Tablets.pptx

Tablets-

Tablets are unit dosage form in which one usual dose of the drug has been accurately placed.

Advantages
Unit dosage form, greatest dose precision and least content variability.
Lowest cost
Lightest and most compact form
Easiest and cheapest to package
Product identification is also cheap no additional processing required
Provide greatest ease of swallowing.
Special release profile can formed
Chemical, Mechanical and microbiologic stability.
Suitable for large scale production
Disadvantages
Some drugs not suitable for compression (amorphous, flocculents , low density )
Drugs with por wetting , slow disslution, intermediate to large dosage are difficult to formulate into tablet.
Bitter tasting, objectional odor, drugs sensitive to oxygen may require coating
( capsule prefer at low cost)
Tablets used for Ingestion
Compressed Tablets or Standard compressed Tablets
Standard uncoated tablets made by compression- wet granulations, double compaction or direct compression.

Rapid disintegration & drug release

Most of tablets containing drugs which gives local effect.( GIT- Water insoluble drugs – Antacids and adsorbents)

Some drugs produced systemic effect ( aqueous solubility- Disintegrate and dissolve in GI contents)
2. Multiple compressed Tablets
Either two components or three components systems
A tablet within a tablet
Tablet within tablet within a tablet.
3. Chewable Tablets
Chew in mouth prior to swallowing & not intended to be swallowed intact.
Infants and children or for elderly
Bitter and foul tasting drugs not suitable.
E.g.- Antacid tablets

( large dose of antacid can be given and better acid neutralization)
4. Sugar and Chocolate coated
5. Film coated Tablets

Polymers such as Hydroxypropyl cellulose (HPC), Hydroxypropyl methyl cellulose(HPMC), widely used with suitable plasticizer.
Advantages
Better mechanical strength
Avoid sugar for significant segments of population
Retain debossed markings
Tasteless Tablet
- Disadvantge
Physical appearnce ( Elegancy) not match with sugar coated tablets.
6. Repeat action Tablets

The core of tablet is coated with shellac or an enteric polymer so drug not releases into stomach.
Second dose added into sugar coatings.
7. Delayed action And Enteric coated Tablets

Enteric coated Tablets are a type of delayed action tablet.
But not all types of delayed type of tablets are enteric.
Why enteric coating?
Some drugs irritate gastric mucosa (Aspirin)
Some drugs destroyed in stomach (Erythromycin)
For local effect in intestine( antibacterial, Vermifuge)
Cellulose acetate phthalate, polyvinyl acetate phthalate, HPMC phthalate
Acid esters ( insoluble in GI media)
Esterases in intestinal fluid break down ester linkages.
8. Controlled release Tablets
Tablets used for oral cavity
1. Buccal & Sublingual Tablets

These tablets are small & somewhat flat
Buccal tablets intended to be held between the cheek and teeth or in the cheek pouch
Sublingual tablets intended to held beneath the tongue.
Drugs admi

1. Tablets By- Miss.Vaishali P. Wasnik Assistant Professor P. R. Patil Institute of Pharmacy Talegaon ( S.P.)

2. VPW, PRP, Talegaon ( s.p .) Tablets- Tablets are unit dosage form in which one usual dose of the drug has been accurately placed.

3. Adavantages & Disadvantages Advantages Unit dosage form, greatest dose precision and least content variability. Lowest cost Lightest and most compact form Easiest and cheapest to package Product identification is also cheap no additional processing required Provide greatest ease of swallowing. Special release profile can formed Chemical, Mechanical and microbiologic stability. Suitable for large scale production Disadvantages Some drugs not suitable for compression (amorphous, flocculents , low density ) Drugs with por wetting , slow disslution , intermediate to large dosage are difficult to formulate into tablet. Bitter tasting, objectional odor, drugs sensitive to oxygen may require coating ( capsule prefer at low cost) VPW, PRP, Talegaon ( s.p .)

4. VPW, PRP, Talegaon ( s.p .)

5. Tablets used for Ingestion VPW, PRP, Talegaon ( s.p .) Compressed Tablets or Standard compressed Tablets Standard uncoated tablets made by compression- wet granulations, double compaction or direct compression. Rapid disintegration & drug release Most of tablets containing drugs which gives local effect.( GIT- Water insoluble drugs – Antacids and adsorbents) Some drugs produced systemic effect ( aqueous solubility- Disintegrate and dissolve in GI contents)

6. 2. Multiple compressed Tablets VPW, PRP, Talegaon ( s.p .) Tablets used for Ingestion Layered Tablet Compression coated Tablet Either two components or three components systems A tablet within a tablet Tablet within tablet within a tablet.

