This document provides an overview of non-sterile tablet manufacturing processes. It begins with definitions of non-sterile dosage forms including tablets, capsules, ointments, suspensions and emulsions. It then discusses various aspects of tablet manufacturing including formulation, equipment used, granulation techniques, compression, and quality control tests. The document focuses on tablet manufacturing processes and quality checks to ensure consistent and quality tablets are produced.

1. Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune -
411018.
PRESENTED BY :DNYANESHWAR KHODSE
ROLL NO.:-537
(PHARMACEUTICAL QUALITY ASSURANCE)
GUIDED BY : Dr. R.K.NANDA
( Associate professor )
NON STERILE MANUFACTURING
PROCESS TECHNOLOGY

2. CONTENTS
• Introduction
• Types
• Tablets
• Formulation
• Plant layout for tablets manufacturing
• Manufacturing flow charts
• Equipments used in tablet manufacturing
• Problems in tablet manufacturing process
• IPQC tests for tablets
• Coating technology
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3. INTRODUCTION
 Non-sterile compounding involves creating a medication in a clean
environment but does not require the environment to be completely
free from all microorganisms.
Non sterile dosage forms-
• Tablets
• Capsules (Hard & Soft)
• Ointments
• Suspension
• Emulsion
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4. TABLET MANUFACTURING PROCESS
DEFINITION :-
• Tablet is defined as a compressed solid dosage form
containing medicaments with or without excipients.
• According to the Indian Pharmacopoeia Pharmaceutical
tablets are solid, flat or biconvex dishes, unit dosage form,
prepared by compressing a drugs or a mixture of drugs,
with or without diluents.
• It is the most popular dosage form and 70% of the total
medicines are dispensed in the form of Tablet.
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5. Advantages Of The Tablet Dosage Form
1. Cost is lowest of all oral dosage form.
2. Lighter and compact.
3. Easiest and cheapest to package and strip.
4. Easy to swallowing with least tendency for hang-up.
5. Sustained release product is possible by enteric coating.
6. Objectionable odour and bitter taste can be masked by
coating technique.
7. Suitable for large scale production.
8. Greatest chemical and microbial stability over all oral
dosage form.
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6. Disadvantages of Tablet dosage form
Drugs which are amorphous and low density character are
difficult to compress into tablet.
Hygroscopic drugs are not suitable for compressed
tablets.
Sensitive to oxygen drugs may require special
coating.
Cost of production may be increase because of
coating and encapsulation to remove bitter and
unpleasant taste.
Some tablet may cause problem in bioavailability.
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7. Formulation-
1) API
2) Exicipients
1) API - (Active Pharmaceutical Ingredients)
It is main drug which gives therapeutic effect
2) Exicipients -
Excipients are substances, other than the active drug substance, or
finished dosage form, that have been appropriately evaluated for safety &
are included in drug delivery systems:
• To protect, support, or enhance stability, bioavailability or patient
acceptability.
• To assist in product identification.
• To enhance any other attribute of the overall safety, effectiveness, or
delivery of the drug during storage or use.
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Excipient functions-

9. Plant layout for tablets manufacturing-
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12. Granulation-
Granulation is the process in which dry primary
powdered particles are processed to adhere to form
larger multiparticle entities called granules.
Types of granulation –
1) Dry granulation
2) Wet granulation
1) Dry granulation -
A) Slugging :
a. Blend is forced into dies of large capacity tablet
press and compacted using flat faced punches.
b. compacted masses are called slugs and process
is called slugging.
c. Slugs milled or screened to produce good free
flowing granules for compression.
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Fig.-Slugging euipment

13. B) Roller compaction-
On a large scale compression granulation can also be performed on a
roller compactor.
Granulation by dry compaction can also be achieved by passing powders
between two rollers that compact the material at pressure of up to 10 tons
per linear inch.
Materials of very low density require roller compaction to achieve a bulk
density sufficient to allow encapsulation or compression. One of the best
examples of this process is the densification of aluminum hydroxide.
Roller compactor is capable of producing as much as 500 kg/hr of
compacted ribbon like materials which can be then screened and milled in to
granules for compression.
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Fig.- Roller compacter

