1. SALMAN BIN ABDULAZIZ UNIVERSITY
COLLEGE OF PHARMACY
TABLETS
Solid Dosage Forms
Dr. Mohammad Khalid Anwer -

2. Tablets
Tablets defined as solid pharmaceutical dosage forms containing drug substances with or without suitable diluents and prepared by compression (large scale production) or molding methods (small scale operations).

3. It is probable that at least 90% of all drugs used to produce systemic effects are administered by the oral route.
Of drugs that are administered orally, solid oral dosage forms represent the preferred class of product.
Tablets are the
most commonly
used solid dosage
forms.

4. Advantages of solid dosage forms
Accurate dosage.
Easy shipping and handling.
Less shelf space needed per dose than for liquid.
No preservation requirements.
No taste masking problem.
Generally more stable than liquids, with longer expiration dates.

5. Advantages of Tablets
Precision and low content variability of the unit dose.
Low manufacturing cost.
The lightest and most compact, thus easy to package and ship.
Simple to identify by employing an embossed or monogrammed punch face.

6. Easy to swallow.
Appropriate for special-release forms.
Best suited to large-scale production.
Most stable of all oral dosage forms.
Essentially tamperproof.

7. In comparison to other oral dosage forms, tablets provide advantages to:
The pharmacist
In minimal storage space requirements
Ease of dispensing
The patient
In convenience of use, optimum portability, and lowest cost.
The physician
In flexibility of dosage (with bi­sected tablets), and in accuracy and precision of dosage in general.

8. Disadvantages of Tablets
Some drugs resist compression into dense compacts, owing to their amorphous nature or flocculent, low-density character.
Some drugs (e.g., those with an objectionable taste or odor, those sensitive to oxygen or atmospheric moisture) require encapsulation or entrapment before compression. These drugs are more appropriate in capsule form.
Some drugs with:
Poor wetting.
Slow dissolution properties.
Intermediate to large doses.

9. Characteristics of ideal tablets
It should be an elegant product having its own identity and Free of defects (e.g., chips, cracks, discoloration, contamination).

10. Strong enough to withstand the mechanical stresses of production packaging, shipping, and dispensing.
Chemically and physically stable over time.
Capable of releasing medicinal agents in a predictable and reproducible manner.

11. Tablet Types and Classes
Tablets are classified according to their route of administration, drug delivery system, and form and method of manufacture.
Tablets used in the oral cavity
Buccal tablets.
Sublingual tablets.
Lozenges, Troches and dental cones.
Tablets for oral ingestion
Compressed tablets.
Multiple compressed tablets
- Layered tablets.
- Compression-coated tablets
Repeat-action tablets.
Delayed-action and enteric-coated tablets.
Sugar and chocolate-coated tablets.
Film-coated tablets.
Chewable tablets.
Tablets used to prepare solutions
Effervescent tablets.
Dispensing tablets.
Hypodermic tablets.
Tablet triturates.

12. Tablets for oral ingestion
Tablets for oral ingestion are designed to be swallowed intact, with the exception of chewable tablets.

13. (1) Compressed Tablets (CT)
Compressed tablets are formed by compression and have no special coating.
They are made from powdered, crystalline, or granular materials, alone or in combination with excipients such as binders, disintegrants, diluents, and colorants.

14. After compression, some compressed tablets may be coated with various materials.
Most compressed tablets are employed for the oral administration of drugs, but some may be used for the sublingual, buccal, or vaginal administration of drugs.

15. (2) Multiple Compressed Tablets (MCT)
Multiple compressed tablets are layered or compression- coated.
(a) Layered tablets are prepared by compressing a tablet granulation over a previously compressed granulation to form a two- or three-layered tablet, depending upon the number of separate fills.
Generally each portion of fill is colored differently to prepare a multiple-colored as well as a multiple-layered tablet.

16. (b) Compression-coated, or dry-coated,
tablets are prepared by feeding previously compressed tablets into a special tableting machine to compress an outer shell around the tablets.
This process applies a thinner, more uniform coating than sugar-coating, and it can be used safely with drugs that are sensitive to moisture.
This process can be used to:
Separate incompatible materials.
Produce repeat action or prolonged-action products.

