1. tablets

2. Tablets - definition
Tablets are solid preparations each containing a single dose of one or more active substances.
They are obtained by compressing uniform volumes of particles or by another suitable manufacturing technique, such as extrusion, moulding or freeze-drying (lyophilisation).
Tablets are intended for oral administration. Some are swallowed whole, some after being chewed, some are dissolved or dispersed in water before being administered and some are retained in the mouth where the active substance is liberated.
The particles consist of one or more active substances with or without excipients such as diluents, binders, disintegrating agents, glidants, lubricants, substances capable of modifying the behaviour of the preparation in the digestive tract, colouring matter authorised by the competent authority and flavouring substances.
Tablets are usually straight, circular solid cylinders, the end surfaces of which are flat or convex and the edges of which may be bevelled. They may have break-marks and may bear a symbol or other markings. Tablets may be coated.

3. categories of tablets Uncoated tablets
Coated tablets (including film-coated and sugar- coated tablets)
Soluble tablets
Dispersible tablets
Effervescent tablets
Chewable tablets
Tablets for use in the mouth (including sublingual and buccal tablets) -modified-release tablets (including delayed-release tablets (gastro- resistant/enteric-coated tablets) and sustained- release tablets (extended- /prolonged- release tablets)
Controls
Uniformity of mass
Uniformity of content
Dissolution/disintegration

4. Uncoated tablets are made in such a way that the release of active ingredients is unmodified. A broken section, when examined under a lens, shows either a relatively uniform texture (single-layer tablets) or a stratified texture (multilayer tablets), but no signs of coating.
Coated tablets are tablets covered with one or more layers of mixtures of substances such as natural or synthetic resins, polymers, gums, fillers, sugars, plasticizers, polyols, waxes, colouring matters, flavouring substances, and sometimes also API. A broken section, when examined under a lens, shows a core which is surrounded by a continuous layer of a different texture. Three main categories of coated tablet may be distinguished: sugar- coated, film-coated, and certain modified-release tablets.

5. Modified-release tablets are coated or uncoated tablets, or matrix tablets that contain special excipients or are prepared by special procedures, or both, designed to modify the rate, the place or the time at which the active substance(s) are released.
Modified-release tablets include sustained-release tablets and delayed-release tablets
Sustained-release tablets (extended-/prolonged-release tablets): designed to slow the rate of release of the APIs in the gut.
Delayed-release tablets (gastro-resistant/enteric-coated tablets): intended to resist gastric fluid but disintegrate in intestinal fluid.

6. Soluble tablets are uncoated or film-coated tablets
Soluble tablets are uncoated or film-coated tablets. They are intended to be dissolved in water before administration. The solution produced may be slightly opalescent due to the added excipients used in the manufacture of the tablets.
Effervescent tablets are uncoated tablets generally containing acid substances and carbonates or hydrogen carbonates, which react rapidly in the presence of water to release carbon dioxide. They are intended to be dissolved or dispersed in water before administration.

7. Tablets - advantages
They are unit dosage form and offer the greatest capabilities of all oral dosage form for the greatest dose precision and the least content variability.
Cost is lowest of all oral dosage form.
Lighter and compact.
Easiest and cheapest to package and strip.
Easy to swallowing with least tendency for hang-up.
Sustained release product is possible by enteric coating.
Objectionable odour and bitter taste can be masked by coating technique.
Suitable for large scale production.
Greatest chemical and microbial stability over all oral dosage form.
Product identification is easy and rapid requiring no additional steps when employing an embossed and/or monogrammed punch face.

8. Delayed release (DR)
- Extended release (ER)
- Immediate release (IR)

9. Tablets - Disadvantages
Mistaken as candy
Cannot be administered to patients if vomiting or unconscious
Some patients have difficulty swallowing tablets especially children
Formulation sometimes limited: large dose drugs usually lack the properties to be formed into tablets
Problems in attaining acceptable content uniformity (accuracy and precision of unit dose content) for low dose drugs
Compromised bioavailability (poor drug solubility; malformulation); Drugs with poor wetting, slow dissolution properties, optimum absorption high in gastrointestinal (GIT) may be difficult to formulate or manufacture as a tablet that will still provide adequate or full drug bioavailability.
Some drugs resist compression into dense compacts, owing to amorphous nature, low density character.
Bitter testing drugs, drugs with an objectionable odor or drugs that are sensitive to oxygen may require encapsulation or coating. In such cases, capsule may offer the best and lowest cost

