Saturday , October 16 2021

Tablet defects

Tablet defects or manufacturing defects of tablet are not acceptable. But often tablet defects embarrass tablet manufacturers or formulators to design a new tablet. This article outlines various remedies that resolve various tablet defects. We explain various tablet defects with pictures. If you are an industrial pharmacist or work in product development or formulation research and development, you must know about these tablet defects and remedies. A formulator or product developer usually encounters all of the tablet defects during the manufacturing of tablets. Tablet coating defects and remedies. 

Presently the tablet is the most broadly used dosage form for drug delivery because of some benefits include economical, patient convenience, and compliance. Tablet defects are either related to functional defects or visual defects or both.  Tablet defects of the are associated with imperfections in any one or more of the following factors:

  1. Formulation of Tablet
  2. Tableting equipment
  3. Manufacturing process of Tablet

Table of Contents

List of tablet defects

  1. Capping
  2. Lamination
  3. Chipping
  4. Sticking
  5. Picking
  6. Cracking
  7. Binding / Binding in the die
  8. Edging / Flashing of tablet
  9. Mottling
  10. High friability
  11. Weight Variation
  12. Hardness Variation
  13. Aging of tablets/ Loss of hardness
  14. Protracted Hardness (Hardness increases with time)
  15. Disintegration time too long
  16. Uneven Breakage
  17. Black Spot/Stain
  18. Double Impression
  19. Bisected/ Score line/ breakline or imprint or logo not sharp or well-defined
  20. Splitting of Layered tablets or layer separation
  21. Layers not sharply defined bilayer tablet

Generally, tablet defects are appeared by either one or more causes such as capping is occurred when the granules are too dry and/or the lubricant amount is high. Know all of the tablet defects and remedies and make sure the smooth production of tablets. One by one, all possible tablet defects with picture and remedies are discussed below:

Capping

Capping is a term used to describe the partial or complete separation of the top or bottom crowns of a tablet from the main body of the tablet [1]. In another word, capping is a laminar splitting along the edge of the crown or band of a compressed tablet [2]. Generally, capping is a common tablet defect during tablet manufacturing.

Capping tablet defect

Causes and Remedies of capping of tablet associated with the formulation

Causes Remedies
High quantity of fine powder materials in the granules. Use granular or less fine material such as MCC type 102 or 200 instead of MCC type-101.

Make proper granules with an optimum amount of fine powder.

Air-entrapment in the granular materials. Increase the dwell time by reducing the turret speed.
Too dry granules. Dry the granules carefully to obtain optimum LOD.  Moisten the granules by the solvent used in granulation. Add hygroscopic excipients to maintain an optimum moisture level.
Excessive elastic or waxy excipients in the formulation. Reduce the amount or change the elastic or waxy excipients.
Inadequate quantity of binder or inappropriate binder. Enhance the quantity of binder. Add dry binder such as pregelatinized starch (starch Rx-1500).
Presence of too much lubricant. Use an optimum amount of lubricant.
Too soft granules. Make granules properly and keep optimum LOD.
Granular mass is too cold to compress firmly. Compressed at room temperature.

Causes and remedies of capping associated with equipment (punches, dies, & compression machine)

Causes Remedies
Poor tooling choice such as the use of deep concave or extra deep concave of punches. Use shallow or standard concave punches.
Excessive compaction force. Use optimum compaction force.
Incorrect setup of dies and punch such as lower punch remains below the face of the die during ejection.  Set up of dies and punches properly.
Improper sweep-off setting. To facilitate proper ejection, adjust sweep-off blade suitably.

Lamination

Lamination is the separation of a tablet into two or more distinct horizontal layers. It is a tablet defect in which a tablet splits or separates into layers.

Lamination

Causes and Remedies of Lamination of tablet associated with the formulation

Causes Remedies
High quantity of fine powder materials in the granules. Use granular or less fine material such as MCC type 102 or 200 instead of MCC type-101.

Make proper granules with an optimum amount of fine powder.

Too dry granules. Dry the granules carefully to obtain optimum LOD. Add hygroscopic excipients to maintain an optimum moisture level.
Oily, elastic, or waxy excipients in granules. Mixing properly or change of oily, elastic, or waxy excipients.
Air-entrapment in the granular material. Increase the dwell time by reducing the turret speed.
Presence of too much lubricant. Use an optimum amount of lubricant.
Inadequate quantity of binder or inappropriate binder. Enhance the quantity of binder such as copovidone, pregelatinized starch.

Causes and remedies of Lamination associated with equipment

Causes Remedies
Die wall binding Use an adequate amount of lubricant or use tapered dies.
Damaged tooling such as poorly finished dies. Use finely polish dies.
Excessive compaction force. Use optimum compaction force.
Rapid decompression Use precompression and reduce the final compression pressure.

