Friday, September 17, 2021

Common Tablet Defects: Causes and Remedies

by | February 22, 2021 0

Tablet defects are deficiencies that are usually encountered in tablet formulation. Depending on experience, machinery and excipient used, produced or compressed tablets can develop certain defect which may be immediately apparent or appear only after storage.

Listed below are problems associated with tablet manufacturing.

1. Capping and Lamination

Capping is the removal or separation of the top or the bottom of a compressed tablet from the main body of the tablet. This can occur during ejection from the tablet die or during subsequent operations, such as coating, packing, or shipment.

Lamination on the other hand is the transverse cracking and separation of the compressed tablet into two or more layers. It is when cracks form within the body of the compact, resulting in the tablet splitting apart into layers.

Causes of capping and lamination

  1. Presence of air pockets in the granules that is, inadequate removal of air from the granules in the die cavity before and during compression.
  2. Presence of too many fines or small and tiny particles in the granules.
  3. Undue elastic compression of the tablet due to the use of too high a pressure at the compaction stage.
  4. Inadequate binding of particle to form cohesive tablets.
  5. Wearing of the dies bores, particularly by hard inorganic fillers.
  6. Use of worn-out punches and die.
  7. Use of over-dried granules or granules with very low moisture content (leading to loss of proper binding action).
  8. Insufficiently dried granules or not thoroughly dried granules.
  9. Presence of excessive lubricant.
  10. Induced stresses due to sticking of the compact to the die wall or punch components.

How do you solve capping and laminating problems during tablet manufacture?

  1. Use tapered dies (dies which are tapered outwards toward the top of the die to allow the air to escape).
  2. Change granulation procedures.
  3. Remove some or all fines through 100 to 200 mesh screen.
  4. Reduce compaction speed.
  5. Use pre-compression prior to the main compression.
  6. Increase the binder concentration, or change the type of binder in the granule.
  7. Use wear-resistant steel for the dies or special hardened die inserts.
  8. Polish the punches and dies properly or replace them.
  9. Moisten the granules suitably.
  10. Add hygroscopic substance e.g., sorbitol, methylcellulose, or PEG 4000.
  11. Dry granules properly.
  12. Adjust the lubricant levels.
  13. Spray the lubricant into the punch and die cavity immediately before die filling and hence directly coat the surfaces of the tooling (this latter approach requires modification of the tablet press).

2. Sticking

In some instances, a small amount of the compact material may stick to the tooling surfaces’ faces and is referred to as sticking. As compacts are repeatedly made in this station of tooling, the problem gets worse as more and more material gets added to that already stuck to the punch face. The problem tends to be more prevalent on upper punches.

Causes of sticking

  1. Insufficient or a limited extent of lubrication.
  2. Surface roughness of the tooling.
  3. Slight dampness of the granulation.

How to prevent sticking during tablet manufacture

  1. Mix the lubricant properly.
  2. Use coated tooling.
  3. Polish punch faces.
  4. Decrease moisture content of the granules.
  5. Increase hardness by making the tablet thinner and increase dwell time to make the wet granules adhere to other granules, rather than adhering to the punch faces.

3. Picking

Picking happens when a part of the tablet gets sticks to the punch surface and gets eroded from the tablet surface. It is a more specific term that describes product sticking within the letters, logos, or designs on the punch faces.

Causes of picking

  1. Compression of granules that are not properly dried.
  2. Use of scratched punches during tablet compression.

How to prevent picking during tablet manufacture

  1. Decrease moisture content of the granules.
  2. Polish the punch face.

4. Mottling/ Mottled appearance

This is typically seen with colored granules. Mottling is defined as an unequal distribution of color on a tablet with light and dark areas.

Causes of mottling

  1. Drug color different from other components
  2. Dye migration to either the small or large granules during the granulation process
  3. Uneven distribution of color when using a colored adhesive gel solution

How to prevent mottling during tablet manufacture

  1. Reduce drying temperature.
  2. Grind to smaller particle size.
  3. Change the binder system.
  4. Change the solvent system.
  5. Addition of appropriate coloring agent.

