Tablet Dosage Form

Ph. Dr. Adnan Burhan

 Tablet Dosage Form
Topics

 Introduction & Definitions.

 Advantages & Disadvantages of tablet dosage form.
 General characteristics of tablet.
 Tablet Components.
 Tablet Manufacturing Process.

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 Introduction:

• Different routes of drug administration, oral route is mostly

preferred. About 90% of drugs are administered orally for
systemic effect.

• Since the 19th century to date, the oral solid dosage form, such
as tablets, has been the most predominant and frequently used
medication form.

• This is not only because of the convenience of administration

for patients but also because of their cost-effectiveness in
manufacturing.

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Tablets
• Tablets are oral solid unit dosage form of medicaments with or
without suitable diluents, prepared either by molding or compression.

• They vary greatly in shape, size and weight which depend upon the
amount of medicament used and mode of administration.

• They also vary in hardness, thickness, disintegration and

dissolution characteristics.

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Tablets are popular due to:

1. A convenient and safe way of drug administration.

2. Are more physically & chemically stable.

3. Enables more accurate dosing , easy to use.

4. Can be prepared in different ways.

5. Tablets are provides a sealed covering.

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 Tablets are popular due to:

6. The manufacturing cost of tablets is low.

7. The unpleasant taste and odor can be easily masked.

8. Tablets provide administration of very small dose of drug in an

accurate amount.

9. Special release could be formulated (EC., SR., & LA …)

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Disadvantages of tablet:
1. Not Suitable for poorly water-soluble or poorly absorbable
drugs, less bioavailability.

2. Enhances local irritant effect.

3. Some drugs resist compression into dense compacts.

4. Hygroscopic drugs are not suitable candidate.

5. Drugs having bitter taste, unpleasant odor or oxygen sensitive

requires special treatment, increase their production cost.

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General properties of tablet dosage form:

1. A tablet should have elegant product identity.

2. Its weight, size and appearance should be consistent.

3. Should have sufficient strength.

4. Should have the chemical and physical stability.

5. The tablet must be able to release the medicinal agents.

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 Tablet Ingredients / (excipients)
A typical tablet contains:

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 1- Diluents or Filler
Role:
• Low dose of a potent drugs require addition of a filler to increase the
bulk volume of the powder hence the size of the tablet.

Eg . Dexamethasone 0.5 mg/tablet.

levothyroxine sodium 0.05mg/tablet.

• To make required bulk of the tablet .

• To provide better tablet properties such as to improve cohesion.
To permit use of direct compression manufacturing & To improve
flow.

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 1- Diluents or Filler
• Usually the range of diluent may be vary from 5-80%.

• Most common fillers in tablets:

1. Lactose, Sucrose, Mannitol, Sorbitol; frequently used, water soluble,
improves tablet disintegration. (Lactose-anhydrous and spray dried
lactose).

2. Dicalcium phosphate dihydrate, insoluble in water, disintegrating

agent is a must.
3. Dextrose
4. Directly compressed starch-Sta Rx 1500
5. Hydrolyzed starch-Emdex and Celutab
6. Microcrystalline cellulose-Avicel (PH 101, 102)
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 1- Diluents or Filler

Selection of diluents:

• Based on the experience of the manufacturer, as well as on the cost

of the diluent and its compatibility with other tablet ingredients.

• The proper diluent could be chosen after considering its properties

such as compatibility, flowability, solubility, disintegration
quality, hygroscopy, lubricity and stability.

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 1- Diluents or Filler
Selection of diluents:

• Calcium salts cannot be used as fillers for Tetracycline products

because calcium interferes with the absorption of Tetracycline
from GIT.

• When drug shows low water solubility, it is recommended that

water soluble diluents be used to avoid possible bioavailability
problems.

• The combination of amine bases and salts, with lactose in the

presence of alkaline lubricant results in discoloration upon ageing.
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 2- Disintegrants
Role:
To ensure that the tablet, when in contact with a fluids in GIT,
breaks up into small fragments, which promotes rapid drug
dissolution.

Mode of action:
1. Facilitate water uptake into the pores of tablet,
e.g. surface active agents

2.Facilitate rupture of tablet by swelling during water sorption,

e.g. Sodium –starch glycolate, Crosscarmelose- cross linked cellulose; modified
cellulose, Ac-Di-Sol

3. Release of gases to disrupt the tablet structure, normally carbon dioxide, in

contact with water. e.g. effervescent tablets.
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Commonly Used Disintegrants:

1. Starch: - conc. Up to 5-20% of tablet weight

-Swell in contact with water.

2. Super disintegrants (e.g. Crossecarmelose, Sodium starch

glycolate (Explotab) 1-5 % , Crosspovidone-cross linked povidone)
Swells up to ten fold within 30 seconds when contact water.