Chipping

Chipping is the breaking of tablet edges during the press process or during the subsequent handling and coating.

Chipping tablet defect

Causes and remedies of chipping related to the formulation

Causes Remedies
Too dry granules. Moisten the granules; Add hygroscopic substances.
Too much or too low binding. Optimize binding, or use dry binders.
Sticking on punch faces Dry the granules properly or increase lubrication.

 Causes and remedies of chipping related to equipment

Causes Remedies
Sharp edge, elongated tablets Change the tablet punch
Lower punch setting too low at tablet take-off Adjust lower punch flush with the die face
Poor finish or worn punches and dies Polish, reface, or replace punches and dies
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
Tablet sweep-off blade on feed frameset too high Adjust setting

Sticking

Sticking is a defect of the tablet where the tablet surface sticks to the punch face or adhesion of tablet material to the die wall during compression. Simply, sticking is the adherence of material to the faces of tablet press punches or dies after compression [2]. In sticking, the tablet surface sticks to the lower punch face but a small portion from the tablet surface not detached or the pitted surface will not occur.

Sticking tablet defect

Causes and remedies of sticking related to formulation

Causes Remedies
Excess moisture in granules Properly dry the granules to keep optimum moisture.
Inadequate lubrication. Increase the amount of lubricant, Use microfine lubricants.
Too much binder. Lessen the amount of binder.
Too much hygroscopic excipients. Lessen the humidity in the compression room.
Sticky API or sticky excipient. Make granules by wet granulation properly. Add colloid silicon dioxide or microcrystalline cellulose or change the sticky excipient.
Low melting point materials. Mix low melting point materials by microcrystalline cellulose (MCC). Exchange with higher melting point materials.

Causes and remedies of sticking related to equipment

Causes Remedies
Punch concavity too deep. Decrease punch concavity or use shallow concave or flat face punches.
Embossed letters or logo on the punch surface. Avoid embossed (letters or logo) punch or Use shallow embossing punches.
Punch tips burred. Refinish or replace the punch.
Poor finish on punch faces Polish punch faces; refinish

Picking

Picking is the term used when a small amount of material from a tablet is sticking to and being removed from the tablet-surface by a punch [1]. In other word, the removal of material from the surface of the tablet, and its adherence to the face of punch is called picking.

Picking tablet defect

Causes and remedies of picking related to formulation

Causes Remedies
Inappropriate dried granules. Properly dry the granules to keep optimum moisture.
Inadequate lubrication. Increase the amount of lubricant. Use microfine lubricants.
Low melting point materials in high concentration. Mix low melting point materials by microcrystalline cellulose. Exchange with higher melting point materials.
Too warm granules when compressing. Sufficiently cool before compression. compression vs compaction
Too much binder. Lessen the amount of binder.
Hygroscopic excipients. Lessen the humidity in compression room.

Causes and remedies of picking related to equipment

Causes Remedies
Rough or scratched punch surfaces. Polish faces to high luster.
Engraving or embossing letters or logo on punch faces. Avoid embossed (letters or logo) punch or Use shallow embossing punches.
Bevels or break lines too deep. Reduce depths and sharpness.

Cracking

Cracking is a defect of tablet where small, fine cracks observed on the upper and lower central surface of tablets, or very rarely on the sidewall. Easily visible in the tablet that contains pigment or dye.

Cracking tablet defect

Causes and remedies of cracking related to the formulation

Causes Remedies
Large size of granules. Reduce granule size. Use proper granular size with sufficient fine materials but fine materials should not be more than 15%.
Too dry granules. Dry properly. Moisten the granules properly.
Inadequate binder Use a proper quantity of binder.
Rapid expansion of tablets Improve granulation. Add dry binders.
Elastic excipients in granules. Exchange or lessen elastic excipients.
Granulation too cold. Compress at room temperature.

Causes and remedies of cracking related to equipment

Causes Remedies
Tablet expands on ejection due to air entrapment. Use tapered die.
Deep concavities cause cracking while removing tablets Decrease punch concavity or use shallow concave or flat face punches.

Binding / Binding in the die

Binding is tablet defect where a tablet adheres, seize or tear in the die or a film is formed on the die area and hindered the ejection of the tablet or splits during the molding/pressing process. The powder adheres to punch edges and dies punches may bind in dies difficult ejection.

Binding or Binding in the die tablet defects

Causes and remedies of binding related to formulation

Causes Remedies
Too moist granules. Dry the granules properly.
Excessive binder. Use proper amount of binder.
Inadequate lubrication. Increase or change lubricant; Increase lubricant blending time. Use microfine lubricants.
Too hard granules for the lubricant to be effective. Modify granulation. Reduce granular size.
Granular material very abrasive and cutting into dies. If coarse granules, reduce its size.

