Tablet Defects and Remedial action in Pharma

Tablet Defects and Remedial action in Pharma

In the routine manufacture of tablets, various defects are observed. The source of the problem or the defect is the formulation, the compression or coating equipment, or a combination of these. Tablet defects are deficiencies that are usually encountered in tablet formulation. Depending on experience, machinery, and excipient used, Some defects are noticed immediately during manufacturing but others may be noticed during storage as in the case of capping.

Tablets Defect can Be classified

• Process Related
• Formulation related
• Machine related

Process Related Defect –

• Capping
• Lamination
• Cracking
• Chipping

Formulation related

• Sticking
• Picking
• Binding

Machine related

• Double Impression

Listed below are problems associated with tablet manufacturing.

1. Capping and Lamination

Capping :The upper or lower segment of the tablet separates horizontally, either partially or completely from the main body, and comes off like a cap, during ejection from the tablet press, or during subsequent handling.

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

Lamination: The separation of a tablet into two or more distinct horizontal layers 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.

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

Causes of capping and lamination

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

Remedial action

• Use tapered dies (dies that are tapered outwards toward the top of the die to allow the air to escape).
• Change granulation procedures.
• Remove some or all fines through 100 to 200 mesh screens.
• Reduce compaction speed.
• Use pre-compression prior to the main compression.
• Increase the binder concentration, or change the type of binder in the granule.
• Use wear-resistant steel for the dies or special hardened die inserts.
• Polish the punches and dies properly or replace them.
• Moisten the granules suitably.
• Add hygroscopic substances e.g., sorbitol, methylcellulose, or PEG 4000.
• Dry granules properly.
• Adjust the lubricant levels.
• Spray the lubricant into the punch and die cavity immediately before die filling and hence directly coat the surfaces of the tooling.

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

Causes of capping and lamination

• The large size of granules.
• Too dry granules.
• Tablets expand.
• Granulation is too cold.
• Tablet expands on ejection due to air entrapment.
• Deep concavities cause cracking while removing tablets.

Remedial Action

• Reduce granule size and additional fines.
• Moisten the granules properly and add the proper amount of binder.
• Improve granulation and add dry binders.
• Compress at room temperature.
• Use tapered die.
• Use special take-off.

2. Sticking

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 that is already stuck to the punch face. The problem tends to be more prevalent on upper punches.

Causes of sticking

• Insufficient or a limited extent of lubrication.
• Surface roughness of the tooling.
• Slight dampness of the granulation.

Remedial Action

• Mix the lubricant properly.
• Use coated tooling.
• Polish punch faces.
• Decrease moisture content of the granules.
• 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

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

Remedial Action

• Decrease moisture content of the granules.
• Polish the punch face.

Mottling

Mottling 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

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

Remedial Action

• Reduce drying temperature.
• Grind to a smaller particle size.
• Change the binder system.
• Change the solvent system.
• Addition of appropriate coloring agent.

5. Chipping

Breaking of tablet edges, while the tablet leaves the press or during subsequent handling and coating operations. Due to Incorrect machine settings, specially mis-set ejection take-off.

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

• Sticking on punch faces Dry the granules properly or increase lubrication.
• Too dry granules – Moisten the granules to plasticize. Add hygroscopic substances
• Poor tablet finish.
• Worn out punches and die.
• Incorrect machine settings, especially the ejection take-off plate being set too high.
• Excessively harsh handling of compacts after they leave the press.
• High setting of machine sweep off blade.
• Too much binding causes chipping at bottom. Optimize binding, or use dry binders.

Remedial action

• Moisten the granules to plasticize.
• Polishing of punches/ replacement.
• Reducing the speed of sweep off blade.
• Adjusting the lower punch.

6.Binding in the die

Binding 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

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

Remedial Action

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

7.Embossing

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

Causes of embossing

• Faulty punch design
• Use of too coarse granules
• Picking and sticking of granules on punches.

Remedial Action

• Correct faulty punch embossing design
• Reduce granule size

8.Low tensile strength

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:

Causes of Low tensile strength

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

Causes of Weight variation

• Due to either poor flow characteristics of the granule,
• 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,
• Incorrectly lubricated
• Have components with widely differing densities or sizes, May all contribute to weight variation.

Remedial Action

• 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.
• 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.

Causes of Double Impression

Encountered with punches that have a monogram or other engraving on them

Remedial Action

Rotation of punches

Adjust antiturning devices

Use keyed punches

Other Defects

DIRT IN PRODUCT (BLACK SPECKS) :

• Dust,dirt,or press lubrication in the granulation
• Clean press more frequently
• Excessive or wrong press lubrication
• Use proper punch dust caps
• Rubbing of feeder components

CHIPPING OR SPLITTING

• Poor surface finish on punch tips; worn punches and dies
• Poor tooling design (e.g., sharp embossing or bisect lines)
• Polish punch tips; replace punches and dies

DEFECTS IN SUGAR COATED TABLETS/ CHIPPING OF COATINGS:

• Sugar coatings are inherently brittle and thus prone to chipping if mishandled.
• Excessive use of insoluble fillers and pigments tends to increase the brittleness of sugar coatings.
• Avoid them where ever it is possible
• Addition of small quantities of polymers(such as cellulosics, polyvinylpyrrolidine, acacia,or gelatin) to improve structural integrity.

CRACKING OF COATINGS:

Tablet cores that expand, either during or after coating, are likely to cause the coating to crack.

Such expansion may result from

1.Moisture absorption by the tablet core.

http://2.By stress relaxation of the core after compaction.

Moisture sorption can be minimized by appropriate use of seal coat.

