Manufacturing Defects of Tablets

Manufacturing Defects of Tablets processing problems can be due to the problem in the formulation or in the compression equipment, or both of them. Thus we can classify the problems into following types:

Manufacturing Defects of Tablets

Overview of 21CRF

DEFECTS RELATED TO TABLETTING PROCESS
DEFECT	DEFINITION	CAUSES	REMEDY
CAPPING	_{upper or lower segment of the tablet separates horizontally, either partially or completely from the main body of a tablet and comes off as a cap, during ejection from the tablet press, or during subsequent handling.}	_{Large amount of fines in the granulation Too dry or very low moisture content (leading to loss of proper binding action). Not thoroughly dried granules. Insufficient amount of binder or improper binder. Insufficient or improper lubricant. Granular mass too cold.}	_{Remove some or all fines through 100 to 200 mesh screen. Moisten the granules suitably. Add hygroscopic substance e.g.: sorbitol, methyl- cellulose or PEG4000. Dry the granules properly. Increasing the amount of binder. Adding dry binder such as pre-gelatinized starch, gum acacia, powdered sorbitol, PVP, hydrophilic silica or powdered sugar. Increase the amount of lubricant or change the type of lubricant. Compress at room temperature.}
LAMINATION	_{separation of a tablet into two or more distinct horizontal layers.}	_{Oily or waxy materials in granules. Too much of hydrophobic lubricant. Magnesium-stearate.}	_{Modify mixing process. Add adsorbent or absorbent. Use a less amount of lubricant or change the type of lubricant.}
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}	_{Large size of granules. Too dry granules. Tablets expand. Granulation too cold.}	_{Reduce granule size. Add fines. Moisten the granules properly and add proper amount of binder. Improve granulation. Add dry binders. Compress at room temperature.}
DEFECTS RELATED TO EXCIPIENT
CHIPPING	_{breaking of tablet edges, while the tablet leaves the press or during subsequent handling and coating operations.}	_{Sticking on punch faces Too dry granules. Too much binding causes chipping at bottom.}	_{Dry the granules properly or increase lubrication. Moisten the granules to plasticize. Add hygroscopic substances.}
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.}	_{Granules not dried properly. Too little or improper lubrication. Too much binder Hygroscopic granular material. Oily or way materials Too soft or weak granules.}	_{Dry the granules properly. Make moisture analysis to determine limits. Increase or change lubricant. Reduce the amount of binder or use a different type of binder. Modify granulation and compress under controlled humidity. Modify mixing process. Add an absorbent. Optimize the amount of binder and granulation technique.}
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.}	_{Excessive moisture in granules. Too little or improper lubrication. Low melting point substances, may soften from the heat of compression and lead to picking. Low melting point medicament in high concentration. Too warm granules when compressing. Too much amount of binder.}	_{Dry properly the granules, determine optimum limit. Increase lubrication; use colloidal silica as a polishing agent, so that material does not cling to punch faces. Add high melting-point materials. Use high meting point lubricants. Refrigerate granules and the entire tablet press. Compress at room temperature. Cool sufficiently before compression. Reduce the amount of binder, change the type or use dry binders.}
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.}	_{Too moist granules and extrudes around lower punch. Insufficient or improper lubricant. Too coarse granules. Too hard granules for the lubricant to be effective. Granular material very abrasive and cutting into dies. Granular material too warm.}	_{Dry the granules properly. Increase the amount of lubricant or use a more effective lubricant. Reduce granular size, add more fines, and increase the quantity of lubricant. Modify granulation. Reduce granular size. If coarse granules, reduce its size. Use wear-resistant dies. Reduce temperature. Increase clearance if it is extruding}
DEFECTS RELATED TO MORE THAN ONE FACTOR
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.}	_{A coloured drug used along with colourless or white-coloured excipients. A dye migrates to the surface of granulation while drying. Improperly mixed dye, especially during Direct Compression. Improper mixing of a coloured binder solution.}	_{Use appropriate colourants. Change the solvent system, Change the binder, Reduce drying temperature and Use a smaller particle size. Mix properly and reduce size if it is of a larger size to prevent segregation. 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.}
DEFECT RELATED TO MACHINE
DOUBLE IMPRESSION	_{Double Impression involves only those punches, which have a monogram or other engraving on them.}	_{Free 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. Newer presses have anti-turning devices, which prevent punch rotation.}
DEFECT RELATED TO COATING
BLISTERING	_{It is local detachment of film from the substrate forming blister}	_{Effect of temperature on the strength, elasticity and adhesion of the film.}	_{Use mild drying condition.}
CRATERING	_{It is defect of film coating whereby volcanic-like craters appears exposing the tablet surface.}	_{Inefficient drying. Higher rate of application of coating solution.}	_{Use efficient and optimum drying conditions. 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 part.}	_{Inefficient drying. Higher rate of application of coating solution}	_{Use optimum and efficient drying conditions or increase the inlet air temperature. 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.}	_{Inappropriate drying (inlet air ) temperature.}	_{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.}	_{High concentration and low molecular weight of plasticizer.}	_{Decrease plasticizer concentration and increase molecular weight of plasticizer.}
BLUSHING	_{It is defect best described as whitish specks or haziness in the film.}	_{High coating temperature. 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.}	_{Decrease the drying air temperature. 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 colour of the film.}	_{Improper mixing, uneven spray pattern, insufficient coating, migration of soluble dyes-plasticizers and other additives during drying.}	_{Go for geometric mixing, reformulation with different plasticizers and additives or use mild drying conditions.}
INFILLING	_{It is defect that renders the intagliations indistinctness}	_{Bubble or foam formation because of air spraying of a polymer solution.}	_{Add alcohol or use spray nozzle capable of finer atomization.}
ORANGE PEEL EFFECT	_{It is surface defect resulting in the film being rough and nonglossy. Appearance is similar to that of an orange.}	_{Rapid Drying High solution viscosity}	_{Use mild drying conditions. 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).}	_{Internal stress in the film exceeds tensile strength of the film, due to high or low molecular weight polymers.}	_{Use of correct polymers}
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.}	_{Low plastisizer or non-compatible plastisizer}	_{Increasing the plasticizer content or changing the plasticizer can decrease the incidence of bridging.}