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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5395_Библиотеки_им_академика_М_И_Перельмана
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Optimization of Tablet Coating 111
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(ii) Perforated Coating Pan
Perforated pans are mainly divided into two types: partially perforated
pans and fully perforated pans. The coating system contains process airflow
controllers and spray nozzles along with a perforated drum placed horizontally.
The perforated pan coating unit provides an efficient drying capacity compared
to the conventional pans. Utilizing blades and baffles increases friction between
pans and the core material that results in a high amount of dust production
during coating. Thus, inventors concentrated on the application of perforated
pans to enhance air transport to the core material and subsequently upsurge the
drying and mixing efficiency. Hostetler developed a side-vented pan in which
the peripheral wall was modified with perforations, and at the lower peripheral
region, an air supplying inlet was positioned. The modification was intended to
enlarge the contact area of the substrate with the coating solution and increase
air transfer and core movement [1]. Glatt coater, Hi-coater system, Dria coater
pan and Accela Cota system are the main types of perforated coating systems.
The underlying principle of the pan coating process is complex which
makes the prediction of the performance of a coated product quite difficult.
For achieving desirable coating, several aspects need to be considered such as
tablet properties, formulation components of tablets, coating formulation and
processing conditions during coating. A proper balance needs to be established
between the spray rate of the coating material and the thermodynamic drying
settings (temperature, humidity and airflow). Combined determination of liquid
flow rate and drying conditions leads to adequate solvent evaporation and
helps to obtain aesthetically acceptable and uniform coat. The coating factors
affecting the pan coating can be broadly classified as pan coater factors,
spraying system factors, thermodynamic factors, coating formulation factors
and substrate/core factors [7]. The classification of factors affecting the coating
process in a pan coater is represented in Fig. 3.
Coating Formulation Factors
The coating formulation factors affecting the pan coating process are the type
of excipient, solvent volatility, solid content, surface tension and viscosity of
solution/suspension. The solid content in the coating solution should be higher to
lessen the coating time. However, very high solid content also results in a highly
viscous coating solution which can cause issues in the coating process. Moreover,
with higher solid content, the surface of the film coat might also get affected if
the drying conditions or the spray droplet are not adjusted adequately. Conversely,
low solid content in coating solution leads to the increased relative humidity in
the coating pan that results in poor drying efficiency. The droplet characteristics
from the spray gun get affected by the viscosity of the formulation and the changes
in solid content; thus, to optimize the spray gun parameters, the solid content
needs to be studied. There is a strong interdependency between formulation factors
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Fig. 3 Factors affecting coating process in a pan coater
and coating process parameters; the DOE approach can be implemented to study
the effect of the coating process variable and formulation variables together [8].
Through experiments, the CMAs are recognized, and after the ideal formulation
characteristics are established, they can be kept constant.
Core/Substrate Factors
The substrate aspects such as density, size, shape, friability, hardness, porosity,
surface hydrophobicity and surface roughness can influence the film coating
procedure. The mixing dynamics and ease of coating inside the pan can be affected
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by the size and shape of the substrate. The coating of a small round-shaped tablet is
simpler compared to oval- or oblong-shaped tablets [9]. In the case of odd-shaped
substrates, high coating levels are required to ensure the covering of edges properly
and achieve uniform coating and desired release. There is a requirement of longer
coating runs for tablet surface coverage of odd-shaped substrates [10]. Moreover, to
prevent erosion or chipping of tablets during the coating process, the tablet strength
parameters such as hardness and friability need to be established. To tolerate the
stress throughout the pan coating process, the tablets having adequate strength
must be selected. For establishing the tablet strength, measurement of only tablet
hardness can be deceptive as it is a measurement based on geometry of the tablet
alone. Measurements of parameters such as Young’s modulus, tensile strength of
tablet and tablet fracture energy are more accurate measurement parameters than
the present USP hardness measurement. Tablets having tensile strength ≥1MPa
and 15% porosity have desired hardness that can endure several types of pressures
underwent bya substrate duringthe pan coating process. The tabletdensity, porosity,
surface roughness and hydrophobicity influence the film adherence on the tablet
surface and the ease of applicability. Selection of the coating solution composition
should be done on the basis of tablet surface characteristics. While conducting the
coating operation, some of the substrate factors which are the CQAs for the film
coating quality should be identified and kept constant.
