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This system also oversees and optimizes speed, efciently utilizes tools, assesses
tableting data, documents errors, and performs statistical evaluations throughout the
manufacturing process.
The Fette Perfecta 2000 Cooltex, a tablet press system, enables compression at
lower temperatures by connecting a well-designed press to a cooling unit, allowing
the press to reach temperatures as low as −6°C (Sambhamurti 2005).
6.5 Issues Concerning theProcess ofTablet Manufacturing
6.5.1 Capping
Capping occurs when either the top or bottom of a tablet separates horizontally from
its central section, either partially or entirely, and it separates in a manner akin to a
cap, while being discharged either from the tablet press or through subsequent
handling.
Reason: Capping commonly occurs because air gets trapped within the tablet
during compression, leading to the tablet expanding when it’s ejected from the die
(Remington 2006; Shah 2011).
6.5.1.1 The Causes andRemedies ofCapping Related
toFormulation (Granulation)
Causes
1. Excessive presence of ne particles within the granulated material.
2. Inadequate moisture content, resulting in ineffective binding.
3. Granules are not adequately dried.
4. Insufcient binder quantity or unsuitable binder type.
5. Insufciency or incorrect use of lubricants.
6. Granule mass at an excessively low temperature.
Remedies
1. Eliminate a portion or all of the ne particles using a 100–200 mesh screen.
2. Adequately add moisture to the granules by introducing a hygroscopic substance
like sorbitol, methylcellulose, or PEG 4000.
3. Ensure thorough drying of the granules.
4. Incorporate a dry binding agent like pregelatinized starch, gum acacia, pow-
dered sorbitol, PVP, hydrophilic silica, or powdered sugar to improve granule
cohesion.
6.5.1.2 The Causes andRemedies ofCapping Related toMachine
(Dies, Punches, andTablet Press)
Causes
1. Inadequately polished dies.
2. Punches with signicant concavity or punches featuring beveled edges.
N. N. Jitendra et al.
159
3. The lower punch doesn’t rise above the die surface during ejection.
4. Incorrectly set sweep-off blade.
5. Elevated rotation speed of the turret.
Remedies
1. Ensure thorough polishing of dies. Explore alternative steel or material options.
2. Opt for punches with at surfaces.
3. Set the lower punch appropriately for ejection.
4. Ensure effective ejection by nely tuning the sweep-off blade.
5. Extend the dwell period by decreasing the rotational speed of the turret.
6.5.2 Lamination
The term “lamination” refers to the splitting of a tablet into multiple separate hori-
zontal layers.
Reason: The phenomenon of air getting trapped during compression and subse-
quently released upon ejection becomes more noticeable as the turret speed increases
(Picta 2011).
6.5.2.1 The Causes andRemedies ofLamination Related
toFormulation (Granulation)
Causes
1. Presence of greasy or oily substances within the granules
2. Excessive use of water-repellent lubricants
3. Magnesium stearate
Remedies
1. Make modications to the mixing procedure by adding an adsorbent or absor-
bent material.
2. Decrease the quantity of lubricating substance used or transition to an alternative
lubricant variant.
6.5.2.2 The Causes andRemedies ofLamination Related toMachine
(Dies, Punches, andTablet Press)
Causes
1. Quick relaxation of the tablet’s outer edges as it is ejected from a mold
2. Quick depressurization
Remedies
1. Use dies that have a tapered conguration, where the upper section of the die
bore slopes outward, incline ranging from 3 to 5°.
2. Integrate an initial compression stage, lower the rotational speed of the turret,
and decrease the nal compression pressure.
6 Advances inTablet Production andTablet Coating
160
6.5.3 Chipping
Chipping is the term used to describe the breaking of tablet edges, which can occur
either when the tablet is ejected from the press or during later handling and coat-
ing stages.
Reason: Inadequate machine settings, specically the improper calibration of
the ejection take-off mechanism (Remington 2006).