3. Clays: Bentonite, Veegum 10 % level in coloured tablet only.

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 3- Binder and adhesive

Role:

To promote cohesive compacts during direct compression

and ensure the tablet remaining intact after compression.

To promote granulation (i.e. as granulator) to ensure free

flowing properties of the particles.

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 3- Binder and adhesive

• Binders are used either in a solution or in a dry form

depending on the materials in the formulation & the
method of preparation.

Examples:
Starch paste 5-25%
Gelatin solution 10-20%,
Natural Gum, acacia, tragacanth, 10-25%
Glucose Solution 25-50%
Cellulose derivative, ethtylcellulose solution 5%
Polyvinylpyrrolidone 2% (PVP), PEG

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 4- Lubricants
Role:

• Lubricants prevent adherence of granule/powder to die

wall and promote smooth ejection from the die after
compaction,

(reduce the friction occurs between the walls of the tablets

and the walls of the die cavity when the tablet is ejected )

• Improve the rate of flow of the tablet granulation.

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 Commonly used Lubricants

A. Water- insoluble (Fatty acids-based) lubricant

• Magnesium Stearate less than 1% most common
• Calcium Stearate
• Stearic Acid, stearic acid salt
• Talc 5 %
• Silica derivative- colloidal silica such as Cab-O-Sil, Aerosil in 0.25-3% conc.

B. water-soluble lubricant
- PEG 6000; less effective
- Magnesium lauryl sulfate; good lubrication and surface wetting effect

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Disadvantages of lubricants
Lubricants tend to be hydrophobic, so their levels (typically 0.3 –
2%) need to be optimized:
– Under-lubricated blends tend to flow poorly and show
compression sticking problems.

– Over-lubricated blends can adversely affect tablet hardness

and dissolution rate, as well as tablet strength.

To overcome these problems;

- Optimum conc. < 2%
- Addition of SAA (surfactant)
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 5- Glidants
Role:
• Promote the flow of the tablet granules or powder by
reducing friction between particles.

• They are used in the formulation for direct compression.

• They are also added to the granules before tableting to ensure

proper flowability of the tablet mass for high production speed.

• Common Glidants:
1. Talc (at concentration 1-2 %).
2. Colloidal silica (Aerosil ®) (0.2 %).
3. Corn Starch 5-10%
4. Magnesium Stearate also used as Glidant in less than 1%
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 6- Antiadherents

Role:

• Reduce sticking or adhesion of the tablet granules or powders to the

faces of the punches or the die walls.

• Such adherence specially occurred if the tablet punches have

markings or symbols.

• Many lubricants, such as magnesium stearate, have also

antiadherent properties. Also talc, corn starch and colloidal silica,
can act as antiadherents.

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 7- Flavours
Role:

Flavours give the tablet a more pleasant taste or

to mask an unpleasant one. (Chewable tablet)

• Flavouring agents are often thermolabile and so cannot be added

prior to an operation involving heat. They are often mixed with the
granules as an alcohol solution.
Ex: Flavour oil

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 8- Colorants
Role:
• It is added to tablets to aid identification,
• Improve patient compliance.
• Mask of off color drug
• Production of more elegant product.

All coloring agents must be approved and certified by FDA.

Two forms of colors are used in tablet preparation – FD &C and D & C
dyes. These Dyes are applied as solution in the granulating agent or
Lake form of these dyes.

Lakes are dyes absorbed on hydrousoxide and employed as dry

powder coloring.
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 9- Sweeteners
Role:
They are used in chewable tablet to exclude or limit the use of sugar
in the tablets.

e.g. Mannitol, Lactose, Sucrose, Dextrose 72% as sweet as sucrose.

Saccharin, 500 times sweeter than sucrose.

Disadvantage: has a bitter after taste.

Aspartame, largely replace saccharin., 180 times sweeter than sucrose

Disadvantage: lack of stability in the presence of moisture and heat.
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 10. Wetting Agents
Role:
In tablet formulation aid water uptake and thereby enhancing
disintegration and assisting in drug dissolution.

 Incorporation of anionic surfactant like Sodium Lauryl Sulphate

(SLS) is known to enhance the dissolution.

 Wetting agents are mainly added when hydrophobic drug is to

be formulated into tablet.

 SLS, Sodium diisobutyl sulfosuccinate are used as wetting agent

in tablet formulation.

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 Active Ingredient ( Drug Substance )
Ideal properties of API for formulating tablets
 1. High Purity
 2. High stability
 3. Good compatibility with excipients
 4. Optimum bulk powder properties
 5. Optimum and Uniform particle size-particle size distribution
 6. Spherical shape
 7. Good flowability
 8. Absence of static charge on surface
 9. Good organoleptic properties

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 Review

Introduction & Definitions.