Pan Coater Factors
Pan Load
Estimation of the batch size is essential when a particular product is to be coated for
the first time. The coating pans usually have a definite brim volume capacity. The
brim volume is the volume capacity of the pan if loaded to the verybottom of the pan
opening. The acceptable operating range for film coating is using a fill volume of
50–95% ofthe brim volume. A batchsize towards higher brim volume range helpsto
maximize the batch throughput and also enhances the drying capacity as the issue of
bypass of inlet air directly to the exhaust plenum is circumvented. The higher batch
size aids proper drying as the inlet air passes through the tablet bed in a proper
manner. In the case of an underloaded pan, the pan walls and baffles get directly
exposed to the spray which leads to a build-up of coating material on these exposed
surfaces and sticking of the substrate on them. However, occasionally after for some
of the products which undergo high weight gain or change in product movement
after coating may demonstrate issues with the acceptable pan load decided initially.
Thus, to optimize the pan load is necessary [11].
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Pan Speed
For optimizing the coating quality, the mixing of the tablets should be such that
each tablet goes under the spray zone for the equal time duration. If there is an issue
in tablet mixing, then the first parameter to be evaluated is pan speed. Ideally, the
lowest pan speed providing a continuous product flow via the spray zone should
be selected. Selecting such speed will keep minimum attrition between the tablets
and also allow the uniform application of the film coat. The product mixing can be
evaluated by recording the number of tablet pass via spray zone per unit time by
using radioactively marked tablets and a counter attached on the spray bar. Also,
tablets of different colours can be used to perform the mixing studies. After placing
different colour tablets in differentzones, the impact of tablet speed can be evaluated
by taking tablet samples at set time intervals. After determining the pan speed, the
scale-up can be done by duplicating the peripheral edge speed. By multiplying the
small pan speed with the ratio of the small pan to large pan diameter, the scale-up
can be done.
Baffle Size/Number/Type
The key function of baffles is to move the substrate between the front and back
of the pan during the coating process and enable uniform mixing. Usually, the
coating pans are designed with a standard design baffle which works properly for
major products. There is a requirement of different baffle designs for substrates of
unusual sizes or shapes. When working with smaller batches, the use of reduced
baffle size is necessary. If the standard baffles are used for small batch, then the
product movement will be non-uniform, and the spray gun-to-bed distance will also
vary. Whenever the fill volume is lesser than 75% of the brim volume, a small batch
baffle usage is recommended.
Spray-Related Factors
Spray Gun Design
The most extensively employed spray gun design is a pneumatic spray gun. In
pneumatic spray gun, the atomization takes place by impingement of compressed
air stream on liquid stream after emerging from nozzle. The utilization of pneumatic
spray guns permits the usage of variable spray rates. Previously, hydraulic spray
guns were widely utilized, though they do not provide flexibility in spray rates. For
changing the spray rate, an alteration in the fluid nozzle is often required. In some of
the spray guns, the spray nozzle configuration and the air cap produce a programmed
ratio of atomization to pattern air. In other guns, distinct controls are provided for
controlling the pattern air and volume of atomization. This permits adjustment of air
pattern or atomization without changing the solution nozzle or air cap. The droplet
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size of the spray gets controlled by the volumeof atomization controls, and the spray
width is controlled by the pattern air volume controls. The solution stream breaks
into droplet size by atomization air, whereas the pattern air flattens the spray into a
fan-shaped pattern.
Quantity of Spray Guns
An adequate quantity of spray guns is required to provide uniform exposure to the
entire product bed. To achieve uniform coating, the spray zone must ideally involve
the front to the back edge of the product bed. Adding a greater number of spray
guns does not assure that an increased spray rate can be attained. The need for
adding spray guns is justified only if the prevailing guns are inadequate to cover the
entire tablet bed from front to back edge. The set-up of the spray guns must be such
that wide spray patterns can be obtained without overlapping. If the spray pattern
overlaps, then it can cause overwetting of the product bed [12].
