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Tablet manufacturing processs and defects of tablets

Authors:
  • HIMACHAL PHARMACY COLLEGE

Abstract and Figures

Introduction The oral route of drug administration is the most important method of drug administration for systemic effects. The Parenteral route of administration is important in treating the medical emergencies in which subject is comatose or can not swallow and in providing various types of maintenance therapy. Nevertheless, about 90% of all the drugs used to produce systemic effects are administered by the oral route. Among the drugs that are administered orally, solid dosage form represents the preferred class of product. Solid dosage form provides best protection to the drug against temperature, humidity, oxygen, light and stress during transportation and also ensures accuracy of dosage, compactness, portability, blandness of taste, and ease of administration. Although the basic medicinal approach for their manufacture has remained the same, tablet technology has undergone great improvement. Efforts are being made continually to understand more clearly the physical characteristics of powder compaction and the factors affecting the availability of the drug substance from the dosage form after oral administration. Tabletting equipment continues to improve in both production speed and the uniformity of the tablets compressed. Although tablets frequently are discoid in shape, they also exist in several shapes such as round, oval oblong, cylindrical or triangular etc. They may differ greatly in size and weight depending on the amount of the dug substance present and the intended method of administration. They are divided in to two general classes by whether they are made by compression or molding. Compressed tablets usually are prepared by large-scale production methods, while molded tablets generally involve small-scale operations. Types of tablets Compressed Tablets The tablets are formed by compression of powdered, crystalline, or granular active materials (API), alone or in combination with certain expients as required, such as binders, disintegrants, sustained release polymers, lubricants, diluents, flavors and colorants. A) Sugar coated tablets (sct) B) Film coated tablets (fct) C) Enteric-coated tablets (ect) D) Multi compessed tablets (mct): these are compressed Tablets made by more than one compression cycle. I) Layered tablets ii) Press coated tablets E) Sustained release tablets F) Tablets for solution G) Effervescent tablets H) Compressed suppositories or inserts I) Buccal and sublingual tablets Molded tablets or tablet triturates (tt) Tablet triturates usually are made from moist material, using a mold that gives them the shape of cut sections of cylinder. Such tablets must be completely and rapidly soluble. Suitable water-soluble lubricant is many times a constraint. Dispensing Tablets (Dt) These tablets provide a convenient quality of potent drug that can be incorporated readily in to powders and liquids, thus circumventing the necessity to weigh small quantities. These tablets are supplied primarily as a convenience for extemporaneous compounding and never dispensed as a dosage form. Hypodermic Tablets (Ht) Hypodermic tablets are soft, readily soluble tablets. Though these tablets are now made for oral administration they are not yet recognized by the official compendia. Advantages of the tablets The additional advantages of tablet dosages forms are as follows: • Their cost is lowest of all the dosage forms. • They are in general the easiest and cheapest to package and ship of all oral dosage forms. Tele: E-mail addresses: debjit_cr@yahoo.com
. Stage Occurring During Compression Auxiliary Equipments I. Granulation Feeding Device: In many cases, speed of die table is such that the time of die under feed frame is too short to allow adequate or consistent gravity filling of die with granules, resulting in weight variation and content uniformity. These also seen with poorly flowing granules. To avoid these problems, mechanized feeder can employ to force granules into die cavity. II. Tablet weight monitoring devices:- High rate of tablet output with modern press requires continuous tablet weight monitoring with electronic monitoring devices like Thomas Tablet Sentinel, Pharmakontroll and Killan control System-MC. They monitors force at each compression station by starin gage technology which is then correlated with tablet weight. III. Tablet Deduster: In almost all cases, tablets coming out of a tablet machine bear excess powder on its surface and are run through the tablet deduster to remove that excess powder. IV. Fette machine Fette machine is device that chills the compression components to allow the compression of low melting point substance such as waxes and thereby making it possible to compress product with low meting points. Packaging Pharmaceutical manufacturers have to pack their medicines before they can be sent out for distribution. The type of packaging will depend on the formulation of the medicine. 'Blister packs' are a common form of packaging used for a wide variety of products. They are safe and easy to use and they allow the consumer to see the contents without opening the pack. Many pharmaceutical companies use a standard size of blister pack. This saves the cost of different tools and to change the production machinery between products. Sometimes the pack may be perforated so that individual tablets can be detached. This means that the expiry date and the name of the product have to be printed on each part of the package. The blister pack itself must remain absolutely flat as it travels through the packaging processes, especially when it is inserted into a carton. This poses interesting problems for the designers. Extra ribs are added to the blister pack to improve its stiffness.
