Pharmaceutical tableting

By Dr. Karim Maarif

Plan
Introduction
Compression
•Intermolecular bonding forces
•Punches (tooling)
•Punches and dies terminology
•Tablet forms
•Tabletting cycle
 Filling
Compression (Pre-compression & compression)
Ejection

TABLETING MACHINES
• Single - Punch Tableting Machines (Presse à comprimés alternative)
•Rotary Tableting Machines
•Applications de la presse à comprimés

IMPROTANT FACTORS DURING MANUFACTURING PROCESS :

•Optimization of Die Filling
•Tablet Weight Control
•Control of Mixing Homogeneity
•Lubrification
•Cleaning

PROBLEMS DURING TABLET MANUFACTURING

• Capping and Lamination
•Picking and Sticking
•Mottling
COMPRESSION
Introduction
• Tablets are the most important pharmaceutical dosage from,

• Compression is defined as the reduction in the bulk volume of a

material.

• 4 mechanisms are basically involved in the process of compression of

particles:
 Deformation,
 Densification,
 Fragmentation,
 Attrition

• In order to compress a powder or granulation product into a tablet of

specific hardness, a defined compression force must be applied.

• By compressing a constant mass of powder, any variation in the

applied force causes a change in tablet mechanical strength.
Introduction
• If the powder has good compressibility, then the force needed for
compression would be low.

• This compressibility will depend on powder characteristics (Specfic

surface area, cristalinity, density etc… and thermodynamic behavior).

• As tablet formulation is a multicomponent system, its ability to form a

good compact is dictated by the compressibility and compactibility
characteristics of each component:

 Compressibility is the ability of a powder to decrease in volume under pressure.

 Compactibility is the ability of the powder to be compressed into a tablet of specific
tensile strength.

• Two stages involved in the compaction:

 Initial compression: to push the particles closer together and
 Deformation: where closely packed particles no longer reduce the packing volume
by simple movement around each other but deform either by brittle fracture or by
plastic flow or both
Intermolecular bonding forces
• The processes of brittle facture and plastic flow increase the
surface contact and bond formation

• The Types of Bonding That can be responsible for tablet

Formation:

1) Solid bridges: are formed between two particles by processes such as

crystallization of amorphous portions of solid, or chemical reactions (such as salt
formation between adjacent particles).

2) Moveable liquids: compaction is assisted by the presence of some moisture.

3) Non–freely moveable binders: include the binders used in wet granulation

processing (PVP), which make powders into better compact.

4) Attraction between solid particles: By long-range attractive forces :

- Electrostatic: during mixing and other dry processing events
- Van der Waal and hydrogen bonding: major contribution during
tabletting.

5) Mechanical interlocking
Punches
• Internationally there are two recognized
standards for tablet compression tooling,
the TSM and the EU standards.

• Both TSM and EU standards identify the

physical tool configuration for B and D
type compression tools, their critical
dimensions and associated tolerances
assuring tablet quality and smooth press
operation

*TSM “Tablet Specification Manual” tooling standard is recognized in the

Americas and is considered exclusive in the United States.
Punches
Punches

The domed head configuration

provides:

1) A smoother transition into the

compression cycle of the tablet press,

2) Reducing stress,
Punches

* Advantage: To increase the tablet press output.

* Disadvantage: risk of head fracturing (outside of the neck diameter)
Punches

• The lower punch tip creates a tremendous

amount of friction as it travels the full length of
the die through the various stages of tablet
compression.

• When compressing sticky products or products

with a low melting point, the friction created by
the lower punch tip can cause lower punch
binding.

• Reducing the bearing surface of the lower

punch tip
Punches
 Product wedged between the punch tip and die wall may cause excessive heat and thermal
expansion of the punch tip. This could result in:
* Punch binding and/or seizure,
* Premature head wear,
* Tablet discoloration or burning
* Dark particles contaminating the tablet.

 A “ bakelite relief ” assures a sharp edge to assist with removing product adhered to the
die wall allowing the punch tip to move freely in the die

 A “double deep relief” increases the depth of the lower punch relief and provides the
same results as
the bakelite relief;
Tablet forms
Undesirable Shapes:
to be avoided in order to provide maximum tablet output and
satisfactory tool life
*A tablet shape too close to round may cause a condition known as punch-to-die binding or
self-locking.

* The corner radius less than 0.032 inch can cause excessive stress and failure of tablet
compression
Tablet forms
Tablet forms
Punches

• The lower punch tip creates a tremendous

amount of friction as it travels the full length of
the die through the various stages of tablet
compression.

