume outside of the fluidization air volume. As mentioned previously,
the partition, with the partition at rest on the orifice the goal is to have a rapid and relatively smooth down
plate. Loading of product only in the area outside of the bed. This is not always possible, depending somewhat
partition helps to ensure that the nozzle remains clear at on particle size (small particles are difficult, if not
the beginning of the process. This is especially impor- impossible, to fluidize without bubbling), but to a
tant for fine particle or pellet coating. For tablet coating, greater extent on the tackiness of the product during
up to half of the volume inside the partition can also be spraying. Some coating materials are inherently tacky
used. As the bed becomes fluidized, the dense phase or or move sluggishly due to temperature sensitivity. If
surface of the down bed will drop, indicating that there this is the case, it is more important to keep the entire
is room for the batch to expand as coating is applied. In bed moving and involved by marginally over-fluidizing
some cases, it may appear that there is more than (turbulence or bubbling in the down bed), rather than
enough, and that batch size could easily be increased. attempting to achieve a smooth flow. This can be
The danger is that the level of the bed is dynamic— accomplished by raising the partition somewhat or
varying in depth in response to the behavior of the up using a more permeable down-bed plate, to allow extra
bed and surface properties of the substrate during air to percolate through the descending product. The
spraying. Should the substrate begin to drop down into risk in not doing this is that, as the process progresses,
the partition against the desired flow, the up bed would the bed may stall in some region on the orifice plate,
be seriously disturbed, agglomeration would be likely, and a portion of the batch may not receive all of the
and the batch might be lost. desired coating. Typically, this happens in the back por-
The minimum batch size is approximately 20 25% tion of the product container, usually out of sight from
of working capacity. It is critical that there be sufficient the operator. The reason for this is that, in most installa-
material in the up-bed region to accumulate all or most tions, the process air enters the inlet plenum via a duct
of the coating material being sprayed or “efficiency” behind the machine. More air enters the product bowl
(actual yield vs expected) will suffer. The down bed in the front, due to momentum because the air has
acts as a material reservoir, “feeding” the base of the mass and needs to make a sharp turn upwards. This
partition (entrance to the coating zone), and if its depth can be minimized by increasing the pressure drop
is insufficient, the up bed will be too sparse, favoring across the bottom plate using a retention screen with a
spray drying. In a more extreme case, coating of the lower porosity.
inner wall of the partition may be experienced (this is In general, tablets require a large air volume in the
more common in very small laboratory-scale inserts). down bed to keep it well-aerated. The partition region
Use of such a small volume of the product container is of the plate is also selected to allow only sufficient air
recommended only if the final batch size is significantly flow to minimize the distance tablets travel out of parti-
larger than the starting volume (eg, layering). Early in tion to avoid attrition. By contrast, the orifice plates for
the process, the coating efficiency is compromised. This pellet coating may differ significantly. The plate is per-
inefficiency diminishes as the batch size increases, meable inside of the partition, and the down-bed sec-
improving mass flow through the coating zone. When tion is only perforated to the extent that the product
approximately half of the down bed working capacity flows downward in near-weightless suspension.
is occupied, the efficiency will be at or near its maxi- Achieving this condition typically requires only about a
mum for the formulation being executed. Ultimately, one-fourth of the open area needed for tablet coating.
the inefficiency seen at the beginning of the process Finally, plates designed for powders are even less per-
should be of little or no consequence to the finished meable in the down-bed region (and boiling may be
batch. impossible to control, due to the flow properties of fine
After the layering step, it is strongly recommended materials).
that the minimum batch size be increased to approxi- Another critical process variable in the fluidization
mately 50% of the working volume if a thin film is to pattern for Wurster processing is the height of the par-
be applied. For film-coating, inefficiency will likely tition above the orifice plate. The height is also
impact the resultant dissolution behavior. Some substrate-dependent. For instance, tablets, a compara-
amount of spray drying may result in unexpectedly tively large substrate, would require a substantial par-
rapid release of drug, particularly for a sustained- tition height, such that a sufficient number of them
release coating. could pass through the gap per unit time to accept the

III. DESIGN, DEVELOPMENT AND SCALE-UP OF FORMULATION AND MANUFACTURING PROCESS

 35.6 PROCESS VARIABLES 1003
TABLE 35.1 Partition Height as a Function of Substrate and Atomizing air pressure and droplet size
Wurster Coating-Insert Size 50

Mean droplet size (μm)

Substrate Partition height 40

Tablets 25 50 mm in small machines 30

50 100 mm in 18v Wursters and larger 20

Pellets Approximately 15 25 mm small machines 10

Approximately 35 60 mm in 18v Wursters and larger 0

1 2 3 4 5 6
Powders Approximately 25 50 mm in all machines Atomizing air pressure (bar)

970/0.8 mm. 25 g/min

maximum amount of coating being sprayed into the

FIGURE 35.13 The relationship between atomizing air pressure
partition area. Pellets and intermediate particles do not and droplet size for a Schlick 970 series nozzle spraying water.
need as high a partition height as tablets, and fine par-
ticles and powders need only a small gap to result in
an ideal fluidization pattern. Table 35.1 profiles sug- Atomizing air pressure and droplet size
50

Mean droplet size (μm)

gested conditions for partition height as a function of
substrate and Wurster coating-chamber size. 40

30

20
35.6.3 Atomizing air pressure and volume 10
Droplet size should be small, relative to the particle 0
size of product to be coated. For example, coating of 1 2 3 4 5 6
tablets may need less than 2 bar (30 psi) pressure. (a) Atomizing air pressure (bar)
Higher pressure and air volume will result in a higher 940/0.8 mm. 40 g/min 940/0.8 mm. 100 g/min
atomization air velocity, increasing kinetic energy at 940/0.8 mm. 250 g/min 940/0.8 mm. 500 g/min
the interface between the spray pattern and slower-
moving substrate. The potential for causing attrition of
Droplet size as a function of atomizing air pressure
the tablets by accelerating them into machine compo- HS series nozzle (pilot and production Wurster only)
nents is also enhanced. Finally, the high atomizing air Water, 1000 g/min, 1.8 mm port
velocity may distort the fluidization pattern. 100
90
When coating small particles, a somewhat higher
Mean droplet size (μm)