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Debjit Bhowmik
et al./ Elixir Pharmacy 70 (2014) 24368-24374
24368
Introduction
The oral route of drug administration is the most important
method of drug administration for systemic effects. The
Parenteral route of administration is important in treating the
medical emergencies in which subject is comatose or can not
swallow and in providing various types of maintenance therapy.
Nevertheless, about 90% of all the drugs used to produce
systemic effects are administered by the oral route. Among the
drugs that are administered orally, solid dosage form represents
the preferred class of product. Solid dosage form provides best
protection to the drug against temperature, humidity, oxygen,
light and stress during transportation and also ensures accuracy
of dosage, compactness, portability, blandness of taste, and ease
of administration. Although the basic medicinal approach for
their manufacture has remained the same, tablet technology has
undergone great improvement. Efforts are being made
continually to understand more clearly the physical
characteristics of powder compaction and the factors affecting
the availability of the drug substance from the dosage form after
oral administration. Tabletting equipment continues to improve
in both production speed and the uniformity of the tablets
compressed. Although tablets frequently are discoid in shape,
they also exist in several shapes such as round, oval oblong,
cylindrical or triangular etc. They may differ greatly in size and
weight depending on the amount of the dug substance present
and the intended method of administration. They are divided in
to two general classes by whether they are made by compression
or molding. Compressed tablets usually are prepared by large-
scale production methods, while molded tablets generally
involve small-scale operations.
Types of tablets
Compressed Tablets
The tablets are formed by compression of powdered,
crystalline, or granular active materials (API), alone or in
combination with certain expients as required, such as binders,
disintegrants, sustained release polymers, lubricants, diluents,
flavors and colorants.
A) Sugar coated tablets (sct)
B) Film coated tablets (fct)
C) Enteric-coated tablets (ect)
D) Multi compessed tablets (mct): these are compressed
Tablets made by more than one compression cycle.
I) Layered tablets
ii) Press coated tablets
E) Sustained release tablets
F) Tablets for solution
G) Effervescent tablets
H) Compressed suppositories or inserts
I) Buccal and sublingual tablets
Molded tablets or tablet triturates (tt)
Tablet triturates usually are made from moist material,
using a mold that gives them the shape of cut sections of
cylinder. Such tablets must be completely and rapidly soluble.
Suitable water-soluble lubricant is many times a constraint.
Dispensing Tablets (Dt)
These tablets provide a convenient quality of potent drug
that can be incorporated readily in to powders and liquids, thus
circumventing the necessity to weigh small quantities. These
tablets are supplied primarily as a convenience for
extemporaneous compounding and never dispensed as a dosage
form.
Hypodermic Tablets (Ht)
Hypodermic tablets are soft, readily soluble tablets. Though
these tablets are now made for oral administration they are not
yet recognized by the official compendia.
Advantages of the tablets
The additional advantages of tablet dosages forms are as
follows:
Their cost is lowest of all the dosage forms.
They are in general the easiest and cheapest to package and
ship of all oral dosage forms.
Tele:
E-mail addresses:
debjit_cr@yahoo.com
© 2014 Elixir All rights reserved
Tablet manufacturing processs and defects of tablets
Debjit Bhowmik
1,*
, S.Duraivel, Rajalakshmi. A.N
2
and K.P.Sampath Kumar
3
1
Nimra College of Pharmacy, Ibrahimpatnam, Vijayawada, Andhra Pradesh.
2
Mother Theresa post Graduate and Research Institute of Health Sciences, Puducherry.
3
Department of Pharmacy, Coimbatore Medical College, Coimbatore.
ABSTRACT
Tablet is defined as solid pharmaceutical dosage form containing drug substance
generally with suitable diluents and prepared by either compression or molding
methods. Tablets remain p opular as a dosage form because of the advantages
afforded, both to the manufacturer (e.g. simplicity and economy of the preparation,
stability, and convenience in packing, shipping and dispensing) and the patient.
Because of their composition, method of manufacture or intended use, tablets present
a variety of characteristics and consequently there are several categories of tablets.
Tablet formulation and design may be described as the process where by the formulator
ensures that the correct amount of the drug in the right form is delivered at or over the
proper time at the proper rate and in the desired location, while having its chemical
integrity protected to that point. Latest concepts and regulations focus on bioavailability,
bioequivalence and validation etc. impact formulation designing and manufacture.