Use wear-resistant dies.

Hygroscopic Ingredients Process under low humidity conditions
Adhesive excipients Increase the lubricant level. Add 0.5% Cab-O-Sil® or Syloid

Causes and remedies of binding related to equipment

Causes Remedies
Poor finish or worn punches and dies Polish, reface, or replace tooling
Undersized dies. Too little clearance. Rework to the proper size. Increase clearance.

Edging / Flashing of tablet

Edging is a defect of tablets in which burrs (raised edges)/ sharp edges appear on the final compressed tablet. This type of tablet defect also known as collaring of tablet or flashing.

Edging or Flashing of tablet defect

Causes and remedies of Edging / Collaring of tablet / Flashing related to the formulation

Causes Remedies
Waxy or elastic API or excipients in formulation. Milled these materials and mix properly.
Moisture in granules. Dry properly.

 Causes and remedies of Edging / Collaring of tablet / Flashing related to equipment

Causes Remedies
Higher compression pressure Lessen the compression pressure
Poor design punch or wear punch. Polish, reface, or replace tooling

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 [1]. This type of tablet defect occurs in tablet formulation with a dry coloring agent. Simply, mottling is a tablet defect where dark and light patches on the tablet surface occur.

Mottling tablet defect

Causes and remedies of mottling

Causes Remedies
Unequal particle size of coloring agent or pigment. Sieved before use to make equal size particles.
A colored drug used along with colorless or white-colored excipients. Use appropriate colorants.
A dye migrates to the surface of granulation while drying. Increase dry mixing time during granulation. Use a proper and fine binder. Use a smaller particle-sized dye.
Improperly mixed dye, especially during ‘Direct Compression’. Mix properly and reduce the size if it is of a larger size to prevent segregation. Use microfine lake dye. Increase blending time. Mill lake dye with 5% excipient.
Too small amount of colorant. Increase quantity of colorant.
Preferential absorption of soluble dye by component of mix. Replace soluble dye with microfine lake pigment.

High friability

Causes and remedies of High friability

Causes Remedies
Inadequate binder. Increase binder level or change or stronger binder.
Over drying of granules Dry the granules properly.
Some excipient such as microcrystalline cellulose gives low friability at lower hardness/machine pressures. Replace the excipient; make a tablet with optimum hardness.
Too much or too little compression pressure. Adjust pressure for acceptable friability.
Over-lubrication Use sufficient lubricant with optimum blending time.

Weight Variation

Weight variation is a common defect of tablets occur during tablet manufacturing where average or individual weight of tablet may outside of the accepted limit. According to USP, BP & IP the accepted limit of weight variation given below:

IP/BP

  Accepted Limit

USP
Tablet weight 80 mg or less

± 10%

Tablet weight 130 mg or less
More than 80 mg or Less than 250mg

± 7.5%

130 mg to 324 mg
250 mg or more

± 5%

More than 324 mg

Weight Variation tablet defect

Causes and remedies of Weight Variation

Causes Remedies
Poor or erratic flow of granules from the hopper. Make uniform size granules; Avoid excess fines excipient for direct compression
Improper amount of glidant Use a sufficient amount of glidant.
Particle size range too wide. Make uniform size granules; Avoid excess fines excipient for direct compression
Improper drying. Dry the granules properly.
Abnormal uniform mixing of all excipients. Confirm proper mixing; Increase mixing time.
Particle segregation as press RPM’s increase Narrow the particle size range; Make granules by wet granulation.
Particle size not suitable for die diameter Adjust particle size range to recommended optimum for die diameter
Lower punch “hang up”  (material between the lower punch and die wall or  lower punch and punch guide) Check for proper clearance between die wall and lower punch; Increase lubricant concentration in the formulation; Remove below 200 mesh fines.
Improper tool setting of machine. Hi-speed running of the machine. Use optimum speed.

Hardness Variation

Tablet hardness does not remain constant but it has a range. Hardness variation is a common defect of tablets where individual hardness of tablets may outside the accepted limit. Unlike weight variation, hardness variation limit is determined by prototype trial of that tablet.

Causes and remedies of Hardness Variation

Causes Remedies
Over-blending. Optimize the blending time.
Weight variation in granules filled in die. Solve the causes of Weight variation.
Improper mixing of lubrication Mixing properly.
Uneven die-fill. Set the compression machine properly.

Aging of tablets/ Loss of hardness

It a tablet defect where hardness of tablet decreases with time.