14. 2) Wet granulation
 The most popular method (over 70% )Granulation is done
• To prevent segregation of the constituents of the powder blend.
• To improve flowability of the powder mixture.
• To improve the compaction characteristics of the powder mixture
due to better distribution of the binder within the granules.
• To improve homogeneity and thus ensure content uniformity Wet
granulation is a process of using a solution binder to the powder
mixture.
 The amount of liquid can be properly managed;
overwetting -the granules to be too hard,
underwetting -too soft and friable.
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15. Limitations of wet granulation:
1) Multiple separate steps are involved.
2) Not suitable for heat and moisture sensitive drugs
Equipments Traditionally, dry mixing in wet granulation process has been
carried out using,
Sigma blade mixer. Heavy-duty planetary mixer.
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High Shear granulation:
i)Little ford Lodgie granulator
ii)Little ford MGT granulator
iii)Diosna granulator
iv)Gral mixerGranulator
with drying facility:
i) Fluidized bed granulator
ii) Day nauta mixer processor
iii) Double cone or twin shell processor
iv) Topo granulator
Special granulator:
i) Rotor granulator
ii) Marumerizer
Fig.-Fluidized bed granulator
Fig.-Rotor granulator
List of equipments used in granulation

17. Advanced Granulation Techniques
• Spheronization / Extrusion –
Spheronization or marumerization, is a rapid and flexible process where
pharmaceutical products are made into small spheres, or spheroids of diameter
ranging from about 0.5mm to 1mm where as in marumerizatin 0.6mm t0 1.2mm.
Spheronization process-
Dry mixing of ingredients – to achieve a homogeneous powder dispersion;
Wet massing – to produce a sufficiently plastic wet mass.
Extrusion – to form rod shaped particles of uniform diameter .
Spheronization – to round off these rods into spherical particles .
Drying - to achieve the desired final moisture content.
Screening -to achieve the desired narrow size distribution
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There are many designs of extruders,
based on their feed mechanism-
A) Screw-feed extruders-
1) Axial
2) radial
B) Gravity-feed extruders-
1) Cylindrical roll
2) Gear roll
C) Piston-feed extruders
Fig.- Spheronizer
Fig.- Gear roll Fig.- Radial Screw-feed
extruders
Fig.- Axial Screw-feed extruders

20. Compression Tableting procedure
Filling
Compression
Ejection
Tablet compression machines
• Hopper- for holding and feeding granulation to be compressed
• Dies- that define the size and shape of the tablet
• Punches- for compressing the granulation within the dies
• Cam tracks- for guiding the movement of the punches
• Turrets - Holding the upper and lower punches
• Feeding mechanisms for moving granulation from the hopper into
the dies.
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21. Single punch machine-
Bench – top models that make one tablet at
a time (single station presses)
Disadvantages-production of small batches
of tablets.(200 tab.per min)
• Multi-station rotary presses-
The head of the tablet machine that holds
the upper punches, dies and lower
punches in place rotates
As the head rotates, the punches are guided
up and down by fixed cam tracks, which
control the sequence of filling,
compression and ejection.
The portions of the head that hold the
upper and lower punches are called the
upper and lower turrets
The portion holding the dies is called the
die table
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Single punch machine
Multi-station rotary presses