5. Chipping

Sometimes compacts after leaving the press, or during subsequent handling and coating operations, are found to have small chips missing from their edges. This fault is described as “chipping” and, in addition to the obvious formulation deficiencies, may be caused by compaction conditions which make too soft (low mechanical strength) or too brittle tablets.

Causes of chipping

  1. Too dry granules.
  2. Poor tablet finish.
  3. Worn out punches and die.
  4. Incorrect machine settings, especially the ejection take-off plate being set too high.
  5. Excessively harsh handling of compacts after they leave the press.
  6. High setting of machine sweep off blade.

How to prevent chipping during tablet manufacture

  1. Moisten the granules to plasticize.
  2. Polishing of punches/ replacement.
  3. Reducing the speed of sweep off blade.
  4. Adjusting the lower punch.

6. Binding in the die

This is characterized by excessive side scraping of the die with the compact ejection forces being high, with the resulting compact edges being rough and scored.

Causes of binding in the die

  1. High die wall friction.
  2. Poor lubrication or blemished
  3. Worn dies or tooling.
  4. Too large a clearance between the lower punch and die bore.
  5. Too moist granules and extrudes around the lower punch

How to prevent binding in the die during tablet manufacture

  1. Increase the concentration of the lubricant or use appropriate lubricant.
  2. Polishing of dies/ replacement.
  3. Use wear-resistant dies.
  4. Dry the granules properly.

7. Embossing

This is the imprint or spur line on the tablet not being clear.

Causes of embossing

  1. Faulty punch design
  2. Use of too coarse granules
  3. Picking and sticking of granules on punches

How to prevent embossing during tablet manufacture

  1. Correct faulty punch embossing design
  2. Reduce granule size

8. Low tensile strength

In general, the higher the compaction pressure then the denser the compact will be, and hence the higher the resulting tensile strength of the compact. Consequently, too low a compaction pressure will lead to low tensile strength or “soft” and crumbly compacts. Alternative reasons are excessive coverage of the granulation by a lubricant, such as a stearate, reducing the potential to form strong interparticle bonds. This over lubrication can be caused by:

  • Too high an initial level of the lubricant,
  • Excessive shear during the lubrication stage,
  • Excessive lubrication time.

Over lubrication, particularly during formulation development assessment, can also occur if incomplete sets (for example half sets or singles sets) of tooling are used on rotary presses to conserve granule usage. This will be because of extended residence time in the feeder resulting in overworking of the granule particularly feeders with paddles.

An additional cause can be the weakening of the intergranular bonds by air entrapment, even when this is not sufficient to cause capping.

9. Weight variation

Poor weight uniformity is usually due to poor die filling. This can be due to either poor flow characteristics of the granule, or due to inadequate filling mechanisms on the compression machine. Granules or powders that are too large, too fine or contain a large proportion of fine material, or are incorrectly lubricated or have components with widely differing densities or sizes, may all contribute to weight variation.

If it is due to poor granule flow then the addition of glidants, such as silica or talc, can be employed. Some particles may acquire a frictional electrostatic charge when handled and this mutual repulsion of the particles and may be sufficient to impede die filling. Talc (at up to 1%) or sodium lauryl sulphate (at up to 2%) are substances which have been used to reduce this charging and which can also have lubricant and anti-adherent properties. Lubricants, such as magnesium stearate, may or may not promote granule flow, depending on the level at which they are used higher levels tending to impede flow.

Occasionally, with high-weight tablets, more uniform weight and improved appearance can be obtained by slowing the machine speed so allowing more time for die-cavity filling.

10. Double Impression

A double impression involves only lower punches that have a monogram or other engraving on them. The punch can make double impressions on a tablet surface during the ejection process. This can be avoided by incorporating antiturning devices for the punches.

References

  • Dash, A., Singh, S. and Tolman, J. (2014). Pharmaceutics: Basic Principles and Application to Pharmacy Practice. USA: Elsevier.
  • Tovey, G. (2018). Pharmaceutical Formulation: The Science and Technology of Dosage Forms. Royal Society of Chemistry.



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