7. 3 . Chewable Tablets Chew in mouth prior to swallowing & not intended to be swallowed intact. Infants and children or for elderly Bitter and foul tasting drugs not suitable. E.g.- Antacid tablets ( large dose of antacid can be given and better acid neutralization) VPW, PRP, Talegaon ( s.p .)

8. 4. Sugar and Chocolate coated VPW, PRP, Talegaon ( s.p .)

9. VPW, PRP, Talegaon ( s.p .) 5 . Film coated Tablets Polymers such as Hydroxypropyl cellulose (HPC), Hydroxypropyl methyl cellulose(HPMC), widely used with suitable plasticizer. Advantages Better mechanical strength Avoid sugar for significant segments of population Retain debossed markings Tasteless Tablet - Disadvantge Physical appearnce ( Elegancy) not match with sugar coated tablets.

10. 6. Repeat action Tablets The core of tablet is coated with shellac or an enteric polymer so drug not releases into stomach. Second dose added into sugar coatings. VPW, PRP, Talegaon ( s.p .) Immediate release Delayed release

11. 7. Delayed action And Enteric coated Tablets Enteric coated Tablets are a type of delayed action tablet. But not all types of delayed type of tablets are enteric. Why enteric coating? Some drugs irritate gastric mucosa (Aspirin) Some drugs destroyed in stomach (Erythromycin) For local effect in intestine( antibacterial, Vermifuge ) Cellulose acetate phthalate, polyvinyl acetate phthalate, HPMC phthalate Acid esters ( insoluble in GI media) Esterases in intestinal fluid break down ester linkages. VPW, PRP, Talegaon ( s.p .)

12. 8 . Controlled release Tablets VPW, PRP, Talegaon ( s.p .)

13. Tablets used for oral cavity 1 . Buccal & Sublingual Tablets These tablets are small & somewhat flat Buccal tablets intended to be held between the cheek and teeth or in the cheek pouch Sublingual tablets intended to held beneath the tongue. Drugs administered by this route are intended to produce systemic effects. The drugs used for this kind of tablets must have good absorption properties through oral mucosa. By using this route of administration , first pass metabolism of drugs are avoided. VPW, PRP, Talegaon ( s.p .)

14. Advantages The drugs which are degraded in GI environment like steroids, hormones, may be avoided as the well absorbed from mouth. More rapid onset of action First pass effect may be avoided No disintegration required These tablets formulated by excipients which do not stimulate salivation. 15-30 min period slow dissolution is required for effective absorption. VPW, PRP, Talegaon ( s.p .)

15. 2. Troches & Lozenges They are intended to exert local effect in the mouth or throat. These tablets forms are commonly used to treat sore throat or to control coughing in the common cold. They may contain local Anesthetics, Antiseptics, Antibacterial & Antitussives. Lozenges also called cough drops Made with the drug and flavored hard candy sugar by compression or fusion or by a candy moulding process. Troches made by compression. VPW, PRP, Talegaon ( s.p .)

16. 3 . Dental cones These are minor tablets that are designed to be placed in empty socket after tooth extraction. Use- To avoid infection To reduce bleeding Tablet slowly dissolve or erode for 20-40 min. VPW, PRP, Talegaon ( s.p .)

17. VPW, PRP, Talegaon ( s.p .) Tablets administered by other routes 1. Implantation Tablets Implantation or depot tablets are designed for subcutaneous implantation in animals or man. To provide prolonged drug effect ( Months to Years) These tablets are small , cylindrical or rosette shape & not more that 8 mm in length. Drawback - Needs surgical technique for administration and Discontinue therapy. Tissue toxicity problem Special injecter ( Kern injecter ) for rod shaped tablets.

18. VPW, PRP, Talegaon ( s.p .) 2 . Vaginal Tablets Vaginal tablets are designed to undergo slow dissolution and drug release in vaginal cavity. The tablet are oval or pear shaped to improve retention into vagina. These tablets used to release antibacterial, antiseptics or astringents to treat vaginal infections. To release steroids for systemic absorption. Vehicle used for these tablets is slowly soluble material . Plastic tube inserter is used to place the tablet in upper vaginal tract.