Spray Rate
The spray rate is an imperative processing parameter that has a significant impact
on the coating process thermodynamics. If the API or the formulation is sensitive or
not very stable in high moisture conditions, then the spray rate is a very important
aspect. The tablet bedenvironment and the rate of solventevaporation are influenced
by the spraying rate of the coating solution. While determining the spray rate, some
of the factors such as spray pattern width, solution viscosity and product movement
should be considered. The spray pattern width will be similar to the spray gun
spacing if the spray pattern width is set up correctly. The spray rate per gun can
be increased by choosing the broader spray pattern width (spray width that does
not overlap the adjacent spray pattern). The solution viscosity affects droplet size
distribution. Higher viscosity leads to decreased ability of spray gun to produce
suitable droplet size distribution. Higher viscosity limits the highest spray rate
that may be utilized. In the case of product movement, with the faster and more
consistent the product movement, higher spray rate is achievable [13].
Gun-to-Bed Distance
The gun-to-bed distance is the total distance amongst the spray nozzle tip and the
surface of the cascading bed of substrate. It can be defined as the distance covered by
the spray droplets before striking the tablet surface. If the distance between gun and
bed is very low, then it may lead to overwetting of the substrate which may result
in tablet defects such as twinning and surface dissolution. Contrarily, if the gun-tobed distance is very high, smaller droplets reach the substrate which may result in
lesser processing proficiency and defects such as logo infilling and rough surface.
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In a research work done by Pandey et al., various processing parameters were
evaluated to investigate their impact on tablet logo bridging. It was concluded in the
study that gun-to-bed distance and solid content in the suspension were the highly
sensitive process parameters [14]. The typical gun-to-bed distance for productionsized coating pan is 20–25 cm. If the distance is higher than 25 cm, then, ideally,
the inlet process temperature must be decreased so that excessive spray drying can
be circumvented. On the contrary, if the distance is less than 20 cm, then the issue
of shortened evaporation time can be resolved by increasing the inlet or product
temperature reducing the spray rate.
Spray Gun Angle and Uniform Gun-to-Gun Solution Delivery
Preferably, the spray gun angle to the moving bed should be 90
◦
, and the spray gun
must be placed amidst the leading and trailing edges, i.e. middle of the substrate bed.
The substrate may not get proper time to dry if the spray guns are placed too low
on the substrate bed. Contrarily, if they are pointed more towards the leading edge
of the substrate bed, there is a possibility that the spray gets smeared on the mixing
baffles or the pan walls. Moreover, if the spray guns are not positioned at a 90
◦
angle
to the substrate bed, the spray solution might build up on the wings of the air cap
while exiting from the solution nozzle. All the spray guns should supply an equal
amount of coating solution so that uniformity in the coating can be achieved. The
latest inclination in coating systems is towards employing a single pump assorted
for several spray guns. It is mandatory for such systems that calibration should
be executed on fixed intervals for ensuring that all the spray guns will deliver an
equal amount of coating solution. It is highly preferred that the calibration should
be performed with the coating solution itself rather than water as the viscosity of the
coating solution will be significantly higher than that of water.
Thermodynamic Factors
The first law of thermodynamics is the fundamental law that influences the
environment of the coating pan. The evaporation rate of coating solution from
the surface of the substrate is governed by the thermodynamic factors such as
moisture content/humidity, airflow volume and the temperature [15]. A change in
any of above-mentioned parameter will affect the operating conditions downstream;
thus, to sustain equilibrium throughout the coating process, modification in other
processing parameters will be essential. For instance, if the spray rate is increased,
the amount of moisture in the pan increases which leads to a decrease in drying
capacity. Thus, on increasing the spray rate, to increase the drying capacity, factors
such as temperature and airflow volume need to be adjusted. To evaluate the
thermodynamic environment, parameters such as tablet bed temperature and relative
humidity can be monitored, and the influence of drying or spraying factors can
be understood. As changes in thermodynamic parameters often have a noteworthy
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effect on the coating quality, it is necessary to understand the relationship between
coating process parameters and thermodynamic factors.