17. (3) Repeat-action tablets:
Repeat-action tablets are layered or compression-coated tablets in which the outer layer or shell rapidly disintegrates in the stomach. The components of the inner layer or inner tablet are insoluble in gastric media, but soluble in intestinal media.
Example., Dexchlor tablets

18. (4) Delayed-action and Enteric-Coated Tablets (ECT)
These tablets delay the release of a
drug from a dosage form.
This delay is intended to:
Prevent destruction of the drug by gastric juices.
To prevent irritation of the stomach lining by the drug.
To promote absorption, this is better in the intestine than in the stomach.
Agents used to coat these tablets include fats, fatty acids, waxes, shellac, and cellulose acetate phthalate.

19. Enteric­ coated tablets are tablets with a coating that resists dissolution or disruption in the stomach but not in the intestines, thereby allowing for tablet transit through the stomach in favor of tablet disintegration and drug dissolution and absorption from the intestines.
e.g. Voltaren

20. (5) Sugar- and chocolate-Coated Tablets (SCT)
The tablet that contains active ingredient(s) of unpleasant taste may be covered with sugar to make it more palatable.
This type of tablet should be administered in whole form.
Example: Vitaferro, Quinine.

21. (6) Film-Coated Tablets (FCT)
The tablet is coated with a membrane of polymeric substances that improves physicochemical stability of the drug and delays the rate of drug absorption.
e.g. Augmentin
(7) Chewable tablets
The tablets are placed in the mouth, chewed and swallowed.
e.g. Talcid, Aspirin Direct

22. Tablets used in the oral cavity
Tablets used in the oral cavity are allowed to dissolve in the mouth.
(1) Sublingual tablets
The tablet is placed under the tongue
Sublingual tablets are absorbed quickly into the bloodstream
e.g. Nitroglycerin, Uprima
(2) Buccal and sublingual tablets
Buccal tablets are placed in the pouch between the cheek and gum
They are usually small, flat and oval in shape
e.g. Progesterone taqblet

23. (2) Troches, lozenges Troches (lozenges or pastilles)
The tablets contain a drug substance in flavored base.
Lozenges are allowed to dissolve in the mouth. They are commonly used for cold and sore throat.
e.g. Chlorhexidine

24. Tablets used to prepare solutions
Tablets used to prepare solutions are dissolved in water before administration.
(1) Effervescent tablets
Effervescent tablets are prepared by
compressing granular effervescent
salts or other materials (e.g., citric acid, tartaric acid, sodium bicarbonate) that release carbon dioxide gas when they come into contact with water to musk undesirable taste or to encourage rapid dissolution and absorption.

25. Tablet Ingredients (Formulation)
In addition to the active or therapeutic ingredient (s), tablets contain a number of inert materials. (additives or excipients) that have special functions.

27. Tablet excipients must meet certain criteria in the formulation:
Their cost must be low.
Nontoxic
Be commercially available
Be physiologically inert.
Must not be contraindicated by themselves (e.g., sucrose).

28. Physically and chemically stable by themselves and in combination with the drug(s) and other tablet components.
Free of any unacceptable microbiologic "load."
Be color-compatible (not produce any off-color appearance).
If the drug product is classified as a food, (certain vitamin products), the diluent and other excipients must be approved direct food additives.
Have no deleterious effect on the bioavailability of the drug(s) in the product.

29. (1) Diluents
Diluents are fillers designed to make up the required bulk of the tablet when the drug dosage amount is inadequate.
Diluents may improve cohesion, permit direct compression, or promote flow.
Common diluents include:
kaolin, lactose, mannitol,
starch, microcrystalline
cellulose, powdered sugar,
and calcium phosphate.

30. Selection of the diluent is based on:
the experience of the manufacturer
the cost of the diluent
its compatibility with the other ingredients.
For example, calcium salts cannot be used as fillers for tetracycline products because calcium interferes with the absorption of tetracycline from the gastrointestinal tract.
The dose of some drugs is sufficiently high that no filler is required (e.g., aspirin and certain antibiotics).

31. Microcrystalline cellulose, (Avicel), is a direct
Lactose is the most widely used diluent in tablet
formulation.
but Lactose may discolor in the presence of amine drug bases or salts of alkaline compounds.
Spray-dried lactose is one of several diluents now available for direct compression.
Microcrystalline cellulose, (Avicel), is a direct
compression material.
Two tablet grades exist:
PH 101 (powder).
PH 102 (granules).