10. Tablet properties Physical shape Mechanical and physical strength
Should have sufficient strength to withstand mechanical shock during its production packaging, shipping and dispensing.
Chemical nature of tablet ingredients
Should have the chemical and physical stability to maintain its physical attributes over time
Must have a chemical stability over time so as not to follow alteration of the medicinal agents.
Hygroscopicity
Mechanical and physical strength
A tablet should have elegant product identity while free of defects like chips, cracks, discoloration, and contamination.
Should have sufficient strength to withstand mechanical shock during its production packaging, shipping and dispensing.
Smooth surface
The tablet must be able to release the medicinal agents in a predictable and reproducible manner.

12. Tablets ingredients – excipients
Tablet ingredients in addition to active ingredients, tablet contains a number of inert materials known as additives or excipients.
Two types of excipients
General/classical excipients
Excipients for direct compression

13. Tablets ingredients – general excipients
Tablet ingredients in addition to active ingredients, tablet contains a number of inert materials known as additives or excipients. Different excipients are:
Diluent
Binder and adhesive
Disintegrants
Lubricants and glidants
Colouring agents
Flavoring agents
Sweetening agents

14. diluent
Diluents are fillers used to make required bulk of the tablet when the drug dosage itself is inadequate to produce the bulk.
Functions : increase the bulk volume: final product has the proper volume for patient handling
Drugs used at low doses: < 50 mg and diameter of tablet higher than 5 mm
To minimise incompatibilities: the contact can be reduced by dilution
Selection criteria: compressibility, compactibility, flow
Secondary reason is to provide better tablet properties such as improve cohesion, to permit use of direct compression manufacturing or to promote flow.
Filler requirements: inert, non-hygroscopic, soluble, cheap, compactable, tasteful

15. diluent A diluent should have following properties:
They must be non toxic
They must be commercially available in acceptable grade
There cost must be low
They must be physiologically inert
They must be physically & chemically stable by themselves & in combination with the drugs.
They must be free from all microbial contamination.
They do not alter the bioavailability of drug.
They must be color compatible.

17. Commonly used tablet diluents
Lactose-anhydrous and spray dried lactose
Lactose: most widely used diluent in tablet formulation.
Lactose has no reaction with most drugs, whether it is used in hydrous or anhydrous form.
Lactose is incompatible with amino acids, aminophylline and amphetamine
Anhydrous lactose has advantage over lactose that it does not undergo maillard reaction which is browning and discolouration of tablets due to the interaction of amine drug with lactose.
Spray dried lactose in concentration 20-25% of active ingredient is used for direct compression

18. Commonly used tablet diluents
Starch
Directly compressed starch - Sta Rx 1500
Hydrolyzed Starch - Emdex and Celutab
Microcrystalline cellulose-avicel (PH 101and PH 102)
Starch (rice, wheat, corn, potato) starch has no listed incompatibilities filler, binder, disintegrant, glidant
Sta-Rx 1500 is free flowing, direct compressible starch used as diluent, bider and/or disintegranting agent.
two hydrolysed starch Emdex and Celutab, which are combination of 90-92% of dextrose and 3-5% of maltose are free flowing and direct compressible

19. Commonly used tablet diluents
Microcrystalline cellulose
having trade name Avicel: used for direct compression.
These are two type : PH101 (Powder) and PH102 (Granules),
Sucrose
Some sugar-based diluents are used for direct compression. They are:
Sugartab: 90-93% sucrose and 7-10% invert sugar
DiPac: 97% sucrose and 3% modified dextrin
Nu Tab: 95% sucose and 4% invert sugar with small amount of corn starch and magnesium stearate

20. Commonly used tablet diluents
Dibasic calcium phosphate and calcium sulphate
used as diluents but incompatible with tetracycline antibiotics, indomethacin, aspirin, aspartame, ampicillin, cephalexin and erythromycin
Others
Mannitol
Sorbitol
Dextrose

