PROBLEMS CAUSES AND REMEDIES IN TABLET MANUFACTURING Venkatesh.T, M.Pharm, SKIPS.
Problem in tablets are either related toimperfections in any one or more of thefollowing factors:I. Tableting ProcessII. ExcipientIII. Machine
Process related problems :• CAPPING: It is due air-entrapment in the granular material.• LAMINATION: It is due air-entrapment in the granular material.• CRACKING: It is due to rapid expansion of tablets when deep concave punches are used.
Excipient related problems :• CHIPPING: It is due to very dry granules.• STICKING: It is due to excess moisture preasent in the granules.• PICKING: It is due the improper drying of the granules.• BINDING: It is due the excessive binder present in the granules.• MOTTLING: uneven distribution of colour
Machine related problems :• DOUBLE IMPRESSION: It is due to free rotation of the punches, which have some engraving on the punch faces.
CAPPING:Capping happened when the upper or lowersegment of the tablet separates horizontally,either partially or completely from the mainbody of a tablet and comes off as a cap, duringejection from the tablet press, or duringsubsequent handling.Reason: Capping is usually due to the air–entrapment in a compact during compression,and subsequent expansion of tablet on ejectionof a tablet from a die.
CAPPING RELATED TO ‘FORMULATION’(GRANULATION)Sr.No. CAUSES REMEDIES Large amount of fines in Remove some or all fines through 100 to 200 1. the granulation mesh screen Too dry or very low Moisten the granules suitably. Add hygroscopic moisture content (leading 2. substance e.g.: sorbitol, methyl- cellulose or to loss of proper binding PEG-4000. action). Not thoroughly dried 3. Dry the granules properly. granules. Increasing the mount of binder OR Insufficient amount of Adding dry binder such as pre-gelatinized starch, 4. binder or improper binder. gum acacia, powdered sorbitol, PVP, hydrophilic silica or powdered sugar. Insufficient or improper Increase the amount of lubricant or change the 5. lubricant. type of lubricant. Granular mass too cold to 6. Compress at room temperature. compress firm.
CAPPING RELATED TO ‘MACHINE’ (DIES, PUNCHESAND TABLET PRESS)Sr.No CAUSES REMEDIES Polish dies properly. Investigate other 1. Poorly finished dies steels or other materials. Deep concave punches or 2. Use flat punches. beveled-edge faces of punches. Lower punch remains below the Make proper setting of lower punch 3. face of die during ejection. during ejection. Incorrect adjustment of sweep- Adjust sweep-off blade correctly to 4. off blade. facilitate proper ejection. Reduce speed of turret (Increase 5. High turret speed. dwell time).
Lamination /Laminating• Definition: ‘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.
LAMINATION RELATED TO FORMULATION (GRANULATION) Sr. No CAUSES REMEDIES Oily or waxy materials in Modify mixing process. Add 1. granules adsorbent or absorbent. Too much of hydrophobic Use a less amount of lubricant or 2. lubricant e.g.: change the type of lubricant. Magnesium-stearate. Lamination related to MACHINE (Dies, Punches and Tablet Press) Sr. No. CAUSES REMEDIES Rapid relaxation of the Use tapered dies, i.e. upper part of 1. peripheral regions of a the die bore has an outward taper tablet, on ejection from a die. of 3° to 5°. Use pre-compression step. Reduce 2. Rapid decompression turret speed and reduce the final compression pressure.
Chipping• Definition: ‘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) Sr. No CAUSES REMEDIES Dry the granules properly or 1. Sticking on punch faces increase lubrication. Moisten the granules to plasticize. 2. Too dry granules. Add hygroscopic substances. Too much binding causes chipping at Optimize binding, or use dry 3. bottom. binders.CHIPPING RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS) Sr. No CAUSES REMEDIES Groove of die worn at compression Polish to open end, reverse or 1. point. replace the die. Barreled die (center of the die wider 2. Polish the die to make it cylindrical than ends) Edge of punch face turned 3. Polish the punch edges inside/inward. Concavity too deep to compress Reduce concavity of punch faces. 4. properly. Use flat punches.