6.5.3.1 The Causes andRemedies ofChipping Related
toFormulation (Granulation)
Causes
1. Adherence to the punch surfaces.
2. Granules with insufcient moisture.
3. Excessive binding leads to chipping at the base.
Remedies
1. Ensure thorough drying of the granules or enhance lubrication.
2. Add moisture to the granules for plasticization.
3. Incorporate substances with hygroscopic properties.
4. Fine-tune the binding process or employ dry binders.
6.5.3.2 The Causes andRemedies ofChipping Related toMachine
(Dies, Punches, andTablet Press)
Causes
1. Wear on the die’s groove where compression occurs.
2. Conical die (the center of the die is broader than the ends).
3. The punch face’s edge has been reversed inward.
4. Excessive depth of concavity hinders proper compression.
Remedies
1. Polish the die by exposing its open end, turning it around, or obtaining a new one.
2. Rene the die’s surface to achieve a cylindrical shape.
3. Buff the edges of the punch.
4. Minimize the indentation on the punch faces and employ at punches.
6.5.4 The Defect Related totheMachine
6.5.4.1 Double Impression
Double impression occurs exclusively with punches that bear a monogram or some
form of engraving.
N. N. Jitendra et al.
161
Reason: Throughout the compression process, the tablet takes on the impression
of the punch. In specic machines, the lower punch descends without restraint,
briey moves freely, and then ascends along the ejection cam to eject the tablet from
the die. While undergoing this unrestricted movement, the punch may rotate, poten-
tially leading to a fresh imprint on the tablet’s underside, leading to a dual imprint
(Lachman etal. 1986).
Cause: During tablet ejection, the lower punch can spin freely without restriction.
Remedies
1. Include keying within the tooling, which involves inserting a key beside the
punch to align with and hinder punch rotation.
2. More recent presses feature anti-rotation mechanisms that inhibit punch rotation.
6.6 Tablet Coating
Coating plays a signicant role in the manufacturing process of various solid oral
dosage forms like tablets and granules. The main goal of lm coating is to apply a
ne layer of polymer onto the surface of a tablet or granule that holds active phar-
maceutical ingredients (APIs). Recent years have seen over 50% of all pharmaceuti-
cal tablets being subjected to coating. In the present day, manufacturing sugar-coated
tablets is infrequent because the process is intricate and requires a high level of skill
and expertise from operators. Instead, tablets are commonly coated using contem-
porary machinery like drum and pan coaters, employing polymer lms of diverse
compositions (Hemchand etal. 2017). Figure6.4 shows the different types of coat-
ings for tablet.
Fig. 6.4 Types of tablet coating
6 Advances inTablet Production andTablet Coating
162
Abbott Laboratories introduced the initial pharmaceutical lm-coated tablet
for commercial use in 1954. These tablets were manufactured within a uidized bed
coating column using the Wurster principle as the foundation (Ahmed etal. 2021).
6.6.1 Sugar Coating
Within the pharmaceutical sector, sugar-coating tablets are utilized to enhance the
aesthetics, taste, and longevity of oral medications. However, sugar coating has
become less prevalent and has been substituted with polymer lm coating. Typically,
the sugar coating on tablets dissolves easily in liquid environments like gastrointes-
tinal uid due to its water-soluble nature. An objective of sugar coating is to safe-
guard the drug within the tablet and serve as a protective barrier against potential
environmental contamination.
Advantages
• It is not a critical process as compared to lm coating.
• It provides the attractiveness to tablet coating.
• It is easily swallowed due to its sugar-coating mask.
• It is inexpensive compared to other methods.
Disadvantages
• It requires specialized personnel.
• It consumes a long processing time.
• It increases the weight and size of the tablet (Qiao etal. 2010).
6.6.2 Film Coating
There are several methods for applying lm coatings, including spraying a liquid,
immersion, application of a powder via an electrostatic method, or condensing from
supercritical uids. This method has been substituted with lm coating technology
because the sugar-coating approach requires a lot of time. The procedure includes
applying a solution containing polymer, pigments, and plasticizer onto a tablet bed
in rotation, creating a thin and even lm on the tablet’s surface (Bagade etal. 2014).