21. Binders AND ADHESIVES Binders / aggregates or agglutinants (2-10%)
These materials are added either dry or in wet-form to form granules or to form cohesive compacts for directly compressed tablet.
Type of binders
Dry powder added to the mixture prior to the wet granulation process
Solution that is used in the wet granulation process
Add right before the tabletting process (direct compression)

22. Binders AND ADHESIVES Binder functions:
To ensure mechanical strength of tablets and granules
To “glue” (promote adhesion) the particles together into granules helping to hold the overall tablet together: improves compactibility
To provide the ¨cohesiveness¨ to a formulation enhancing its compressibility and flow properties (maintain the integrity of the tablet)
To improve the mechanical strength of a tablet
To improve the flowability of the powder or granules or both drawback: significant effect on bioavailability and therapeutic efficacy, because it affects hardness and friability of tablet.

23. Commonly used binders
Hydrophillic cellulose derivatives (1-4%, water, alcohol…) hydroxypropylcellulose, carboxymethylcellulose, ethylcellulose, methylcellulose
Starch (starch 1500) (1-4%)
Polyvinylpyrrolidone (PVP): plasdone (2-5%, alcohol, water)
Saccharose / sucrose / glucose (2-20%, water)
Gelatine (1-4%, water)
Acacia gum (2-5%, water, alcohol), tragacanth gum (1-3%, water)
PEG 4000 y 6000, palmitate stearate glycerol / PEG
Sodium alginatr
Others: glucose, sorbitol, excipients for direct compression

24. To be continue

25. disintegrants
Added to a tablet formulation to facilitate its breaking or disintegration when it contact in water in the GIT.
Disintegrant functions: to ensure that when tablets are in contact with water, they are rapidly breaking into smaller fragments, facilitating their dissolution.
Important for immediate release products where rapid release is required
more effective if added 50% intragranularly, and 50% extra-granularly
some tablet fillers (e.G., Starch and MCC) aid in disintegration
selection criteria: active / drug disolution, bioavailability

26. disintegrants Example: Starch- 5-20% of tablet weight
Starch derivative- Primogel and Explotab (1-8%)
Starch and starch derivatives (5-15%)
Cellulose derivatives: avicel RC591®: mixture of MCC and sodium CMC
Polysaccharides: alginic acid, sodium alginate, tragacanth gum, guar gum
Methylated caseine: Esma Spreng®
Colloidal silicon dioxide: aerosil®, cab-o-sil® [lubricant group]
Magnesium Aluminum Silicate: veegum F®
Clays- Veegum HV, bentonite 10% level in colored tablet only
PVP (Polyvinylpyrrolidone) cross-linked

27. Superdisintegrants: Swells up to ten fold within 30 seconds when contact water
Superdisintegrants ( %, for hard gelatin capsules 4-8%)
Sodium starch glycolate: Primojel®, Explotab® (1-6%) high concentrations may cause gelling and loss of disintegration.
Croscarmellose sodium / carboxymethylcellulose: Vivasol®, Ac-Di-Sol (0.5-5%)
Soy polysaccharides: Emcosoy®
Crospovidone / cross-linked PVP: Polyplasdone® XL (2-4%)
L-HPC low-substituted hydroxypropyl cellulose (1-5%)

28. Example: Crosscarmellose- crosslinked cellulose, Crosspovidone-crosslinked povidone (polymer), Sodium starch glycolate-cross linked starch. These cross-linked products swell up to 10 fold within 30 seconds when in contact with water. A portion of disintegrant is added before granulation and a portion before compression which serve as glidants or lubricants. Evaluation of carbon dioxide in effervescent tablets is also one way of disintegration.

29. Lubricants and glidants
Definition
To prevent the compacted powder from sticking to the equipment during the tabletting. Its aids ejecting of the tablet from the dies, and may improve powder for

30. Lubricants and glidants
Lubricants roles
True lubricants role
Reducing friction between sliding surface, at the tablet-die wall interface during tablet formation and ejection. Also applies to capsule plugs.
Antiadhesion role
Preventing sticking to surface. To reduce adhesion between te powder and the punch faces and thus prevent tablet sticking to the punches
Glidant roles
Improving flow by modifying the interaction between particles
Example
Lubricantss : Stearic Acid, Stearic Acid Salt- Stearic Acid, Magnesium Stearate, Talc, Peg (Poluethylene Glycols), Surfactants
Glidants: Corn Starch (5-10%), Silica Derivatives-colloidal Silicas Such As Cab-o-sil.Syloid, Aerosol In % Conc.

