problems during granulation & compression

Technical session 2012

Problems during Granulation ,Compression

&

their RectificationSaima Naz(Production Officer)

Oral Solid Mfg

Introduction

Granulation & Compression are two processes used in tablet formulation.

Both granulation & Compression affect the final dosage form.

So it is important that proper Granulation & Compression must be done to produce tablet of good quality, strength, hardness.

Granulation

“ Granulation is the process of collecting particles together by creating bonds between them. Bonds are formed by compression or

by using a binding agent.”

Granulation

Granulation in pharma industry is of two types;

1.Wet Granulation

2.Dry Granulation

Pharmaceutical products are processed all over the world using the wet-granulation, or dry-granulation methods. Which method is chosen depends on the ingredients’ individual characteristics and ability to properly flow, compress, eject, and disintegrate. Choosing a method requires thorough investigation of each ingredient in the formula, the combination of ingredients, and how they work with each other. Then the proper granulation process can be applied.

Granulation

In the pharmaceutical industry, most products are manufactured using the wet granulation process. Wet granulation offers a wide range of capabilities for forming granules, from the production of light granules to the production of very dense granules. More than 70% of the global industry’s granulations are made using this method.

Importance of granulation

A tablet with good characteristics is not made on a tablet press; it is made in the granulation process. Joining particles within a given granulation process will improve;

flow and compression characteristics

reduce segregation

improve content uniformity

eliminate excessive amounts of fine particles.

Importance of granulation

The results will be

Improved yields

Reduced tablet defects

Increased productivity and

Reduced down time.

The objective of the process is to combine ingredients to produce a quality tablet.

Why granulation?

When powders are very fine, fluffy, will not stay blended, or will not compress, then they must be granulated. Fluffy is not a technical term, but it fits the problem well; it means that the required quantity of powder physically will not fit into the die cavity on the tablet press. The volume of fill (bulk density) is greater than that which is mechanically allowed.

Wet granulation

“Traditional wet granulation, is the process of mixing and adding solution(wet massing) and then transferring the product to FBD/& Tray dryer.”

“Wet massing is the process of adding a solution to a blended powder and mixing for a predetermined period of time at a given mechanical speed”

The process can be very simple or very complex depending on the characteristics of the powders, the final objective of tablet making, and the equipment that is available.

Instruments used in wet granulation

Mixer & granulator: for wet mixing

FBD & Tray dryers: for drying of granules

Oscillating granulator: for granulation of dried mass

MDM mixer: for lubrication

Compression

“It is the process by which prepared granules are compacted into the core

tablet form.”

Instrument use for compaction of granules is called rotary press

compression machine.

Dies & punches are used to give shape , strength, weight adjustment & hardness to tablets. Because granules are filled in

dies & punches compressed them.

Problem that we face at granulation phase are;

1. Density of Granules: if speed of granulator & mixer is very high & optimum time is not given for “mixing & granulation” of raw material, too dense or very low dense granules are formed. Too dense granules lead to prolong disintegration time. Very less dense granules not obtain proper disintegration time. so density of granules should be optimum. For optimum density the speed of “mixer & granulator” & time for which mixing & granulation is done should be controlled… if speed of mixer & granulator is slow , more time require to produce optimum density granules & vice versa. Speed & time also important for uniform mixing of all ingredients.

PROBLEMS DURING GRANULATION &

COMPRESSION

Problems during granulation & compression

2. Drying of granules: Too much dry granules loose all moisture & during compaction process tablets not achieve the required strength & my be caped or show lamination & if drying of granules is not proper ..wet mass lead to sticking of granules with punches & adhered to dye.. So drying of granules should be optimum. For proper & optimum drying the temperature of FBD & timing for drying should be taken in account & controlled.. Some materials are hygroscopic in nature. they are almost complete dried & very less moisture level (approximately < 1% ) should be retained in them.


3. Content uniformity: During lubrication stage, the mixing time for lubrication must be proper & controlled. Because this is the stage after which granules are going to be compacted into tablet form.. If mixing is not proper the content uniformity of active in tablet is not achieved & flow of granules into the dies also affected & improper flow lead to weight variation of tablet.


Tablets defects appeared during compression process are mostly related with granulation stage & little with compression stage.

Problem that we face at compression phase are of two types;

1.One are those which relates with rotary press efficacy & operator.

2.2nd are those which comes in tablet during compression because of problems in granulation phase.

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Characteristics of ideal tablets

1- Free of defects ,such as

chips ,cracks ,discoloration &contamination

2-Have the strength to withstand the mechanical

stress of production

3-Chemically & physically stable over time

4-Release the medicinal agents in a predictable&

reproducible manner


Problems in tablets are;

1.Sticking

2.Picking

3.Capping

4.Lamination

5.Weight variation

6.Double impression

7. Disintegration time

8. Hardness

Problems during granulation & compression1.Sticking: is adhesion of tablet material to a die wall. this is the defect in tablet in which granules are Sticked in die of rotary press & tablets ejection becomes difficult & Punches required greater force to eject the tablet. As a result of it, edges of tablets are broken down during ejection. Tablet show pitted surface rather than smooth surface.

Reasons:

I. Too wet granules

II. Wear off punches

III. Proper cleaning of punches is not done.

IV. Lubrication is not proper

V. Substances with low melting temperatures in the formulation


Sticking Rectification:

I. Proper cleaning & polishing of punches should be done by operator.

II. Wear off punches must be replaced with newer ones. & proper cleaning & maintenance of punches, dies & machine must be done by operator.

III. Proper Lubrication of punches & of granules must be done.

Sticking, Picking & Filming:

Adhesion of the material to the punch faces.

• Sticking : (whole adhesion)

is usually due to improperly dried or lubricated granulation causing the whole tablet surface to stick to the punch faces → dull, scratched, or rough tablet faces.

• Picking : (localized adhesion)

is a form of sticking in which a small portion of granulation sticks to

the punch face & a portion of the tablet surface is missed.

Filming: is a slow form of sticking and is largely due to excess moisture in the granulation

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2. Picking: is removal of a tablet’s surface material by a punch. In this case a cavity is appeared on tablet surface.

Capping & Laminating:

Capping occurs when the upper segment of the

tablet separates from the main portion of the tablet &

comes off as a cap.

- Most annoying problem

- Can appear immediately after compression, or hours, even days after preparation.

• It is usually due to air entrapped

in the granulation which is compressed

in the die during the compression & then expands when the pressure is released.

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Reasons of capping :

1. large amount of fines in the granulation &/or the lack of sufficient clearance between the punch and the die wall.

2. In new punches and dies that are tight fitting.

3. Too dry granules.

Lamination is due to the same causes as capping except that the tablet splits at the sides into two or more parts.

If tablets laminate only at certain stations, the tooling is usually the cause.

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Solutions for capping & laminating:

1. Increasing the binder.

2. Adding dry binder such as gum acacia polyvinylpyrrolidone (PVP).

3.Decreasing the upper punch diameter.

4. Certain degree of moisture in the granules

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4. Mottling:

It is an unequal distribution of color on the surface of the tablet.

Cause :

1. A drug that differs in color from its excipients or whose degradation products are highly colored.

2. Migration of a dye during drying of a granulation (change the solvent system, reduce the drying temperature, or grind to a smaller particle size).

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problems during granulation & compression

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