Principle Tablet Compression Machine :
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The machine works by pressing upper and lower punches inside a die hole to form a tablet.
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Hydraulic pressure is the key force used.
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Pressure applied to the fluid is spread equally in all directions (Pascal’s law).
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By controlling the pressure, the compression force can be increased or decreased.
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Higher pressure = harder tablet.
Different Stages of Tablet Compression Process:
Tablet compression process is divided into four distinct stage. These stage including filling, metering, compressing and ejection.
Tablet compressing stage
Filling Formulation is overfilled at the compressing station
Metering Overfill is removed
Compression Tablet is formed by pressure of punches within die
Ejection Tablet is ejected from die
1. Filling:
- In this stage, the processed powder or granules (made by wet granulation, dry granulation, or sizing) are transferred for compression.
- These materials are blended to make a uniform mix.
- The blend flows into the punch-die cavity of the compression machine.
- The cavity is formed by the die and the lower punch.
- The position of the lower punch controls the cavity size → which decides how much material (tablet weight) is filled.
- To make sure the cavity is completely filled, a little extra powder (overfill) is placed on the die table.
2. Metering:
- This stage removes extra granules so that the right amount of material stays in the die.
- The tablet weight is controlled by the height of the lower punch inside the die.
- The metering cam (dosage cam) adjusts the lower punch to the correct level.
- Extra granules on top of the die table are scraped off, leaving only the exact amount needed.
- Example: It’s like baking → when a measuring cup is overfilled with flour, the extra is scraped off with a knife, leaving the correct amount in the cup.
3. Compression:
- This is the stage where the tablet is actually formed.
- The upper and lower punches come together inside the die under high pressure.
- The punches are pressed by two large wheels called pressure rolls.
- The distance between punches controls:
- Thickness of the tablet
- Hardness of the tablet
- Closer punches → thin, hard tablet
- Farther punches → thicker, softer tablet
- The goal is to find the right balance of thickness and hardness, while keeping the tablet weight constant
4. Ejection:
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In this stage, the tablet is removed from the die.
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First, the upper punch moves up and out of the die cavity.
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Then, the lower punch rises, pushing the tablet to the surface of the die table.
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A scraper (tablet rake-off) pushes the tablet off the die table into a collection container.
What are Tablet In Process Testing/QC Test?
Weight variation,
Disintegration,
Dissolution and Drug content.
Non-Official Tests Hardness and Friability.
Official tests Weight variation test (uniformity of weight)
• Weigh 20 tablet selected at random, each one individually. X1, X2, X3… Xz
• Determine the average weight
X= (X1+X2 +X3+…+ Xz)/20
Formula:
Average Weight of Tablet – Individual Weight of Tablet / Average Weight of Tablet
* 100.
Limit Upper limit = average weight + (average weight *% error)
Lower limit = average weight - (average weight * % error)
The individual weights are compared with the upper and lower limits, NMT two of the tablets differ from the average weight of tablet.
Disintegration test (U.S.P.)
What are Core/Uncoated Tablets and Coated Tablets Defects and their remedies?
TABLET DEFECTS AND REMEDIES
The defects related to Tableting Process
Capping:
It is partial or complete separation of the top or bottom of tablet due air-entrapment in the granular material.
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.
Capping Related to Formulation
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.
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:
It is separation of tablet into two or more layers due to air-entrapment in the granular material. Lamination Related To Formulation (Granulation)
Causes
1. Oily or waxy materials in granules.
2. Too much of hydrophobic lubricant. Eg. Magnesium-stearate.
Remedies
1. Modify mixing process. Add adsorbent or absorbent.
2. Use a less amount of lubricant or change the type of lubricant.
Lamination Related To Machine‘(Dies, Punches and Tablet Press)
Causes
1. Rapid relaxation of the peripheral regions of a tablet, on ejection from a die.
2. Rapid decompression
Remedies
1. Use tapered dies, i.e. upper part of the die bore has an outward taper of 3° to 5°.
2. Use pre-compression step. Reduce turret speed and reduce the final compression pressure
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.
Cracking Related To Formulation (Granulation)
Causes
1. Large size of granules.
2. Too dry granules.
3. Tablets expand.
4. Granulation too cold.
Remedies
1. Reduce granule size. Add fines.
2. Moisten the granules properly and add proper amount of binder.
3. Improve granulation. Add dry binders.
4. Compress at room temperature.
Cracking Related To Machine (Dies, Punches And Tablet Press)
Causes
1. Tablet expands on ejection due to air entrapment
2. Deep concavities cause cracking while removing tablets
Remedies
1. Use tapered die.
2. Use special take-off.
CHIPPING
Chipping it is due to very dry granules. 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.