© 2014 Elixir All rights reserved
AR T I C L E I N F O
Art i c l e hi s t or y :
Received: 6 November 2013;
Received in revised form:
10 May 2014;
Accepted: 23 May 2014;
Key w o r ds
Tablets,
Physical characteristics,
Tablet Processing,
Direct Compression.
Elixir Pharmacy 70 (2014) 24368-24374
Pharmacy
Available online at www.elixirpublishers.com (Elixir International Journal)
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et al./ Elixir Pharmacy 70 (2014) 24368-24374
24369
They may provide the greatest ease of swallowing with the
least tendency for “hang-up” above the stomach, especially
when coated, provided that tablet disintegration is not
excessively rapid.
They lend themselves to certain special release profile
products, such as enteric or delayed release products.
They are better suited to large-scale production than the other
unit oral forms.
They have the best-combined properties of chemical,
mechanical and microbiological stability of all the oral forms.
Disadvantages of the tablets
For very few disadvantages, these dosage forms are most
suitable and widely accepted:
Some drugs resist compression in to dense particles, owing
to their amorphous nature or flocculent, low density character.
Drugs with poor wetting, slow dissolution properties,
intermediate to large dosages, optimum absorption high in the
GIT or any combination of these features are very challenging
for the formulators.
Tablet Processing
Pharmaceutical products are processed all over the world
using the direct compressing, wet granulation, or dry granulation
methods. Method chosen depends on the ingredients’ individual
characteristics like flow property, compressibility etc. Right
choice of method requires thorough investigation of each
proposed ingredient in the formula for comprehensive approach
for intractions and stability.
Direct compression:
The tablets are made by directly compressing the powdered
materials without modifying the physical nature of the materials
itself. Direct compression is generally done for the crystalline
materials having good physical properties such as flow property,
compressibility etc. Main advantages of direct compression are
time saving, safety of operations and low cost.
Wet granulation:
This is the most widely used method of tablet preparation.
In this method the powders are bound by suitable binder by
“adhesion”. The binder is added by diluting with suitable
solvent prior to addition to the blended powders to form wet
granules which in turn are dried suitably to expel the solvent
forming dried granules. The surface tension forces and capillary
pressure are primarily responsible for initial granules formation.
The main advantage being it meets all the requirements for
tablet formation though it is multistage, time consuming.
Dry granulation:
The dry granulation process is used to form granules
without using a liquid solution. This type of process is
recommended for products, which are sensitive to moister and
heat. Forming granules without moisture requires compacting
and densifying the powders. Dry granulation can be done on a
tablet press using slugging tooling. On large-scale roller
compactor commonly referred to as a chilsonator. The
compacted mass is called slugs and the process is known as
slugging. The slugs are then screened or milled to produce a
granular form of tablet materials, which have the good flow
properties then original powder mixture. The main advantage of
dry granulation is it requires less equipment and eliminates the
addition of moisture and the application of heat, as found in wet
massing and drying steps of the wet granulation method.The
manufacture of oral solid dosage forms such as tablets is a
complex multi-stage process under which the startingmaterials
change their physical characteristics a number of times before
the final dosage form is produced. Traditionally, tablets have
been made by granulation, a process that imparts two primary
requisites to formulate: compactibility and fluidity. Both wet
granulation and dry granulation (slugging and roll compaction)
are used. Regardless of weather tablets are made by direct
compression or granulation, the first step, milling and mixing, is
the same; subsequent step differ. Numerous unit processes are
involved in making tablets, including particle size reduction and
sizing, blending, granulation, drying, compaction, and
(frequently) coating. Various factors associated with these
processes can seriously affect content uniformity,
bioavailability, or stability.
Figure.1 . Various Unit Operation Sequences In Tablet
Manufacturing
Figure 2. Typical Manufacturing Process Of Tablet
Table.1 . Typical Unit Operation Involved In Wet
Granulation, Dry Granulation And Direct Compression(13)
Wet granulation
Dry granulation
Direct compression
1.Milling
and mixing of drugs
and excipients
1.Milling
and mixing of drugs and
excipients
excipients
2.Preparation
of binder solution
2.Compression
into slugs or r
oll
compaction
tablet
3.Wet
massing by addition of
binder solution
or granulating solvent
3.Milling
and screening of slugs and
compacted powder
4.Screening
of wet mass
4.Mixing
with lubricant and
disintegrant
5.Drying
of the wet granules
5.Compression
of tablet
6.Screening
of dry granules
7.Blending
with lubricant and
disintegrant to produce
“running powder”
8.Compression
of tablet
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Dispensing (weighing and measuring)
Dispensing is the first step in any pharmaceutical
manufacturing process. Dispensing is one of the most critical
steps in pharmaceutical manufacturing; as during this step, the
weight of each ingredient in the mixture is determined according
to dose. Dispensing may be done by purely manual by hand
scooping from primary containers and weighing each ingredient
by hand on a weigh scale, manual weighing with material lifting
assistance like Vacuum transfer and Bag lifters, manual or
assisted transfer with automated weighing on weigh table,
manual or assisted filling of loss-in weight dispensing system,
automated dispensaries with mechanical devices such as vacuum
loading system and screw feed system. Issues like weighing
accuracy, dust control laminar air flow booths, glove boxes),
during manual handling, lot control of each ingredient, material
movement into and out of dispensary should be considered
during dispensing.