Cracking• Definition: 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) Sr. No. CAUSES REMEDIES 1. Large size of granules. Reduce granule size. Add fines. Too dry granules. Moisten the granules properly and add 2. proper amount of binder. 3. Tablets expand. Improve granulation. Add dry binders. 4. Granulation too cold. Compress at room temperature.CRACKING RELATED TO MACHINE (DIES, PUNCHES AND TABLETPRESS) Sr. No. CAUSES REMEDIES Tablet expands on ejection due 1. Use tapered die. to air entrapment. Deep concavities cause cracking 2. while Use special take-off. removing tablets
Sticking• Definition: ‘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.
STICKING RELATED TO FORMULATION(GRANULATION) Sr. No. CAUSES REMEDIES Granules not dried Dry the granules properly. Make moisture 1. properly. analysis to determine limits. Too little or 2. improper Increase or change lubricant. lubrication. Reduce the amount of binder or use a different 3. Too much binder type of binder. Hygroscopic Modify granulation and compress under 4. granular material. controlled humidity. Oily or way 5. Modify mixing process. Add an absorbent. materials Too soft or weak Optimize the amount of binder and granulation 6. granules. technique.
STICKING RELATED TO MACHINE (DIES,PUNCHES AND TABLET PRESS)Sr. No. CAUSES REMEDIES 1. Concavity too deep for granulation. Reduce concavity to optimum. 2. Too little pressure. Increase pressure. 3. Compressing too fast. Reduce speed.
Picking• Definition: ‘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)Sr.No CAUSES REMEDIES Dry properly the granules, determine 1. Excessive moisture in granules. optimum limit. Increase lubrication; use colloidal silica Too little or improper 2. as a ‘polishing agent’, so that material lubrication. does not cling to punch faces. Low melting point substances, may soften from the heat of Add high melting-point materials. Use 3. compression and lead to high meting point lubricants. picking. Low melting point medicament Refrigerate granules and the entire 4. in high concentration. tablet press. Too warm granules when Compress at room temperature. Cool 5. compressing. sufficiently before compression. Reduce the amount of binder, change 6. Too much amount of binder. the type or use dry binders.
PICKING RELATED TO MACHINE (DIES,PUNCHES AND TABLET PRESS)Sr.No CAUSES REMEDIES 1. Rough or scratched punch faces. Polish faces to high luster. Design lettering as large as possible. Embossing or engraving letters Plate the punch faces with chromium 2. on punch faces such as B, A, O, to produce a smooth and non-adherent R, P, Q, G. face. 3. Bevels or dividing lines too deep. Reduce depths and sharpness. Pressure applied is not enough; 4. Increase pressure to optimum. too soft tablets.
Binding• Definition: ‘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.
BINDING RELATED TO FORMULATION(GRANULATION)Sr.No CAUSES REMEDIES Too moist granules and 1. extrudes around lower Dry the granules properly. punch. Insufficient or improper Increase the amount of lubricant or use a 2. lubricant. more effective lubricant. Reduce granular size, add more fines, and 3. Too coarse granules. increase the quantity of lubricant. Too hard granules for the 4. Modify granulation. Reduce granular size. lubricant to be effective. Granular material very If coarse granules, reduce its size. 5. abrasive and cutting into Use wear-resistant dies. dies. Granular material too Reduce temperature. 6. warm, sticks to the die. Increase clearance if it is extruding.
BINDING RELATED TO MACHINE (DIES,PUNCHES AND TABLET PRESS)Sr.No CAUSES REMEDIES . 1. Poorly finished dies. Polish the dies properly. Rough dies due to abrasion, Investigate other steels or other materials 2. corrosion. or modify granulation. Undersized dies. Too little Rework to proper size. 3. clearance. Increase clearance. Too much pressure in the Reduce pressure. OR 4. tablet press. Modify granulation.
