CDA PROJECT

ON

“Problems in tablet manufacturing in small scale and their solutions”

Submitted to
Jayoti Vidyapeeth Women’s UniVersity

Jaipur, rajasthan, India

In partial fulfillment of the requirement for

The award of the degree Of
masters of Pharmacy
SUPERvISED BY SUBMITTED BY
JV’n ms. preeti singh “JV’n bhaVana panchal”
Jv-p/18/2787
M.pharm (pce)
FACULTY OF PHARMACEUTICAL SCIENCE
Jayoti Vidyapeeth Women’s UniVersity
JAIPUR-303122, RAJASTHAN, INDIA
2018 - 2019
 CERTIFICATE

This is to certify that the project work entitled “A REPORT ON Problems in tablet
manufacturing in small scale and their solutions” submitted by “JV’N
KHUSHBU” towards the partial fulfillment of the requirements for the award of the degree of
Bachelor of Pharmacy (B. Pharm.) at Jayoti Vidyapeeth Women’s University, Jaipur
(Rajasthan), India, is a record of students own work carried out by her in the “ Faculty of
Pharmaceutical Science, Jayoti Vidyapeeth Women’s University, Jaipur (Rajasthan), India”
under the supervision of JV’N MR. DHARMENDRA AHUJA.

The work contained in the project work is original and has not been submitted in part or in full
for the award of any other diploma or degree of this or any other university.

JV’N MR DHARMENDRA AHUJA DR.ANUREKHA JAIN

HOD DEAN
Faculty of Pharmaceutical Science Faculty of Pharmaceutical Science
 ACKNOWLEDGEMENT
The task of preparing the dissertation has been an overwhelming experience, an achievement in
itself and even as I rejoice in post completion euphoria, it affords me an immense pleasure to
acknowledge with gratitude the help and guidance rendered to me by a host of people of whom I
owe a substantial measure in the completion of my project work.
I can hardly find any words enough to express heart full thanks to my PARENTS whose
tremendous encouragement, support, prayer and love which has proved to be real source of
inspiration, and will remain so for the life to come, without which it would have been impossible
for me to achieve this success.
I would like to thank JV’N Mrs. Vidushi Garg, (Hon’ble Chairperson) and JV’N Dr. Pankaj
Garg (Founder and Advisor), Jayoti Vidyapeeth Women’s University, Jaipur, Rajasthan, for
providing facilities so that we can able to complete our research work in due course of time.
I take this golden opportunity to express my humble gratitude and respect to my research
guide JV’N MR. DHARMENDRA AHUJA (HOD, Faculty of Pharmaceutical Science)
for his constant invaluable guidance, encouragement and support throughout the project work.

I also heartedly thank Dr. Anurekha Jain (DEAN, Faculty of Pharmaceutical Science)
for her marvelous support throughout my work.

Finally I owe my thanks and gratitude to all the peoples who helped me in various ways
in the completion of this work

Place : Jaipur

Date : Sign: JV’n bhavana panchal

JV-p/18/2787
 ABSTRACT

Tablet defects can come from any of the unit operation

upstream and from the tablet press. The raw materials may be of poor
quality or do not meet specification, causing excessive fines that lead to
a host of defects. The formulation may be the source of defects if the
material do not compress well or the processing step specified within the
formulation fail to produce a powder a good flow, compressibility, and
ejection properties. The processing and granulation of powder is often
the source of defect.
Every product behaves differently on a tablet press, even
if it‘s the same product run on a different day. The variation often stems
from changes in the properties of the raw materials—active ingredients
and excipients- from batch to batch. Naturally, the goal is to minimize
these changes. Tablet press operators, however, don‘t have any control
over formulation and granulation.
Tablet specifications are tight, and the list of possible
defects is long: Variable weight, sticking, picking, capping, lamination,
variable hardness, among others. This article focuses on these variations.
It pinpoints the possible causes of these defects and offers advice on
preventing and fixing the source of the problems.
Introduction
A tablet is a pharmaceutical dosage form. Tablets
may be defined as the solid unit dosage form of medicament or
medicaments with or without suitable excipients and prepared either by
molding or by compression. It comprises a mixture of active substances
and excipients, usually in powder form, pressed or compacted from a
powder into a solid dose.
The excipients can include diluents, binders or
granulating agents, glidants (flow aids) and lubricants to ensure efficient
tabletting; disintegrants to promote tablet break-up in the digestive tract;
sweeteners or flavours to enhance taste; and pigments to make the
tablets visually attractive or aid in visual identification of an unknown
tablet. A polymer coating is often applied to make the tablet smoother
and easier to swallow, to control the release rate of the active ingredient,
to make it more resistant to the environment (extending its shelf life), or
to enhance the tablet's appearance.