Sizing
The sizing (size reduction, milling, crushing, grinding,
pulverization) is an impotent step (unit operation) involved in
the tablet manufacturing. In manufacturing of compressed tablet,
the mixing or blending of several solid ingredients of
pharmaceuticals is easier and more uniform if the ingredients are
approximately of same size. This provides a greater uniformity
of dose. A fine particle size is essential in case of lubricant
mixing with granules for its proper function. Advantages
associated with size reduction in tablet manufacture are as
follows:
i) It increases surface area, which may enhance an active
ingredient’s dissolution rate and hence bioavailability.
ii) Improved the tablet-to-tablet content uniformity by virtue of
the increased number of particles per unit weight.
iii) Controlled particle size distribution of dry granulation or mix
to promote better flow of xture in tablet machine.
iv) Improved flow properties of raw materials.
V) Improved colour and/or active ingredient dispersion in tablet
excipients.
vi) Uniformly sized wet granulation to promote uniform drying.
There are also certain disadvantages associated with this unit
operation if not controlled properly. They are as follows:
i)A possible change in polymorphic form of the active
ingredient, rendering it less or totally inactive, or unstable.
ii) A decrease in bulk density of active compound and/or
excipients, which may cause flow problem and segregation in
the mix.
iii)An increase in surface area from size reduction may promote
the adsorption of air, which may inhibit wettability of the drug
to the extent that it becomes the limiting factor in dissolution
rate.
A number of different types of machine may be used for the dry
sizing or milling process depending on whether gentle screening
or particle milling is needed. The ranges of equipment employed
for this process includes Fluid energy mill, Colloidal mill, Ball
mill, Hammer mill, Cutting mill, Roller mill, Conical mill, etc.
Powder blending
The successful mixing of powder is acknowledged to be
more difficult unit operation because, unlike the situation with
liquid, perfect homogeneity is practically unattainable. In
practice, problems also arise because of the inherent
cohesiveness and resistance to movement between the individual
particles. The process is further complicated in many system, by
the presence of substantial segregation influencing the powder
mix. They arise because of difference in size, shape, and density
of the component particles.
The powder/granules blending are involved at stage of pre
granulation and/or post granulation stage of tablet
manufacturing. Each process of mixing has optimum mixing
time and so prolonged mixing may result in an undesired
product. So, the optimum mixing time and mixing speed are to
be evaluated. Blending step prior to compression is normally
achieved in a simple tumble blender. The Blender may be a
fixed blender into which the powders are charged, blended and
discharged. It is now common to use a bin blender which blends.
In special cases of mixing a lubricant, over mixing should be
particularly monitered. The various blenders used include “V”
blender, Oblicone blender, Container blender, Tumbling
blender, Agitated powder blender, etc. But now a day to
optimize the manufacturing process particularly in wet
granulation the various improved equipments which combines
several of processing steps (mixing, granulation and/or drying)
are used. They are “Mixer granulator” or“High shearmixing
machine”.
Granulation
Following particle size reduction and blending, the
formulation may be granulated, which provides homogeneity of
drug distribution in blend.
Drying
Drying is a most important step in the formulation and
development of pharmaceutical product. It is important to keep
the residual moisture low enough to prevent product
deterioration and ensure free flowing properties. The commonly
used dryer includes Fluidized – bed dryer, Vacuum tray dryer,
Microwave dryer, Spray dryer, Freeze dryer, Turbo – tray dryer,
Pan dryer, etc.