22. Compression cycle
• Granules from hopper empty in the feed frame (A) containing several
interconnected compartments.
• These compartments spread the granulation over a wide area to provide
time for the dies (B) to fill.
• The pull down cam (C) guides the lower punches to the bottom,
allowing the dies to overfill
• The punches then pass over a weight-control cam (E), which reduces
the fill in the dies to the desired amount
• A swipe off blade (D) at the end of the feed frame removes the excess
granulation and directs it around the turret and back into the front of the
feed frame
• The lower punches travel over the lower compression roll (F) while
simultaneously the upper punches ride beneath the upper compression
roll (G).
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23. • The upper punches enter a fixed distance into the dies, while the
lower punches are raised to squeeze and compact the granulation
within the dies
• After the moment of compression, the upper punches are withdrawn
as they follow the upper punch raising cam (H)
• The lower punches ride up the cam (I) which brings the tablets flush
with or slightly above the surface of the dies
• The tablets strike a sweep off blade affixed to the front of the feed
frame (A) and slide down a chute into a receptacle
• At the same time, the lower punches re-enter the pull down cam (C)
and the cycle is repeated
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26. Problems in tablet manufacturing-
An ideal tablet should be free from any visual defect or functional
defect.
Defects in tablet are related to imperfections in any one or more of
the following factors:
a) Machine related
b) Formulation related
c) Tableting Process related
tablet defects-
1.Capping 5.Sticking
2.Lamination 6.Chipping
3.Cracking 7.Mottling
4.Picking 8.Double impression
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27. 1.Capping
• Capping is the term used, when the
upper or lower segment of the
tablet separates horizontally during
ejection from the tablet press, or
during subsequent handling.
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28. 2.Lamination
• Lamination is the separation of a tablet
into two or more distinct horizontal
layers.
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29. 3.Cracking-
• Small, fine cracks observed on the
upper and lower central surface of
tablets, or very rarely on the
sidewall are referred to as Cracks.
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30. 4.Chipping
• Chipping‘ is defined as the
breaking of tablet edges, while
the tablet leaves the press or
during subsequent handling
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31. 5.Sticking
• Sticking refers to the
tablet material adhering to
the die wall.
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32. 6.Picking
• Picking is a more specific term
that describes product sticking
only within the letters, logos, or
designs on the punch faces.
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33. 8.Mottling
• Mottling is the term used to
describe an unequal
distribution of colour on a
tablet.
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34. 9.Double impression
• It is due to free rotation of punches which have some engraving
or monogram on the punch faces. During his free travel, the
punch rotates and at this point, the punch may make a new
impression on the bottom of the tablet, resulting in 'Double
Impression.
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35. IPQC Tests For Tablets
1.Hardness
2.Friability
3.Thickness
4.Disintegration
5.Weight variation
6.Content uniformity
7.Dissolution
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36. 1. hardness (crushing strength):
• It is the load required to crush the tablet when placed on its edge.
• To determine the need for pressure adjustments on the tableting machine.
• Hardness can affect the disintegration.
• So if the tablet is too hard, it may not disintegrate in the required period of time.
And if the tablet is too soft, it will not withstand the handling during subsequent
processing such as coating or packaging.
Some of devices used to test tablet hardness are :
1. Monsanto tester
2. Strong-cobb tester
3. Pfizer tester
4. Erwica tester
Limits: 5 kilograms minimum and 8 kilograms maximum.
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Fig.- Monsanto tester

37. 2.Friability
It is the tendency of tablets to powder, chip, or fragment and
this can affect the elegance appearance, consumer
acceptance of the tablet.
• Friability is a property that is related to the hardness of the
tablet.
• friabilator is used to evaluate the ability of the tablet to
withstand abrasion in packaging, handling, and shipping.
Friability (% loss) = It must be less than or equal to1%.
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Fig.-Friabilator
3. Thickness test:
The thickness of a tablet depends on the upper and
lower punches at the moment of compression.
it can be tested using vernier calipers.
The range varies with +/- 5.0%
Fig.- Vernier caliper

38. 4.Disintegration
It is the time required for the tablet to break
into particles, the disintegration test is a
measure only of the time required under a
given set of conditions for a group of
tablets to disintegrate into particles.
Disintegration test-
The disintegration USP device uses 6 glass
tubes that are 3 inches long open at the top
and held against a 10mesh screen at the
bottom end of the basket rack assembly.
Frequency of basket is 28-32 cycles/min .
The test is done on 6 tablets and the test is
passed when all the 6 tablets disintegrate.
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Fig.- disintegration test
appratus

39. IP limits
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Type of tablet liquide Disintegration time
(min)
Dispersible tablet Water 3 min
Effervescent tablet Water 5 min
Uncoated tablet Water 15 min
Film coated tablet Water 30 min
Sugar coated tablet Water 1 hr
Enteric coated tablet 0.1 N HCL with
phosphate buffer
Should not disintegrate
within 2 hr in gastric
fluid and must
disintegrate 1 hr in
intestinal fluid
Vaginal tablets water 30 min