31. Lubricant issues Concept of a "lubricant system“
Frequently two substances are used in a formulation to maximize lubricant effect in all three areas: combining magnesium stearate with a colloidal silica
Lubricant issues
The most effective true lubricants are hydrophobic and if too much is used, they can interfere with disintegration and dissolution
Lubricant generally interfere with bonding and can soften tablets
Alkaline metal stearates are incompatible with some drugs, e.g. Aspirin and AA
Laminar lubricants (mg stearate, Ca stearate) are "mixing sensitive” under the rigors of mixing they delaminate: effect equivalent to adding too much lubricant
Lubricants are always added last after all other components have been thoroughly mixed (mixing time of 2-5 min)
Water soluble lubricants are not as effective: for water soluble tablets

33. Colouring agent
The use of colours and dyes in a tablet has three purposes:
Masking of off colour drugs
Product identification
Production of more elegant product
All colouring agents must be approved and certified by FDA.
Two forms of colors are used in tablet preparation – FD & C and D & C dyes.
Example: FD & C yellow 6- sunset yellow
FD & C yellow 5- Tartrazine
FD & C green 3- Fast green
FD & C blue 1- Brilliant blue
FD & C blue 2- Indigo carmine
D & C red 3- Erythrosine
D and C red 22 – Eosin Y

34. others
Flavouring agents: for chewable tablet – flavour oil are used Sweetening agents: for chewable tablets : sugar, mannitol, Example: Saccharine (artificial): 500 times sweeter than sucrose Disadvantage: bitter aftertaste and carcinogenic Aspartame (artificial) Disadvantage: lack of stability in presence of moisture

35. excipients for direct compression
Characteristics
Generally, direct compression Filler-binders are common fillers that have been physically modified.
Fillers posseses both diluent and binders properties; sometimes, also glidants
In general, these excipients are used in a large amount (50-80%)
Main aspect: Improving flowability (add glidants)
Today, tableting equipment compressing 8,000 to 10,000 tablets per minute. It is critical to have an excellent flowing granulation/powder blend. Many sugar-based excipients, such as maltose, mannitol, and sorbitol are not compressible in their natural state and need to be modified for use in direct compression tableting
Classification: 4 groups
Cellulose derivatives
Starch derivatives
Sugars
Mineral products

36. 1. Celullose And Derivatives Microcrystaline Cellulose, MCC
Binder properties: tablet compactibility: low friability
Inherent lubricant properties: tablets self disintegrate and require little lubricant
Most compactible material available for pharmaceutical use
Example
Avicel PH-101, PH-102, PH-103, PH-105, PH-112, PH-200
Emcocel®: Contains a little amount of calcium phosphate
Prosolv SMCC™: Combination of MCC and Colloidal Silicon Dioxide.
Others: Vivacel®, Vivapur®
Powdered Celluloses
Elcema ® : -Cellulose
Solka-floc® and Justfiber®

37. 2. Starch And Starch Derivatives
Binder, self-lubricant: permits to reduce the amount of traditional lubricants
Super disintegrant: 2-10% of starch 1500 provides disintegrant action
Flow aid: excellent flow properties.
In formulations containing starch, it is necessary to include excipients able to increase the compactability (the hardness of the resulting tablet): 5-10% Silartex® Or Compressil®
Starch 1500
Sta-Rx® 1500
Paygel® 90

38. 3. Sugars
a)Lactose
Lactochem®
Lactopress®: Lactopress® Spray-dried And Lactopress® Anhydrous
Microcelac 100 Is A Spray-dried Compound Containing 75% -Lactose Monohydrate And 25% MCC.
Ludipress®: Lactose (93.4%), Kollidon® 30 (3.2% PVP, Binder) And Kollidon® CL (3.4% Cross-linked PVP, Flow Aid).
Starlac: Lactose / Starch (85:15)
Others: Zeparox®, DCL-30®, Pharmatose®, Tablettose®, Lactose Fast Flow®, Flowlac 100, Cellactose 80
b) Compressible Sugar
Compressible Sugar (95-98% Sucrose)
Di-pac®: It Contains 97% Sucrose And 3% Maltodextrines.
SugarTAB®
Compressuc®: Saccharose + Maltodextrines.
Others: NU-TAB® 4001, Sucre CD1®: Tabfine S100 I