Types
1. Pills :- Today, pills include tablets, capsules, and variants thereof
like caplets—essentially anything with medication that can be
digested, minus the liquid forms, colloquially falls into the pill
category.
2. Caplet :- A caplet is a smooth, coated, oval-shaped medicinal
tablet in the general shape of a capsule. Many caplets have an
indentation running down the middle so they may be split in half
easier.
 3. Orally disintegrating tablet (ODT) :- An orally disintegrating
tablet or orodispersible tablet (ODT), is a drug dosage form
available for a limited range of over-the-counter (OTC) and
prescription medications.

Tabletting formulations
In the tablet-pressing process, it is important that all
ingredients be fairly dry, powdered or granular, somewhat uniform in
particle size, and freely flowing. Mixed particle sized powders segregate
during manufacturing operations due to different densities, which can
result in tablets with poor drug or active pharmaceutical ingredient (API)
content uniformity but granulation should prevent this. Content
uniformity ensures that the same API dose is delivered with each tablet.

Some APIs may be tableted as pure substances, but this

is rarely the case; most formulations include excipients. Normally, a
pharmacologically inactive ingredient (excipient) termed a binder is
added to help hold the tablet together and give it strength. A wide
variety of binders may be used, some common ones including lactose,
dibasic calcium phosphate, sucrose corn (maize) starch, microcrystalline
cellulose, povidone polyvinylpyrrolidone and modified cellulose (for
example hydroxypropyl methylcellulose and hydroxyethylcellulose).

Often, an ingredient is also needed to act as a

disintegrant to aid tablet dispersion once swallowed, releasing the API
for absorption. Some binders, such as starch and cellulose, are also
excellent disintegrants.
Advantages and disadvantages
Tablets are simple and convenient to use. They
provide an accurately measured dosage of the active ingredient in a
convenient portable package, and can be designed to protect unstable
medications or disguise unpalatable ingredients. Colored coatings,
embossed markings and printing can be used to aid tablet recognition.
Manufacturing processes and techniques can provide tablets with special
properties, for example, sustained release or fast dissolving
formulations.

Some drugs may be unsuitable for administration

by the oral route. For example, protein drugs such as insulin may be
denatured by stomach acids. Such drugs cannot be made into tablets.
Some drugs may be deactivated by the liver when they are carried there
from the gastrointestinal tract by the hepatic portal vein (the "first pass
effect"), making them unsuitable for oral use. Drugs which can be taken
sublingually are absorbed through the oral mucosa, so that they bypass
the liver and are less susceptible to the first pass effect.

The oral bioavailability of some drugs may be low

due to poor absorption from the gastrointestinal tract. Such drugs may
need to be given in very high doses or by injection. For drugs that need
to have rapid onset, or that have severe side effects, the oral route may
not be suitable. For example, salbutamol, used to treat problems in the
respiratory system, can have effects on the heart and circulation if taken
orally; these effects are greatly reduced by inhaling smaller doses direct
to the required site of action.

A proportion of the population have difficulties

swallowing tablets either because they just don't like taking them or
because their medical condition makes it difficult for them (dysphagia,
vomiting). In such instances it may be better to consider alternative
dosage form or administration route.
Manufacturing
Manufacture of the tableting blend
In the tablet pressing process, the main guideline is to
ensure that the appropriate amount of active ingredient is in each tablet.
Hence, all the ingredients should be well-mixed. If a sufficiently
homogenous mix of the components cannot be obtained with simple
blending processes, the ingredients must be granulated prior to
compression to assure an even distribution of the active compound in the
final tablet. Two basic techniques are used to granulate powders for
compression into a tablet: wet granulation and dry granulation. Powders
that can be mixed well do not require granulation and can be compressed
into tablets through direct compression.