32. (2) Binders and adhesives
Binders and adhesives are added in either dry or liquid form to promote granulation or to promote cohesive compacts during direct compression.
Common binding agents include:
10%-20% aqueous preparation of corn­starch;
25%-50% solution of glucose; molasses;
Various natural gums (e.g., acacia); (usually contaminated with bacteria)
Cellulose derivatives (e.g., methylcellulose,
carboxymethylcellulose, microcrystalline cellulose);
Gelatins; and povidone.

33. (3) Disintegrants
Disintegrants are added to tablet formulations to facilitate disintegration when the tablet contacts water in the gastrointestinal tract.
Disintegrants function by drawing water into the tablet, swelling, and causing the tablet to burst.
Tablet disintegration may be critical to the subsequent dissolution of the drug and to satisfactory drug bioavailability.

34. Common disintegrants include:
Corn starch and potato starch;
Starch derivatives (sodium starch glycolate);
Cellulose derivatives (sodium carboxymethyl­ cellulose);
Clays (e.g., Veegum, bentonite);
A portion of disintegrant can be added, with the lubricant, to the prepared granulation of the drug. This approach causes double disintegration of the tablet.
The tablet break into small pieces, or chunks.
The pieces of tablet break into fine particles.

35. (4) Lubricants, anti-adherents, and glidants
Lubricants reduce the friction that occurs between
the walls of the tablet and the walls of the
die cavity when the tablet is ejected.
Ex.: Talc, magnesium stearate, and
calcium stearate.
(b) Antiadherents reduce sticking, or adhesion, of the
tablet granulation or powder to the faces
of the punches or the die walls.
(c) Glidants promote the flow of the tablet granulation
or powder by reducing friction among
particles.

36. (5) Colors and dyes
Colors and dyes provide product identification, and produce a more aesthetically appealing product.
The availability of natural vegetable colors is limited, and these colors are often unstable.
Two forms of color have typically been used in tablet preparation (FD&C and D&C dyes) which are applied as solutions.
Lakes are dyes that have been absorbed on a hydrous oxide. and used as dry powders.

37. (6) Flavoring agents
Flavoring agents are usually limited to chewable tablets or tablets that are intended to dissolve in the mouth.
Water-soluble flavors usually have poor stability.
For this reason, flavor oils or dry powders are used.
Usually, the maximum amount of oil that can be added to a granulation without affecting its tablet characteristics is 0.5%-0.75%.

38. (7) Artificial sweeteners
Artificial sweeteners, like flavors, are typically used only with chewable tablets or tablets that are intended to dissolve in the mouth.
Some sweetness may come from the diluent (e.g., mannitol, lactose).
Other agents (e.g., saccharin, aspartame)
Saccharin has an unpleasant aftertaste.

39. (8) Adsorbents
Adsorbents (e.g., magnesium oxide, magnesium carbonate, bentonite, silicon dioxide) hold quantities of fluid in an apparently dry state.

40. Methods of Tablet Preparation
The three basic methods for the preparation of compressed tablets are:
Wet granulation method.
Dry granulation method.
Direct compression.

42. The Wet Granulation Method
This method has more operational manipulations, and is more time-consuming than the other methods.
The wet granulation method is not suitable for drugs which are thermolabile or hydrolyzable by the presence of water in the liquid binder.

43. General steps involved in a wet granulation process are:
The powdered ingredients are weighed and mixed intimately by geometric dilution.
The granulating solution or binder is prepared.
The powders and the granulating solution are kneaded (pressed) to proper consistency.
The wet mass is forced through a screen or wet granulator.

44. The granules are dried in an oven or a fluidized bed dryer.
The dried granules are screened to a suitable size for compression.
A lubricant and a disintegrating agent are mixed with the granulation.
The granulation is compressed into the finished tablet.

45. Wet Granulation Manufacturing Steps

46. The Dry Granulation Method
The granulation is formed by compacting large masses of the mixture and subsequently crushing and sizing these pieces into smaller granules.
By this method, either the
active ingredient or the diluent must have cohesive properties in order for the large masses to be formed
This method is especially applicable to materials that cannot be prepared by the wet granulation method due to their degradation by moisture or to the elevated temperatures required for drying.

47. Direct Compression
In the direct compression of tablets, the tableting excipients used must be materials with properties of fluidity and compressibility.
Some granular chemicals like potassium chloride and methenamine possess free flowing as well as cohesive properties that enable them to be compressed directly in a tablet machine without need of either wet or dry granulation.