39. Neosorb60 (10%max>315 M), Neosorb60w (105-420 M)
f) Mannitol
Pearlitol®: It Allows Sugar-free Formulations (Including Chewing Gums)
g) Maltose
Advantose™ 100: It Can Be Also Used As Sugar Substitute For Great-tasting Sugar-free And Low- calorie Products.
h) Maltitol
Maltisorb® Is Well Suited To The Formulation Of Powder Forms (Sachets, Dry Syrups, Capsules) And Tablet Forms, Whether Chewable, Suckable, Coated Or Effervescent. ®
c) Glucose / Dextrose
Emdex®: Glucose (90-92%), Maltose (3- 5%) And Little Amount Polysaccharides.
Tabfine D97 Hs®: Glucose (97%) And Starch (3%) As Binder.
d) Fructose / Levulose
Tabfine F94 M®: Fructose (96%) And Maltose (4%)
e)Sorbitol
Neosorb®:
Neosorb60 (10%max>315 M), Neosorb60w ( M)

40. C. Calcium Sulphate: Ca(So4); CaSo4·2H2O
Compactrol, CAL-TAB®
D. Hydrated Magnesium Silicate
Silartex®, Compressil®
4. Mineral Products
A. Dibasic Calcium Phosphate Dihydrate: CaHPo4·2H2O
Emcompress® (Dibasic Calcium Phosphate Dihydrate)
Emcompress Anhidrous®: Especially Designed For Drugs Sensible To Moisture
A-TAB® (Anhidrous), Calstar®, Di-tab®
B. Tribasic Calcium Phosphate: Ca3(PO4)2 ; Ca5(OH)(PO4)3
Tri-cal® WG, Tri-tab®

42. Overview of manufacturing methods

43. Overview of Manufacturing Methods
Methods of Tablet Preparation
Wet Granulation
Dry Granulation
Direct Compression

44. Wet granulation
Improve compressibility, flowability, and content uniformity of powder blend
Step:
Size drug, weigh and blend with excipients
Add liquid binder to prepare damp mass
Adhesion of powdered particles to form granules for tableting (granulation) aids in holding tablet together after compression
Binding agents: aqueous or organic
Cautions: overwetting/underwetting
Screen damp mass
Dry and size: spread evenly on shallow trays temperature and humidity controlled ovens drying in fluid- bed apparatus
Second screening: smaller mesh screen
Lubricate formulation
Compress into tablets

45. Wet granulation process

46. Dry granulation Dry Granulation Method (Slugging) Steps
Size drug, weigh and blend with excipients
Filler, binder, lubricant (disintegrant, glidant)
Compact large masses of powders : no moisture/binding agent added
Crush and size pieces into smaller granules
Lubricate
Disintegrant, lubricant
Compress into tablets
Active or diluent/filler must have cohesive properties
Drugs that degrade in moisture or heat

47. Direct compression
Direct Compression: Must be a free-flowing and compressible mixture
Steps:
Size drug
Weigh appropriate amounts of active and excipients
Blend with excipients
Compress into tablets
Direct Compression Problems
Problems with high-dose drugs: compressibility
Problems with low-dose drugs: content uniformity
May require glidant to improve flowability
Segregation in hopper possible
Blending of lubricant critical: weaker tablets, slower drug release

48. Direct compression Strategies
Decrease the size of drug particles: micronisators
Firstly, mix the fine drug with filler-binder product.
Then, add the rest of ingredients and
Magnesium stearate at the end (mix 3 minutes and compress).
Never mix all the ingredients of the formula (drug and excipients) in only one step

49. Tableting / compression

51. Tablet presses: single ended compression

52. Tablet presses: single-ended compression

55. Tablet presses multistation / rotary punch

57. https://upload. wikimedia

63. Quality control of finished tablets