19. VPW, PRP, Talegaon ( s.p .) Tablets used to prepare solutions 1. Effervescent Tablets Designed to produce solution rapidly with release of CO2 Prepared by compressing Organic Acids ( citric acid, tartaric acid and sodium bicarbonate) When tablet comes in contact with water a chemical reaction initiated. The reaction is rapid ( 1 Min) Such tablet produce flavored carbonated drink which mask the taste of certain drug. Fro producing clear solution the drug must be soluble in alkaline pH. Advantages - Preparing a solution containing an accurate dose of drug Disadvantage Difficult to produce chemically stable product

20. VPW, PRP, Talegaon ( s.p .) 2 . Dispensing Tablets These tablets are intended to be added to a given volume of water by the consumer to produce a solution of a given drug concentration. Silver proteinate Bichloride of mercury Merbromin Quaternary ammonium compounds Buffering tablets and isotonicity tablets.

21. VPW, PRP, Talegaon ( s.p .) 3. Hypodermic Tablets These tablets composed of one or more drug with other readily water soluble ingredients and are intended to be added to sterile water or water for injection. 4. Tablets triturates These are small , cylindric, molded or compressed tablets.

22. Excipients , Formulation of Tablet VPW, PRP, Talegaon ( s.p .)

23. Criteria for selection of excipients for tablet They must be non toxic and acceptable to the regulatory agencies in all countries where the product is to be marketed. They must be commercially available in an acceptable grade in all countries where the product is to be manufactured. Their cost must be acceptably low. They must not be contraindicated by themselves or because of a component in any segment of population. They must be physiologically inert.

24. 6. They must be physically and chemically stable by themselves and in combination with drug and other tablet components . 7. They must be free of any unacceptable microbiologic “load ”. 8. They must be color compatible. 9. If drug product is also classified as food , the diluent and other excipients must be approved direct food additives . 10. They must have no deleterious effect on the bioavailability of the drugs in the product.

25. Formulation Components Diluents Binders and adhesive Disintegrants Lubricants,Antiadherents and Glidants Colors Flavours Sweeteners

26. Diluents Diluents are fillers designed to make up the required bulk of the tablet when the drug dosage itself is inadequate to produce this bulk. Round tablets- 3/16 to 1/2 inch. Below 3/16 inch difficult to handle by elderly. Larger than ½ inch become difficult to swallow.

27. Tablet weight range- 120 to 700 mg Diluents for secondary purpose To provide better tablet properties like cohesion To permit use of direct compression manufacturing To promote flow Tablet formulator should remember that physical and chemical interactions between formulation components may be promoted by the intimate contact between potential reactants that are tightly compressed together in a tablet compact. e. g.( Lactose + magnesium stearate)= Gradual Discoloration of tablet ( Maillard reaction)

28. Lactose- Most widely used Have no reaction with most drugs Anhydrous lactose does not undergo Maillard reaction For wet granulation Hydrous form of lactose is used. Two grade are available- Coarse(60-80 mesh) - Regular ( 80-100 mesh) Lactose granules show rapid drying , good drug release and disintegration. Low cost diluent Spray dried lactose available for direct compression with good flow property. Spray dried lactose prone to darkening in the presence of excess moisture and amines- so Neutral or acid lubricants should be used.

29. Strach - Corn, wheat, potato USP grade has poor flow property and compression and have high moisture content 11-14%. Directly compressible starches available commercially Sta-Rx-1500 - Binder, diluent and Disintegrating agent It contains 10% moisture and and prone to softening when combined with excessive amount of magnesium stearate. Emdex and Celutab – Hydrolysed starches ( 90-92% dextrose + 3-5% maltose) They are free-flowing and directly compressible Replaces manitol in chewable tablet due to sweet taste and smooth feeling in mouth.

