TABLET EVALUATION

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Narmdeshwar Dev Mishra M.Pharm (Pharmaceutics) narmdeshwar25@rediffmail.com Mob. No.9039822909 Monika Bhairam M.Pharm (Pharmaceutics) monikab430@gmail.com Columbia Institute Of Pharmacy Raipur (C.G) TABLET EVALUATION, EQUIPMENTS & PROCESSING PROBLEMS IN TABLET

TABLET EVALUATION: 

TABLET EVALUATION Introduction. General appearance. ( i ) Size & shape. (ii) Organoleptic properties. Weight variation Content uniformity. Mechanical strength of tablet. ( i ) Hardness. (ii) Friability (iii) Tensile strength. Disintegration test. Dissolution test .

Why to evaluate tablets?: 

Why to evaluate tablets? To monitor the product quality. For quantitative evaluation & assessment of tablet properties. To check chemical breakdown. To check the interactions between physical components of tablets.

GENERAL APPEARANCE : 

GENERAL APPEARANCE Size & shape . Tablet thickness varies with changes in- ( i ) Die fill, (ii) Particle size distribution and (iii) Packing of the powder mix being compressed & with tablet weight. The thickness of tablet is measured with a micrometer. Tablet thickness should be controlled within a ±5% variation of a standard value.

GENERAL APPEARANCE : 

GENERAL APPEARANCE Organoleptic properties Colour (no mottling) Odour (e.g. film coated tablets). Taste (e.g. chewable tablets).

WEIGHT VARIATION: 

WEIGHT VARIATION Weight variation The USP has provided limits for the average weight of uncoated compressed tablets. Average weight (mg) Percent difference (%) 130 mg or less 10 >130 mg but <324 mg 7.5 324 mg or more 5

CONTENT UNIFORMOTY: 

CONTENT UNIFORMOTY Content uniformity Every tablet contains the amount of drug substance intended with little variation among tablets within a batch. The content uniformity test has been included in the monographs (coated and uncoated tablets, capsules). For content uniformity test, representative samples of 30 tablets are selected and 10 are assayed individually. Nine of the 10 tablets must contain not less than 85% or more than 115% of the labeled drug content.

CONTENT UNIFORMITY: 

CONTENT UNIFORMITY Content uniformity The three factors that directly contribute to content uniformity problems: ( i ) non-uniform distribution of drug substance throughout the powder mixture or granulation. (ii) segregation of powder mixture or granulation during various manufacturing processes. (iii) tablet weight variation.

MECHANICAL STRENGTH OF TABLETS: 

MECHANICAL STRENGTH OF TABLETS It provides a measure of the bonding potential of the material concerned and this information is useful in the selection of excipients . Excessively strong bonds prevents rapid disintegration & subsequent dissolution. Can be quantified by ( i ) Friability (ii) Hardness (iii) Tensile strength

FRIABILITY: 

FRIABILITY Friability The friability test is closely related to tablet hardness and is designed to evaluate the ability of the tablet to withstand abrasion in packaging, handling and shipping. Measured by the use of the Roche friabilator . Method: ( i ) A number of tablets (say 20) are weighed and placed in the apparatus where they are exposed to rolling and repeated shocks as they fall 6 inches in each turn within the apparatus.

FRIABILITY: 

FRIABILITY ( ii) After four minutes of this treatment or 100 revolutions, the tablets are weighed and the weight compared with the initial weight. The loss due to abrasion is a measure of the tablet friability. (iii) The value is expressed as a percentage. (iv) A maximum weight loss of not more than 1% of the weight of the tablets being tested during the friability test is considered generally acceptable and any broken or smashed tablets are not picked up.

FRIABILITY APPARATUS: 

FRIABILITY APPARATUS

HARDNESS: 

HARDNESS Hardness Hardness or crushing strength determinations are made during tablet production, are used to determine the need for pressure adjustment on tablet machine. The force required to break the tablet is measured in kilograms and a crushing strength of 4Kg is usually considered to be the minimum for satisfactory tablets The Monsanto or Stokes hardness tester. The Strong-Cobb apparatus. Schleuniger apparatus.

HARDNESS: 

HARDNESS Oral tablets have 4 to 10 kg hardness. hypodermic and chewable tablets are usually much softer (3 kg) and some sustained release tablets are much harder (10-20 kg). Tablet hardness have been associated with other tablet properties such as density and porosity.

MONSANTO HARDNESS TESTER: 

MONSANTO HARDNESS TESTER

STRONG COBB APPARATUS: 

STRONG COBB APPARATUS

TENSILE STRENGTH: 

TENSILE STRENGTH Tensile strength This is the force required to break a tablet in a diametric compression test. The radial tensile strength, T, of the tablets can be calculated from the equation: T = 2 F / π d H Where F is the load needed to break the tablet, d and H are the diameter and thickness respectively. It is determined by static & dynamic methods.

