Tablets Lecture Notes PDF

Tablets Dr. Ahmed A. El-Shenawy Department of Pharmaceutics and Pharmaceutical Technology Glidants  Are materials that improve the flow characteristics of granulations by reducing interparticulate friction.  They increase the flow of materials from larger to smaller a...

Tablets Dr. Ahmed A. El-Shenawy Department of Pharmaceutics and Pharmaceutical Technology Glidants  Are materials that improve the flow characteristics of granulations by reducing interparticulate friction.  They increase the flow of materials from larger to smaller apertures, from the hopper into the die cavities of the tablet press.  The improvement is dependent on the size and concentration of the fine particles; the smaller the particles, the lower the concentration required to enhance the flow.  As the silica-type glidants. 2  Coloring agents  Provide a more uniform and more acceptable appearance to the consumer as titanium dioxide (white), iron oxide (brown and red), carmine (red and purple), chlorophyll (green), and turmeric (yellow).  Adsorbents  Are substances capable of holding quantities of fluids in an apparently dry state. Oils or drug-oil solutions may be mixed with adsorbents and then granulated and compressed into tablets, as magnesium carbonate and magnesium oxide. 3  Antiadherents  Some materials have strong adhesive properties towards the metal of punches and dies or the tablet formulation containing excessive moisture. Therefore antiadherents are added, which prevent sticking to punches and die walls as talc, magnesium stearate, and corn starch.  Wetting agents  Aid water uptake and thereby enhancing disintegration and assisting in drug dissolution. Incorporation of anionic surfactant like sodium lauryl sulphate (SLS) is known to enhance the dissolution. 4  Dissolution retardants Added when controlled release of drug is required. Example: waxy materials like stearic acid and their esters.  Dissolution enhancers Alter the molecular forces between ingredients to enhance the dissolution of solute in the solvent as povidone.  Buffers Maintain a required pH since a change in pH may cause significant alteration in stability as sodium bicarbonate, calcium carbonate, and sodium citrate. 5 Tableting methods 6 Preparation of components for compression The techniques for preparing tablets may follow one or a combination of several established methods. These are: 1. Dry methods: Direct compression and Granulation by compression. 2. Wet methods: Wet granulation. Granulation methods: 1. Wet granulation. 2. Dry granulation.  The ideal characteristics of granules include: Uniformity, good flow, and compactability. 7 Wet granulation steps 1. The active ingredient and excipients are weighed and mixed. 2. The wet granulate is prepared by adding the liquid binder- adhesive to the powder blend and mixing thoroughly. 3. Screening the damp mass through a mesh to form pellets or granules. 4. Drying the granules: a conventional tray-dryer or fluid- bed dryer. 5. After the granules are dried, they are passed through a screen of smaller size than the one used for the wet mass to create granules of uniform size. 8 Dry granulation  Do not use moisture or heat to process powders into densified granules.  Create granules by light compaction of the powder blend under low pressures.  The compacts so-formed are broken up gently to produce granules (agglomerates).  This process is often used when the product to be granulated is sensitive to moisture and heat.  Slugging and roller compaction. 9 Advantages of wet granulation 1. Enhances fluidity and compactability, suitable for high-dose drugs with poor flow and/or compactability. 2. Reduces air entrapment and dustiness. 3. Suitable for dispersion of low-dose drugs in solution to ensure content uniformity. 4. Enhances wettability of powders. 10 Disadvantages of wet granulation 1. Several proceeding steps are required increase the time, loss of material, and effort. 2. Solvents are required in this process; this may lead to various problems such as drug degradation and the heat required to remove the solvent, this could result in degradation of the thermally-labile drugs. 3. Overall more costly than direct compression. 11 Dry granulation Advantages Disadvantages 1. We used conventional grades 1. Special equipment is required. of excipients. 2. Segregation may occur post 2. No heat or solvent is mixing. required. 3. The final tablet produced by dry granulation tends to be softer than these of wet granulation rendering them difficult for further process such as coating. 4. Slugging or roller compaction may lead to the generation of dust and cross contamination. 12 Directly compressible vehicles  A directly compressible vehicle is an inert substance which may be compacted with no difficulty and which may do so even when quantities of drugs are mixed with it. 1. Anhydrous lactose. 2. Spray dried lactose. 3. Dicalcium phosphate dehydrate. 4. Granular mannitol. 5. Sorbitol. 6. Microcrystalline cellulose. 7. Calcium phosphate. 8. Lactitol and xylitol. 13 Properties of an ideal directly compression vehicle 1. Good flowability and compressibility. 2. Physiologically inert. 3. Compatible with all type of drugs. 4. Stable to various environmental conditions. 5. Colorless or tasteless. 6. Inexpensive. 7. Proper mouth feel. 8. Compatible with the drugs. 9. Possess good hardness after compression. 14 Examples of direct compression excipients 1. Spray dried lactose. 2. Tabletose: agglomerate form of lactose. 3. Fast-flow lactose. 4. Di-pac: Composed of 97% sucrose and 3% modified dextrin. 5. Nu-tab: 95.8% sucrose, 4% invert sugar (equimolecular mixture of laevulose and dextrose) and 0.1 to 0.2% each of corn starch and magnesium stearate. 6. Emdex (Celutab, Spray crystalline dextrose): 90-92% dextrose, 3-5% maltose and the remainder higher glucose polysaccharides. 15 Examples of direct compression excipients 7. Mannitol. 8. Sorbitol. 9. Maltodextrin (Maltrin). 10. Sta-Rx 1500 (Starch 1500). 11. Era-Tab: Spray-dried rice starch. 