Wet granulation
Wet granulation is a process of using a liquid binder to
lightly agglomerate the powder mixture. The amount of liquid has to be
properly controlled, as over-wetting will cause the granules to be too
hard and under-wetting will cause them to be too soft and friable.
Aqueous solutions have the advantage of being safer to deal with than
solvent-based systems but may not be suitable for drugs which are
degraded by hydrolysis.
Procedure
1. The active ingredient and excipients are weighed and mixed.
2. The wet granulate is prepared by adding the liquid binder–adhesive to the powder blend and
mixing thoroughly. Examples of binders/adhesives include aqueous preparations of cornstarch,
natural gums such as acacia, cellulose derivatives such as methyl cellulose, gelatin, and
povidone.
3. Screening the damp mass through a mesh to form pellets or granules.
4. Drying the granulation. A conventional tray-dryer or fluid-bed dryer are most commonly used.
5. After the granules are dried, they are passed through a screen of smaller size than the one used
for the wet mass to create granules of uniform size.

Low shear wet granulation processes use very simple mixing equipment, and can take a
considerable time to achieve a uniformly mixed state. High shear wet granulation processes use
equipment that mixes the powder and liquid at a very fast rate, and thus speeds up the
manufacturing process. Fluid bed granulation is a multiple-step wet granulation process
performed in the same vessel to pre-heat, granulate, and dry the powders. It is used because it
allows close control of the granulation process.

Dry granulation
Dry granulation processes create granules by light compaction of the powder blend under low
pressures. The compacts so-formed are broken up gently to produce granules (agglomerates). This
process is often used when the product to be granulated is sensitive to moisture and heat. Dry
granulation can be conducted on a tablet press using slugging tooling or on a roll press called a roller
compactor. Dry granulation equipment offers a wide range of pressures to attain proper densification
and granule formation. Dry granulation is simpler than wet granulation, therefore the cost is reduced.
However, dry granulation often produces a higher percentage of fine granules, which can compromise
the quality or create yield problems for the tablet. Dry granulation requires drugs or excipients with
cohesive properties, and a 'dry binder' may need to be added to the formulation to facilitate the
formation of granules.

Problems And Remedies

1. Problem due to excipient: chipping, picking, binding, sticking,
mottling.
2. Problems during process: capping, lamination.
 3. Problem due to machine: double impression.

Picking:
o Picking happens when a part of the tablets gets sticks to the punch surface and
gets eroded from the tablet surface.

o This mostly happens with the upper punch. And if this is left unchecked then
this may lead to weight variation too.

Sno Cause Remedy

1. Due to engraving or
embossing on the upper punch large size particularly on small punches,
2. Rough punch surface
3. Sticky surface of tablet
4. Too deep dividing lines
5. Excess moisture.
6. Hot granules while
compression
7. Excess binder.
The letters to be embossed should be in
or the size of the tablet be increased.
The punch surface should be coated with
chromium so as to get a smooth non
adherent face of punch.
Colloidal silica may be added in the
formula as polishing agent to avoid
sticking to the punch
Reduce the depth of the division.
Proper drying of granules.
The granules are to be dried so that they
do not stick.
Reduce the amount or change the binder
so that the adhesive force is reduced and
more cohesive it becomes.

Sticking:
o It refers to the sticking of the tablet material with the die walls.

o Due to this sticking with the die walls, additional force is required to eject the
tablet form the die walls.
o Sticking also causes production of tablets with rough edges.

o If this problem persists, then this can cause chipping of the tablet.

o It produced unusual stress on the cam track and punch heads resulting in their
damage!

Sno Cause Remedy

1. Low pressure Increase the pressure of punching
2. Fast compression Increase the contact time by reducing the
speed
3. Greater concavity of the punch Reduce the concavity of the punch to
optimum level.

Binding:
o Binding is sticking of the tablet to the die and does not eject properly out of the
die.

o It may be mainly due to lack of proper lubricant or less quantity of lubricant, or

may be due to excess moisture in the tablet.

Sno Cause Remedy

1. Less or incorrect lubricant
2. High moisture content of the
tablet material
3. Hard granules reducing the
effectiveness of lubricant
4. Worn out dies walls
5. Excess pressure in the die
Increase the conc of lubricant or use
appropriate lubricant
The granules are to be properly dried.
Reduce the size of the granules by
passing through 30 mesh so that
increased surface area can increase the
chances of even binding of the lubricant.
Polish the dies properly
Reduce the pressure with in the die.

Chipping:
o Chipping usually happens around the tablet surface, small pieces are broken out
or chipped out of the tablet.

o It is mainly due to improper machine setting, like ejection of the tablet.

Sno Cause Remedy

1. Too much drying Moistane the granule with an
hygroscopic substance
2. Worn out punches Polish the punch surface to get a smooth
finish
3. Sticking of the tablet material Addition of proper lubricant and properly
to the punch dry the granules.
4. Non cylindrical dies with gap Polish the dies so that they become
in the edges cylindrical shape.

