TABLETS

By Wilwin

Tablets

scope

Introduction

Types Of tablets

Advantages and Disadvantages

Formulation additives

Tablet compression

Processing Problems

Evaluation Of tablets

References

Introduction

In 1843, a patent was granted to Thomas Brockedon (Englishman) for manufacturing pills

and lozenges.

1980 nearly 300 monographs for tablets.

Over 2/3rd dosage forms are tablets.

Def: Tablets are flat or biconvex discs of unit dosage forms containing one or more active

ingredients, compressed along with necessary additives.

Types of tablets

Tablets Ingested Orally:

Compressed Tablets Or Standard Compressed Tablets.

• Both type of action – systemic effect and local effect.

•Rapid disintegration and drug release

•Mostly Antacids and adsorbents.

Multiple Compressed Tablets: For incompatible components these are:

(1)Layered Tablets:

• either two layered (for two components) or three layered (for three components) tablet.

Tablets Ingested Orally

(2)Compressed coated Type:

•Compressed coated type- either tablet within a tablet or tablet within a tablet within a tablet. Tablet in

this category are usually prepared for two reasons

•1. To separate physically or chemically incompatible ingredients.

•2. To produce repeat action or prolong action product.

Compression coated tablets

Tablets Ingested Orally

Repeat Action Tablets :Sugar coated or multiple compressed tablets are usually coated with shellac or an

enteric polymer so that it will not release its drug in stomach but intestine.

Delayed Action And enteric coated TabletsDelayed action tablets are intended to release the drug after some time delay or after passing the drug

through the GIT. Enteric coatings are applied mainly for drugs that are irritating.

Sugar coated tablet: Primary role is to produce an elegant, glossy, easy to swallow, widely utilized in

preparing

multivitamin tablets.

Sugar coating doubled the tablet weight.

Now polymers are used with sugar solution.

Tablets Ingested Orally

Film Coated Tablets

•Advantage of film coated over sugar coated tablets is better mechanical strength and

flexibility of the coating, little increase in tablet weight.

•These are developed as an alternative procedure to the preparation of coated tablets in

which the drug is not required for coating.

Chewable Tablets

•Easily administered for infants and elderly persons

•These are intended to be chewed in the mouth before swallowing. Used for large tablet

of antacid, bitter or foul testing drugs are not suitable for this type tablet.

Tablets Used In Oral Cavity

Buccal And Sublingual Tablets

•Drugs used by this route are for quick systematic action. The tablets are designed not to be

disintegrate but slowly dissolve.

•Troches And Lozenges

These are mainly for treating soar throat and to control coughing in common cold.

•Dental Cones

These are designed to place in the empty

socket after tooth extraction.

Tablets Administered By Other Routes

•Implantation tablets

To provide prolonged drug effects.

used for administration of growth hormone to food producing animal.

•Vaginal Tablets

These are designed to undergo slow dissolution and drug release in vaginal cavity.

Tablets Used To Prepare Solutions

• Effervescent Tablets

Tablets are designed to produce a solution

rapidly with the release of carbon dioxide.

• Dispensing tablets

Tablets are intended to be added to a given volume of water to produce a solution of a given

drug concentration.

• Hypodermic tablets

These tablets are composed of one or more drugs with water-soluble ingredients. Drug is

added to sterile water to prepare sterile solution, which is injectable.

Advantages

Production aspect

– Large scale production at lowest cost

– Easiest and cheapest to package and ship

– High stability

User aspect (doctor, pharmacist, patient)

– Easy to handling

– Lightest and most compact

– Greatest dose precision & least content variability

– Coating can mark unpleasant tastes & improve pt. acceptability

Disadvantages

Some drugs resist compression into dense compacts.

Drugs with poor wetting, slow dissolution, intermediate to large dosages may be

difficult or impossible to formulate and manufacture as a tablet that provide adequate

or full drug bioavailability.

Bitter taste drugs, drugs with an objectionable odor, or sensitive to oxygen or

moisture may require encapsulation or entrapment prior to compression or the tablets

may require coating.

Difficult to swallow in case of children and unconscious patients.

Ingredients used in tablet formulations

Drugs (API)

Diluents:

Diluents are fillers used to make required bulk of the tablet when the drug dosage

itself is inadequate to produce the bulk.

Properties Of diluents:

•They must be non toxic & physiologically inert.

•They must be free from all microbial contamination.