12. Microcrystalline cellulose (Avicel). 13. Dicalcium phosphate (Emcompress or DiTab). 14. Tricalcium phosphate (TriTab). 16 Tablet compression machines  The basic unit of any tablet press consisting of two punches and a die which is called a station.  The die determines the diameter or shape of the tablet; the punches, upper and lower come together in the die that contains the tablet formulation to form a tablet. 17 1. Single punch machine  A single-punch press possesses one die and one pair of punches.  The powder is held in a hopper which is connected to a hopper shoe located at the die table.  The hopper shoe moves to and from over the die, by either a rotational or a translational movement. 18 Compression sequence in single punch machine 1. The upper punch is raised and lower punch is dropped. 2. Feed shoe (hopper) has moved forward over die and granules fall into die, and then moved back. 3. Upper punch has come down compressing granules into tablet. 4. Upper punch has moved upwards and lower punch has moved upwards to eject tablet. 5. The cycle repeated. 19 2. Multi-station (rotary) machine  The head of the tablet machine that holds the upper punches, dies and lower punches in place rotates.  As the head rotates, the punches are guided up and down by fixed cam tracks, which control the sequence of filling, compression and ejection.  The portions of the head that hold the upper and lower punches are called the upper and lower turrets respectively.  The portion holding the dies is called the die table. 20 Comparison between single punch and rotary machines Single punch machine Rotary compressing machine 1. Output is 60-90 tab/min. 1. Out put up to18000 tab/min. 2. Use for batch up to 50000 2. Used for larger number of tablets. tablets 3. Less economic 3. More economic 4. Consists of one compression 4. Consist of up to 92 compression set. sets. 5. The hopper is movable. 5. The hopper is stationary. 6. The upper punch only is 6. The upper and lower punches are movable for compression i.e. the responsible for compression i.e. the upper punch only which stamps granules are squeezed between the the granules into tablets. moving upper and lower punches. 7. The pressure produced from 7. The pressure that produced from the upper punch is high and the upper and lower punches is lower sudden which not allow the than in case of single punch and is liberation of air which is between gradual, so allow the liberation of air ingredients and so produce less in between ingredients and so compact tablets. produces compact tablets. 8. Used in small scale. 8. Used in large scale. 21 Problems of tablet manufacture Binding  It is the adherence of particles on die wall and resisting ejection. Causes:  The granules may be insufficiently or unevenly lubricated causing the tablet to adhere to the die wall after compression.  The granules may have been inadequately dried or they may have absorbed water vapor. Treatment: 1. Increase the amount or efficiency of the lubricant. 2. Change the method of addition of the lubricant. 3. Increase punch-die clearance 4. Tapering of the die. 5. Decrease the size of granules. 6. Compression at lower temperature and humidity. 22 Sticking  It is picking or filming on surface of punches; therefore, if the surfaces of the punches are concave, they become flat after sticking and give flat or irregular tablets. Treatment: 1. Decrease moisture content of granules. 2. Increase the binder ratio. 3. Addition of an adsorbent. 4. Clean the punch faces with 5 % light mineral oil. 5. Polish punch faces.  Sticking occurs much more often in single punch tablet machine than in rotary tablet machine due to the high compression from the upper punch in the former. 23 Capping and lamination  Capping is the partial or complete separation of the top or the bottom of tablet from the main body.  Lamination is the separation of tablet into two or more distinct layer; usually these flaws are apparent immediately after compression.  Causes: 1. Large amount of fines in the granulation. 2. Too dry or very low moisture content. 3. Not thoroughly dried granules. 4. Insufficient amount of binder or improper binder. 5. Insufficient or improper lubricant. 6. Granular mass too cold to compress firm. 7. Poorly finished dies. 24 8. Deep concave punches. 9. Lower punch remains below the face of die during ejection. 10. Incorrect adjustment of sweep-off blade. 11. Oily or waxy materials in granules. 12. Too much of hydrophobic lubricant e.g. magnesium stearate. 25 Treatment: 1. Remove some or all fines through 100 to 200 mesh screen. 2. Moisten the granules suitably. 3. Dry the granules properly. 4. Increase the amount of lubricant or change the type of lubricant. 5. Increasing the amount of binder or adding dry binder. 6. Compress at room temperature. 7. Polish dies properly. 26 8. Use flat punches. 9. Make proper setting of lower punch during ejection. 10. Adjust sweep-off blade correctly to facilitate proper ejection. 12. Modify mixing process. 13. Use a less amount of lubricant or change the type of lubricant. 14. Use tapered dies. 15. Use pre-compression step. 27 Chipping and cracking  Chipping is the breakdown of tablet due to impurities in punch faces.  Cracking is the breakdown of tablet due to entrapped air.  Treatment: 1. Replace or reface nickel or chipped punches. 2. Improve granulation by increasing binder concentration. 3. Polish the punch tips. 4. Reduce the granule size. 5. Remove some or all fines. 28 Tablet expansion  It is an increase in diameter of tablet due to entrapped air. Treatment: 1. Taper the die and remove excess fines. 2. Reduce the diameter of the upper punch. 29 Mottling  It is unequal distribution of the color on the tablet surface. Causes and treatment: 1. The drug may have different color than its excipients or whose degradation products are highly colored. Treatment: using a dye that masks the change. 2. Migration of a dye during drying the granulation. Treatment: change the solvent system, reduce the drying temperature, or grind to smaller particle size. 30