Chipping Related To Formulation (Granulation)
Causes
1. Sticking on punch faces
2. Too dry granules.
3. Too much binding causes chipping at bottom.
Remedies
1. Dry the granules properly or increase lubrication.
2. Moisten the granules to plasticize. Add hygroscopic substances.
Chipping Related To Machine‘(Dies, Punches And Tablet Press)
Causes
1. Groove of die worn at compression point.
2. Barreled die (center of the die wider than ends)
3. Edge of punch face turned inside/inward.
4. Concavity too deep to compress properly.
Remedies
1. Polish to open end, reverse or replace the die.
2. Polish the die to make it cylindrical
3. Polish the punch edges
4. Reduce concavity of punch faces. Use flat punches.
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.
Sticking Related To Formulation (Granulation)
Causes
1. Granules not dried properly.
2. Too little or improper lubrication.
3. Too much binder
4. Hygroscopic granular material.
5. Oily or way materials
6. Too soft or weak granules.
Remedies
1. Dry the granules properly. Make moisture analysis to determine limits.
2. Increase or change lubricant.
3. Reduce the amount of binder or use a different type of binder.
4. Modify granulation and compress under controlled humidity.
5. Modify mixing process. Add an absorbent.
6. Optimize the amount of binder and granulation technique.
Sticking Related To Machine (Dies, Punches And Tablet Press)
Causes
1. Concavity too deep for granulation.
2. Too little pressure.
3. Compressing too fast.
Remedies
1. Reduce concavity to optimum.
2. Increase pressure.
3. 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.
Picking Related To Formulation (Granulation)
Causes
1. Excessive moisture in granules.
2. Too little or improper lubrication.
3. Low melting point substances, may soften from the heat of compression and lead to picking.
4. Low melting point medicament in high concentration.
5. Too warm granules when compressing.
6. Too much amount of binder.
Remedies
1. Dry properly the granules, determine optimum limit.
2. Increase lubrication; use colloidal silica as a polishing agent‘, so that material does not cling to punch faces.
3. Add high melting-point materials. Use high meting point lubricants.
4. Refrigerate granules and the entire tablet press.
5. Compress at room temperature. Cool sufficiently before compression.
6. Reduce the amount of binder, change the type or use dry binders.
Picking Related To Machine (Dies, Punches And Tablet Press)
Causes
1. Rough or scratched punch faces.
2. Bevels or dividing lines too deep.
3. Pressure applied is not enough; too soft tablets.
Remedies
1. Polish faces to high luster.
2. Design lettering as large as possible.
3. Plate the punch faces with chromium to produce a smooth and non-adherent face.
4. Reduce depths and sharpness.
5. 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.
Binding Related To Formulation (Granulation)
Causes
1. Too moist granules and extrudes around lower punch.
2. Insufficient or improper lubricant.
3. Too coarse granules.
4. Too hard granules for the lubricant to be effective.
5. Granular material very abrasive and cutting into dies.
6. Granular material too warm.
7. sticks to the die.
Remedies
1. Dry the granules properly.
2. Increase the amount of lubricant or use a more effective lubricant.
3. Reduce granular size, add more fines, and increase the quantity of lubricant.
4. Modify granulation. Reduce granular size.
5. If coarse granules, reduce its size.
6. Use wear-resistant dies.
7. Reduce temperature.
Binding Related To Machine (Dies, Punches And Tablet Press)
Causes
1. Poorly finished dies.
2. Rough dies due to abrasion, corrosion.
3. Undersized dies. Too little clearance.
4. Too much pressure in the tablet press.
Remedies
1. Polish the dies properly.
2. Investigate other steels or other materials or modify granulation.
3. Rework to proper size. Increase clearance.
4. Reduce pressure. Or Modify granulation.
The defect related to more than one factor
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 Double Impression: It is due to free rotation of the punches, which have some engraving on the punch faces.
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
1. Free rotation of either upper punch or lower punch during ejection of a tablet.
Remedies
1. Use keying in tooling, i.e. inset a key alongside of the punch, so that it fits the punch and prevents punch rotation.
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.
Causes
1. A coloured drug used along with colourless or white-coloured excipients.
2. A dye migrates to the surface of granulation while drying.
3. Improperly mixed dye, especially during ‗Direct Compression‘.
4. Improper mixing of a coloured binder solution.
Remedies
1. Use appropriate colourants.
2. Change the solvent system, Change the binder, Reduce drying temperature and Use a smaller particle size.
3. Mix properly and reduce size if it is of a larger size to prevent segregation.
4. 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.