40. 5.Weight variation
The volumetric fill of the die cavity determines the weight of the
compressed tablet . The weight of the tablet is the quantity of the
granulation that contains the labeled amount of the therapeutic
ingredient.
•After the tablet machine in operation the weights of the tablets are
routinely checked to ensure that proper tablet weights are made.
•Compare the individual weight of tablets with avg weight.
•Not more than 2 tablets should deviate from avg weight by percent
deviaton and none should deviate more than twice the percentage
Limits according to U.S.P-
·Weight of tablet 130 mg or less then % deviation ±10%
·Weight of tablet 130-324 mg then %deviation= ±7.5%
·Weight of tablet 324 mg or more then %deviation = ±5%
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41. 6)Content uniformity
• This test is done to ensure that every tablet contains the amount of
drug substance intended with little variation within a batch
• In this test 30 tablets are randomly selected for the sample and atleast
10 of them assayed individually .
• 9 of the 10 tablets must contain not less than 85% or more than 115
% of labeled drug content.
• 10th tablet may not contain less than 75% or more than 125% of
labeled content .
• If this conditions are not meet the tablet remaining from the 30 must
be assayed individually and none may fall outside 85 to 115 %
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42. 7) Dissolution Test-
- Dissolution is performed to check the percentage release
from the dosage form i.e. tablets breaks down into
small particles which offers a greater surface area to the
dissolving media.
- Disintegration test does not gives assurance that particles
will release drug in solution at an appropriate rate,
that’s why dissolution tests and its specifications
developed for all tablet products.
a)USP dissolution appatarus I(basket method):
- A single tablet is placed in a small wire mesh basket
attached to the bottom of the sahft connected to a
fariable speed motor.the baket is immersed in a
dissolution medium (as specified in momograph)
contained in 1000 ml flask .The flask is cylindrical
wuth a hemi-spericial bottom. The flask is maintained
at 37+0.5 0celacius
- By a constant temperature bath.the motor is adjusted to
turn at the specified speed and sample of the liquid are
withdrawn at intervals to determine the amount of drug
in a solutions.
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Fig.- paddle type
Fig.-Rotating basket

43. b) USP dissolution apparatus II (paddle method):
it is same as apparatus-I, except the basket is replaced by a paddle. The dosage form
is allowed to sink to the bottom of the flask before stirring. For dissolution test
USP specifies the dissolution test medium and volume, type of apparatus to be
used,rpm of the shaft,time limit of the and assay procedure for. The test tolerance
is expressed as a % of the labelled amount of drug dissolved in time limit.
Dissolution testing and interpretation IP standards-
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D is the amount of dissolved active ingredient specified in the individual monograph,
expressed as a percentage of the labelled content.

44. TABLET COATING -
“Tablet coating is the application of coating material to the exterior of
a tablet with the intention of conferring benefits and properties to a
dosage form over the uncoated variety.”
Why To Coat ???
Mask Bitter taste
Mask unpleasant odour.
Protecting the drug from surroundings.
To increase the Stability.
Handling & ease of ingesting by patients.
Mechanical protection from breakage.
Avoid Light incompatibility.
Protection from Environmental Oxidation.
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45. In- elegent core.
To modifying the drug release profile.
For Product identity.
Types of Coating
Sugar coating
Film coating
Enteric coating
Controlled release coating
Specialized coating
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46. Steps involved in Coating
1) Sealing/Seal coating
2) Sub-coating
3) Grossing/Smoothing
4) Coloring
5) Polishing/Finishing
6) Printing
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47. Types of coating pans
1.Conventional coating pans
A) Pelligrini pan
B) Immersion sword type
C) Immersion tube type pan
2.Perforated coating pans
A) Accela cota pan
B) Hi-coater
C) Dria coater
D) Glatt pan-coating equipment
E) Huttlin butterfly pan
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Fig.- Immersion tube type pan
Fig.- Immersion sword type pan

48. References –
1. Leon Lachman, Herbert A. Lieberman, “The Theory and Practice
of Industrial Pharmacy” Special Indian Edition 2009, Page no: 293
to 334.
2. Herbert A. Lieberman, Leon Lachman, Joseph B.Schwartz,
“Pharmaceutical Dosage Forms: Tablets” Volume 1, Second
Edition, Page no: 88 to 121.
3. Joseph P. Remington, Paul Beringer, “ The Science and Practice of
Pharmacy” Published by: Philadelphia: Lippincott Williams and
Wilkins, 21st Edition, Page no:889 to 913.
4. Michael E. Aulton, Kevin M. G.Taylor, “The Design and
Manufacture of Medicine” Published by: Churchill Livingstone,
Fourth Edition, Page no: 465 to 549.
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THANKYOU!