The selection of the polymer predominantly relies on whether the intended drug
release location is the stomach or the intestine, or on the desired rate of release. The
most commonly used technique for lm coating is liquid spraying, which usually
includes three stages:
• This process involves the application of atomized liquid onto a moving target
surface through spraying.
• It maintains precise control by introducing heated airow to the target surface.
• It achieves the desired coating amount through this procedure (Basu etal. 2013).
N. N. Jitendra et al.
163
6.7 Recent Advancements inTablet Coating Technology
6.7.1 Electrostatic Coating
Historically, a pan-coater system was employed to implement an electrostatic dry
powder coating method for tablets. This approach enables achieving a polished
tablet surface, excellent uniformity in the coating, and controlled release in a par-
ticular solvent grade. The electrostatic coating technique plays a crucial role in
various production elds, such as paint technology, the food industry, metal coat-
ing, and the pharmaceutical sector, particularly in coating solid dosage forms.
Following the principle of electrostatic powder coating, a blend of small granules
and polymers is applied to the substrate surface without requiring any solvent. The
substrate is then heated in an oven for drying, causing the powder mixture to melt
into a lm (Pawar Avinash etal. 2010). Electrostatic dry coating system is shown
in Fig.6.5.
There are two categories of spraying units, determined by the charging
mechanism:
• Corona charging
• Tribo charging
6.7.1.1 Mechanism ofCorona Charging
In this technique, high voltage is applied to a sharp, needle-like electrode (also
known as a charging tip) at the gun’s outlet, which causes electrical disruption and
ionizes the air. The negative ions are picked up by the granular particles as they
travel from the cannon to the substrate. A mixture of electrical and mechanical ener-
gies transports the particles between the substrate and the charging cannon. The
electrical eld can be modied to regulate the design’s size, form, and volume as the
powder is discharged from the gun (Ahmed etal. 2021).
Fig. 6.5 Diagrammatic representation of electrostatic dry coating system
6 Advances inTablet Production andTablet Coating
164
6.7.1.2 Mechanism ofTribo Charging
Tribo charging works based on friction charging coupled with dielectric attributes.
Therefore, neither free ions nor electrical elds exist among the grounded element
and the spray cannon. The repulsion force present between the particles in the tribo
charging cannon is caused by electrical forces. When forces of attraction occur
among the ground substrate and the surrounding space, charged substances can
enter the region, which causes the particles to settle on the substrate, and charged
atom homogeneity on the earthy substrate is caused by mechanical forces. Forces
ultimately become equal because the forces of attraction and repulsion are equal,
which prevents particles from sticking to the substrate and inhibits the thickness of
the coating substance from increasing. Pharmaceutical tablet cores and electrically
nonconducting materials are signicantly more challenging to electrostatically
coating than conventional coating methods (Remington 2006).
The efcacy of powder coating, including transfer efciency, lm thickness,
association, and physical form, is signicantly inuenced by the chemical makeup,
tribo and corona charging properties, electrical resistance, hygroscopicity, uidity,
and shape uniformity. The electrostatic coating method is greatly inuenced by dis-
tance, nozzle shape, and the prior solution composition (Porter 2001).
6.7.2 Aqueous Film Coating Technology
The lm coating method has substituted the time-consuming sugar-coating proce-
dure, which is dependent on the coating operator’s expertise. Due to environmental
and regulatory concerns, aqueous lm coating has substituted the organic solvents
previously employed in this process, such as methylene salt. In addition, the price
for any particular organic solvent is signicantly higher compared to the price of
pure water. Consequently, transitioning from coating with organic solvent to using
aqueous solvent improves the effectiveness of the coating process. The disadvan-
tages of lm coating using organic solvents and the advantages of utilizing aqueous-
based systems have been extensively recognized. As a result of recent advancements
in lm coating technology, aqueous coating is now more preferred instead of the
exception (Ganguly etal. 2022).