Temperature
The temperature control in the coating process can be achieved by controlling the
exhaust, inlet or substrate/product temperature. Controlling the inlet air temperature
is the extensively used process control parameter. The process control established
on the product or exhaust temperature often occurs at a slower pace due to the heat
sink effect of tablet bed. In inlet temperature control, there is a slight drop in exhaust
temperature after the spray is started. The drop in temperature occurs as a result of
evaporative cooling. All the product, exhaust and inlet temperatures are important
as the drying of moisture content from the spray droplets occurs by both conduction
(due to product temperature) and convection (due to process air). Several factors
have a control on the desired exhaust temperature, for instance:
(a) Product temperature limits: The product must be kept under temperature
boundaries if it displays instability issues at higher temperatures. It is very
crucial to maintain this temperature limit during preheating of tablet bed as
at that time evaporative cooling will not occur and if the pan is not constantly
rotated, then the product may not achieve uniform heat. Also, after stopping the
spray, the temperature of the product might increase immediately owing to the
loss ofthe evaporative cooling effect. Thus,after the spray cycle gets completed,
there might be a need to start a cool-down cycle immediately.
(b) Coating solution characteristics: If the coating gets tackier on drying, then
the product or exhaust temperature must be increased to prevent overwetting
defects.
Vo l u m e
The coating pans employ airflow along with elevated temperatures for evaporating
the coating solvent on the tablets into vapour and transfer it away from the coated
tablets. Usually, the quantity of water vapour that can be withdrawn is proportionate
to the volume of air that passes via the coating pan. Thus, it would be beneficial to
utilize high airflow to achieve maximum evaporative capacity. Ideally, the process
air volume must be accustomed to the highest volume that can yield a nonturbulent
laminar flow. A nonturbulent flow is desired as a turbulent airflow leads to distortion
of the air pattern. The manufacturers generally mention the maximum airflow
which produces an acceptable turbulence level. The capacity of the process air to
hold water vapour increases by heating the air stream. Compared to exhaust air
volume, the inlet air volume is a better marker of the evaporative capacity. This is
because the inlet air is the air that passes via the tablet bed and then evaporates the
coating solution from the tablets. Moreover, the exhaust air volume will usually be
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somewhat higher than that of inlet air volume owing to adding up of water vapour
and atomizing air by the spray guns. The inlet air temperature must be as high
as possible if the rate-limiting factor is maximum evaporative capacity. However,
the spray rate is constrained by the spray zone size available and the number of
spray guns, rather than evaporative capacities. Thus, between different-sized pans,
the airflow capacity must be proportional directly to the spray zone. For instance, if
a coating pan with two spray guns with 20-cm spray pattern airflow of 100 CMH
(cubic metres per hour) is used, then in scale-up to a pan comprising of four spray
guns, the airflow of 2000 CMH should be ideally employed.
Humidity
The process air utilized during the coating process is either unconditioned or
conditioned. Day-to-day variations in moisture content exist in either type of air
utilized in the air stream. The spray drying is highly affected by the moisture
content present in the air stream. Thus, there is an emerging trend towards using
the dehumidified air stream. Employing a dehumidified air stream not only provides
steady coating conditions but also offers higher evaporative capacity. This provides
an advantage of achieving higher moisture evaporation at a given temperature
and airflow than a more humid airflow. The dew point temperature is a measure
representing the moisture content of the air stream. A chilled mirror-type sensor
and capacitance are used to measure the dew point temperatures. To maintain proper
drying rate, the dew point should be maintained in a controlled range. Pandey et al.
utilized PyroButton (data logging device) that records temperature and humidity
of the tablets throughout the coating process via relating the end product quality
characteristics such as chemical stability, bilayer tablet delamination when kept
for stability and logo bridging. Pyrobuttons (16-mm-diameter tablet-sized devices)
were allowed to tumble in the tablet bed along with the tablets. On comparing with
the conventional monitoring, the relative humidity measured by Pyrobuttons was
found to be more sensitive. It provides real-time detailed information regarding the
coating process thermodynamics [16]. Some of the case studies are published that
demonstrates the utilization of Pyrobuttons for evaluating coating thermodynamics.
A study was conducted for establishing the film coating spray rate, exhaust
temperature and tablet hardness on delamination of bilayer tablets when kept for
stability. It was observed that high tablet bed relative humidity led to greater
delamination of bilayer tablets [17]. Another case study was done to establish
the effect of various processing parameters on tablet bed microenvironment by
employing logo-bridging defect as the coating quality attribute. It was observed that
the relative humidity of the tablet bed significantly affected the logo bridging, and
suspension solid percentage and gun-to-bed distance that influenced the tablet bed
microenvironment significantly [14].