Mottling• Definition: ‘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 And Remedies Of Mottling:Sr.No. CAUSES REMEDIES A coloured drug used along with colourless or 1. Use appropriate colourants. white-coloured excipients. Change the solvent system, A dye migrates to the Change the binder, 2. surface of granulation Reduce drying temperature and while drying. Use a smaller particle size. Improperly mixed dye, Mix properly and reduce size if it is of a larger 3. especially during size to prevent segregation. ‘Direct Compression’. Incorporate dry colour additive during powder Improper mixing of a blending step, then add fine powdered 4. coloured binder adhesives such as acacia and tragacanth and solution. mix well and finally add granulating liquid.
Double impression Double impression• Definition: ‘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’.• If the upper punch is uncontrolled, it can rotate during the short travel to the final compression stage and create a double impression.
CAUSES AND REMEDIES OF DOUBLE IMPRESSION:Sr. No. CAUSE REMEDIES -Use keying in tooling, i.e. inset a key alongside of the punch, so that it fits the Free rotation of either punch and upper punch or lower 1. prevents punch rotation. punch during ejection of a tablet. -Newer presses have anti-turning devices, which prevent punch rotation.
TABLET COATING DEFECTS• PICKING AND STICKING• TWINNING• COLOR VARIATION• ORANGE PEEL• ROUGHNESS• BRIDGING• BLISTERING• EROSION• PEEALING AND FROSTING
TWINNING• This is the term for two tablets that stick together, and it’s a common problem with capsule shaped tablets.
REMEDY• Assuming you don’t wish to change the tablet shape, you can solve this problem by balancing the pan speed and spray rate. Try reducing the spray rate or increasing the pan speed. In some cases, it is necessary to modify the design of the tooling by very slightly changing the radius. The change is almost impossible to see, but it prevents the twinning problem.
COLOR VARIATION• This problem can be caused by processing conditions or the formulation. Improper mixing, uneven spray pattern and insufficient coating may result in color variation. The migration of soluble dyes, plasticizers and other additives during drying may give the coating a mottled or spotted appearance. REMEDY: 1. The use of lake dyes eliminates dye migration.
ORANGE PEEL• Inadequate spreading of the coating solution before drying causes a bumpy or “orange-peel” effect on the coating• REMEDY: Thinning the solution with additional solvent may correct this problem.
ROUGHNESS• A rough or gritty surface is a defect often observed when coating is applied by a spray. Some of the droplets may dry too rapidly before reaching the tablet bed, resulting in the deposits on the tablet surface of “spray dried” particles instead of finely divided droplets of coating solution.• REMEDY: Moving the nozzle closer to the tablet bed and reducing the degree of atomization can decrease the roughness.
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• REMEDY: Increasing the plasticizer content or changing the plasticizer can decrease the incidence of bridging.
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. REMEDY: Milder drying conditions are warranted in this case.
EROSION• This can be the result of soft or friable tablets (and the pan turning too fast), an over-wetted tablet surface, inadequate drying, or lack of tablet surface strength.
Peeling and frostingThis is a defect where the coating peelsaway from the tablet surface in a sheet.Peeling indicates that the coating solutiondid not lock into the tablet surface. Thiscould be due to a defect in the coatingsolution, over-wetting, or high moisturecontent in the tablet core which preventedthe coating to adhering.
REFERENCES• http://www.labequipmentsindia.com/product/image/2252.jpg• http://product-image.esuppliersindia.com/00431839/s/3/Tablet-Punching-M• http://www.gmpchina.net/image/p/gzpt1060.jpg• The theory and practice of industrial pharmacy by Leon Lachman, Herbert A Lieberman. http://www.authorstream.com/Presentation/sabapathi-369361-problems-ta• http://www.justice.gov/dea/programs/forensicsci/microgram/mg0206/mg02• http://upload.wikimedia.org/wikipedia/en/2/27/Tabletfailure.jpg