30. Dextrose- - Cerelose - Hadrate and anhydrous form - Sometimes replace with spray dried lactose Mannitol - Most expensive sugar Negative heat of solution Slow solubility Pleasant feeling in mouth Non hygroscopic Poor flow property so require high amount of lubricants. Chewable tablet Vitamins

31. Sorbitol- Optical isomer of mannitol Sometimes combine with mannitol formulations to reduce cost It is hygroscopic at humidities above 65%. Sucrose- Sugartab ( 90-93% sucrose + 7-10% invert sugar) DiPac ( 97% sucrose + 3% Modified dextrins ) Nu Tab ( 95% sucrose + 4% invert sugar + Corn starch and magnesium stearate) Directly compressible Used with mannitol for chewable tablet All grades hygroscopic at elevated moistures

32. - Microcrystalline cellulose- Avicel Directly compressible Two grades – pH 101 ( Powder) - pH 102 ( Granules) Good flow property Acts as disintegrating agent Expensive

33. Binders Either added as dry or liquid Wet granulation To promote cohesive compacts. Accacia & Tragacanth 10- 25% alone or in combination. More effective when used in solutions than dry form. Heavily contaminated with bacteria. To reduce microbial proliferation – Wet granualation masses quickly dried

34. Gelatin- Used in combination with accacia . Starch Paste- Starch + Water During heating , starch hydrolysed to Dextrin and Glucose Translucent Paste is Formed

35. -Liquid Glucose- 50 % solution in water is used as wet granulating agent. Produce hard but somewhat brittle compacts. Low cost adhesive Bacterial proliferation may be a problem Modified natural plymers like alginates and cellulose derivatives- ( MC, HPMC, HPC) Polyvinylpyrolidone is a synthetic polymer – used as dry binder

36. Disintegrants A disintegrant is added to most tablet formulation to facilitate a brekup or disintegrantion of the tablet when it contacts water in the GIT. It draws the water into the tablet , swelling and causing the tablet to burst apart. DA mixed at two stages During the formation of granules, prior to wetting the granulating fluid. ( Intragranular ) At the second mixing stage during compaction of granules into tablet ( E xtragranular )

37. Starch USP and other starch derivatives Range 5-20% of tablet weight. Modified starches- Primogel and Explotab are used in lower concentarion 1-8% - 4% is Optimum. Pregelatinised starches- used in 5% concentarion . Clays Veegum HV & Bentonite - 10% But produces offwhite color so limitedly used Microcrystalline cellulose Super disintegrants Sodium starch glycolate , Crospovidone , C roascarmellose and polacrilin poatassium

38. Lubricants , Antiadherents and Glidants A material that is primarily described as an Antiadherents is typically a lubricant , with some Glidant properties as well. Lubricants - these are intended to reduce the friction during tablet ejection between the walls of the tablet and the walls of the die cavity in which the tablet was formed. Antiadherents - These are added for the purpose of reducing sticking or adhesion of any of the tablet granulataion or powder to the faces of the punches or to the die wall. Glidants - These are intended to promote flow of the tablet granulation or powder materials by reducing friction between the particles.

39. -Most widely used Lubricants have been stearic acid and various stearic acid salts and derivatives. Calcium and magnesium salts of stearic acid are the most common salts . Talc- Most of talc samples are found to contain trace quantities of iron. So talc is care fully added in those formulations containing drug whose breakdown is catalysed by the presence of iron. Polyethylene glycols and some polymeric surfactants used as water soluble lubricants. ( Less effective)

40. Talc, magnesium stearate and starch as well as starch derivatives possess Antiadherents property. Glidants Talc- 5% Corn starch- 5-10% Colloidal silicas such as Cab-O- Sil , Syloid , Arrosil - 0.25-3% ( gives Drier environment)

41. Colors, Flavours and Sweeteners Why colors are used? Disguising off color drugs Product identification Production of more elegant product. Natural colors Availability is limited Unstable Two types of colors typically used in tablet preperation 1) FD&C 2) D&C dyes Lakes & dyes use as a dry powder for coloring Water soluble dyes & pastel shades show least mottling.

42. Flavours - Specially for chewable and other tablets that dissolve in mouth. Water soluble flavours have found little acceptance because of poor stability. Flavour oils are added to tablet granulation in solvents, or dispersed on clays or emulsified in aqueous granulating agents Sweeteners Mannitol 72% as sweet as Sucrose Saccharin - Artificial sweetener- 500 time sweet than sucrose But it has bitter aftertaste and it is carcinogenic New artificial sweetener to replace the Saccharin is Aspartame It lacks stability in the presence of moisture.