• When compressing sticky products or products

with a low melting point, the friction created by
the lower punch tip can cause lower punch
binding.

• Reducing the bearing surface of the lower

punch tip
Tabletting cycle

 Filling

 Compression

Ejection
Tabletting cycle

Filling
 Is a volumetric process
 The filling depth is determined by the height of the die cavity
 The filling volume is determined by the diameter of the die hole and the
filling depth
Tabletting cycle

Compression

 Is the central stage of tablet production

 Compression not only depends on the machine but mainly on the material properties
of a tablet formulation.

 The elastic recovery or relaxation of the tablet starts when one punch leaves the
tablet and continue after ejection
Tabletting cycle

Ejection

 Usually the lower punch moves upward to eject the tablet from the die
 The upper punch has already left the die when the process of ejection starts.
TABLETING MACHINES
TABLETING MACHINES

Single - Punch Tableting Machines

TABLETING MACHINES

Rotary Tableting Machines

Application of Tableting Machines

• In summary, the single - punch tableting machines still being used are
mostly for research, whereas rotary machines are predominantly used for
production;

• For rotary machines in most cases it is not machine speed that determines
the production rate but material flow and compression properties.
IMPROTANT FACTORS DURING
MANUFACTURING PROCESS
IMPROTANT FACTORS DURING
MANUFACTURING PROCESS
Optimization of Die Filling:

• Two problems arise generally:

1- Either the product demixes and tablet weight and content uniformity are no
longer controlled
2- or the die is not completely filled and thus tablet weight also varies.

• At low machine speeds the die is usually completely filled; at high machine speeds
this becomes more difficult. Thus special filling devices using one or more paddles
have been developed to improve filling.
IMPROTANT FACTORS DURING
MANUFACTURING PROCESS
Tablet Weight Control:

To control tablet weight different possibilities exist.

• To weight (IPC) a number of tablets manually and to adjust machine settings

according to the results when necessary

• For high - speed rotary machines automatically working weighing systems have
been developed to be controlled by control of compression force.
IMPROTANT FACTORS DURING
MANUFACTURING PROCESS
Control of Mixing Homogeneity:

• The systems to control weight uniformity are not able to control uniformity of the
mixture
• When during fi lling of the die the tableted material demixes, tablet weight usually
tends to vary. However, these variations can be small and not easy to detect

• To monitor mixing uniformity in the final tablet: (Spectroscopic techniques )

1- Raman spectroscopy
2- Near - Infrared (NIR) spectroscopy
3- Special online sensors have been build into the machine and they measure the
spectrum for each tablet.
IMPROTANT FACTORS DURING
MANUFACTURING PROCESS
Lubrication:

• Adhesion forces between the material and punches and dies result in sticking of the
tablets at the punches and dies.

• Adhesion forces are further influenced by RH

• à
• If adhesion forces at the punches and dies >>>> the cohesion forces between the
particles inside the tablet  tablets stick at the punches and can cap

• To overcome this problem, lubrication (internal and external) is the method of

choice:

1-Internal: by mixing the tableted product shortly before the tableting process with a solid
lubricant, thus lowers bonding (for plastically deforming materials).

2- External: punches and dies can be manually lubricated with a fluid

IMPROTANT FACTORS DURING
MANUFACTURING PROCESS
Cleaning :

• To ensure product quality, cleaning is of utmost importance

• It involves:

1- The addition of spray systems, tank cleaners, nozzles, and seals into the tableting
machine in order to automate the cleaning process.

• 2- The wash -off - line procedure : by cleaning the exchangeable compression

modules after it is removed from the tablet press.
PROBLEMS DURING TABLET
MANUFACTURING
PROBLEMS DURING TABLET
MANUFACTURING
Capping and Lamination

 Common problems that can be experienced during tableting.

 Capping is defi ned as the splitting of one or both lids of a tablet from its body.

 Lamination is a precursor to capping since it involves the occurrence of layers in

a compact parallel to the punch face.

• Sometimes capping is noticed not during the process but during physical testing:
such as friability and hardness or during the coating (early stage)
PROBLEMS DURING TABLET
MANUFACTURING
Capping and Lamination

• Lamination could be relatedto radial elastic recovery of the compacted material

during ejection.

• Capping is the result of air entrapped in the tablet under pressure which tries to
escape during ejection but does not affect lamination.

• materials having sufficient plasticity may not be susceptible to lamination.