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Fig. 4 Coating mechanism in top, bottom and tangential spray-fluidized bed coater
3.2 Fluidized Bed Coating
The fluidized bed technology has been employed in the pharmaceutical industry
since a long duration. The process involves placing the feed material into the
processing chamber (a cylindrical column) where it is held in the fluidized state
with the help of carrier gas, usually air. The fluidization of the feed occurs in a
columnar pattern in which the feed raises in the centre of the column because of the
maximum entry of air in the centre. The feed falls in a downward direction towards
the outer wall from where it re-enters the air stream again from the bottom region.
The coating solution is sprayed on the feed via spraying nozzles that are placed in
the top, bottom or side of the chamber. A schematic diagram of the top, bottom and
tangential spray-fluidized bed coating is represented in Fig. 4. Compared to coating
pans, the fluidized bed coating equipment is more efficient of water removal due to
high airflow. The top spray technique is majorly used for odour- and taste-masking
purposes as this technique results in highly porous coating, and it is difficult to
achieve uniform film thickness by top spraying.
In the bottom spray technique, an inner cylindrical chamber (Wurster insert)
is used. Dr. Dale Wurster, in 1959, introduced Wurster system at the University
of Wisconsin. The Wurster technique is widely used for applying rate-controlling
polymers because highly uniform film thickness can be achieved. It is compatible
for delayed coating, enteric coating as well as controlled release coating of tablets. It
is used commercially tocoat particles from size less than 100-μm tablets. In Wurster
coating, the atomized polymer droplets are sprayed from the bottom direction in the
inner column with the product concurrently moving through it. Thereafter, due to
product deceleration and gravitational forces, the particles fall outside the Wurster
insert towards the bottom of the equipment. The recirculation of the feed occurs
continuously which makes multiple passes of the feed via the spray zone. An orifice
plate is there at the bottom of the chamber that is separated into two regions. A high
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volume of air with a high velocity transports the feed vertically inside the Wurster
column. A spray nozzle is placed at the centre of the up-bed orifice plate from
which the atomized coating liquid is introduced on the feed material. The spray
angle ranges from 30
◦
to 50◦with a spray pattern like a solid cone of droplets.
The outside region of the Wurster insert is usually identified as the down bed.
The orifice plate in this area is configured on the basis of the density and size of
the substrate to be processed. The down-bed region also requires airflow to keep
the feed in a near-weightless suspension and to make it travel down rapidly (for
minimizing the cycling time) and thereafter be dragged into the gap of the base
partition. Usually, the larger feed such as tablets necessitates a high amount of air
to create this condition compared to fine particles or pellets. Thus, the selection
of the orifice plate is done accordingly for different substrates. Another processing
variable in Wurster coating is the height at which the partition (Wurster insert) sits
on the orifice plate that manages the feed flow in the horizontal direction into the
coating zone. A relatively lesser gap is convenient for smaller particle coating. The
expansion area height above the Wurster insert should be less for tablets as too high
expansion height may lead to attrition of tablets. The partition height and the orifice
plate need to be optimized as such tablets travel to a very little distance upwards
outside the partition [18].
A Wurster coating equipment is usually recommended only when the film quality
is very significant which is the case most probably in modified-release tablets. The
film coating achieved by Wurster coater is of high quality because of high drying
efficiency. Some of the modifications are done in the Wurster coating process for
tablet coatingsuch as modificationin partition geometry, spray nozzle surrounds and
airflow [19]. The processing variables affecting the tablet coating in Wurster coater
are batch size, fluidization pattern, the impact of fluidized bed on spray pattern,
evaporation rate and product temperature [20].
Batch Size
For Wurster coater, the working capacity is the volume outside the Wurster
insert/partition and the partition at rest on the orifice plate. At the beginning
of the process, the product is loaded only in the outer volume of the Wurster
insert. However, this is done only for pellets or fine particle coating. For tablet
coating usually up to one-half of the volume within the Wurster insert is also
utilized. Around 20–25% of the working capacity is the minimum batch size. For
accumulation of maximum of the coating solution/suspension being sprayed, it is
important that sufficient feed is present in the up-bed region. However, sometimes
in a small volume batch, the coating of partitions’ inner wall may be experienced.
Thus, small volume batch is only recommended when the final volume of the batch
will be significantly higher than the starting volume (e.g. in the case of layering).
When a batch size of approximately half of the working capacity of down bed is
used, nearly maximum efficiency of the coater can be achieved.
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