DISINTEGRATION: 

DISINTEGRATION disintegration For a drug to be absorbed from a solid dosage form after oral administration, it must first be in solution, and the first important step toward this condition is usually the break-up of the tablet; a process known as disintegration. The disintegration test is a measure of the time required under a given set of conditions for a group of tablets to disintegrate into particles which will pass through a 10 mesh screen.

DISINTEGRATION: 

DISINTEGRATION The disintegration test is carried out using the disintegration tester which consists of a basket rack holding 6 plastic tubes, open at the top and bottom, the bottom of the tube is covered by a 10-mesh screen. The basket is immersed in a bath of suitable liquid held at 37 O C, preferably in a 1L beaker. For most uncoated tablets, the BP requires that the tablets disintegrate in 15 minutes (although it varies for some uncoated tablets) while for coated tablets, up to 2 hours may be required.

DISINTEGRATION: 

DISINTEGRATION To test for disintegration time, one tablet is placed in each test tube & basket rack is positioned in a 1L beaker of water, simulated gastric fluid at 37 o C ± 2 o C, such that tablets remain 2.5 cm below the surface of liquid on their upward movement. A standard motor driven device is used to move the basket assembly, at a frequency of 28-32 cycles/min. To be in USP standards, tablet must disintegrate & all particles must pass through 10 mesh screen in specified time.

DISINTEGRATION: 

DISINTEGRATION Uncoated USP Tablets = 5 min (Aspirin tablets). Majority of tablets have a disintegration time of 30 min. Enteric coated tablets = 2 hrs + time specified in monograph (Simulated intestinal fluid).

USP DISINTEGARTION APPARATUS: 

USP DISINTEGARTION APPARATUS

DISSOLUTION: 

DISSOLUTION Dissolution Dissolution is the process by which a solid solute enters a solution. Pharmaceutically, it may be defined as the amount of drug substance that goes into solution per unit time under standardized conditions of liquid/solid interface, temperature and solvent composition. Dissolution kinetics is important in determining the bioavailability of a drug.

DISSOLUTION: 

DISSOLUTION Two objectives in the development of in-vitro dissolution tests are to show ( i ) that the release of the drug from the tablet is as close as possible to 100%. (ii) that the rate of drug release is uniform batch to batch. Thus we can say that Rate of dissolution α efficacy of product. Rate of dissolution α bioavailability.

DISSOLUTION: 

DISSOLUTION It is carried out in ( i ) USP dissolution apparatus Type I (Basket type). (ii) USP dissolution apparatus Type II (Paddle type). In general, a single tablet is placed in a small wire mesh basket fastened to the bottom of the shaft connected to a variable speed motor. The basket is immersed in the dissolution medium (as specified in the monograph) contained in a flask. The flask is maintained at constant temperature of 37 o C ± 5 o C by a constant temperature bath.

DISSOLUTION: 

DISSOLUTION The motor is adjusted to turn at the specified speed, and samples of fluid are withdrawn at intervals to determine the amount of drug in solution. For example: for methyldopa tablets the dissolution test calls for a medium of 900 ml of 0.1 N HCl , apparatus 2 turning at 50 rpm, & time limit of 20 min. The accepted amount dissolved in 20 min is not less than 80% of the labeled amount of methyldopa.

DISSOLUTION APPARATUS: 

DISSOLUTION APPARATUS

PROCESSING PROBLEMS IN TABLETS: 

PROCESSING PROBLEMS IN TABLETS The processing problems in tablets is due to three reasons: ( i ) Tableting process (Capping, Lamination & cracking). (ii) Excipients (Picking, Sticking, Mottling & Binding). (iii) Machine related (Double impression).

1.CAPPING: 

1.CAPPING ‘Capping’ is the term used, when the 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. 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.

REMEDIES: 

REMEDIES S.No . Causes Remedies 1. Fines in granulation Remove some or all fines through 100-200 mesh screen. 2. Too dry or very low moisture content (leading to loss of proper binding action). Moisten the granules suitably. Add hygroscopic substance e.g.: sorbitol , methyl- cellulose or PEG-4000. 3. Not thoroughly dried granules Dry the granules properly.

REMEDIES: 

REMEDIES S. No. Causes Remedies 4. Insufficient amount of binder or improper binder. Adding dry binder such as pre-gelatinized starch, gum acacia, powdered sorbitol, PVP, hydrophilic silica or powdered sugar. 5. Insufficient or improper lubricant. Increase the amount of lubricant or change the type of lubricant.