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.
PROBLEMS AND REMEDIES FOR TABLET COATING BLISTERING
It is local detachment of film from the substrate forming blister.
Reason: Entrapment of gases in or underneath the film due to overheating either during spraying or at the end of the coating run.
Cause
1. Effect of temperature on the strength, elasticity and adhesion of the film.
Remedy
1. Use mild drying condition.
CRATERING
It is defect of film coating whereby volcanic-like craters appears exposing the tablet surface.
The coating solution penetrates the surface of the tablet, often at the crown where the surface is more porous, causing localized disintegration of the core and disruption of the coating.
Causes
1. Inefficient drying.
2. Higher rate of application of coating solution.
Remedies
1. Use efficient and optimum drying conditions. 2. Increase viscosity of coating solution to decrease spray application rate.
PICKING
It is defect where isolated areas of film are pulled away from the surface when the tablet sticks together and then parts.
Reason:
Conditions similar to cratering that produces an overly wet tablet bed where adjacent tablets can stick together and then break apart.
Cause
1. Inefficient drying.
2. Higher rate of application of coating solution.
Remedy
1. Use optimum and efficient drying conditions or increase the inlet air temperature.
2. Decrease the rater of application of coating solution by increasing viscosity of coating solution.
PITTING
It is defect whereby pits occur in the surface of a tablet core without any visible disruption of the film coating.
Reason: Temperature of the tablet core is greater than the melting point of the materials used in the tablet formulation.
Cause
1. Inappropriate drying (inlet air ) temperature.
Remedy
1. Dispensing with preheating procedures at the initiation of coating and modifying the drying (inlet air) temperature such that the temperature of the tablet core is not greater than the melting point of the batch of additives used.
BLOOMING
It is defect where coating becomes dull immediately or after prolonged storage at high temperatures.
Reason:
It is due to collection on the surface of low molecular weight ingredients included in the coating formulation. In most circumstances the ingredient will be plasticizer.
Cause
1. High concentration and low molecular weight of plasticizer.
Remedy
1. Decrease plasticizer concentration and increase molecular weight of plasticizer.
BLUSHING
It is defect best described as whitish specks or haziness in the film.
Reason:
It is thought to be due to precipitated polymer exacerbated by the use of high coating temperature at or above the thermal gelation temperature of the polymers.
Causes
1. High coating temperature.
2. Use of sorbitol in formulation which causes largest fall in the thermal gelation temperature of the Hydroxy Propyl Cellulose, Hydroxy Propyl Methyl Cellulose, Methyl Cellulose and Cellulose ethers.
Remedies
1. Decrease the drying air temperature.
2. Avoid use of sorbitol with Hydroxy Propyl Cellulose, Hydroxy Propyl Methyl Cellulose, Methyl Cellulose and Cellulose ethers.
Colour variation
A defect which involves variation in color of the film.
Reason:
Alteration of the frequency and duration of appearance of tablets in the spray zone or the size/shape of the spray zone.
Cause
1. Improper mixing, uneven spray pattern, insufficient coating, migration of soluble dyes-plasticizers and other additives during drying.
Remedy
1. Go for geometric mixing, reformulation with different plasticizers and additives or use mild drying conditions.
INFILLING
It is defect that renders the intagliations indistinctness.
Reason:
Inability of foam, formed by air spraying of a polymer solution, to break.
The foam droplets on the surface of the tablet breakdown readily due to attrition but the intagliations form a protected area allowing the foam to accumulate and settle.
Once the foam has accumulated to a level approaching the outer contour of the tablet surface, normal attrition can occur allowing the structure to be covered with a continuous film.
Cause
1. Bubble or foam formation because of air spraying of a polymer solution.
Remedy
1. Add alcohol or use spray nozzle capable of finer atomization.
ORANGE PEEL/ROUGHNESS
It is surface defect resulting in the film being rough and nonglossy.
Appearance is similar to that of an orange.
Reason:
Inadequate spreading of the coating solution before drying.
Causes
1. Rapid Drying
2. High solution viscosity
Remedies
1. Use mild drying conditions.
2. Use additional solvents to decrease viscosity of solution.
Cracking/Splitting
It is defect in which the film either cracks across the crown of the tablet (cracking) or splits around the edges of the tablet (Splitting).
Reason:
Internal stress in the film exceeds tensile strength of the film.
Cause
1. Use of higher molecular weight polymers or polymeric blends.
2. Use lower molecular weight polymers or polymeric blends. Also adjust plasticizer type and concentration.
BRIDGING
This occurs when the coating fills in the lettering or logo on the tablet and is typically caused by improper application of the solution, poor design of the tablet embossing, high coating viscosity, high percentage of solids in the solution, or improper atomization pressure.
