methods for the preparation of manufacturing of tablets

1. METHODS USED FOR THE MANUFACTURE OF TABLETS
Prepared By:
DR. ANANDA KUMAR.CH
Assoc. Prof
Department of pharmaceutics
Lydia college of pharmacy
Subject: Pharmaceutical
Formulation
Pharma. D IIIrd Year

2. CONTENTS
• DEFINITION
• WET GRANULATION
• DRY GRANULATION
• DIRECT COMPRESSION

3. DEFINITION OF TABLETS
A tablet is a pharmaceutical dosage form. It comprises of a
mixture of active substances and excipients, usually in powder
form, passed are compacted into a solid dose.
Excipients:
1. Diluents, binders or granulating agents, glidents and
lubricants to ensure efficient tabletting;
2. Disintegrates: to promote tablet break up in the digestive
tract;
3. Sweeteners or flavours: to enhance the taste;
4. Polymer coating: it is to 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.

4. MANUFACTURE OF TABLETS
• There are three methods by which tablets are manufactured;
1. Wet granulation
2. Dry granulation
3. Direct compression
Manufacturing process is dependent on several factors, including
the compression properties of the therapeutic agents, the
particle size of the therapeutic agent, excipients and the
chemical stability of the therapeutic agent during the
manufacturing process.

5. MANUFACTURE OF TABLETS STEPS
1. Mixing of the therapeutic agents with the excipients
2. Granulation of the mixed powders(this is not performed in
direct compression)
3. Mixing of the powders or granules with other
excipients(mostly lubricants)
4. Compression into tablets
5. The details of each of these steps will vary depending on the
manufacturing method used.

6. Wet granulation
• It is most commonly used method for the manufacturing of
tablets.
• Water is frequently used as the granulation fluid (and heat is
employed to dry the formed granules), it is important to ensure
that the therapeutic agent is chemically stable during the
granulation process.
• The wet granulation exhibit sufficient mechanical properties to
be subsequently exposed to other unit operations, Eg: film
coating.
• Tablet quality is directly affected by the choice and
concentration of binder and the type and volume of granulation
fluid. Due to the number of unit operations to the required, the
manufacture of tablets by wet granulation is not as efficient as
other methods. eg: direct compression

7. Advantages & disadvantages
1. Reduced segregation of formulation components during storage
and processing. Leading to reduced intra and inter batch
variability.
2. It uses low concentration of therapeutic agent.
3. It is not dependent on the inclusion of special grades of
excipients (is spray dried excipients used in direct compression
method).
4. Tablets produced by wet granulation are amenable to post
processing unit operations, eg: tablet coating techniques.
Disadvantages:
1. It has several processing steps
2. Solvents are required in the process: this leads to a number of
concerns, eg: drug degradation may occur in the presence of the
solvent. This is particularly relevant if water is used as the
granulation medium due to the susceptibility of some drugs to
hydrolysis

8. Advantages & disadvantages
• To overcome this concern, a hydroalcoholic (water/alcohol) or
an alcohol (ethanol or isopropanol) granulation medium should
be used.
3. The drug may be soluble in the granulation fluid. During the
drying process the drug will then precipitate/crystallise,
resulting in possible changes in the polymorphic form. If the
drug and some excipients soluble in the granulation medium,
subsequent drying will result in deposition of these components
on the surface of the insoluble particles and in so doing, this
may enhance the hardness of the granule
4. Heat is required to remove the solvent. This may result in the
degradation of thermo labile therapeutic agents. In addition
drying is a costly operation and furthermore, if alcohols are
used in the granulation medium, there are issues regarding
solvent recovery and flammability.

9. DRY GRANULATION
• When tablet ingredients are sensitive to moisture and unable to
withstand elevated temperature during drying and when the
tablet ingredient have insufficient cohesive properties, slugging
may be used to form granules.
• This technique is used in preparation of aspirin, aspirin
combination, acetophenetidin.
Excipients used in this method:
1. Diluents/ filler: anhydrous lactose/ lactose monohydrate,
starch, dibasic calcium phosphate, and MCC
2. Disintegrants: Starch, MCC, Sodium starch glycolate,
Croscarmellose sodium, Crospovidone.
3. Lubricants: Stearates (Mg. stearate, steric acid), Glyceryl fatty
acid esters, polyoxyethylene stearates, SLS.
4. Glidants: Talc, Colloidal silicon dioxide.
5. Miscellaneous Excipients: Colours, sweetening agents, etc.

10. Advantages & disadvantages
• This technique popularity has decreased in recent years,
having been superseded by direct compression.
• However both slugging and roller compaction are still
employed in tablet manufacture.
Advantages:
1. Both roller compaction and slugging require conventional
grades of excipients.
2. These methods are not generally associated with alterations
in drug morphology during processing.
3. No heat or solvent are required.

11. Advantages & disadvantages
Disadvantages:
1. Specialist equipment is required for granulation by roller
compaction.
2. Segregation of components may occur during post mixing.
3. There may be issues regarding powder flow.
4. The final tablets produced by dry granulation tend to be softer
than those produced by wet granulation, rendering them more
difficult to process using post tabletting techniques, eg: film
coating.
5. Slugging and roller compaction lead to the generation of
considerable dust. Therefore there may be a reduction in the
yield of tablets.

12. Direct compression
• Wet granulation and dry granulation methods having series of
unit operations, both time consuming and potentially costly.
• Potentially more attractive option for the manufacture of
tablets involves powder mixing and subsequent compression
of the powder mix, thereby obviating the need for granulation.
This process is called direct compression.
• The mechanism of particle-particle interactions in tablets
produced by direct compression are similar to those operative
in tablets produced by dry granulation and roller compaction.

13. Direct compression
Excipients:
1. Diluents/filler: spray dried lactose(lactopress spray dried,
lactopress), spray dried 250, Dicalcium phosphate, Mannitol,
Sorbitol, MCC.
2. Disintegrants: MCC (eg: Avicel) pregelatinised starch
(starch1500), Sodium starch glycolate, Croscarmellose and
Sodium Crospovidone.
3. Lubricants: Magnesium stearate, stearic acid, Sodium stearyl
fumarate.
4. Glidants: Talc, Colloidal Silicon dioxide.

14. Advantages & disadvantages
• Advantages:
1. There are fewer processing steps and therefore the method is
potentially more cost effective than other methods.
2. Direct compression does not require the use of water or other
solvents. Therefore negates potential problems regarding the
stability of therapeutic agents in the presence of the solvents.
In addition heating is not required in direct compression.
3. Lubrication is performed in the same vessel as powder
mixing, thereby reducing both transfer losses and
contamination of equipment.

15. Advantages & disadvantages
Disadvantages:
1. Special grade excipients are required.
2. The quality and uniformity of the final dosage form depends
on the excipients.
3. There may be issues regarding powder flow into the tableting
machine.
4. The final tablets produced by direct compression tend to be
softer than those produced by wet granulation, rendering
them more difficult to process using post tableting
techniques, eg: film coating
5. It is not used if a colourent is required in the formulation due
to the mottled appearance of the resulting dosage form.