80
atomization air pressure may be necessary, to achieve 70
small droplet size and thereby avoid agglomeration. 60
There is some risk, however, that the high shear associ- 50
ated with pressures in the 3 6 bar (45 90 psi) range, 40
depending on the type and size of the spray nozzle, 30
may cause breakage of fragile core material. The 20
Gustav Schlick Company in Coburg, Germany, is a 10
0
supplier of spray nozzles in widespread use in Wurster 1 2 3 4 5 6
processing. The 970 series nozzle is found in small (b) Atomizing air pressure (bar)
(3.5v, 4v, 6v, 7v, and 9v) Wurster bottom-spray coaters.
With water-like materials, it is useable in a spray-rate FIGURE 35.14 (a) The relationship between atomizing air pres-
sure and droplet size for a Schlick 940 series nozzle at various spray
range of approximately 0 100 g/minute. Fig. 35.13
rates using water. (b) The relationship between atomizing air pres-
shows the influence of atomization air pressure on sure and droplet size for a Schlick HS Wurster nozzle at 1000 g/min
mean droplet size for water sprayed at 25 g/minute spraying water.
(data by Schlick). Interestingly, increasing the pressure
beyond 2 bar does little to decrease the droplet size. likely a consequence of the increased air velocity and
This is, in part, due to the fact that 25 g/minute is well kinetic energy, not a smaller droplet size.
within the nozzle’s ability to atomize. What should be Looking at the performance envelope of the Schlick
noted is that, if a process is being run in which agglom- 940 series nozzle (Fig. 35.14), which is used in older
eration is a minor problem and increasing the atomiza- style 12v, 18v, 24v, 32v, 46v, and 55v Wurster coaters, it
tion air pressure seems to improve the situation, it is can be seen that droplet size increases with faster spray

III. DESIGN, DEVELOPMENT AND SCALE-UP OF FORMULATION AND MANUFACTURING PROCESS

1004 35. DEVELOPMENT, OPTIMIZATION, AND SCALE-UP OF PROCESS PARAMETERS: WURSTER COATING

rates (at a constant atomization air pressure). In cases Atomizing air pressure and droplet size
60

Mean droplet size (μm)

where the spray rate is 250 g/minute or less, it is possi-
ble to increase atomization air pressure/volume/veloc- 50
ity to achieve droplets smaller than 20 µm. However, 40
the data shown for the 500 g/minute rate demonstrates 30
that even at the highest practical atomization air pres- 20
sure (6 bar), it is not possible to produce 20 µm droplets 10
(spraying water). This is an important consideration in
0
larger capacity equipment, where there may be signifi- 1 2 3 4 5 6
cant drying capacity, and the rate-limiting factor is the Atomizing air pressure (bar)
inability of the nozzle to atomize liquid (to a satisfac-
940/0.8 mm. 100 g/min 940/0.8 mm. 250 g/min
tory droplet size) at the rate at which the process air
940/2.2 mm. 100 g/min 940/2.2 mm. 250 g/min
may remove the resultant water vapor. The only possi-
bility for taking advantage of the increased drying
FIGURE 35.15 The relationship between atomizing air pressure
capacity is to enlarge the nozzle (use more compressed and droplet size for a Schlick 940 series nozzle at 100 and 250 g/min
air at the same pressure). (water) using 0.8 and 2.2 mm nozzle port sizes.
The 940 series nozzle is unable to produce droplets
smaller than 20 µm at 500 g/minute using water, even preferable that they both be low to avoid the need for
at very high atomization air pressures. A process that high atomization air pressure, regardless of the size of
has excessive drying capacity, but is limited by droplet the substrate. If viscosity is an issue (high), nozzle port
size (eg, fine particle coating), will result in unnecessar- size should be selected to accommodate it (to minimize
ily hindered productivity. Upgrading to the HS nozzle, back pressure in the spray pump).
which uses substantially more compressed air at the
same atomization air pressures (approximately three
times the volume of the 940 series nozzle), will result in
a dramatic improvement in drying capacity utilization.
35.6.5 Evaporation rate
The graph in Fig. 35.14b depicts a droplet profile that is Evaporation rate or drying capacity is controlled by
similar to the 940 series nozzle spraying at 250 g/min- fluidization air volume, temperature, and its absolute
ute, with the exception that the HS data is for 1000 g/ humidity (dew point). The temperature of the fluidiza-
minute, a spray rate four times that of the 940 series tion air is generally adjusted to maintain a constant
nozzle. This permits the HS nozzle to be operated at product temperature. The product temperature, in
low atomizing air volumes and pressures, limiting the turn, is influenced by spray rate and humidity of the
potential for attrition due to high kinetic energy. incoming air. First, to take advantage of excess drying
capacity, inlet temperature must be raised to keep
the product temperature from dropping, due to the
increase in evaporative cooling as spray rate is
35.6.4 Nozzle port size
increased within a given batch. Secondly, if the dew
Droplet size is rarely influenced by nozzle port size. point of the incoming air is not controlled, the drying
At a fixed volumetric spray rate, the velocity of the liq- conditions to which the product is exposed will not be
uid into the atomization air is controlled by the nozzle reproducible. The dew point changes seasonally, espe-
port size. The lower the velocity, the more complete the cially in northern climates, and may range from below
atomization of the liquid will be, and the smaller the 0 C during winter to more than 20 C in summer.
mean droplet size; Fig. 35.15 illustrates this data for a These normal variations in weather conditions may
940 series nozzle for two different spray rates. For result in some notable influences in processing.
100 g/minute, the mean droplet size is nearly the same In cold weather, static electricity during fluidization
for all data points, with the exception of the values at may be a problem, and in summer, high humidity con-
2 bar. However, this appears to be an anomaly because ditions may result in substantially slower spray rates,
the mean droplet size is the same for both port sizes at due to erosion of drying capacity, especially for aque-
the lower pressure of 1 bar. At the higher spray rate of ous coatings. This phenomenon is, of course, more
250 g/minute, the mean droplet sizes are the same at pronounced when product temperatures of 30 C and
3 bar and higher. Only at 2 bar is there an appreciable less are desired (thermally sensitive substrates or coat-
difference, owing to the lower liquid velocity, and lon- ing materials). Allowing the process air dew point
ger dwell time for the liquid in the atomizing air to vary will result in a variation in the residual mois-
stream. In addition, factors such as liquid viscosity and ture in the applied film. This can lead to a change in
surface tension influence this behavior; and it is the glass transition temperature for some coatings.

