Manufacturing Defects of Tablets

Tablet processing problems can be due to problems in the formulation or in compression equipment, or both of them. Thus we can classify the problems into the following types:

The Defects related to Tabletting Process 

1. Capping: It is partial or complete separation of the top or bottom of tablet due air-entrapment in the granular material. 
2. Lamination: It is separation of tablet into two or more layers due to air-entrapment in the granular material. 
3. Cracking: It is due to rapid expansion of tablets when deep concave punches are used.

The Defects related to the Excipient

1. Chipping: It is due to very dry granules. 
2. Sticking: It is the adhesion of granulation material to the die wall 
3. Picking: It is the removal of material from the surface of tablet and its adherence to the face of punch. 
4. Binding: These problems (v, vi, vii) are due to more amount of binder in the granules or wet granules. 

The Defect related to more than one factor 

1. Mottling: It is either due to any one or more of these factors: Due to a colored drug, which has different color than the rest of the granular material (Excipient- related); improper mixing of granular material (Process-related); dirt in the granular material or on punch faces; oil spots by using oily lubricant.

The Defect related to Machine 

1. Double Impression: It is due to free rotation of the punches, which have some engraving on the punch faces. Further, in this section, each problem is described along-with its causes and remedies which may be related to either of formulation (granulation) or of machine (dies, punches and entire tablet press). 

ALSO READ: Problems and Remedies for Tablet Coating

CAPPING 

Capping is the term used, when the upper or lower segment of the tablet separates horizontally, either partially or completely from the main body of a tablet and comes off as a cap, during ejection from the tablet press, or during subsequent handling. 

Reason: 

Capping is usually due to the air–entrapment in a compact during compression, and subsequent expansion of tablet on ejection of a tablet from a die. 

The Causes and Remedies of Capping Related To  Formulation (Granulation).

Causes	Remedies
Large amount of fines in the granulation	Remove some or all fines through 100 to 200 mesh screen.
Too dry or very low moisture content (leading to loss of proper binding action).	Moisten the granules suitably. Add hygroscopic substance e.g., sorbitol, methyl-cellulose, or PEG-4000.
Not thoroughly dried granules.	Dry the granules properly.
Insufficient amount of binder or improper binder.	Increasing the amount of binder.
Insufficient or improper lubricant.	Adding dry binder such as pre-gelatinized starch, gum acacia, powdered sorbitol, PVP, hydrophilic silica, or powdered sugar.
Granular mass too cold.	Increase the amount of lubricant or change the type of lubricant.
	Compress at room temperature.

The Causes and Remedies of Capping Related To Machine‘ (Dies, Punches And Tablet Press) 

Causes	Remedies
Poorly finished dies	Polish dies properly. Investigate other steels or other materials.
Deep concave punches or beveled-edge faces of punches.	Use flat punches.
Lower punch remains below the face of die during ejection.	Make proper setting of lower punch during ejection.
Incorrect adjustment of sweep-off blade.	Adjust sweep-off blade correctly to facilitate proper ejection.
High turret speed	Reduce speed of turret (Increase dwell time).

LAMINATION 

Lamination is the separation of a tablet into two or more distinct horizontal layers.

Reason: 

Air entrapment during compression and subsequent release on ejection. The condition is exaggerated by higher speed of turret. 

The Causes and Remedies of Lamination Related To Formulation (Granulation).

Causes	Remedies
Oily or waxy materials in granules.	Modify mixing process. Add adsorbent or absorbent.
Too much hydrophobic lubricant.	Use a lesser amount of lubricant or change the type of lubricant.

The Causes And Remedies of Lamination Related To Machine (Dies, Punches And Tablet Press) 

Causes	Remedies
Rapid relaxation of the peripheral regions of a tablet, on ejection from a die.	Use tapered dies, i.e., upper part of the die bore has an outward taper of 3° to 5°.
Rapid decompression.	Use pre-compression step. Reduce turret speed and reduce the final compression pressure.

ALSO READ: SOP for Reprocessing of Capsules

CHIPPING 

Chipping is defined as the breaking of tablet edges, while the tablet leaves the press or during subsequent handling and coating operations. 