REMEDIES: 

REMEDIES S. No. Causes Remedies 6. Granular mass too cold to compress firm. Compress at room temperature. 7. Deep concave punches or beveled-edge faces of punches. Use flat punches. 8. Poorly finished dies Polish dies properly. Investigate other steels or other materials.

2.LAMINATION: 

2.LAMINATION ‘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.

REMEDIES: 

REMEDIES S.No . Causes Remedies 1. Oily or waxy materials in granules. Modify mixing process. Add adsorbent or absorbent. 2. Too much of hydrophobic lubricant e.g.: Magnesium- stearate . Use a less amount of lubricant or change the type of lubricant. 3. Rapid relaxation of the peripheral regions of a tablet, on ejection from a die. Use tapered dies, i.e. upper part of the die bore has an outward taper of 3° to 5°.

3.CHIPPING: 

3.CHIPPING ‘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.

REMEDIES: 

REMEDIES S. No. Causes Remedies 1. Sticking on punch faces. Dry the granules properly or increase lubrication. 2. Too dry granules. Moisten the granules to plasticize. Add hygroscopic substances. 3. Too much binding causes chipping at bottom. Optimize binding, or use dry binders.

4.CRACKING: 

4.CRACKING Small, fine break marks 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.

REMEDIES: 

REMEDIES S. No. Causes Remedies 1. Large size of granules. Reduce granule size. Add fines. 2. Too dry granules. Moisten the granules properly and add proper amount of binder. 3. Tablets expand. Improve granulation. Add dry binders.

REMEDIES: 

REMEDIES S.No . Causes Remedies 4. Granulation too cold. Compress at room temperature. 5. Tablet expands on ejection due to air entrapment. Use tapered die.

5.STICKING: 

5.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. Reason: Improperly dried or improperly lubricated granules.

REMEDIES: 

REMEDIES S.No . Causes Remedies 1. Granules not dried properly. Dry the granules properly. Make moisture analysis to determine limits. 2. Too little or improper lubrication. Increase or change lubricant. 3. Hygroscopic granular material. Modify granulation and compress under controlled humidity.

REMEDIES: 

REMEDIES S. No. Causes Remedies 4. Oily or waxy materials. Modify mixing process. Add an absorbent. 5. Too soft or weak granules. Optimize the amount of binder and granulation technique. 6. Too much binder Reduce the amount of binder or use a different type of binder.

6.PICKING: 

6.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. Reason: Picking is of particular concern when punch tips have engraving or embossing letters, as well as the granular material is improperly dried.

REMEDIES: 

REMEDIES S. No. Causes Remedies 1. Excessive moisture in granules. Dry properly the granules. 2. Too little or improper lubrication. Increase lubrication; use colloidal silica so material does not cling to punch faces. 3. Too much amount of binder. Reduce the amount of binder, change the type or use dry binders.

REMEDIES: 

REMEDIES S. No. Causes Remedies 4 Low melting point substances, may soften from the heat of compression and lead to picking. Add high melting-point materials. Use high meting point lubricants. 5. Low melting point medicament in high concentration. Refrigerate granules and the entire tablet press.

7.BINDING: 

7.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. Reason: Binding is usually due to excessive amount of moisture in granules, lack of lubrication and/or use of worn dies.

REMEDIES: 

REMEDIES S. No. Causes Remedies 1. Too moist granules and extrudes around lower punch. Dry the granules properly. 2. Insufficient or improper lubricant. Increase the amount of lubricant or use a more effective lubricant. 3. Too coarse granules. Reduce granular size, and increase the quantity of lubricant.

8.MOTTLING: 

8.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.

REMEDIES: 

REMEDIES S.No . Causes Remedies 1. A coloured drug used with white or colourless excipients Use appropriate colourants. 2. A dye migrates to the surface of granulation while drying. Change the solvent system, Change the binder, Reduce drying temperature. 3. Improperly mixed dye, during ‘Direct Compression’. Mix properly and reduce size if it is of a larger size to prevent segregation.

9.DOUBLE IMPRESSION: 

9.DOUBLE IMPRESSION ‘Double Impression’ involves only those punches, which have a monogram or other engraving on them. Reason: At compression, the tablet receives the imprint of the punch. On some machines, the lower punch freely drops and travels uncontrolled for a short distance before riding up the ejection 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’.

REMEDIES: 

REMEDIES S.No . Causes Remedies 1. Free rotation of either upper punch or lower punch during ejection of a tablet. Use keying in tooling, i.e. insert 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.

PROCESSING PROBLEMS & REMEDIES FOR TABLET COATING: 

PROCESSING PROBLEMS & REMEDIES FOR TABLET COATING Blistering. Chipping. Cratering . Pitting Blooming Blushing. Picking. Colour variation. Orange peel / Roughness.