Tablet compression
After the preparation of granules (in case of wet
granulation) or sized slugs (in case of dry granulation) or mixing
of ingredients (in case of direct compression), they are
compressed to get final product. The compression is done either
by single punch machine (stamping press) or by multi station
machine (rotary press). The tablet press is a high-speed
mechanical device. It 'squeezes' the ingredients into the required
tablet shape with extreme precision. It can make the tablet in
many shapes, although they are usually round or oval. Also, it
can press the name of the manufacturer or the product into the
top of the tablet. Each tablet is made by pressing the granules
inside a die, made up of hardened steel. The die is a disc shape
with a hole cut through its centre. The powder is compressed in
the centre of the die by two hardened steel punches that fit into
the top and bottom of the die.
The punches and dies are fixed to a turret that spins round.
As it spins, the punches are driven together by two fixed cams -
an upper cam and lower cam. The top of the upper punch (the
punch head) sits on the upper cam edge .The bottom of the
lower punch sits on the lower cam edge. The shapes of the two
cams determine the sequence of movements of the two punches.
This sequence is repeated over and over because the turret is
spinning round.
The force exerted on the ingredients in the dies is very
carefully controlled. This ensures that each tablet is perfectly
formed. Because of the high speeds, they need very
sophisticated lubrication systems. The lubricating oil is recycled
and filtered to ensure a continuous supply.
Common stages occurring during compression
Stage1: Top punch is withdrawn from the die by the upper cam
Bottom punch is low in the die so powder falls in through the
hole and fills the die
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Stage2: Bottom punch moves up to adjust the powder weight-it
raises and expels some powder
Stage 3: Top punch is driven into the die by upper cam Bottom
punch is raised by lower cam Both punch heads pass between
heavy rollers to compress the powder
Stage 4: Top punch is withdraw by the upper cam Lower punch
is pushed up and expels the tablet Tablet is removed from the
die surface by surface plate
Stage 5: Return to stage 1
Figure.3 . Stage Occurring During Compression
Auxiliary Equipments
I. Granulation Feeding Device:
In many cases, speed of die table is such that the time of die
under feed frame is too short to allow adequate or consistent
gravity filling of die with granules, resulting in weight variation
and content uniformity. These also seen with poorly flowing
granules. To avoid these problems, mechanized feeder can
employ to force granules into die cavity.
II. Tablet weight monitoring devices:-
High rate of tablet output with modern press requires
continuous tablet weight monitoring with electronic monitoring
devices like Thomas Tablet Sentinel, Pharmakontroll and Killan
control System-MC. They monitors force at each compression
station by starin gage technology which is then correlated with
tablet weight.
III. Tablet Deduster:
In almost all cases, tablets coming out of a tablet machine
bear excess powder on its surface and are run through the tablet
deduster to remove that excess powder.
IV. Fette machine
Fette machine is device that chills the compression
components to allow the compression of low melting point
substance such as waxes and thereby making it possible to
compress product with low meting points.
Packaging
Pharmaceutical manufacturers have to pack their medicines
before they can be sent out for distribution. The type of
packaging will depend on the formulation of the medicine.
'Blister packs' are a common form of packaging used for a wide
variety of products. They are safe and easy to use and they allow
the consumer to see the contents without opening the pack.
Many pharmaceutical companies use a standard size of blister
pack. This saves the cost of different tools and to change the
production machinery between products. Sometimes the pack
may be perforated so that individual tablets can be detached.
This means that the expiry date and the name of the product
have to be printed on each part of the package. The blister pack
itself must remain absolutely flat as it travels through the
packaging processes, especially when it is inserted into a carton.
This poses interesting problems for the designers. Extra ribs are
added to the blister pack to improve its stiffness.
Recent advances in tablet formulation technology
The recent trends in tablet formulation are
1.Versatile immediate release tablet systems including fast
dissolving drug delivery systems, orally disintegrating tablets/
orally dispersible tablets, orally dispersible mini tablets, mouth
dissolving/ fast dissolving tablets, novel fixed dose combination
tablet
ACCU-BREAK technology inactive layer between two
different drug layers), conventional effervescent, uncoated and
film–coated tablets etc.
2. Modified release tablet formulations including ring cap coated
tablet ALZA, layered tablets (in lay, tablet in tablet, bilayered
tablet), novel chewable sustained release tablet and direct
compression medicated chewing gum.
3. Excipient technology is advancing to produce directly
compressible materials for both immediate release as in mouth
dissolving systems, or for sustained release systems. The
research in excipients is meeting pace with the high throughput
production of tablets. Research is also advancing into obtaining
excipients from natural sources. Various commercial excipients
such as Lycoat, Readily coat, Instamodel and Instanute DR are
available in the market.