Development of Film Coating Formulation
The development of a lm coating may need to be optimized to raise coating dura-
bility, reduce bridging of integrations, enhance coating adherence to the core mate-
rial, or enhance any additional characteristic that the formulator considers to be
lacking. Flexibility, tensile force, and interaction between the lm and the tablet
interface are the three main variables that the formulation scientist must consider
while determining the performance of the lm. Because of these crucial elements, it
is essential to utilize the optimal coating preparations to obtain the greatest results
(Aulton 2002).
N. N. Jitendra et al.
165
6.7.3 Supercell Coating Technology (SCT)
A disruptive tablet with Supercell coating technology can endure excessively
hygroscopic materials and have hard coating elements put on top of it. In some situ-
ations, this method produces nonhomogeneous results because of deciencies and
unpredictable results. The edges of the tablets have uneven coating thickness com-
pared to their surfaces, and their ends are trimmed using the Supercell coating tech-
nique to achieve a uniform nish. This prevents the stacking of tablets in the rotating
pan and prevents airow through the pan. As a result of the coating components
being deposited, the modied release of coating is reduced. Niro Pharma Systems
developed the Supercell coating technique, which uses a compact modular architec-
ture to aid with a variety of issues (Kumar etal. 2011).
Moreover, the current technology is incapable of notably coating hygroscopic
tablets, as well as tablets with at shapes or unconventional congurations. For the
prevention of “twinning,” in which two or more tablets attach to one another, this
procedure must be carried out carefully. The purpose of this study is to look into
Supercell coating, a virtual tablet coater system that uses a distinctive airow
arrangement. To determine the impact of various moisture conditions on the level of
quality of the coats generated, tablets coated at various spray velocities (4, 6, 8, 10,
and 12mL/min) are studied. The degree of roughness is observed to be lower at
6mL/min compared to different spray rates, and the coat looks smoothest, with the
droplets appearing to be joined together. When sprayed at faster rates, the droplets
resemble scale-like patterns with branching arms.
The continuous small-batch coating technique used by SCT is reliable and effec-
tive. In SCT, the number of units of tablets that are coated ranges from 30 to 120g,
and they scale up uniformly to reach production levels. To achieve a more effective
process, the coating spray is applied to the tablets in the same way as the drying gas.
The tablets move rapidly and uniformly across the spray zone due to the special air
circulation plate design used by SCT.This allows for enhanced coating accuracy
because the tablets receive only a tiny quantity of coating per pass. Since this pro-
cedure takes less time, in minutes or seconds rather than hours, it is easier to the
tablets.
Additionally, Supercell coating technology can be used to cover brittle tablets in
addition to at or extremely oval tablet shapes. Particularly hygroscopic tablets can
be coated using this method since drying occurs very quickly. The Niro Company
asserts that the traditional approaches to tablet coating yield irregular and suboptimal
outcomes, causing inconsistencies that could potentially impact the tablet’s perfor-
mance. This outcome could introduce a degree of diversity, which becomes more
important when a limited batch of tablets is manufactured for clinical testing. In the
usual coating machines, tablets are placed inside big rotating pans and then exposed
to hot air for drying. However, this process can result in the abrasion of tablet edges,
lling in any engraved markings with the coating material, and uneven coating thick-
ness on edges and corners compared to the tablet faces. According to Niro, these
kinds of errors restrict the adoption of specic release coatings (Ahmed etal. 2021).