III. DESIGN, DEVELOPMENT AND SCALE-UP OF FORMULATION AND MANUFACTURING PROCESS

 35.7 CASE STUDIES FOR LAYERING AND FINE PARTICLE COATING 1005
For latex materials, residual moisture may result in threshold of 60%, the water removal rate for a product
“aging” effects—changes in dissolution with time temperature of 40 C is approximately 100% higher
(product instability). For most products, a dew-point than for a product temperature of 30 C. Water content
range of approximately 10 20 C throughout the year in air is an exponential function—for high product tem-
is recommended, to minimize this so-called “weather peratures, the water removal rate is dramatically
effect.” If the product is very sensitive to moisture in increased without fear of agglomeration.
the process air or even thermally sensitive, a desiccant
dryer is suggested, which will produce dew points
well below 0 C. In any case, process air dewpoint con-
trol is recommended in the system’s air handling unit. 35.7 CASE STUDIES FOR LAYERING AND
FINE PARTICLE COATING

With an understanding of the range of application

35.6.6 Product temperature of the Wurster process, plus the process and product
All air suspension processes are noted for their high variables that influence its performance, it is interest-
heat and mass transfer capability. A wide range of ing to look at some case studies. The first involves the
product temperatures may be used. Values below 30 C use of an 18v HS Wurster coater for solution layering
may be used for heat-sensitive materials. Values (refer to Figs. 35.16 and 35.17 for in-process data). A
exceeding 50 C may actually be used with little or no water-based drug solution was made, using a high
spray drying of the applied coating. High product tem- solids concentration. The goal of the trial was to find
peratures are especially attractive for water-based the maximum possible spray and production rates,
spray liquids. The rate-limiting step for most processes avoiding agglomeration as much as possible. The start-
is related to the physical properties of the liquid being ing material is very fine, initially requiring a reduced
applied. The use of psychrometry is effective in deter- spray rate (400 g/minute). However, as the particles
mining the threshold at which moisture applied to the grow larger, the spray rate can be elevated as the sur-
surface of the substrate begins to remain in the applied face area of individual particles increase. The finished
layer, rather than to leave with the process air. This particle size is less than 200 µm, and the potential for
inflection point is where agglomeration begins to take productivity using the Wurster process is clearly evi-
place. The surface tackiness promotes the sticking dent here. The majority of the spray liquid is applied
together of substrate particles. This so-called exit air at 900 g/minute. Heat and mass-transfer rates are very
relative humidity threshold is related to the product high. The inlet air temperature is more than 90 C, the
temperature. For example, for an exit humidity product temperature is approximately 35 C, and the

18″ HS Wurster batch

100 1200

90
1000
80

70 Spray rate (g/min)

800
Temperature (°C)

60

50 600

40
400
30

20
200
10

0 0
10:35:05 10:46:07 11:02:56 11:18:27 11:33:58 11:49:30 12:05:03 12:20:34 12:36:05 12:51:35 13:07:08 13:22:39 13:38:11
Time

Process dewpt (°C) Product temp (°C) Exhaust temp (°C)

Process air temp (°C) Spray flow rate (g/min)

FIGURE 35.16 In-process data (temperatures and spray rate) for an 18v HS Wurster solution layering process.

III. DESIGN, DEVELOPMENT AND SCALE-UP OF FORMULATION AND MANUFACTURING PROCESS

1006 35. DEVELOPMENT, OPTIMIZATION, AND SCALE-UP OF PROCESS PARAMETERS: WURSTER COATING

18″ HS Wurster batch

Product differential pressure and process air volume
450 1200

Product differential pressure (mmWC)

400 1000

Process air volume (cfm)

350 800

300 600

250 400

200 200

150 0
10:35:05 10:50:07 11:14:15 11:35:24 11:56:34 12:17:44 12:38:55 13:00:05 13:21:14 13:42:24 14:03:34
Time

Process air vol (cfm) Product differential pressure (mmwc)

FIGURE 35.17 In-process data (process air volume and product differential pressure) for solution layering in an 18v HS Wurster coater.

process air volume is 900 cfm. Using psychrometry

software, the exit air humidity is found to be at 85%
relative humidity, indicating that the vast majority of
available drying capacity is being used. An interesting
tracing is that of the product differential pressure,
shown in Fig. 35.17, as the starting batch size is
approximately one-quarter of the finished product
weight. As bed depth increases in the down bed, the
particles react differently to the up bed process air
flow. There is a near-absence of oscillation in the early
readings because the down bed is shallow, and there is
minimal coalescence of air bubbles as they enter and
pass through the bed. However, as batch size
increases, the down bed deepens. Small air bubbles,
entering through the orifice plate and product reten-
tion screen, coalesce into larger bubbles. Back-flow or
turbulence in the down bed becomes evident. The
FIGURE 35.18 Uncoated acetaminophen (APAP) crystals (283
escalating peak-to-trough values indicate bubbling air magnification).
flow in the down bed. This is of no consequence to the
process, provided that the down-bed cycling time
remains rapid, so that the mass flow in the “coating their fragility. As the particle size data shown in
zone” continues to be high in density and velocity. A Tables 35.2 and 35.3 reveals, the material is very prone
consequence of adverse fluidization properties would to fracture. Within a few minutes of product warm-up
be agglomeration, however, in this particular pilot- (prior to spraying), the content of material smaller
scale trial, this was essentially nonexistent. than the 80 mesh screen (180 µm) escalates from noth-
The second case study involved coating fine granu- ing to more than 3%, and continues to climb early in
lar acetaminophen particles for sustained release. The the spraying process until sufficient coating has been
uncoated crystals, shown in Figs. 35.18 and 35.19, illus- applied to improve the strength of the primary core
trate a good substrate for coating. They are uniform in material. It is important that the fines that exist in the
size distribution, and do not contain an appreciable initial product, in addition to those generated during
amount of fines. What is not seen by SEM, however, is the early stages of coating, are treated in one of two