Expansion due to post compaction stress relaxation can be resolved by extending the time between the compaction event and commencement of sugar coating.

TWINNING (OR BUILD OF MULTIPLES)

• By their very nature, sugar-coating formulations are very sticky, particularly as they begin to dry, and allow adjacent tablets to stick together.
• Build up of multiples really becomes a problem when the tablets being coated have flat surface which can easily come into contact with one another.
• Troublesome with high-dose, capsule-shaped tablets that have high edge walls.
• Appropriate choice in tablet punch design can be effectively used to minimize the problem.

UNEVEN COLOR

• Uneven distribution of color, particularly with the darker colors, is often visually apparent, and thus a major cause of batch rejection.
• Poor distribution of coating liquids during application
• Uniform mixing of tablets in the coating process
• Addition of sufficient coating liquids
• Color migration of water-soluble dyes while the coating is drying
• Change the solvent system
• Reduce the drying temperature
• Grind to a small particle size

Unevenness of the surface of the sub-coat

• Achieve desired surface smoothness
• Washing back of pigment-colored color coatings
• Replace aluminum lakes
• Use combinations of dyes and pigments
• Excessive drying between color applications
• Reduce rate of drying
• Reduce drying temperature

BLOOMING AND SWEATING

Residual moisture in finished sugar-coated tablets can often be a problem. over a period of time, this moisture can diffuse out and affect the quality of the product.

• Moderate levels of moisture egress cause the polish of the product to take on a fogged appearance, a phenomenon often termed blooming.
• At higher levels of moisture egress, the moisture may appear like beads of perspiration on the tablet surface, a phenomenon often termed sweating.
• Sweating can be much more serious, since tablets stored in closed containers will ultimately stick together.
• Obtain appropriate levels of moisture.

MARBLING

• To achieve a high-quality, sugar coated product it is important to ensure that color is uniformly distributed in the color layer, and at the end of the application of the color coating that a smooth coating surface is obtained.
• Failure to achieve the requisite smoothness often results in a marbled appearance on polishing.
• This problem occurs as the result of the collection of wax in the small surface depressions of a rough coating and is particularly evident with darker colors.
• Check for smooth surface at the end of color coating.

DEFECTS IN FILM COATED TABLETS(PICKING):

• It results when the coating on two adjacent tablets is not sufficiently dry before contact between them occurs.
• As the partially dried coating is extremely tacky, once the two tablets make contact they adhere to one another.
• Once the coating has dried they break apart later under the influence of attrition.
• In extreme cases the tablets may become permanently glued together so that twinning occurs.
• Over wetting typically occurs when the spray rate is excessive for the drying conditions in the process.

Adjust the spray rate

• Adjust the temperature of drying
• Check for the proper functioning of the spray guns
• Certain types of coating formulations(e.g., those based on hydroxypropylcellulose, and several of the acrylic aqueous latex coating systems) are inherently tackier during application.
• Replace with other polymer systems.

ORANGE PEEL(ROUGHNESS)

Inadequate spreading of the coating solution before drying causes a bumpy or orange-peel effect on the coating.

• This indicates that spreading is impeded by too rapid drying or by high solution viscosity.
• This is caused by process conditions which include low spray rates coupled with excessive drying conditions and use of excessive atomizing air pressures.
• Adjust the spray rate and drying conditions
• Coating liquids with high viscosities
• Thinning the coating solution with additional solvents In brief optimize the coating process.

EDGE WEAR(CHIPPING)

• Tablet edges are often exposed to attritional effects, so fracture at this point results in parts of the surface being exposed, referred as chipping.
• Seen with brittle film coatings that offer insufficient protection to tablet edges.
• Addition of small quantities of polymers(such as cellulosics,polyvinylpyrrolidine,acacia,or gelatin) to improve structural integrity.

FILM CRACKING

• Cracking of film coating occurs when the internal stress exceeds the tensile strength of the coating.
• The problem is exacerbated when significant differences exist between the thermal expansion coefficients for the core and coating.
• Totally unacceptable for products where the applied coating is a major factor in modifying drug-release characteristics.
• Minimize the internal stresses by adjusting the plasticizer type, pigment type and their concentration.
• Increase the tensile strength of the film by using high molecular-weight polymers or polymer blends.

FILM PEELING

• During application of aqueous coating formulations, cohesive failure(cracking) of the coating occurs.
• This coating may peel back from the surface of the substrate and result in peeling.
• Cohesive and adhesive failure( both linked to internal stress)
• Increase the tensile strength of the film
• Decrease the internal stress

BRIDGING OF LOGOS(INTAGLIATIONS)

• This phenomenon occurs when a component of the internal stress becomes sufficiently high so as to cause partial or complete detachment of the coating ( from the substrate) in the region of logo.
• As a result of such detachment, the film is able to shorten and thus partially relieve the stress within the film.
• This defect can be so severe that the monogram or bisect is completely obscured.
• Improve film adhesion by adjusting plasticizer content
• Appropriate design of tablet punches with respect to logo

IN-FILLING OF LOGOS

• In-filling of logos typically occurs during the spray application of aerated aqueous film-coating solutions.
• When a foamy coating solution impinges on a regular part of the tablet surface it will, under the shear forces generated, form a film with normal characteristics.
• Those droplets of coating liquid that reside in the logo, being protected from shear forces at the surface, gradually dry to form a solid foam that eventually obliterates the bisect.
• Judicious monitoring of the fluid application rate and thorough mixing of the tablets in the pan prevent filling.

BLISTERING

• When coated tablets require further drying in ovens, too rapid evaporation of the solvent from the core and the effect of high temperature on the strength, elasticity, and adhesion of the film may result in blistering.
• Use milder drying conditions.