48. Tableting excipients having the desired characteristics are used include:
Fillers: lactose, microcrystalline cellulose, and dicalcium phosphate;
Disintegrating agents: starch, sodium carboxymethyl cellulose
Lubricants-magnesium stearate and talc;
Glidants: silicon dioxide.

49. Tablet Compression Machines
The basic units in tablet compression machine are two steel punches within a steel die cavity.
The tablet is formed by the pressure exerted on the granulation by the punches within the die cavity,
The tablet takes the size and shape of the punches and dies used.

50. The use of the tablet sometimes determines its shape;
Effervescent tablets are usually large, round and flat,
Vitamin tablets are prepared in capsule-shaped forms.
Tablets prepared using deep-cup punches appear to be round and when coated take the appearance of pills.
Veterinary tablets often have a bolus shape and are much larger than those used in medical practice.

51. (1) Single Punch Machine
The simplest tableting machines
The majority are power driven, and several are hand-operated models.
Compression is accomplished on a single-punch machine.
The feed shoe filled with the granulation is positioned over the die cavity which then fills.

52. Upper punch lowers to compress the granulation within the die cavity.
The upper punch retracts and the low punch rises to eject the tablet.
As the weight of the tablet is determined by the volume of the die cavity; the lower punch is adjustable to increase or decrease the volume of granulation, thus increasing or decreasing the weight of the tablet.

54. (2) Rotatory Tablet Machine:
Rotary machines are used for increased production.
A head carrying a number of sets of punches and dies revolves continuously while the tablet granulation runs from the hopper, through a feed frame and into the dies placed in a large, steel plate revolving under it.
This method promotes a uniform fill of the die and therefore an accurate weight for the tablet.

55. Compression takes place as the upper and lower punches pass between a pair of rollers.

56. Processing Problems Capping and Lamination
Capping is the partial or complete separation of the top or bottom crown from the main body of the tablet.
Lamination is separation of a tablet into two or more distinct layers.
Capping (top) and lamination (right)

57. Capping and lamination may occur hours or even days later.
These problems are usually caused by entrapment of air among the particles or granules and do not escape until the compression pressure is released.
Rapid decompression results in tablets fracture.
Often, deep concave punches produce tablets that cap.
A granulation that is too dry tends to cap or laminate for lack of cohesion.

58. Tablet lamination or capping problems can be eliminated by:
Precompression.
Slowing the tabletting rate.
Reducing the final compression pressure.
4.Addition of a hygroscopic substance
5.Use Flat punches
6. Use force feeder

59. Picking and Sticking
Picking is removal of the surface material of a tablet by a punch.
Sticking is adhesion of tablet material to a die wall.
These problems are caused by excessive moisture in the formulation.
Low-melting-point substances, either active ingredients or additives such as stearic acid and polyethylene glycol, may soften from the heat of compression to cause sticking.

60. Picking and Sticking can be eliminated by:
The tablet can be reformulated to a larger size.
Plating of the punch faces with chromium is a
method for producing a smooth, non-adherent
face.
Dilution of the active ingredient with higher-
melting-point materials
Drying of the granules

61. Mottling
Mottling is unequal color distribution, with light or dark areas standing on a uniform surface.
This problem occurs when a drug has a different color than the tablet excipients or when a drug has colored degradation products.

62. Mottling can be eliminated by:
The formulator may change the solvent system, change the binder system, reduce the drying temperature, or grind to a smaller particle size.

63. Weight Variation Poor Flow.
The weight of a tablet is determined by the amount of granulation in the die prior to compression.
Therefore, anything that can alter the die-filling process can alter tablet weight and weight variation.
Granule Size and Size Distribution Before Compression.
Poor Flow.

64. Depending on the geometry of the hopper, two causes for poor flow: "arching" or "bridging," and "rat-holing." phenomena may arise.
Bridging
rat-holing

65. Weight variation due to poor flowability can be eliminated by:
The addition of a glidant such as talcum or colloidal silica, or an increase in the amount already present, may be helpful.
When poor hopper flow occurs, it may be controllable with vibrators attached to the hopper sides to induce the granulation flow.

66. Hardness Variation
Hardness variation is a problem that has the same causes as weight variation.
Hardness depends on the weight of material and the space between the upper and lower punches at the moment of compression.
If the volume of material or the distance between punches varies, hardness is unacceptable.