6 Advances inTablet Production andTablet Coating
166
Distinctive characteristics of the Supercell coating technology:
1. Coating without interruption
2. Reduced processing duration
3. Adaptable design with modular exibility
4. Technology enhancement
5. Coating with multiple layers
6. Challenging shapes for coating
7. Easily breakable tablets
8. “Low humidity process” suitable for materials sensitive to moisture
9. Empowering technology
6.7.4 Magnetically Assisted Impaction Coating (MAIC)
A method is created to predict the duration needed for coating within a magnetically
assisted impaction coating (MAIC) apparatus. The combination of guest, host, and
magnetic particles is believed to remain in a uidized condition, characterized by a
velocity distribution following the Maxwell-Boltzmann model. The assumption is
made that particle collisions play a crucial role in directing the guest particles onto
the host particle surfaces, thereby creating a partially lasting coating on those sur-
faces. The duration of coating relies on various factors, such as the host particle’s
number density, the ratio of host particle diameter to guest particle diameter, the
height of the uidized particle bed, and the material characteristics of both host and
guest particles. There is a specic height for a bed where the coating process takes
the least amount of time. When the bed height strays from the ideal value, whether
it’s smaller or larger, and when the size of the host particles increases, the coating
time experiences a noticeable and substantial increase. Several dry coating tech-
niques have emerged, including compression coating, plasticizer dry coating, heat
dry coating, and electrostatic dry coating. Typically, these approaches allow for the
application of increased shearing stresses, powerful impact forces, or higher tem-
peratures during the coating process. These intense mechanical forces, coupled with
the resulting heat, can lead to the guest particles being layered or even incorporated
into the surface of the host particles. Magnetically assisted impaction coating
(MAIC) devices offer the capability to coat delicate organic host and guest particles
without altering their physical dimensions. Despite the occurrence of slight particle
collisions within the MAIC process, resulting in minimal heat production, this
effect is insignicant. This attribute becomes especially benecial when working
with temperature-sensitive powders like pharmaceuticals. The ongoing advance-
ment of magnetically assisted impaction coating (MAIC) aims to enhance the ef-
ciency of blending powders containing nano-sized particles, all without requiring
solvents or heat. Generally, achieving consistent blending of nanoscale materials
poses greater challenges compared to larger particles. As this technology continues
to be rened, it holds the potential to assist manufacturing processes in generating
superior-quality products (Pawar Avinash etal. 2010).
N. N. Jitendra et al.
167
6.7.4.1 Mechanism ofCoating intheMAIC Process
The process of MAIC coating involves various stages:
Stage I: Activation of magnetic particles
Stage II: Dispersal of guest particles (coating material)
Stage III: Alignment and dispersion of guest particles on the host particle surface
(material to be coated)
Stage IV: Interaction between magnetic host particles
Stage V: Interaction between magnetic host particles and the chamber wall
Stage VI: Generation of coated products
6.7.5 Dip Coating
The application of coating involves immersing the tablets in a liquid coating, after
which the damp tablets are dried in traditional coating pans. The procedure might
involve multiple rounds of dipping and drying to attain the aspired coating thick-
ness. However, this method limits the speed, adaptability, and dependability of
spray coating methods (Ahmed etal. 2021).
6.7.6 Vacuum Film Coating
This innovative coating method utilizes a custom-designed pan with bafes, featur-
ing a hot water jacket and the ability to be vacuum-sealed. Tablets are positioned
within the pan, and nitrogen is introduced to displace the air until the desired vac-
uum level is reached. An airless spray system is employed to apply the coating solu-
tion, while a vacuum system removes the vapors of evaporated solvents. This
technique enables the efcient utilization of organic solvents, accompanied by envi-
ronmental solid safety measures (Ahmed etal. 2021).
6.7.7 One-Step Dry-Coating (OSDrC
®
)
To address challenges associated with traditional dry coating methods and the for-
mation of Tablet-in-Tablet, a groundbreaking development known as the one-step
dry-coating (OSDrC
®
) equipment was introduced, sparking a signicant transfor-
mation in tablet manufacturing. OSDrC
®
is a registered trademark of Sanwa Kagaku
Kenkyusho Co. Ltd. in Japan. This innovative technique allows scientists to regulate
drug release by altering the thickness of the outer coating layer formulation
(Maiti 2014).
At rst, the space between the lower-center punch and lower-outer punch is lled
with powder for the outer coating layer. Subsequently, precompression is carried out
using the upper-center punch. Subsequently, as the upper-center punch advances the
pre-compressed rst-outer layer, the lower-center punch moves downward. The
6 Advances inTablet Production andTablet Coating