1.BLISTERING: 

1.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.

REMEDIES: 

REMEDIES S. No. Causes Remedies 1. Effect of temperature on the strength, elasticity and adhesion of the film. Use mild drying condition.

2.CHIPPING: 

2.CHIPPING It is defect where the film becomes chipped and dented, usually at the edges of the tablet. Reason : Decrease in fluidizing air or speed of rotation of the drum in pan coating.

REMEDIES: 

REMEDIES S. No. Causes Remedies 1. High degree of attrition associated with the coating process. Increase hardness of the film by increasing the molecular weight grade of polymer.

3.CRATERING: 

3.CRATERING It is defect of film coating whereby volcanic-like craters appears exposing the tablet surface. Reason: 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.

REMEDIES: 

REMEDIES S. No. Causes Remedies 1. Inefficient drying. Use efficient and optimum drying conditions. 2. Higher rate of application of coating solution. Increase viscosity of coating solution to decrease spray application rate.

4.PICKING: 

4.PICKING It is defect where isolated areas of film are pulled away from the surface when the tablet sticks together and then part. Reason: Conditions similar to cratering that produces an overly wet tablet bed where adjacent tablets can stick together and then break apart.

REMEDIES: 

REMEDIES S. No. Causes Remedies 1. Inefficient drying. Use optimum and efficient drying conditions or increase the inlet air temperature. 2. Higher rate of application of coating solution. Decrease the rate of application of coating solution by increasing viscosity.

5.PITTING: 

5.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.

REMEDIES: 

REMEDIES S. No. Causes Remedies 1. Inappropriate drying (inlet air ) temperature. 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.

6.BLOOMING: 

6.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 .

REMEDIES: 

REMEDIES S. No. Causes Remedies 1. High concentration and low molecular weight of plasticizer. Decrease plasticizer concentration and increase molecular weight of plasticizer.

7.BLUSHING: 

7.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.

REMEDIES: 

REMEDIES S. No. Causes Remedies 1. High coating temperature. Decrease the drying air temperature.

REMDIES: 

REMDIES S. No. Causes Remedies 2. Use of sorbitol in formulation which causes fall in the thermal gelation temperature of the Hydroxy Propyl Cellulose, Hydroxy Propyl Methyl Cellulose, Methyl Cellulose. Avoid use of sorbitol with Hydroxy Propyl Cellulose, Hydroxy Propyl Methyl Cellulose, Methyl Cellulose and Cellulose ethers.

8.COLOUR VARIATION: 

8.COLOUR VARIATION A defect which involves variation in colour 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.

REMEDIES: 

REMEDIES S. No. Causes Remedies 1. 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.

9.ORNAGE PEEL / ROUGHNESS: 

9.ORNAGE PEEL / ROUGHNESS It is surface defect resulting in the film being rough and non glossy. Appearance is similar to that of an orange. Reason: Inadequate spreading of the coating solution before drying.

REMEDIES: 

REMEDIES S. No. Causes Remedies 1. Rapid Drying. Use mild drying conditions. 2. High solution viscosity. Use additional solvents to decrease viscosity of solution.

TABLET EQUIPMENTS: 

TABLET EQUIPMENTS Granulator Tablet presses (Single presses & Rotary presses).

GRANULATOR: 

GRANULATOR Granulation process involved the hand process of mixing of wet mass. Increasing batch size made bulk granulation procedure necessary. Current granulating methods are classified in to 4 categories: ( i ) Traditional methods (ii) High shear mixing (iii) Fluid bed granulation (iv) Single pot processing.

TABLET PRESSES: 

TABLET PRESSES Tablet compression machines (tablet presses) are designed with basic components. Hopper (holding and feeding). Dies (shape & size). Punches (compressing). Cam tracks (guiding the punch movement). Feeding mechanism (from moving granulation from hopper in to dies).

SINGLE PUNCH: 

SINGLE PUNCH All the compression is applied by the upper punch, making the single punch machine a stamping press .

SINGLE PRESS: 

SINGLE PRESS

MULTI STATION PRESSES: 

MULTI STATION PRESSES Rotary presses because the head of the tablet machine that holds the upper punches in place rotates. As the head rotates the punches are guided up an down by fixed cam tracks. Cam tracks control the sequence of filling, compressing & ejection .

MULTI STATION PRESS: 

MULTI STATION PRESS

REFERENCES: 

REFERENCES Leon Lachman , H. A. Lieberman, J. L. Kanig , The Theory & practice of Industrial Pharmacy, 296, 311 (1991). Banker & Rhodes, Modern Pharmaceutics, Tablet dosage forms .

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