III. DESIGN, DEVELOPMENT AND SCALE-UP OF FORMULATION AND MANUFACTURING PROCESS

 35.7 CASE STUDIES FOR LAYERING AND FINE PARTICLE COATING 1007
ways. First, using a comparatively high spray rate ini- outlet filter media can be selected such that fines are
tially, they may be incorporated in the lower layers of permitted to exit the processor (to be collected in a
film, such that the majority of the remaining film gov- remote dust collector). If attrition is serious or if fines
erns the coated-product release properties. Second, an are continually incorporated in the developing film, as
was the case using the conventional 18v Wurster
coater, the release properties of the film will be
affected, and in all likelihood, challenging to repro-
duce. In Figs. 35.20 and 35.21, the acetaminophen crys-
tals have been coated to a 28% coating level (final
potency of 78.1%) with AquaCoat (FMC), a pseudo-
latex of ethylcellulose. The standard version 18v
Wurster equipment was used in a Glatt model GPCG-
60 fluid-bed processor, using the HS nozzle, but no HS
nozzle surround, and a (then) contemporary version of
an up-bed plate referred to as “high mass flow.” This
plate may be described as having a gradient of holes
(and permeability) from the outer perimeter to the
spray nozzle. The highest permeability is in close prox-
imity to the nozzle. The intent of this design was to
enhance the pressure gradient at the partition gap and
increase the flow of material into the coating zone.
What became apparent during these trials was that
FIGURE 35.19 Uncoated acetaminophen crystals (1003 this resulted in a high concentration of substrate close
magnification). to the tip of the nozzle and the developing spray

TABLE 35.2 Sieve Analysis (During Spraying Without Nozzle Surround)

Time 130 140 160 180 1100 Pan Comments

0 min 0.0038 g 2.691 g 33.247 g 6.154 g 0.029 g 0.018 g

0.01% 6.39% 78.89% 14.6% 0.07% 0.04% Starting material
3 min 0.0011 g 0.0658 g 23.441 g 4.519 g 0.327 g 0.461 g
0.04% 2.24% 79.69% 15.36% 1.11% 1.57% Start spray
24 min 0.013 g 0.151 g 15.670 g 6.553 g 1.121 g 2.018 g
0.05% 0.59% 61.39% 25.67% 4.39% 7.91% Pressure from 3.5 to 2.7, increased
spray rate from 200 to 270 g/min
37 min 0.031 g 0.561 g 15.873 g 6.729 g 1.661 g 3.828 g
0.11% 1.96% 55.34% 23.46% 5.79% 13.35% Pressure to 2.2 bar, increased
spray rate from 270 to 325 g/min
58 min 0.062 g 3.322 g 17.098 g 7.166 g 1.459 g 3.852 g
0.19% 10.1% 51.9% 21.7% 4.4% 11.7% 325 g/min

75 min 0.074 g 3.413 g 15.903 g 6.172 g 1.366 g 3.880 g

0.24% 11.1% 51.6% 20.0% 4.4% 12.6% 325 g/min
87 min 0.128 g 5.604 g 14.852 g 5.331 g 1.304 g 3.289 g
0.42% 18.4% 48.7% 17.5% 4.3% 10.8% 325 g/min
128 min 0.563 g 9.305 g 13.806 g 5.137 g 1.305 g 2.267 g

1.77% 29.2% 43.3% 16.1% 4.3% 7.1% 325 g/min

178 min 2.120 g 10.63 g 11.226 g 4.124 g 0.988 g 1.067 g
7.0% 35.2% 37.2% 13.7% 3.3% 3.5% 28% coating
Machine configuration: 18v Wurster coater, HS nozzle, High-mass flow-up bed plate, no nozzle surround, initial atomizing air pressure 3.5 bar.

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1008 35. DEVELOPMENT, OPTIMIZATION, AND SCALE-UP OF PROCESS PARAMETERS: WURSTER COATING

TABLE 35.3 Sieve Analysis (During Spraying With Nozzle Surround)

Time 130 140 160 180 1100 Pan Comments

0 min 0.0065 g 1.358 g 29.037 g 5.266 g 0.24 g 0.008 g

0.02% 3.8% 81.% 14.8% 0.07% 0.2% Starting material
4 min 0.0052 g 0.094 g 26.846 g 3.747 g 0.246 g 0.787 g
0.02% 0.30% 84.6% 11.8% 0.8% 2.5% Begin spray
33 min 0.0061 g 0.223 g 23.958 g 4.701 g 0.749 g 1.451 g
0.02% 0.72% 77.1% 15.1% 2.4% 4.67% 11.5 kg applied

68 min 0.020 g 1.382 g 22.495 g 5.619 g 0.826 g 1.614 g

0.06% 4.3% 70.4% 17.6% 2.6% 5.1% 26 kg applied
99 min 0.0359 g 3.500 g 20.138 g 4.651 g 0.749 g 1.018 g
0.12% 11.6% 66.9% 15.5% 2.5% 3.4% 39 kg applied
130 min 0.0902 g 7.147 g 24.915 g 5.297 g 0.703 g 0.759 g
0.23% 18.4% 64.0% 13.6% 1.8% 2.0% 28% coating

Machine configuration: 18v HS Wurster coater (with nozzle surround), “B” down bed, “G” up-bed plate, atomizing air pressure 3.5 bar throughout.