Reason: 

Incorrect machine settings, specially mis-set ejection take-off.

The Causes And Remedies Of Chipping Related To Formulation (Granulation).

Causes	Remedies
Sticking on punch faces	Dry the granules properly or increase lubrication.
Too dry granules.	Moisten the granules to plasticize. Add hygroscopic substances.
Too much binding causes chipping at bottom.	Optimize binding, or use dry binders.

The Causes And Remedies of Chipping Related To Machine (Dies, Punches And Tablet Press)

Causes	Remedies
Groove of die worn at compression point.	Polish to open end, reverse, or replace the die.
Barreled die (center of the die wider than ends)	Polish the die to make it cylindrical.
Edge of punch face turned inside/inward.	Polish the punch edges.
Concavity too deep to compress properly.	Reduce concavity of punch faces. Use flat punches.

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. 

Reason: 

It is observed as a result of rapid expansion of tablets, especially when deep concave punches are used. 

The Causes And Remedies Of Cracking Related To Formulation (Granulation).

Causes	Remedies
Large size of granules.	Reduce granule size. Add fines.
Too dry granules.	Moisten the granules properly and add proper amount of binder.
Tablets expand.	Improve granulation. Add dry binders.
Granulation too cold.	Compress at room temperature.

The Causes And Remedies of Cracking Related To Machine (Dies, Punches And Tablet Press)

Causes	Remedies
Tablet expands on ejection due to air entrapment	Use tapered die.
Deep concavities cause cracking while removing tablets	Use special take-off.

ALSO READ: Use of Binder in Tablet Formulation

STICKING 

Sticking refers to the tablet material adhering to the die wall. Filming is a slow form of sticking and is largely due to excess moisture in the granulation.

Reason: 

Improperly dried or improperly lubricated granules.

The Causes And Remedies of Sticking Related To Formulation (Granulation).

Causes	Remedies
Granules not dried properly.	Dry the granules properly. Make moisture analysis to determine limits.
Too little or improper lubrication.	Increase or change lubricant.
Too much binder	Reduce the amount of binder or use a different type of binder.
Hygroscopic granular material.	Modify granulation and compress under controlled humidity.
Oily or waxy materials	Modify mixing process. Add an absorbent.
Too soft or weak granules.	Optimize the amount of binder and granulation technique.

The Causes And Remedies of Sticking Related To Machine (Dies, Punches And Tablet Press) 

Causes	Remedies
Concavity too deep for granulation.	Reduce concavity to optimum.
Too little pressure.	Increase pressure.
Compressing too fast.	Reduce speed.

PICKING 

Picking is the term used when a small amount of material from a tablet is sticking to and being removed off from the tablet surface by a punch face. The problem is more prevalent on the upper punch faces than on the lower ones. 

The problem worsens, if tablets are repeatedly manufactured in this station of tooling because of the more and more material getting added to the already stuck material on the punch face. 

Reason: 

Picking is of particular concern when punch tips have engraving or embossing letters, as well as the granular material is improperly dried.

The Causes and Remedies of Picking Related To Formulation (Granulation).

Causes	Remedies
Excessive moisture in granules.	Dry the granules properly, determine the optimum limit.
Too little or improper lubrication.	Increase lubrication; use colloidal silica as a polishing agent, so that material does not cling to punch faces.
Low melting point substances may soften from the heat of compression and lead to picking.	Add high melting-point materials. Use high melting point lubricants.
Low melting point medicament in high concentration.	Refrigerate granules and the entire tablet press.
Too warm granules when compressing.	Compress at room temperature. Cool sufficiently before compression.
Too much amount of binder.	Reduce the amount of binder, change the type, or use dry binders.

The Causes And Remedies of Picking Related To Machine (Dies, Punches And Tablet Press) 

Causes	Remedies
Rough or scratched punch faces.	Polish faces to high luster.
Bevels or dividing lines too deep.	Reduce depths and sharpness.
Pressure applied is not enough; too soft tablets.	Increase pressure to optimum.
	Design lettering as large as possible.
	Plate the punch faces with chromium to produce a smooth and non-adherent face.