Mottling:
o Mottling is uneven distribution of the colour on the surface of the tablet, with
dark and light patches on it.

O It is mainly due to different colouration of the excipient or the degradation

product of the tablet is coloured.

Sno Cause Remedy

1. A dye may cause mottling
when it migrates to the surface
during the granulation process.
2. When coloured binder
solution is not evenly
distributed during mixing
process
3. A colored active ingredient
used along with colourless
excipients.
The formulator is intended to change the
solvent system, binder system, drying
temperature.
The addition should in the sequence of
First the powder colorant is added
followed by the binder like acacia or
tragacanth, followed by the addition of
granulating liquid, and properly mixed.
Addition of appropriate colouring agent.
Capping:
o Capping is a complete or partial separation of the upper or lower surface of the
tablet horizontally, when the tablet comes out of the

o When the air is entrapped in between the tablet material in a die, and when the
material gets compressed between the two punches, the air entrapped also gets
compressed, but when the pressure is released on the tablet I.e. when the two
punched move apart and the tablet ejects out of the die, the compressed sir expands
and leads to capping.

Sno Cause Remedy

1. Large number of fines in the To remove the excess of fines the
material granulation material should bee passed
through 100 to 200 mesh.
2. Improperly dried granules Dry the granules properly.
3. Inadequate or improper binder Increase the quantity of binder or use and
appropriate one.
4. Compression may not be firm Compress the tablet material at higher
due to cool temperature temperature.
5. Improper setting of the lower Correct height of the lower punch should
punch, which causes the be adjusted so that the tablet is smoothly
sweep off blade to cut the ejected out.
surface

Lamination:
o It is similar to capping but here the tablet gets separated into layers.

O It can once again occur due to the air entrapment or due to the high speed of
turret.

Sno Cause Remedy

1. Fast decompression of the Precompression step should be included
tablet. in the process, so that the pressure at the
final compression is reduces.
2. Granules may contain oily or Suitable adsorbent or absorbent should
waxy material. be added.
Double impression:
o It is seen when the tablet punches have engraving or monograms on it to be
embossed on the tablet.

o When the tablet material comes into the die for the compression both the
punches come in contact with the tablet material and compress it, the next step is
ejection of the tablet from the die.

o During ejection process the lower punch travels a small distance down and then
comes up to give a gentle push to the tablet, at this point when the lower punch
moves down and comes up it moves in a swirlling motion, due to the free rotation
when it comes in contact with the tablet for the second time to push it up it leaves
another impression on the tablet. Which is leads to double impression.

o To avoid this key are to be used along the sides of the punches, so that it prevents
rotation of the punches.

Conclusion
Tablets are the most common and frequently used among oral dosage forms. This
is due to its relative low cost and ease of administration. Defects in the tablets can
arise during manufacturing processes, storage or transport. These visual defects
can reduce the acceptability by the users and effectiveness of the product. In this
review defects, causes and measures to overcome these defects have been
discussed and that the same could be minimized and prevented.The focus of this
discussion was to establish ways to resolve common defects at the tablet press, and
to identify the root cause of each and finally resolve the defect before it reaches the
tablet press.

References

1 .Lachman L., Lieberman, H. A., Joseph L. K. The Theory and Practice of Industrial Pharmacy;
Varghese Publishing House; Mumbai; Third Edition; Pp .297-321.
2. Lachman L., Liberman H., and Kanig J. The Theory and Practice of IndustrialPharmacy; Third
Edition: 293-345, 346-373.

3. Aulton M. Pharmaceutics: The Science of Dosage Form Design; International StudentEdition:

304-321, 347-668.

4. Ansel H., Allen L., Jr. Popovich N. Ansel‘s Pharmaceutical Dosage Forms and DrugDelivery
Systems; Eighth Edition: 227-259.

5. Remington J. Remington: The Science and Prac tice of Pharmacy; Nineteenth Edition: Volume II
1615-1641.

6. The theory and practice of industrial pharmacy by Leon Lacman, Herbert A Lieberman,
Joseph L.Kang third edition, Varghese publishing house page no -311-314.

7. Pharmaceutical Dosage Forms Tablets, Vol. 1, pg.no- 188-190

8. http://www.labequipmentsindia.com/product/image/2252.jpg.

9. http://product-image.esuppliersindia.com/00431839/s/3/Tablet-Punching-Machine.jpg.

10. http://www.gmpchina.net/image/p/gzpt1060.jpg.