43. Tablet Manufacturing Granulation Methods and Compression of Tablet

44. The Manufacture of granulations for tablet compression may follow one or combination of three established methods Direct compression Compression granulation Wet granulation

45. Direct Compression- Few crystalline substances like Sodium chloride, sodium bromide and potassium chloride that may be compressed directly. Single substance having good compressibility No Disintegration Tablet Drug Disintegrant May interfere compressibility

46. Direct compression materials possessing good flow and compressibility. Inert, tasteless, reworkable. Able to disintegrate and inexpensive. Advantage of Direct compression Simple process Low labor input Economic Dry process so deterioration is decreased Tablet disintegrate into their primary particle rather than granules Increased surface area for dissolution so faster drug release.

47. Limitations Differences in particle size and bulk density between the drug and diluent---------Stratification--------poor content uniformity ( Low dose drug ) Large dose drug having moderate compressibility may create problem in direct compression process. ( diluent may increase tablet weight and cost ) Some times direct compression diluent may react with drug.( Spray dried lactose + Amines= Yellow discoloration) Static charge build up during routine screening and mixing which may prevent uniform distribution of drug .

48. Dry or Compression Granulation When the effective dose of a drug is too high for direct compaction When drug is sensitive to heat , moisture or both . e. g. Aspirin and Vitamins are prepared by compression granulation. Compaction of components of tablet by means of tablet press or specially designed machinery, followed by milling and screening prior to final compression of tablet. Slugging- large tablets ---------- Coarse milling------- Screening --------Produce granular form with good flow ability than previous powder form.

49. Coarse milling- Screening

50. Equipment- Large scale – Specially designed machine ------ Roller compactor

51. Wet granulation- Binding of powders together with an adhesive. Solution, suspension or slurry of binder which is added to powder. At initial stages liquid film will be formed on powder surface and may combine to produce discrete liquid bridges at point of contact. Surface tension and negative capillary pressure in such bridges provide the cohesive force and result in condition called pendular state As the liquid content increases several bridges produced giving rise funicular state More liquid added---mass kneaded to bring particles into closer proximity-no void spaces -------bonding is affected by interfacial forces at the granule surface and by negative capillary pressure-------- Capillary state

52. Further addition of liquid result in droplet formation Particles are held together by surface tension but without intergranular forces ------weak structures Capillary state ------- Maximum strength of wet granules

53. Wet screening To increase particle contact point and increase surface area for drying Converting the moist mass into coarse , granular aggregates by passage through a hammer mill or oscillating granulator Drying --- to remove moisture After drying again screening

54. Tablet Compression Operation Basic Components Hopper - for holding and feeding granulation to be compressed. Dies that define the size and shape of the tablet Punches for compressing granulation within dies Cam tracks for guiding the movement of the punches. A feeding mechanism for moving granulation from the hopper into dies

55. Multi station presses ------------Rotary Die table- rotate A) Feed frame –which has several interconnected compartments B) Dies- --- compartments spread the granulation C) The pull down cam- guides the lower punches D) Wipe off blade – At end of feed frame to remove excess granulation E) Weight control cam – reduces the fill in dies to the desired amount F) Lower compression roll- lower punches travel over lower compression roll G ) Upper compression rol l—Upper punches travel over upper compression roll H) Upper punch raising cam- I ) Lower punch ride up cam-

56. Multi compression process

57. Compression machine Tooling Each tooling set consist of A die and upper and lower punches. BB tooling--- Length--2.5inch Barrel diameter- 0.75 inches Head diameter- 1 inch B Tooling--- Lower punch length- 3 9/16 inch D tolling--- for large tablets Barrel diameter- 1 inch Head diameter- 1 ¼ inch Length- 5.25 inch

58. Dies for Above punches Outside diameter--- 0.945 inch 7/16 inch round tablet 9/16 inch capsule shaped tablet Outside diameter---- 1 3/16 inch 9/16 inch round tablet ¾ inch capsule shaped tablet -Generally steel used to manufacture compression tooling. Size , shape is unlimited Company names or symbols, trade names, dosage strength or National drug code can be cut or engraved into punch face.

59. Evaluation of Tablet General Appearance Size and Shape Unique identification markings Organoleptic Properties Hardness Friability Drug content and Release Content Uniformity Disintegration Dissolution

60. General Appearance

61. https://upload.wikimedia.org/wikipedia/commons/5/5a/Tablet_press_animation.gif By Jeff Dahl - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=3606080 https://youtu.be/4xggZRckfTE