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Manufacturing Defects of Tablets

Tablet processing problems can be due to problem 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). 

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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
  1. Large amount of fines in the granulation
  2. Too dry or very low moisture content (leading to loss of proper binding action).
  3. Not thoroughly dried granules.
  4. Insufficient amount of binder or improper binder.
  5. Insufficient or improper lubricant.
  6. Granular mass too cold.

Remedies
  1. Remove some or all fines through 100 to 200 mesh screen.
  2. Moisten the granules suitably. Add hygroscopic substance e.g.: sorbitol, methyl- cellulose or PEG-4000.
  3. Dry the granules properly.
  4. Increasing the amount of binder.
  5. Adding dry binder such as pre-gelatinized starch, gum acacia, powdered sorbitol, PVP, hydrophilic silica or powdered sugar.
  6. Increase the amount of lubricant or change the type of lubricant.
  7. Compress at room temperature.

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

Causes
  1. Poorly finished dies
  2. Deep concave punches or beveled-edge faces of punches.
  3. Lower punch remains below the face of die during ejection.
  4. Incorrect adjustment of sweep-off blade.
  5. High turret speed

Remedies
  1. Polish dies properly. Investigate other steels or other materials.
  2. Use flat punches.
  3. Make proper setting of lower punch during ejection.
  4. Adjust sweep-off blade correctly to facilitate proper ejection.
  5. 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 
  • Oily or waxy materials in granules. 
  • Too much of hydrophobic lubricant. 
  • Magnesium Stearate. 

Remedies 
  • Modify mixing process. Add adsorbent or absorbent. 
  • Use a less amount of lubricant or change the type of lubricant. 

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

Causes 
  • Rapid relaxation of the peripheral regions of a tablet, on ejection from a die. 
  • Rapid decompression 

Remedies 
  • Use tapered dies, i.e. upper part of the die bore has an outward taper of 3° to 5°. 
  • Use pre-compression step. Reduce turret speed and reduce the final compression pressure. 

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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 
  • Sticking on punch faces 
  • Too dry granules. 
  • Too much binding causes chipping at bottom. 

Remedies 
  • Dry the granules properly or increase lubrication. 
  • Moisten the granules to plasticize. Add hygroscopic substances. Optimize binding, or use dry binders. 

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

Causes 
  • Groove of die worn at compression point. 
  • Barreled die (center of the die wider than ends) 
  • Edge of punch face turned inside/inward. 
  • Concavity too deep to compress properly. 

Remedies 
  • Polish to open end, reverse or replace the die. 
  • Polish the die to make it cylindrical 
  • Polish the punch edges 
  • 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 
  • Large size of granules. 
  • Too dry granules. 
  • Tablets expand. 
  • Granulation too cold. 

Remedies 
  • Reduce granule size. Add fines. 
  • Moisten the granules properly and add proper amount of binder. 
  • Improve granulation. Add dry binders. 
  • Compress at room temperature. 

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

Causes 
  • Tablet expands on ejection due to air entrapment 
  • Deep concavities cause cracking while removing tablets 

Remedies 
  • Use tapered die. 
  • Use special take-off. 

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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 
  • Granules not dried properly. 
  • Too little or improper lubrication. 
  • Too much binder 
  • Hygroscopic granular material. 
  • Oily or way materials 
  • Too soft or weak granules. 

Remedies 
  • Dry the granules properly. Make moisture analysis to determine limits. 
  • Increase or change lubricant. 
  • Reduce the amount of binder or use a different type of binder. 
  • Modify granulation and compress under controlled humidity. 
  • Modify mixing process. Add an absorbent. 
  • Optimize the amount of binder and granulation technique. 

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

Causes 
  • Concavity too deep for granulation. 
  • Too little pressure. 
  • Compressing too fast. 

Remedies 
  • Reduce concavity to optimum. 
  • Increase pressure. 
  • 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
  • Excessive moisture in granules.
  • Too little or improper lubrication.
  • Low melting point substances, may soften from the heat of compression and lead to picking.
  • Low melting point medicament in high concentration.
  • Too warm granules when compressing.
  • Too much amount of binder.

Remedies
  • Dry properly the granules, determine optimum limit.
  • Increase lubrication; use colloidal silica as a  polishing agent, so that material does not cling to punch faces.
  • Add high melting-point materials. Use high meting point lubricants.
  • Refrigerate granules and the entire tablet press.
  • Compress at room temperature. Cool sufficiently before compression.
  • 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
  • Rough or scratched punch faces.
  • Bevels or dividing lines too deep.
  • Pressure applied is not enough; too soft tablets.

Remedies
  • Polish faces to high luster.
  • Design lettering as large as possible.
  • Plate the punch faces with chromium to produce a smooth and non-adherent face.
  • Reduce depths and sharpness.
  • Increase pressure to optimum. 

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
  • Too moist granules and extrudes around lower punch.
  • Insufficient or improper lubricant.
  • Too coarse granules.
  • Too hard granules for the lubricant to be effective.
  • Granular material very abrasive and cutting into dies.
  • Granular material too warm.
  • Sticks to the die.

Remedies
  • Dry the granules properly.
  • Increase the amount of lubricant or use a more effective lubricant.
  • Reduce granular size, add more fines, and increase the quantity of lubricant.
  • Modify granulation. Reduce granular size.
  • If coarse granules, reduce its size.
  • Use wear-resistant dies.
  • Reduce temperature.
  • Increase clearance if it is extruding.

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

Causes
  • Poorly finished dies.
  • Rough dies due to abrasion, corrosion.
  • Undersized dies. Too little clearance.
  • Too much pressure in the tablet press.

Remedies
  • Polish the dies properly.
  • Investigate other steels or other materials or modify granulation.
  • Rework to proper size. Increase clearance.
  • Reduce pressure. or Modify granulation. 


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
  • A coloured drug used along with colourless or white-coloured excipients.
  • A dye migrates to the surface of granulation while drying.
  • Improperly mixed dye, especially during  Direct Compression.
  • Improper mixing of a coloured binder solution.

Remedies
  • Use appropriate colourants.
  • Change the solvent system, Change the binder, Reduce drying temperature and Use a smaller particle size.
  • Mix properly and reduce size if it is of a larger size to prevent segregation.
  • Incorporate dry colour additive during 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 
  • Free rotation of either upper punch or lower punch during ejection of a tablet. 
Remedies
  • Use keying in tooling, i.e. inset a key alongside of 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. 

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