Patented Technologies For Fast Dissolving Tablets
Zydis Technology
Zydis, the best known of the fast-dissolving/disintegrating
tablet preparations was the first marketed new technology tablet.
The tablet dissolves in the mouth within seconds after placement
on the tongue. A Zydis tablet is produced by lyophilizing or
freeze-drying the drug in a matrix usually consisting of gelatin.
The product is very lightweight and fragile, and must be
dispensed in a special blister pack. Patients should be advised
not to push the tablets through the foil film, but instead peel the
film back to release the tablet. The Zydis product is made to
dissolve on the tongue in 2 to 3 seconds. The Zydis formulation
is also self-preserving because the final water concentration in
the freeze-dried product is too low to allow for microbial
growth.
Durasolv Technology
Durasolv is the patented technology of CIMA labs. The
tablets made by this technology consist of a drug, fillers and a
lubricant. Tablets are prepared by using conventional tableting
equipment and have good rigidity. These can be packed into
conventional packaging system like blisters. Durasolv is an
appropriate technology for products requiring low amounts of
active ingredients.
Orasolv Technology
Orasolv Technology has been developed by CIMA labs. In
this system active medicament is taste masked. It also contains
effervescent disintegrating agent. Tablets are made by direct
compression technique at low compression force in order to
minimize oral dissolution time. Conventional blenders and tablet
machine is used to produce the tablets. The tablets produced are
soft and friable and packaged in specially designed pick and
place system.
Flash Dose Technology
Flash dose technology has been patented by Fuisz. Nurofen
meltlet, a new form of ibuprofen as melt-in-mouth tablets,
prepared using flash dose technology is the first commercial
product launched by Biovail Corporation. Flash dose tablets
consists of self binding shearform matrix termed as "floss".
Shearform matrices are prepared by flash heat processing.
Wowtab Technology
Wowtab Technology is patented by Yamanouchi
Pharmaceutical Co. WOW means "Without Water ". In this
process, combination of low mouldability saccharides and high
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mouldability saccharides is used to obtain a rapidly melting
strong tablet. The active ingredient is mixed with a low
mouldability saccharide and granulated with a high mouldability
saccharide and compressed into tablet.
Flashtab Technology
Prographarm laboratories have patented the Flashtab
technology. Tablets prepared by this system consist of an active
ingredient in the form of micro crystals. Drug micro granules
may be prepared by using the conventional techniques like
coacervation, micro encapsulation, and extrusion spheronisation.
All the processing utilized conventional tabletting technology.
Marketed scope in tablet compression technology
The market for tablet compression technology and the
demands placed on equipment manufacturers have changed
quite significantly in recent years. This has been driven by a
number of factors. Firstly, the pharmaceutical industry has seen
a significant shift of investments in solid dosage production
equipment towards generics and contract manufacturing. As the
companies in this segment of the market are, by nature, strongly
focused on cost reduction, a big emphasis is placed on
productivity, flexibility and process yield (i.e., minimal product
loss). Equipment cost and reliability, as well as fast on-site
assistance have also become key selection criteria. research and
development based companies have also been forced to follow
this cost reduction trend. Secondly, the meteoric growth of new
pharmaceutical markets in the Middle East and the Far East
(e.g., India, China, South Korea) has led investments in solid
dosage equipment in these regions to surpass the investments
made in North America and Europe. This puts an increased
pressure on equipment price and has resulted in several Western
based companies moving the design, manufacture and assembly
of their equipment to Asia.
Mottling
Unequal distribution of colour on the tablet surface with
light and dark areas standing out in an otherwise uniform
coloured surface
Cause :
Variation in the colours of ingredients (drug and other
additives)
• Drugs with degradation nature and have different coloured
degraded products
Migration of dye to the surface of granulation during drying.
At high temperature dyes are easily migrate to surface and
spread to upper surface.
• Uneven distribution of colored adhesive gel solutions resulting
in precipitation
• The improper size either large or small particles enhances
color distribution. During preparation dyes are not properly
mixed and not selected ideally or any incompatibility will tends
to enhance appearance of color on tablet surface.
• Improper storage conditions.
Remedy:
• By using bright coloring agent that will mask all the color
variations of the ingredients
Proper drying by reducing the drying temperature
Colored adhesive gel solutions must be added when they are
hot too much cooler powder mixtures to avoid precipitation
• It is better to incorporate fine powder adhesives like acacia and
tragacanth into product before adding the granulating fluid
By changing the solvent system or binder system
• Grinding to small particle size
Special Problem in Compressing Tablet Process
Capping And Laminating
Capping :
Capping Continuously high speed of tablet machine and
high degree of compression setting makes tablet to separate
main surface into individual surface. Avoid defective punches
and dies. High temperature adjustment also favor capping.