FIGURE 35.20 Acetaminophen—28% coating using standard 18v FIGURE 35.21 Acetaminophen—28% coating using standard 18v
Wurster coater (763 magnification). Wurster coater (1543 magnification).

pattern. Recall that this region is high in liquid content expected to be lower, due to the increased particle size.
and atomizing air velocity, which can lead to attrition This type of problem should be resolved or batch-to-
of fragile substrates. batch reproducibility (dissolution) will be difficult to
The HS nozzle, for high-capacity spray rates, was achieve. In this example, the atomizing air pressure
used so that the influence of the perforated plates and had to be reduced to as low as 2.2 bar to slow the gen-
HS nozzle surround could be seen independently of a eration of fines, which ultimately became embedded in
key variable, such as nozzle type. In the SEMs, at both the film.
the low and higher magnifications, the fines generated In Figs. 35.23 and 35.24, the partition plate was
early in the spray process due to the high velocity replaced with a more uniformly permeable type “G,”
atomization air are readily seen embedded in the film. and the HS nozzle surround was installed. The sur-
They are present to the extent that the final particle size round acts to keep the particles away from the highest
is substantially larger than the starting material (see velocity and densest droplet region of the spray pat-
Table 35.2). The resultant porous nature resulted in a tern, as described previously. The result is that the
faster drug-release rate (Fig. 35.22). This occurs in spite atomization air pressure could be maintained at 3.5 bar
of the fact that the total surface area per unit mass is throughout the spraying process, with only minimal

III. DESIGN, DEVELOPMENT AND SCALE-UP OF FORMULATION AND MANUFACTURING PROCESS

 35.8 SCALE-UP OF WURSTER PROCESSING 1009
Dissolution profile–sustained release APAP generation of fines, as evident in the SEMs. The average
18″ Wurster–Standard versus HS particle size after coating was smaller than when using
100
the standard Wurster configuration because fewer fines
Percent dissolved

80 were generated and embedded. This resulted in a less

porous film, and slower drug release, as seen in the
60
accompanying dissolution profile shown in Fig. 35.22.
40 An additional benefit was a reduction in process time,
due to the ability to apply the coating at a higher spray
20
rate (approximately one-third faster).
0 For the experiment involving the standard Wurster
0 1 2 3 4 5 6 7 8
system, the total process time of 3 hours and 39 min-
Time (h)
utes is not unreasonable for production. However, in
18″ Standard Wurster 18″ HS Wurster the sieve analysis, the coarsest fraction disappears
early in the process, and well into spraying the fraction
FIGURE 35.22 Dissolution profile for fine granular acetamino- of material defined as “fines” continues to increase to
phen batches coated in 18v standard and HS Wursters with 28% w/w nearly 20%. Ultimately, these fines are agglomerated
coating of AquaCoat ECD (FMC BioPolymer).
to the main fraction of material, and their final content
is marginal. However, the average particle size shifts
to the coarse side, with more than 40% retained on the
40 mesh screen compared with only 18% found in
the batch coated using the HS components.
The process time using the HS components was
reduced by 48 minutes or approximately 30%. In addi-
tion, the near absence of fines seen in the SEMs will
lead to improved batch-to-batch reproducibility in the
dissolution profile.

35.8 SCALE-UP OF WURSTER

PROCESSING
“Is the process scalable?” is a reasonable and com-
mon question. The answer typically begins “yes, but . . .”
The ability to scale a process successfully depends on
FIGURE 35.23 Acetaminophen—28% coating using 18v HS the magnitude of difference between the small and
Wurster coater (763 magnification). larger-sized batches. In the laboratory, development
may take place with a batch size smaller than 1 kg. This
size of equipment should be considered to be for
screening purposes, without expecting that the formu-
lation developed on the small scale will behave identi-
cally in pilot or production equipment. The batch size
is small, the particle trajectory is comparatively short,
the bed depth is shallow, and the spray nozzle does not
use much compressed air to produce droplets. The
mass of the batch is likely to be insufficient to manifest
problems with attrition due to fragility of the substrate.
Mass flow inside of the partition during spraying, can-
not match that of larger equipment, so the amount of
coating or layer applied to the substrate will not be in
the same proportion as in larger equipment.
Experience has shown that the biggest hurdles in
scale-up occur when moving from a 6v Wurster coater
(or smaller) to a 7v, 9v, 12v, or 18v Wurster coater.
FIGURE 35.24 Acetaminophen—28% coating using 18v HS Usable working volumes (courtesy of Glatt Air
Wurster coater (1523 magnification). Techniques, Inc., Ramsey, NJ) are 3.6 L (6v Wurster