Advantages & Disadvantages.
General characteristics.
Tablet Components.
Diluent (Filler), Disintegrant,
Binder, Lubricant, Glidants,
Antiadherents, Flavour, Colorants,
Sweeteners and Wetting agents.
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 Tablet Manufacturing Process
TOPICS

 Introduction
 Tablet tooling; Tablet Compression Machine, Punches and Dies
 Stages of Tablet Formation (Compaction Cycle)
 Methods of tablet preparation; 1- Direct Compression
 Advantages & Disadvantages of Direct Compression

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Introduction

 The manufacture of oral solid dosage forms such as

tablets is a complex multi-stage process under which the
starting materials change their physical characteristics a
number of times before the final dosage form is produced.

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 Introduction
Powders intended for compression into tablets must possess two
essential properties:

1- Powder fluidity
The material can be transported through the hopper into the die to
produce tablets of a consistent weight.
Powder flow can be improved mechanically by incorporating the
glidant.

2- Powder compressibility
The property of forming a stable, intact compact mass when
pressure is applied

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Tablet Compression Machine “Tablet press ”

• 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.

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Tablet tooling: Tablet Compression Machine
Design:
1. Hopper for holding and feeding granules or powder to be
compressed.

2. Dies that define the size and shape of the tablet.

3. Punches for compressing the granules within the dies.

4. Cam tracks for guiding the movement of the punches.

5. A feeding mechanism for moving granules from the hopper into

the dies.

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 Tablet tooling: Punches and Dies

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 Star Shapes Dies
Caplet Shape Dies

Oval Shapes Dies

Round Shapes Dies

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.
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Types of tablet press
1- Single Punch press (Eccentric Press):
bench-top models that make one tablet at a time (single-station
presses)
Disadvantages: Production of small batches of tablets (200 tablets per
minute).

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Tablet press
2- Rotary Press( Multi station Press):

• It was developed to increase the output of tablets (10 000 tablets per
minute), used for Large scale production.

• It consists of a number of dies and sets of punches ( from 3 up to

60).

• The dies are mounted in a circle in the die table and both the die
table & the punches rotate together during operation of the machine.

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 Rotary Press Machine

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 Stages of Tablet Formation
Basics
Powders fed into a die
Powder compressed between punches
Ejection from a die

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Stages of Tablet Formation (Compaction Cycle)
1- Die filling
Gravitational flow of the powder from hopper via the die table into
the die . (The die is closed at its lower end by the lower punch).

2- Tablet formation
The upper punch descends, enters the die, the powder is
compressed until a tablet is formed.
-after maximum applied force is reached, the upper punch leaves the
powder i.e. compression phase.
3- Tablet ejection
The lower punch rises until its tip reaches the level of the top of the
die.
The tablet is subsequently removed from the die and die table by a
pushing device.
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 Methods of tablet preparation
1- Direct compression:
 The term “Direct compression” is defined as the process by which
tablets are compressed directly from powder mixture of API and
suitable excipients.
 It involves only two unite operations powder mixing and tableting.

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 Primary steps before compression

Regardless of weather tablets are made by Direct compression or

granulation, numerous unit processes are involved in making
tablets, including:

Dispensing (weighing and measuring) of Each ingredients.

Drying It is important to keep the residual moisture low enough to

prevent product deterioration and ensure free flowing properties.

Sizing (size reduction, milling, crushing, grinding, pulverization)

Powder blending The powder/granules blending are involved at stage

of pre granulation and/or post granulation stage of tablet
manufacturing.
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Tablet compression

 After the preparation of ingredients (in case of direct compression),

they are compressed to get final product.

 Compressed tablet prepared, usually as a large-scale production, by

means of great pressure.

 The compression is done either by single punch machine

(stamping press) or by multi station machine (rotary press).

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Prepared tablets are followed by

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.

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.
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 Advantages of Direct Compaction:

1. Reduced production time & cost.

2. Product stability can be improved.

3. Faster drug dissolution.

4. Less number of equipments are required, less process validation.

5. Elimination of heat and moisture.

6. The chances of batch-to-batch variation are negligible.

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 Disadvantages of Direct Compaction

1. Large particles must be used.

2. Many active ingredients are not compressible directly.
3. Problems in the uniform distribution of low dose drugs.
4. High dose drugs having high bulk volume, poor flowability and
poor compressibility are not suitable for direct compression.
5. Non-uniform distribution of colour, especially in tablets of deep
colors.

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Tablet Manufacturing Process

To be continued…………

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