Tablet

This Presentation include tablet formulation methods & instruments

1. S. B. Thoke [M. pharm] TABLET

2. What is Tablet …..?

3. Definition Tablets are solid preparations consisting of one or more active ingredient obtained by compressing uniform volumes of particles into . various shapes and sizes.

4. The ingredient classification used is: Fillers- Lactose, Starch, Dextrose, Mannitol, Sorbitol, Maltodextrin, Sucrose, Cellulose etc. Binders- acacia , gelatin, liquid glucose, sucrose syrup, starch paste, methyl cellulose, CMC, PVP , EC, HPMC etc. Disintegrates Lubricants, Glidants , Anti-adherents Wetting agents Colors and flavors Preservatives

5. List of disintegrants DISINTEGRANTS CONC.  IN GRANULES(%) SPECIAL COMMENTS Starch USP 5-20 Higher amount is required, poorly compressible Starch 1500 5-15 Avicel®(PH 101, PH 102) 10-20 Lubricant properties and directly compressible Cross-linked starch Explotab® 2-8 Sodium starch glycolate, superdisintegrant. Crosscarmellose sodium AC-Di-Sol® 1-3 Direct compression

6. Lubricants In tablet manufacturing one faces the problem of flow of granules from the hopper into the die cavity, sticking of material to the punches and die walls and release free movement of the compressed tablets from the die cavity. To overcome these difficulties Lubricants - prevent adhesion of the tablet material to the surface of the dies and punches, reduce interparticle friction, facilitate an easy ejection of tablets from the die cavity and improves rate of flow of tablet granulation. Eg. T alc, magnesium stearate, calcium stearate, stearic acid, hydrogenated vegetable oil and PEG. The quantity of lubricant significantly varies from 0.1 to 5%.

7. List of Lubricants Lubricants Conc. Comments Stearates(Magnesium Stearate, Calcium Stearate, Sodium stearate) 0.25 -1 Reduce tablet strength; prolong disintegration; widely used. Talc 1 -2 Insoluble but not hydrophobic; moderately effective. Glyceryl behapate (Compritol®888) 1 - 5 Both lubricant and binder;

8. Glidants Glidant - Improves the flow characteristics of a powder mixture. Always added in the dry state just prior to compression. Eg. colloidal silicon dioxide (Cabosil®, Cabot®) and asbestos free talc etc. They are used in concentration less than 1%. Talc is also used and may serve the dual purpose of lubricant/ glidant . Glidants Range Colloidal silica i.e. syloid, pyrogenic silica 0.25% Hydrated sodium silioaluminate 0.75%

9. Antiadherents Some material have strong adhesive properties towards the metal of punches and dies or the tablet formulation containing excessive moisture which has tendency to result in picking and sticking problem. Antiadherent prevent sticking to punches and die walls. Eg. Talc, magnesium stearate and corn starch etc. Antiadherants Range Comments Talc 1 – 5 Lubricant with excellent antiadherents properties Cornstarch 3 –10 Lubricant with excellent antiadherents properties Sodium lauryl sulfate <1 Antiadherents with water soluble lubricant Colloidal silica 0.1 – 0.5 Does not give satisfactory results due to small surface area. Cab-O- Sil ® and Syloid® Stearates <1 Antiadherents with water insoluble lubricant

10. Colors Natural vegetable colors – limited availability & unstable FD&C and D&C approved dyes are used. Either added in dry granulation mix or in vehicle used for wet granulation. Lake dyes ( dyes absorbed on alumina or aluminium hydroxide) are used in dry granulation. Dyes tend to fade on standing and exposure to light leads to mottling. Eg . FD&C approved lakes and dyes – lake sunset yellow, brilliant blue, ferric oxide.

11. Flavors Flavor's are usually limited to tablets intended to dissolve in the mouth. In generally water soluble L ittle acceptance in manufacturing due to poor stability. Do not affect any physical characteristics of the tablet granulation. Incorporated by spraying them on to the granules in the form of solutions in some volatile organic solvent. Also can be incorporated with lubricants Proportion limited to 0.5 % Excess quantity will interfere with free flow of granules e.g. Raspberry, Pineapple, Peppermint, Blackcurrant, Orange, Mango, Strawberry etc.

12. Sweeteners Use is primarily limited to tablets meant to dissolve in oral cavity Mannitol – 72% as sweet as sucrose Earlier saccharin was the only artificial sweetener used. It is 500 times sweeter than sucrose but has a bitter aftertaste and also carcinogenic properties. Aspartame is the new sweetener- disadvantage is its instability in the presence of moisture.

13. Three main manufacturing methods are used to prepare the running powder: Wet granulation Direct compression Dry granulation or slugging Content uniformity Uniform chemical composition. Good mixing is essential, and segregation during the process should be prevented.

14. Wet granulation Wet granulation is a process of dry mixing, wet mixing, and particle size enlargement, and is a process of particle attachment (agglomeration). It consists of six steps: 1. Dry mixing 2. Wet mixing 3. Milling of the wetted mass 4. Drying 5. Milling of the dried mass 6. Final blending

15. Wet Granulation Mix powders Add binder Mill coarsely Dry Mill Blend & lubricate Compress or fill into capsules

16. Advantages of Wet Granulation Physical characteristics of the drug are usually not important. The coalescing of particles locks in blend uniformity. A wide variety of powder materials can be processed into a uniform mix with improved flow. Optimum fill density can be achieved by adjusting the process to create the optimum final particle size distribution. Compressibility and consolidation are improved via the choice of the correct binder and the moisture content of the granules.