III. DESIGN, DEVELOPMENT AND SCALE-UP OF FORMULATION AND MANUFACTURING PROCESS

1010 35. DEVELOPMENT, OPTIMIZATION, AND SCALE-UP OF PROCESS PARAMETERS: WURSTER COATING

coater), 8.3 L (7v), 13.6 L (9v), 37 L (12v), and 102 L (18v). sizes exceeding 5 kg. Smaller batch sizes may be used,
In addition to the increase in volumetric capacity, the and the relationship of the process variables may be
partition length increases, the partition diameter seen, but very small batches may not be indicative of
increases, bed depth and mass effects increase, particle what is seen on a somewhat larger scale. Ideally, design
trajectory increases, and the spray-nozzle dimensions of experiments should be employed to quantify the
increase (in size and consumption of atomizing air vol- magnitude of impact for the key variables.
ume) to accommodate the increased spray rate. High As in any process, there is a multitude of variables to
kinetic energy from the combination of high atomizing consider, including batch size, spray rate, atomizing air
air velocity and volume may be a significant, and in pressure/volume, process air volume, and tempera-
many cases unpredictable, factor in scale-up. tures (product, process air, and dew point). There are
What should be evident is that scaling from any of also equipment considerations—down-bed and up-bed
the laboratory-sized Wurster systems to the pilot-scale orifice plate configuration, partition height above the
18v Wurster coater is the true “scale-up,” presenting plate, and the spray nozzle type, as mentioned
the most significant challenges. Thereafter, production previously.
equipment typically incorporates multiples of the parti- Some concerns are not readily apparent. Equipment
tions and spray nozzles used in the 18v Wurster. may increase in size and batch capacity, but not all com-
In reality, this “scale-up” should be referenced as “scale- ponents increase proportionally. For example, outlet air
out.” Parameters such as process air volume, atomizing filter surface area actually decreases in proportion to
air pressure (and volume), spray rate, and temperatures batch size. This is problematic for products using layer-
derived for the 18v Wurster are typically replicated on a ing or coating materials that cause filter media to blind.
“per partition” basis in the production equipment. When a filter becomes occluded, process air volume is
Hardware components are also duplicated—the spray affected, particularly during shaking. The Wurster pro-
nozzle, partition diameter, and orifice plate configura- cess requires process air flow to be continuous—it is not
tions (permeability in both the up- and down-bed interrupted to shake fines back into the bed. As a conse-
regions) are the same in both scales of equipment. quence, when it is time to shake the filter, air flow is
Partition length is nominally longer, therefore the stopped, but only through the filter segment to be
increase in bed depth is usually inconsequential pro- shaken. In contemporary machines, this means that the
vided that the 18v Wurster coater is used at or near totality of the process air volume must now pass
its working capacity. Examples of the pilot-scale 18v, through the remaining half of the filter media. If the dif-
and production scale 32v HS Wurster coaters are shown ferential pressure across the filter is high, there will be a
in Figs. 35.2 and 35.25. precipitous drop in process air volume. A consequence
Successful scale-up in Wurster processing depends is that the velocity of substrate inside of the partition
on a number of factors. At a minimum, development will momentarily drop, which could cause agglomera-
scientists should have a good understanding of the tion. In an extreme case, with multiple partition
robustness of the process in laboratory equipment. production-scale Wurster systems, a severe drop in total
Experiments bracketing the operating ranges of key process air volume may cause one of the partitions to
parameters should be conducted, preferably on batch stop “spouting.” Under this circumstance, this partition
may be filled from the top by the remaining spouting
partitions. Even after shaking stops, and the process air
volume returns to its set point, the filled partition may
not evacuate. Atomizing air from the spray nozzle
inside of the partition will create a small void, into
which the liquid continues to be sprayed. However, the
material surrounding this void is static, and is quickly
over-wetted. Eventually, agglomerates and wet mass
will make their way outside of the partition, and sam-
pling will reveal a severe problem. By this time, the
batch is essentially lost. Ultimately, if laboratory experi-
mentation has shown that the spray material has a pro-
pensity to cause filter blinding, even to a comparatively
limited extent, filter media must be a strong consider-
ation during scale-up activities.
Relative to the environment in which spraying takes
FIGURE 35.25 Inside view of 32v HS Wurster coater. Source: place (the coating zone), the particle size of the sub-
Photograph courtesy from Glatt Air Techniques, Inc. strate is becoming smaller in scale-up. This may result

III. DESIGN, DEVELOPMENT AND SCALE-UP OF FORMULATION AND MANUFACTURING PROCESS

 35.8 SCALE-UP OF WURSTER PROCESSING 1011
in a higher coating efficiency (coating material applied of lesser benefit in small Wurster equipment. The sur-
with respect to the theoretical or expected yield) in round prevents the flowing substrate from entering
pilot and production equipment versus the laboratory the spray pattern until it is more fully developed. This
scale. If the product is coated on a weight basis, the eliminates local over-wetting, preventing agglomera-
higher coating efficiency may lead to a change in dis- tion in this region. A consequence is that scale-up in
solution (for sustained release coatings, it would the Wurster process may not necessarily mean a signif-
decrease). icant increase in process time, which is a common
occurrence in many types of processes.
35.8.1 Batch size
As mentioned previously, the maximum batch size 35.8.3 Droplet size and nozzle considerations
for a Wurster process is identified as that which occu- Spray conditions represent a challenge for develop-
pies all of the volume outside of the partitions with ment personnel in scale-up. Small Wurster coaters tend
them at rest on the orifice plate. There is some flexibil- to use the same size nozzle (Schlick 970 series), and as
ity in batch size—the process will still work when the product proceeds through small increments in batch
using less than the maximum working capacity. size (from 6v to 7v or 9v units with batch capacities rang-
However, it has been seen in scale-up that batch size, ing from approximately 1 to 10 kg), only atomization air
within a given insert size, may impact finished product pressure needs to be increased to accommodate the
properties. Therefore, it is recommended that the pro- somewhat faster spray rate. However, when shifting to
posed finished batch size be close to the working the 12v or 18v Wurster coater, the potential increase in
capacity of the larger Wurster (approximately 75 100% spray rate forces operation of this small nozzle beyond
based on the finished product density). its performance envelope, and a move to a larger nozzle,
with a higher atomizing air volume, is mandated.
Droplet size is principally related to the air-to-liquid
35.8.2 Spray rate mass ratio, and attempting to keep this in the same
The spray rate for a product is typically a key vari- range in the scale-up efforts is recommended. However,
able, from several perspectives. The first is economic— there is a caution to its use. In some calculations, the air-
long processes result in high manufacturing costs. to-liquid mass ratio may result in atomizing air pressure
Lengthy processes also increase the likelihood of pro- values that are outside of the nozzle’s recommended
blems during the process, particularly nozzle-port clog- operating range. The spray nozzle performs two differ-
ging (there are some hardware alterations that can be ent functions: (1) to produce droplets for the coating or
made to eliminate or at least mitigate this potential layering application, and (2) to attempt to prevent the
problem). Spray rate also dictates the rate of accumula- nozzle from fouling. The atomizing air at the tip of the
tion of solids by the batch, and this is important for fin- nozzle helps to clear the tip of material forming as a
ished dosage form performance. Coated product is result of drying that occurs between the interface of the
nearly always stronger than uncoated core material. If liquid and the very dry atomizing air. If the atomizing
the core sloughs fines, these may be incorporated into air pressure (below approximately 1.5 bar) and volume
the layers of film, altering its release properties (release is too low, the velocity of the atomizing air will be insuf-
will be governed more by imperfection than by the ficient to remove dried film from the nozzle tip. This
intrinsic properties of the film). Consequently, it is a material could eventually grow to a size that impacts or
goal in scale-up to maximize the solids addition rate. diverts the spray pattern, causing a sudden and severe
Drying capacity is a key component in scale-up. The amount of agglomeration. In addition, the atomizing air
starting point for estimating the spray rate is related to velocity must be sufficient to permit shearing of the liq-
the increase in process air volume (at the same temper- uid to produce droplets. If the pressure and velocity are
ature and dew point as used in the laboratory scale), too low, agglomeration will be unavoidable.
not the increased batch size. However, the rate- At the other end of the spectrum, if the air-to-liquid
limiting factor may not be completely related to the mass ratio calculation yields an atomizing air pressure
increase in drying capacity offered by the larger exceeding approximately 3.0 bar in the pilot-scale
Wurster system. Irrespective of the physical properties Wurster, attrition of the core material may be the conse-
of the liquid, the application rate will more likely be quence. Kinetic energy is represented as E 5 1/2 mv2,
strongly controlled by the interface between the accel- where “m” is mass and “v” is velocity. Assume a scale-
erating core material, and the atomized droplets (coat- up from a 7v Wurster machine (laboratory scale), with a
ing zone). There may be significant benefits in using batch size of approximately 5 kg, to a pilot-scale 18v HS
the spray nozzle surround described previously as HS Wurster machine, with a batch size of approximately
Wurster equipment, which is not typically used or is 60 kg. At 2.0 bar atomizing air pressure, the 970 series