BINDING

Binding in the die is the term used when the tablets adhere, seize or tear in the die. A film is formed in the die and ejection of tablet is hindered. With excessive binding, the tablet sides are cracked and it may crumble apart. 

Reason: 

Binding is usually due to excessive amount of moisture in granules, lack of lubrication and/or use of worn dies.

The Causes And Remedies of Binding Related To Formulation (Granulation)

Causes	Remedies
Too moist granules and extrudes around lower punch.	Dry the granules properly.
Insufficient or improper lubricant.	Increase the amount of lubricant or use a more effective lubricant.
Too coarse granules.	Reduce granular size, add more fines, and increase the quantity of lubricant.
Too hard granules for the lubricant to be effective.	Modify granulation. Reduce granular size.
Granular material very abrasive and cutting into dies.	Use wear-resistant dies.
Granular material too warm.	Reduce temperature.
Sticks to the die.	Increase clearance if it is extruding.

The Causes And Remedies of Binding Related To Machine (Dies, Punches And Tablet Press) 

Causes	Remedies
Poorly finished dies.	Polish the dies properly.
Rough dies due to abrasion, corrosion.	Investigate other steels or other materials or modify granulation.
Undersized dies. Too little clearance.	Rework to proper size. Increase clearance.
Too much pressure in the tablet press.	Reduce pressure or modify granulation.

ALSO READ: What is Maximum Compression Force?

MOTTLING 

Mottling is the term used to describe an unequal distribution of colour on a tablet, with light or dark spots standing out in an otherwise uniform surface. 

Reason: 

One cause of mottling may be a coloured drug, whose colour differs from the colour of excipients used for granulation of a tablet.

The Causes And Remedies of Mottling

Causes	Remedies
A coloured drug used along with colourless or white-coloured excipients.	Use appropriate colourants.
A dye migrates to the surface of granulation while drying.	Change the solvent system, Change the binder, Reduce drying temperature, and Use a smaller particle size.
Improperly mixed dye, especially during Direct Compression.	Mix properly and reduce size if it is of a larger size to prevent segregation.
Improper mixing of a coloured binder solution.	Incorporate dry colour additive during the powder blending step, then add fine powdered adhesives such as acacia and tragacanth and mix well, and finally add granulating liquid.

DOUBLE IMPRESSION

Double Impression involves only those punches, which have a monogram or other engraving on them. 

Reason: 

At the moment of compression, the tablet receives the imprint of the punch. Now, on some machines, the lower punch freely drops and travels uncontrolled for a short distance before riding up the ejection cam to push the tablet out of the die, now during this 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.

Cause	Remedies
Free rotation of either upper punch or lower punch during ejection of a tablet.	Use keying in tooling, i.e., insert a key alongside the punch so that it fits the punch and prevents punch rotation.
	Newer presses have anti-turning devices, which prevent punch rotation.

Tablet weight: Sources of variation 

The tablet weights are mainly affected by following reasons :

Product variation: 

• This type of variation can be due to inconsistent powder density and particle size distribution. Density can change on the press, often because of overfilling of the die and re-circulation of the powder on the tablet press, whereas particle size distribution may change when the product becomes unblended during transfer or because of static electricity. 
• This may also change because the product cannot withstand the handling and the mechanical stress it undergoes before reaching the tablet press.

Machine condition: 

The problems caused by a tablet press that is poorly prepared or operated are legion. The up and down motion under load on a new die table should be within 0.003 inch of the setting. Care must be taken to ensure that the pressure rolls and cams are in very good condition. 

Tooling condition: 

The punch working length should be taken in consideration. Working length is an important factor in how punches affect tablet weight. New tools are made to a tolerance of one-thousandth of an inch, the length of each punch is correct and identical. 

Powder flow and feed-rates: 

Various defects are related to powder flow and feed-rates stem, therefore powder flow and feed-rates should be taken in account while manufacturing of tablets. 

ALSO READ: SOP for Disposal of Tablets and Capsules after In-Process Checks