Distance between upper and lower punches will entrap air is
bone factor for capping. Fine particles were susceptible than
coarse particles will affect ideality of tablets. Capping
minimized by keeping the feed material with cohesive nature.
Lamination :
Lamination It is major problem among of all defects. Occur
upon storage period, or soon after compression. Air entrapment
between layers of tablet. Low levels of binding agent. It
minimized by improving lubricant concentration. Change the
method of granulation. By direct compression technique it is
prevented to some extent. Use always dry material (feed).
Table-2
Causes Remedy
Air entrapment in the tablet
among granules or among
particles
By pre-co
mpression, Reducing final
compression, Minimizing
tableting rate
Deformational properties of
formulation during and after
compression
Increasing stress relaxation time
Improper/Deep concave punches Better to use flat punches
Over dried granules (Due to
lack
of cohesion)
By maintaining moisture levels
using hygroscopic materials
like MC (Methyl Cellulose),
Sorbitol, PEG 4000 (Polyethylene
glycol) etc.
Improper tooling:
Concave edges of punches
turning claw shaped
Greater radius of curvature of
punch face
Dies developing a wear ring
shape
Improper adjustment of sweep
off blade
Less rise of lower punch during
ejection of table
Proper tooling:
Checking of punches and
replacing them
Proper checking and replacing
them
Turning the die over so that
compression occurs in an
unworn area above ring
Proper setting of sweep off blade
& lower punch rise
Poor compressibility observed
during direct compression
technique
Relative compressibility is to be
maintained
Picking
Adherence of the tablet material from the surface of a tablet
by a punch.
Causes:
Because of engraving or embossing or debossing on the
punch tips like small enclosed areas in the letters like “A”, “B”,
“D”, “O”, “Q” etc
Remedy:
• Lettering should be designed as large as possible, even the
tablet size can be increased by reformulation
• Colloidal silica can be added as polishing agent to formula
Using additional binder to increase cohesiveness of granules
and thereby causing decreased adherence
• Plating of punch faces with a chromium material to obtain
smooth face which is non-adherent
• Avoid wet granules.
Debjit Bhowmik
et al./ Elixir Pharmacy 70 (2014) 24368-24374
24373
Sticking
Sticking always occurs in low melting point substances, and
moisture supports this defects, lower the speed up of upper and
lower punch leads to weight variation of tablets. It produces
rough and chipping surface tablets. It develops material on both
punches. Lack of drying is basis of this one.
Causes:
Presence of low melting point substances in the formula ex.
Stearic acid, PEG (Polyethylene glycol) etc , which gets soften
due to compressive heat
• Excessive moisture in the granules
Remedy:
Partial or complete substitution of low melting point
components with high melting point materials in the formula
Proper drying of the granules to remove excessive moisture
Selection of Binding agent is essential to solve sticking.
Ideal selection of lubricant in desired proportion will
minimized this problem.
Weight Variation (Granule size and size distribution)
Causes:
• Improper blending of granules
• Lack of sufficient of lubricant
• Abnormal uniform mixing of all excipients.
Improper tool setting of machine. Hi-speed running of
machine.
• improper glidant selection.
Improper drying making tablet with different weight.
Proportion of small to large granules influence the die filling
capacity and thereby results in weight variation of tablets
• If large granules are used to fill small die cavities, even a small
difference in granules results in high percent weight variation of
tablets
Remedies:
• Uniform size distribution (Narrow) and smaller granular size is
preferable
POOR FLOW
Causes:
• Improper design of hopper
• Poor flow of granules
Bridging/arching and rat-holing of granules at the bottom of
the hopper
• Segregation or stratification of particles due to use of flow
promoting devices like vibrators
• Surges of excessive flow above the hopper
Remedies:
• Flow can be improved by using glidants like talc, colloidal
silica etc.