III. DESIGN, DEVELOPMENT AND SCALE-UP OF FORMULATION AND MANUFACTURING PROCESS

1012 35. DEVELOPMENT, OPTIMIZATION, AND SCALE-UP OF PROCESS PARAMETERS: WURSTER COATING

(laboratory) nozzle uses about 2.1 cfm of compressed coater, the target value for the three-partition 32v
air. At the same pressure, the HS nozzle consumes Wurster coater would be 2100 cfm, as previously stated.
nearly 30 cfm, or about 14 times that required for the Initial fluidization with the desired batch size may
laboratory batch. The atomizing air velocities are essen- result in a tilted bed (higher in the rear of the insert
tially the same—both operate at supersonic speeds at than in the front) if product differential pressure was
this pressure. If constant air density is assumed, the insufficient to cause the air to be uniformly distributed.
kinetic energy equation shows that the material in the Raising the partition height somewhat would increase
pilot-scale equipment will be exposed to nearly 14 times the mass flow in the up-bed region, potentially increas-
more energy than the laboratory batch. For most appli- ing overall product differential pressure. If this change
cations using either water- or solvent-based materials, were insufficient, a second approach would be to use a
an atomizing air pressure of 1.8 3.0 bar is sufficient. less permeable down-bed plate. Both of these alterna-
tives are preferred to increasing the process air volume.
The consequent elevated spout height may enhance the
35.8.4 Process air volume potential for attrition, due to collision with the inside
Process air volume is also a key factor in scale-up, components of the filter housing.
providing three major functions. First, it delivers heat to For multiple partition production Wurster systems, it
the product, for evaporation and removal of the coating is prudent to optimize the fluidization pattern prior to
application medium. Second, and perhaps more signifi- actually producing a batch. A “mass flow study,” which
cantly, it strongly affects the fluidization pattern. For involves bracketing of process air volume and partition
scale-up, approximately the same air velocity through height for a set of orifice plates and batch size is recom-
the partition plate for both sizes of inserts is recom- mended. The first step is to configure the Wurster insert
mended. The increase in overall air volume will then be with a set of up- and down-bed orifice plates. The initial
principally related to the increase in the partition plate partition height for the trial would be set at the lowest
area through which the fluidization air will flow in the value selected for the study. Finally, the insert is posi-
larger machine. “Scale-up” generally refers to increasing tioned in the machine tower, and process air is drawn
batch size and equipment geometry from small (6v, 7v, 9v, through it. The range of process air volumes to be tested
and 12v Wurster coaters) to the pilot-scale. Partition should bracket the air volumes to be used for all steps
diameter length increases, up to and including the 18v of the process. At each of the selected air volumes, the
Wurster coater. Beyond the 18v Wurster coater the con- product differential pressure (dP product) should be
cept of “scale-out” may be more applicable, and scaling recorded. These will be the baseline contributions of the
to 32v, 46v, or 55v Wurster coaters is more direct. The orifice plates. When the process is repeated with a batch
larger inserts use multiples of the same diameter parti- in the insert, the difference between the total dP product
tion and spray nozzle found in the 18v Wurster machine. and the baseline will reflect the “mass flow” in the
Therefore, the increase in air flow would be a multiple insert. The goal is to identify the maximum product con-
of the number of partitions (700 cfm in the 18v would tribution, with a minimum of disruption to the fluidiza-
lead to a target air flow of 2100 cfm in the three-partition tion pattern. An example is shown in Figs. 35.26 and
32v Wurster machine). 35.27. In Fig. 35.26, the air volumes tested are 1250, 1500,
The final manner in which the air volume impacts 1750, 2000, 2250, and 2500 cfm. At each increase in air
the process in scale-up is also related to the fluidization volume, there is a slight increase in product differential.
pattern. In multiple-partition Wurster systems (such as
the 32v and 46v coaters), distribution of the process air
across the entirety of the product container is a function
of several factors. Orifice plates in both the up- and
down-bed regions are selected based on the size, den-
sity, and surface properties of the materials being pro-
duced. As stated previously, the goal is to have the
process air delivered to the product bed, such that the
material in the down bed is in “near-weightless suspen-
sion” or behaving like a fluid. To achieve an essentially
level surface requires a minimum of pressure across the
down bed. This pressure is the result of several factors:
core material quantity (initial batch size); partition
height (the influence of the Venturi effect); orifice plate FIGURE 35.26 Product differential pressure in an empty 32v HS
configuration; and finally, process air volume. For Wurster coater fitted with type “B” and “G” orifice plates (air
example, if 700 cfm were used in the 18v Wurster volumes displayed are in cfm).