17. Dissolution is modified through hydrophilization to improve wetting or, with the choice of more insoluble binders, to obtain a modified release pattern. Dust and segregation tendencies are reduced.

18. Disadvantages of Wet Granulation Large number of process steps; each step requires qualification, cleaning, and cleaning validation. Long process time, particularly for drying. High labor and manufacturing costs. Some material loss during processing. Problems associated with heat and solvent sensitive drugs. Capital requirements for extra building space and equipment. Upon aging, dissolution from granules can be slowed after tableting .

19. Assay problems may occur for low dosage drugs due to incomplete extraction if the active ingredient is complexed by the binder, or adsorbed onto one of the other excipients. Still no exact way to determine granulation endpoint (torque, power consumption , etc.).

20. Single-Step Fluid Bed Wet Granulator Fluid-bed granulator Binder solution spray Warm air flow

21. Direct Compression This is , a two-step process involving screening and/or milling and final mixing. An effective binder is needed and should have good compression and consolidation properties as a dry additive, even at low concentrations (< 30%) in the formulation. Good adhesive properties in the dry form are a combination of a rough and porous surface combined with a van der Waal's and/or a hydrophilic bonding mechanism to attach the active ingredient(s) to the excipient. This feature is needed to assure good mixing of drug and excipients and to prevent segregation .

22. Advantages of Direct Compression Economy in labor, time, equipment, operational energy, and space. Problems due to heat and moisture eliminated. Greater physical stability provided; hardness and porosity changes less with time when direct compression is broadly compared to wet granulation systems. Extraction of the drug from the dosage form is not inhibited during the assay procedure (polymer binding). Choice of ingredients allows the formulator to improve or retard dissolution rate.

23. Disadvantages of Direct Compression Critical nature of the raw materials; need for greater quality control in purchasing to assure batch uniformity. Difficulty obtaining dense hard tablets for high-dose drugs. Non-homogenous distribution of low-dose drugs due to segregation after blending (content uniformity). Sensitivity of direct compression 'running' blends to over lubrication. Limitations in color variations . Need for assisted feed and precompression for some high-dose drugs. Need for commensurate particle size or particle size distribution between drug and excipients.

24. Dry Granulation Mixing Roller compaction Milling Screening Final blending Roller Compactor It consists of five steps:

25. Compact Size reduction of compacts into granules Powder to be compacted Roller compactor "Chilsonator”

26. Final Blending Final blending is usually done in a cone or V-type blender, To obtain the final blend, it is necessary to consider the objectives of the mixing steps: To achieve drug content uniformity To obtain uniformity of flow and bulk density To effect distribution of lubricant, color, and surface active agents To reduce or eliminate segregation

27. Final Blending Mill Blend & lubricate Compress or fill into capsules

28. Equipment's used for Mixing, blending and lubrication High share mixers Tumbling mixers Y-cone Rotating cube Double cone Fluidized bed Agitator mixers Ribbon blender

29. tumble blenders

30. dry mixing Equipment's Sigma blade mixer Planetary mixer

31. Littleford Lodige mixers

32. Granulator mixer Diosna mixer RMG

33. Equipment's used in sieving

34. Compression Tableting procedure Filling Compression Ejection Tablet compression machines Hopper for holding and feeding granulation to be compressed Dies that define the size and shape of the tablet Punches for compressing the granulation within the dies Cam tracks for guiding the movement of the punches Feeding mechanisms for moving granulation from the hopper into the dies

35. Single punch machine The compression is applied by the upper punch Stamping press

36. Upper and Lower Collar Collar locker

37. Common stages occurring during compression Stage 1: Top punch is withdrawn from the die by the upper cam. Bottom punch is low in the die so powder falls in through the hole and fills the die Stage 2: Bottom punch moves up to adjust the powder weight-it raises and expels some powder Stage 3: Top punch is driven into the die by upper cam. Bottom punch is raised by lower cam. Both punch heads pass between heavy rollers to compress the powder Stage 4: Top punch is withdraw by the upper cam. Lower punch is pushed up and expels the tablet. Tablet is removed from the die surface by surface plate Stage 5: Return to stage 1

38. Multi-station rotary presses 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. The portion holding the dies is called the die table.

39. Dies & punches D ies Lower punch Upper punch

40. Compression cycle Granules from hopper empty in the feed frame (A) containing several interconnected compartments. These compartments spread the granulation over a wide area to provide time for the dies (B) to fill. The pull down cam (C) guides the lower punches to the bottom, allowing the dies to overfill The punches then pass over a weight-control cam (E), which reduces the fill in the dies to the desired amount

41. A swipe off blade (D) at the end of the feed frame removes the excess granulation and directs it around the turret and back into the front of the feed frame The lower punches travel over the lower compression roll (F) while simultaneously the upper punches ride beneath the upper compression roll ( G) The upper punches enter a fixed distance into the dies, while the lower punches are raised to squeeze and compact the granulation within the dies After the moment of compression, the upper punches are withdrawn as they follow the upper punch raising cam ( H) The lower punches ride up the cam (I) which brings the tablets flush with or slightly above the surface of the dies

42. The tablets strike a sweep off blade affixed to the front of the feed frame (A) and slide down a chute into a receptacle At the same time, the lower punches re-enter the pull down cam (C) and the cycle is repeated

43. HIGH SPEED ROTARY MACHINE MULTI ROTARY MACHINE

44. 49 If any question or further clarifications write to [email protected] Cell: [phone] Thanks 25-02-2013 49