• By proper design of the hopper
• By using flow enhancing devices like vibrators
• By preparing uniform sized and shaped granules
Poor Mixing
Causes:
• Improper mixing of ingredients like glidants and lubricants
useful for proper flow and punching
• Insufficient or inadequate time of mixing
Remedy:
• Proper mixing by maintaining adequate time and using suitable
mixer
Punch Variation
Cause:
Unequal lengths of lower punches which results in variations
of granular volume filled in die
Remedy:
• Proper tooling by using good and uniform sized punches
Hardness Variation
Causes:
• Due to weight variation in granules filled in die
• Space between lower and upper punches
Remedy:
• Proper tooling of machine
Double Impression
Cause:
Uncontrolled movement of punches with engravings on them
Remedy:
Using anti-turning devices
Chipped edge :
Tablets having sharp edge, elongated tablets are prone to
chipped edge. Granules are subject to high temperature will
improve chipped surface (high drying). This defects
accompanied with damaged surfaces at its corners of tablet
,easily fragmented by even smooth handling also. Due to rough
handling. Tablet shape is abnormal than normal. Use optimum
level of binding agent.
Print defect :
It is mainly observed in tablets which having hard
corners/designs on punches. It takes due to improver punch
cycle. Punches having rough surface . Improper blending of total
powder. Letter are designed with uneven surfaces on punches.
HAIR/FIBRE :
HAIR/FIBRE As name itself indicates some unwanted
particles/hair are appeared on tablet surface. Not following SOP.
Operator not implementing cGMP. Lack of attention of
operator. Punches are cleaned before installing in their
respective places. Lack of cleaning/spacious rooms.
Black SPOT/STAIN :
Stains or spots will be appear on tablet surface. Migration of
coloring agent upon storage. High temperature is key factor for
penetration of dye into upper surface. Improper cleaning of
punches. Mainly observed in colored tablets. Observe in high
concentration of dyes. Incompatibility among excipients and
API
Soft Tablets :
The tablets are susceptible to hydrolysis will develop soft
nature. Improper storage. Mainly observed in polymer/coated
tablets. Lack of drying will enhance the softness. Granulation
particles will completely free from moisture by keeping to
drying condition properly. Soft tablet will form initiate/basis for
sticking or picking defects. Use of lubricant that impart waxy
nature. Application of low compaction pressure. The strength of
bond is weakened across granules.
Protracted disintegration :
Disintegration time is extended in tablet. Use of high
compression on punches. Incorporation of lubricant in excess
quantity. Overcome by using proper suitable surfactant
concentration. Addition of more concentration of binding agent.
Too low compression also favors extend disintegration time.
Conclusion
Among the different routes of drug administration, oral
route is mostly preferred. About 90% of drugs are administered
orally for systemic effect. Various kinds of solid dosage forms
like tablet, capsules, pills, syrups etc are administered through
oral route of drug administration. In orally administered dosage
forms, tablet represents the preferred choice of class of product.
The tablet is convenient, in terms of self medication, ease of
administration, compactness, accurate dose, avoidance pain,
versatility and most importantly patient compliance.
Debjit Bhowmik
et al./ Elixir Pharmacy 70 (2014) 24368-24374
24374
References
1. Michael J. Rathbone, “Oral Mucosal Drug Delivery” Drug
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nd
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2. Joseph R R and Vincent H L Lee, “Controlled Drug Delivery”
II
nd
Edition, Vol. 29, Marcel Dekker, Inc., New York, 1987, 42-
43.
3. Edith Mathiowitz, Donald E C and Claus Michael L,
“Bioadhesive Drug Delivery Systems –Fundamentals, Novel
Approaches and Development”, II
nd
Edition, Vol. 98, Marcel
Dekker, Inc., New York, 1999, 541-562.
4. N.K. Jain “Controlled and Novel Drug Delivery”, I
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Edition,
CBS Publishers and Distributors, India, 2004, 52-74.
5. Amir H Shojaei, “Buccal mucosa as a route for systemic drug
delivery”, J.Pharm. Pharmaceut. Sci., 1998, June, 15:30, 15-30.
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16. R K Verma; D M Krishna; S Garg; Formualtion aspects in
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systems; J controlled release; 2002(79); 7-27.
... mg. The weight variations to a considerable degree were observed due to differences in the density of the powder material and partly due to incomplete filling of the dies [31]. ...
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Oral Mucosal Drug Delivery " Drug and Pharmaceutical sciences. II nd Edition
  • J Michael
  • Rathbone
Michael J. Rathbone, " Oral Mucosal Drug Delivery " Drug and Pharmaceutical sciences. II nd Edition,Marcel Dekker Inc., New York.1992.
Controlled Drug Delivery
  • R R Joseph
  • H L Vincent
  • Lee
Joseph R R and Vincent H L Lee, "Controlled Drug Delivery" II nd Edition, Vol. 29, Marcel Dekker, Inc., New York, 1987, 42-43.