III. DESIGN, DEVELOPMENT AND SCALE-UP OF FORMULATION AND MANUFACTURING PROCESS

 35.8 SCALE-UP OF WURSTER PROCESSING 1013
Overall, the pressure contribution from the plates ranges
from about 17 to 55 mmWC. Fig. 35.27 shows the impact
of putting a large batch (approximately 250 kg) of pellets
into the insert (note: it is prudent to use a very strong
substrate for these trials because they will be subjected
to mechanical stress for an extended period of time).
With the partition height set at 50 mm, it is evident that
as air volume is increased, the quantity of product in
motion (mass flow) increases. The values for 1250 and
1500 cfm seem to indicate that the air volume is insuffi-
cient to fluidize the entire batch—for the bed is certainly
stagnant in some region at 1250 cfm. At 1500 2000 cfm,
FIGURE 35.27 Product differential pressure in a 32v HS Wurster
the peak-to-trough values indicate a reasonably
coater fitted with type “B” and “G” orifice plates, with a batch (air
stable fluidization pattern. At 2250 and 2500 cfm, the volumes displayed are in cfm).
enlarged peak-to-trough values reveal that some air bub-
ble coalescence is occurring, resulting in some degree of
back flow or turbulence in the down bed. This is not
necessarily negative—a periodic bubble bursting
through the down bed, along the wall of the product
container, gives assurance that the product is not stag-
nant in this region. The air volume selected for this par-
ticular process was 2250 cfm. In addition to the
fluidization properties, the high volume of air permits
higher rates of heat and mass transfer, which translate
to faster spray rates and a shorter process time.
Higher partition heights, common for pellet coating,
were also tested (60 and 70 mm). Interestingly, the
peak-to-trough values widen at lower air volumes with FIGURE 35.28 Product differential pressure in an empty 32v HS
Wurster coater fitted with type “B” and “H” orifice plates (air
higher partition heights. It is speculated that the
volumes displayed are in cfm).
strength of the venturi at the base of the partition,
which draws product into the up bed, is either lessened
or defeated, allowing air bubbles to move only verti-
cally in the down bed.
The previous example is effective for coating or layer-
ing materials that do not exhibit tackiness in the down
bed—they have a low surface coefficient of friction.
Unfortunately, there are many products that display
tacky behavior, and these same processing conditions
may permit stalling of the batch in some region. Some
users may try to counter this behavior by increasing the
overall process air volume. However, it is likely that the
majority of this increase will flow through the partition,
and this region is not the source of the problem. It FIGURE 35.29 Product differential pressure in a 32v HS Wurster
would be desirable to divert more of the process air vol- coater fitted with type “B” and “H” orifice plates, with a batch (air
volumes displayed are in cfm).
ume to the down-bed region. A method for achieving
this would be to replace the up-bed plates with ones
that are less permeable. In this manner, at the same air now considerably higher. In this case, the range is from
volume, more of the process air is diverted through the approximately 30 to 125 mmWC. When the same batch
down bed, making it more vigorous or turbulent. weight is added, stable down-bed flow occurs at much
Figs. 35.28 and 35.29 illustrate a mass flow study that is lower air volumes—somewhere between 1250 and
a consequence of this change. The “B” down-bed plate 1500 cfm. The peak-to-trough values for higher air
remains, but the “G” up-bed plates were replaced by volumes are very broad compared with the previous
the less permeable “H” plates. Once again, the partition example, indicating significantly more turbulence in the
height is set at 50 mm for the test. What can be seen is down bed. The selected air volume for this trial was
that the dP product contribution of the plates alone is 2000 cfm. The turbulence was sufficient to avoid

III. DESIGN, DEVELOPMENT AND SCALE-UP OF FORMULATION AND MANUFACTURING PROCESS

1014 35. DEVELOPMENT, OPTIMIZATION, AND SCALE-UP OF PROCESS PARAMETERS: WURSTER COATING

regional bed stalling with the tacky coating material, 2 m. Product may also collide into the outlet air filters
and the relatively high air volume allowed for a reason- or other mechanical components of the machine.
ably high spray rate. Further scale-up to the 32v or larger Wurster coaters
from the 18v is somewhat simplified because bed depth
is about the same, and the objective in fluidization is to
35.8.5 Process air and product temperatures keep particle velocity similar in larger equipment to
As is typical of the laboratory scale, the temperature that used in the pilot-scale machine.
of the process air is generally adjusted to maintain a
constant product temperature, and as spray rate is
increased, the process air temperature is adjusted 35.9 SUMMARY
upward. If laboratory trials were conducted using a con-
servative or low product temperature, it may be possi- The Wurster system is widely used for layering and
ble to explore a higher product temperature in the coating because of its ability to apply high-quality films
production-scale equipment to improve productivity. to a broad range of substrates. The orifice plate configu-
However, it is strongly recommended that this is not ration in combination with the partition height and pro-
done if the impact of higher product temperature on fin- cess air volume, organize the substrate in close
ished product attributes has not been explored, particu- proximity to the spray nozzle. Droplets of coating liquid
larly for latex-coating materials. travel only a short distance, and are applied cocurrent
with the accelerating substrate. Productivity is related
to the presentation of substrate surface area per unit
35.8.6 Mass effects time with respect to this quantity of liquid. Layering
The influence of larger batch size (or mass effects, as and/or film coating may be conducted using solutions
they are referred to), is more difficult to predict. In or suspensions of materials in liquids comprising
small-scale equipment, the product must be robust—if organic solvents or water. The interaction between
it must be treated cautiously in laboratory equipment, droplets and substrate is so rapid that materials applied
scale-up to pilot and production machinery will be using even the most volatile solvents are not subject to
nearly impossible. In Wurster processing, the big step spray drying—they are high in quality, and their release
in scale-up is from laboratory equipment (6v, 7v, 9v) to is governed by their intrinsic properties, not by imper-
the pilot-scale 18v Wurster machine. In small machines, fections in the film. In addition, within limits, materials
bed depth rarely exceeds 200 mm, and fluidization can be sprayed from a molten state, congealing onto the
height (substrate travel out of the partition) is princi- surface of the slightly cooler substrate. As a production-
pally limited by machine dimensions to 1.25 m or less. scale batch processor, the Wurster has a moderate batch
In the 18v unit, bed depth may range up to 600 mm, capacity (up to approximately 600 kg), and is efficient in
and fluidization spout height can approach or exceed terms of material balance and productivity.

III. DESIGN, DEVELOPMENT AND SCALE-UP OF FORMULATION AND MANUFACTURING PROCESS