• Normally, drugs such as Paracetamol, Mannitol, Ibuprofen, Phenazone, and

Mefenamic acid have poor compression properties and produce weak tablets and
frequently exhibit capping
PROBLEMS DURING TABLET
MANUFACTURING
Capping and Lamination
PROBLEMS DURING TABLET
MANUFACTURING
Capping and Lamination

• A technique generally applied to characterize and prevent the capping and lamination
of a material intended to be compacted is using the brittle fracture index (BFI).

• The BFI measures the ability of a material to relieve (reduce) stress by plastic
deformation around a defect. It compares the tensile strength of a tablet with a hole
in its center ( T 0 ), which acts as built - in stress concentrator defect, with the tensile
strength of a similar tablet without a hole ( T ), both at the same relative density:

• A material showing a moderate to high BFI > 0.5 is prone to laminate and cap during
the process

• A low value of BFI is desirable to minimize lamination and capping during tablet
production.
PROBLEMS DURING TABLET
MANUFACTURING
Picking and Sticking

• Picking: adherence of powder to the punch surface. It is more problematic when

the punch surfaces are engraved with logos or letters such as B, A, or O .

• Sticking: Occurs when powder tends to adhere to the die leading to the
development of an additional pressure between the formed compact and the die
wall.

• sticking can cause picking or damage the press punches by blocking the free
movement of the lower punches leading to an increase of compaction pressure.

• To solve picking and sticking problems during tablet manufacturing: pptimization of

press tooling, process parameters, and formulationit is important to find the optimal
combination of formulation and process parameters,
PROBLEMS DURING TABLET
MANUFACTURING
Picking and Sticking

• In relation to formulation adjustment: an antisticking agent can be added to the

powdered formulation in order to eliminate picking and sticking during
manufacturing:

 Talc is commonly used

 Colloidal silicon dioxide may be the right choice

• However, when adding colloidal silicon dioxide to the powder formulation, it would
be necessary to add an extra lubricant in order to facilitate ejection of tablets from
the dies.

• When stearic acid or propylene glycol or any other raw material of low melting
point is present in the powder formulation, the heat generated during tableting may
cause softening of these ingredients, thus leading to sticking  To overcome this
problem, it may be needed to refrigerate the powder load to be tableted or to equip
the press machine with a cooling unit.
PROBLEMS DURING TABLET
MANUFACTURING
Picking and Sticking

• Press tooling may need to be adjusted to improve tableting:

 Logo or letters on the punches should be as big as possible.

 Punch tips may be plated with chrome in order to give a smooth and
nonadherent surface.

 Punch surface polishing (risk to dammage the punch surface when

 PROBLEMS DURING TABLET
MANUFACTURING

Picking and Sticking

PROBLEMS DURING TABLET
MANUFACTURING
Mottling

• Is an uneven coloration of tablets or non-uniformity of color over the tablet

surface.
• Causes:
 May be the difference in color between the API and excipients,
 May be the result of degradation of the API which imparts spot zones over
the surface of the tablets.
 Dye migration to the periphery of granules during the drying process
(colored compressed tablets)  changing the solvent used for wet granulation
or the binder agent, using a low drying temperature, or decreasing the
particle size of the excipient.
PROBLEMS DURING TABLET
MANUFACTURING
Mottling
PROBLEMS DURING TABLET
MANUFACTURING
Weight and Hardness Variation

• Tablet weight is mainly affected by factors such as:

Powder variation ( density and PSD)
Tablet press condition,
Tooling,
Flow of powder on the tablet press (overfilling or lack of filling of the die..)
Segregation due to transfer (vibration, mechanical stress) or static
electricity.
Poorly prepared or operated tablet press
Critical dimensions of tablet press tools
The working length of each punch must be correct and identical
Never neglect the level of the product in the hopper.
The fill cam is another factor that can have a profound effect on tablet
weight (it is recommended to overfill it by 10 – 30% of its volume)
PROBLEMS DURING TABLET
MANUFACTURING
Weight and Hardness Variation

• Tablet hardness :

Is intimately related to weight variation

Dwell time might be a source of hardness variation

• When the tablet weight target is kept within limits but hardness varies,
the problem may be due to the formulation.,

• When it becomes hard to achieve tablet hardness, it is recommended to:

- First verify tablet weight and thickness consistency
- Then try to adjust the pre compression.
PROBLEMS DURING TABLET
MANUFACTURING
Punches and dies terminology
Punches and dies terminology