Causes and remedies of Aging of tablets/ Loss of hardness

Causes Remedies
Over-lubrication Use sufficient lubricant with optimum blending time; Replace metallic stearates with other lubricants (e.g., stearic acid).
Tablets with microcrystalline cellulose (MCC) lose some hardness with time at high humidity, but most of the hardness is quickly regained at normal humidity. Use moisture scavenger or moisture adsorbent such as calcium silicate; Storage the tablet with normal humidity or replace MCC from tablet formulation.
Compression force (pressure) too low Increase pressure
Granulation too soft Use sufficient binder.
Some excipients such as too much starch can give a soft tablet. Reduce level of causative excipient.
Moisture content too high Dry the granules properly; Use moisture scavenger or moisture adsorbent such as calcium silicate.
Moisture pick-up Compress and package under low humidity conditions; Use moisture scavenger or moisture adsorbent such as calcium silicate.

Keep tablet containers well closed.

Protracted Hardness (Hardness increases with time)

Causes Remedies
Can be caused by water of crystallization/hydration interacting with ingredients or interactions between active materials-excipients or excipient-excipient. Conduct drug-excipients or excipients-excipients compatibility study and replace causing material.

Disintegration time too long

Causes Remedies
Over-lubrication. Use sufficient lubricant with optimum blending time; Replace metallic stearates with other lubricants (e.g., stearic acid).
Insufficient disintegrant. Use super disintegrant; Increase quantity.
Too much binder. Use optimum quantity binder.
High hardness tablet. Reduce machine pressure.

Uneven Breakage

Many tablets are designed to be broken into smaller dosages with functional score-line / break lines. It is a tablet defect where the tablet breaks unevenly into two parts.

Uneven Breakage or unevenly breakage tablet defect

Causes Remedies
Coarse granules. Reduce particle size of granulation less than 16 mesh.
Improper mixing. Increase mixing time.
Air-entrapment in the granular materials. Increase the dwell time by reducing the turret speed.
Unequal sizes granules. Make granules with sufficient bonder; Milled properly.

Black Spot/Stain

It is defect of tablet where stains or black spots will appear on tablet surface. Mainly observed in colored tablets.

Causes Remedies
High temperature is the key factor for penetration of the dye into the upper surface. Storage tablet at room temperature.
Observe in the high concentration of pigment/dyes. Use an optimum quantity of pigment/dyes.
Incompatibility among excipients and API Replace caustic excipient.
Improper cleaning of punches. Must clean the punches.

Double Impression

Double impression is machine related tablet defect where a monogram or engraving shape or break line/ score line or imprint or logo appears twice on the tablet surface.

Double Impression tablet defect

Causes and remedies of double impression

Causes Remedies
Uncontrolled rotation of either upper punch or lower punch during ejection of a tablet. Use keying in tooling, i.e. inset a key alongside of the    punch, so that it fits the punch and prevents punch rotation.
Uncontrolled movement of punches with engravings on them. Using anti-turning devices.

Bisected/ Score line/ Breakline or Imprint or Logo not sharp or well-defined

Causes Remedies
Granulation too coarse. Reduce particle size of granulation.
Insufficient binder or binder not strong enough. Use an adequate quantity of binder or use a stronger binder.
Faulty punch debossing design Redesign using tapered sides on the punch debossing.

Splitting of Layered tablets or Layer separation

This type of tablet defect mainly appear in bilayer tablet where attached layer is separated.

Causes Remedies
Poor bonding between layers. Use a stronger binder or sufficient quantity.
Compression pressure too high. Compress at lower pressures.
Over-lubrication. Use sufficient lubricant with optimum blending time.
Over dried granules. Dry granules properly.

Layers not sharply defined in bilayer tablet

This type of tablet defect mainly appears in bilayer tablet where attached layer is not sharply defined.

Layers not sharply defined bi-layer tablet

Causes Remedies
Coarse granules Reduce particle size of granulation less than 16 mesh.
Too many fines Remove fines below 200 mesh
Insufficient colorant Use sufficient colorant
Improper mixing Increase mixing time

So, after reading this article you may encounter all of the tablet defects during the manufacturing of tablets.

Keywords: Tablet defects, Manufacturing defects of tablet, Tablet defects with pictures, Defects in Tablets.

Reference 

1. Lachman, Lieberman, H.A. and Kanig, J.L., The Theory and Practice of Industrial Pharmacy, Lea and Febiger, Philadelphia, 3rd edn., 1986.
2. United States Pharmacopeia and National Formulary (USP 43–NF 38). Rockville, MD: United States Pharmacopeial Convention; 2020.

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One comment

  1. What a great great post regarding pharmaceutical tablet defects! I was read many articles about this but this is the most resourceful post. You should use a image of layer separation defect. Thank you.

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