During drying, the film may shrink and pull away from the sharp corners of an intagliation or bisect, resulting in a ―bridging of the surface.
This defect can be so severe that the monogram or bisect is completely obscured.
Remedy:
Increasing the plasticizer content or changing the plasticizer can decrease the incidence of bridging.
What are different types of tablet coating?
Different coatings Tablets can either be
Sugar coated
Film coated
Enteric coated
Coated to modify how the drug is released into the body (modified release).
Each of these coatings are there for different reasons and it is important to understand these reasons before deciding whether it is safe or appropriate to crush tablets.
This page explains why the coat may be on the tablet and what it means if you choose to crush or place the tablet in water to dissolve before swallowing.
Film and sugar coating
A sugar coating is basically is a thick, hard coating of sugar surrounding the tablet. It is no different in design to the sugar coatings placed on Smarties® or Minstrels ®.
This is a traditional method used to hide the flavour of particularly unpleasant tasting drugs e.g. ibuprofen and quinine, both of which are very bitter. The other advantage of a sugar coating is that it can prevent light or moisture from entering the tablet, which causes the drug to break down too quickly.
Due to the increase in tablet size caused by sugar coating, drug manufacturers have largely changed to using ‘film coatings’.
These are very thin layers of a safe ingredient placed around the tablet to again protect the tongue from the flavour of the contents and protect the contents from moisture and light.
The film will break down with agitation and significant amounts of moisture (saliva or stomach acid) and therefore does not significantly affect the way in which the drug is absorbed into the body.
Crushing these tablets therefore may not seriously affect how the drug is released but may cause the resultant mixture to be unpleasant to taste.
Enteric coating If a tablet is described as having an ‘enteric coating’ (e/c) or ‘gastro-resistant’, it means that there is a coating which is designed to hold the tablet together when in the stomach.
This clever science relies on the fact that the stomach is acid and the intestines, where food goes after the stomach, are not.
The coating is designed to hold together in acid conditions and break down in non-acid conditions and therefore release the drug in the intestines.
There are three reasons for putting such a coating on a tablet or capsule ingredient:
- To protect the stomach from the drug To protect the drug from the stomach
- To release the drug after the stomach e.g. in the intestines The drugs which most commonly cause stomach ulcers like aspirin, diclofenac and naproxen are frequently available with enteric coatings.
Omeprazole, which is a drug which stops the stomach from producing acid, is itself broken down in acid and therefore the drug generally has an enteric coating around it either as a granule in the capsules or as a granule in the dispersible form.
Sulfasalazine is used either for the treatment of arthritis or for the treatment of Crohn’s disease which is inflammation of the intestines. When used for arthritis, it is very often given without an enteric coating so that it can be absorbed more quickly.
For Crohn’s, it is needed to work in the intestines so it is given an enteric coating. It can be seen that an enteric coating has advantages and therefore such tablets or the contents of enteric coated capsules should never be crushed before being taken.
Modified release ‘Modified release’ means that the escape of the drug from the tablet has been modified in some way.
Usually this is to slow the release of the drug so that the medicine does not have to be taken too often and therefore makes it easier to remember to take.
The other benefit from modifying release is that the concentration of the drug in the body goes up slowly, is less likely to go very high and therefore reduces the chance of side effects.
Tablets and capsules which are designed to provide modified release often have the letters MR, LA, XL, CR or SR in their names e.g. Diffundox MR, Elantan LA, Dilzem XL Calcicard CR, Dilcardia S.
Sometimes the words ‘slow’ or ‘retard’ can be used to denote modified release e.g. Diclomax retard, Voltarol retard & Slow K.
There are a number of ways in which a medicine can have its release modified. Perhaps the most famous is that used in Contac 400 capsules.
The pellets inside are of different thicknesses and therefore the thinnest release the drug first and the thickest last (Figure 1).
Another method used is to put the drug in a viscous liquid which breaks down slowly itself and therefore releases the drug slowly.
One method which has been tried in the past has been to put a non-dissolving coating around the tablet or capsule, laser a small hole in it and then let the drug only release through the hole.
In such cases, patients frequently report passing the tablet or capsule whole and worrying whether it is actually working.
Frequently, they are just passing the outer coat in their stools as this is how the medicine is designed to work and the drug has long been absorbed.
Modified release products usually have a higher than normal amount of the drug within them and therefore if they are crushed, the whole dose will be released very quickly and could be dangerous.
Modified release products should never be crushed or modified before being taken.
Question 26: What do you mean by drug product specifications?