67. Tablet Coating
Tablets are coated for a number of reasons including:

68. To mask the taste, color, or odor of the drug.
To control drug release.
To protect the drug from the acid environment of the stomach.
To protect the medicinal agent against destructive exposure to air and/or humidity.
To improve appearance.

69. Sugar Coating Tablets
The sugarcoating of tablets may be divided into the following steps:
Waterproofing and sealing
(if needed).
Subcoating.
Smoothing and final rounding.
Finishing and coloring
(if desired).
Polishing.

70. Waterproofing and sealing coats
Sealing tablet core- application of a water impermeable
polymer such as Shellac, cellulose acetate phthalate and
polyvinyl acetate phthalate, which protects the core from
moisture, increasing its shelf life.
Sub coating
by adding bulking agents such as calcium carbonate or
talc in combination with sucrose solution.
Smoothing and final rounding
Remove rough layers formed in step 2 with the
application of sucrose syrup.
Polishing
effectively polished to give characteristic
shine, commonly using beeswax, carnauba wax.

71. Film-Coating Tablets
The film-coating process, which places a thin, skin­tight coating of a plastic-like material over the compressed tablet, was developed to produce coated tablets having essentially the same shape, and size as the originally compressed tablet.

72. Advantages of Film coating :
Minimal weight increase (typically 2 to 3% of table core weight)
Significant reduction in processing times.
Increased process efficiency and output.
Increased flexibility in formulations.
Improved resistance to chipping of the coating.

73. Film-coating solutions may be non-aqueous or aqueous.
The non-aqueous solutions generally contain the following types of materials to provide the desired coating to the tablets:
Film former capable of producing smooth, thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes.
Example: cellulose acetate phthalate.
An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug.
Example: polyethylene glycol.

74. A plasticizer to produce flexibility and elasticity of the coating and thus provide durability.
Example: castor oil.
A surfactant to enhance spreadability of the film during application.
Example: polyoxyethylene sorbitan derivatives.
Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive.
Examples: Opaquant, titanium dioxide.
colorant, F.D.&C. or D.&C. dyes.

75. Sweeteners, flavors, and aromas to enhance the acceptability of the tablet to the patient.
Examples: sweeteners, saccharin; flavors and aromas, vanillin.
A glossant to provide luster to the tablets without a separate polishing operation.
Example: beeswax.
A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective, speedy operation.
Example: alcohol acetone mixture.

76. Tablets are film coated by the application or spraying of the film-coating solution upon the tablets in ordinary coating pans.
The volatility of the solvent enables the film to adhere quickly to the surface of the tablets.

77. A typical aqueous film-coating formulation contains the following:
1) Film-forming polymer (7-18%). Examples: hydroxypropyl methylcellulose, hydroxypropyl cellulose.
2) Plasticizer ( %). Examples: glycerin, propylene glycol, polyethylene glycol.
3) Colorant and opacifier (2.5-8%). Examples: FD&C or D&C Lakes and iron oxide pigments.
4) Vehicle (water, to make 100%).

78. Problems attendants to aqueous film-coating,
The appearance of small amounts (picking)
or larger amounts (peeling)
of film fragments flaking
from the tablet surface.

79. Roughness of the tablet surface due to failure of
spray droplets to coalesce (orange peel effect).

80. An uneven distribution of color on the tablet surface (mottling).
Filling-in of the score-line or indented logo on the
tablet by the film (bridging).

81. Enteric Coating
The design of an enteric coating may be based upon the transit time required for the passage of the dosage form the stomach into the intestines.
This may be accomplished through coatings of sufficient thickness to resist dissolution in the stomach

82. An enteric coating is based upon the pH of the environment, being designed to resist dissolution in the highly acid environment of the stomach but dissolve in the less acid environment of the intestine.
Some enteric coatings are designed to dissolve at pH 4.8 and greater.

83. Enteric coating materials may be applied to either whole compressed tablets or to drug particles or granules used in the fabrication of tablets or capsules.
The coatings may be applied in multiple portions to build a thick coating or they may be applied as a thin film coat.
The coating systems may be aqueous-based or organic-solvent-based so long as the coating material resists breakdown in the gastric fluid.
Materials used in enteric coatings are shellac, hydroxypropyl methylcellulose phthalate, polyvinyl acetate phthalate, and cellulose acetate phthalate and poly-acrylics as Eudragit-L100.

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