•They do not alter the bioavailability of drug.

Commonly used tablet diluents

Lactose-(anhydrous), spray dried lactose ,Directly compressed starch-Sta Rx

1500,Dicalcium Phosphate dihydrate ,e.t.c.,

Binders and Adhesives: These materials are added either dry or in wet- form to form

granules or to form cohesive compacts for directly compressed tablet.

Example: Acacia, tragacanth, Cellulose derivatives-Methyl cellulose, Hydroxy propyl

methyl cellulose, Hydroxy propyl cellulose, Starch paste,e. t.c.,

Disintegrants

To promote breakup of the tablets

To promote rapid release of the drug

Example: Starch- 5-20% of tablet weight, Starch derivative – Primogel and Explotab

(1-8%) , Cellulose derivatives . Lubricants

– To reduce the friction during tablet ejection between the walls of the tablet and

the walls of the die cavity

Example: Stearic acid, Magnesium stearate, Talc, PEG (Polyethylene glycols),

Surfactants

• Glidants

– Reducing friction between the particles

– To improve the flow properties of the granulations\

Example: - Corn Starch – 5-10% conc., Talc-5% conc., Silica derivative - Colloidal

silicas such as Cab-O-Sil, Syloid, Aerosil in 0.25-3% conc.

• Antiadherants

– To prevent adherence of the granules to the punch faces and dies.

Examples:-Talc ,corn starch ,metallic steroids.

ORGANOLEPTIC AGENTSSweetening Agents: Sugar, mannitol. Saccharine (artificial): 500 time’s sweeter than sucrose

Coloring agents:

The use of colors and dyes in a tablet has three purposes:

•Masking of off color drugs

•Product Identification

•Production of more elegant product

Example: FD & C yellow 6-sunset yellow ,FD & C yellow 5- Tartrazine

Flavoring agents:

•These are mostly used in Chewable Tablets

•E.g. Flavor oils

Tablet production

Granulation Properties:Particle size & shape: Particle size of granulation affect the average tablet weight,

weight variation, disintegration time, friability, granule flow ability.

Surface area:

Dissolution of a drug depends on surface area of powder materials or

granules.

Density: Granule density may influence compressibility, tablet porosity, dissolution

and other properties.

Strength & Friability: Granules are aggregation of component particles that is held

together by bonds of infinite strength. Friability is the ability to formation of fines

or fragments.

Flow properties: For the movement of granules from hopper to die cavity sufficient

flow properties are essential.

Angle of repose: It is maximum angle between the surface of a pile of powder and

horizontal plane.

Angle of Repose≤ 30 → Free flowing material

Angle of Repose ≥ 40 → Poorly flowing material

Hopper Flow rate: Granules are allowed to flow from the conical hopper onto a

recording balance device and dw/dt is calculated .

Tableting methods

• Wet methods

– Wet granulation

• Dry methods

– Dry granulation

– Direct compression

WET GRANULATION:

Raw materials → Weighing → Screening → Wet massing → Wet Sieving/Milling →

Drying → Dry Screening → Mixing → Compression

The powder mass is wetted with the binding solution until the mass has the consistency

of damp snow.

If the granulation is over wetted the granules will be hard, if not wetted sufficiently, the

resulting granules will be too soft, breaking down during lubrication.

The wet mass is forced through a suitable sieve.

Moist materials from wet milling steps is placed on large trays and placed in drying

chambers.

After drying granulation, the lubricant or glidants are added as fine powder to promote

flow of granules.

These granules then compressed to get tablet.

DRY GRANULATION:

Raw material → weighing → Screen → Mixing → Slugging → Milling → Screening

→ Mixing → Compression

Compression granulation involves the compaction of the components of a tablet

formulation by means of flat punch. These compact masses are called slug and the

process is called slugging.

Slugs are then milled and screened to produce a granular form.

DIRECT COMPRESSION:

Raw material → Weighing → Screening → Mixing →Compression.

This method is applicable for crystalline chemicals having good compressible

characteristics and flow properties such as: Potassium salt (chlorate, chloride,

bromide), Sodium chloride, Ammonium chloride, Methenamine etc.

Tablets are compressed directly from powder blends of the active ingredient and suitable

excipients

No pretreatment of the powder blends by wet or dry granulation procedures is necessary.

A comparative processing chart of different granulation techniques

TABLET COMPRESSION

Compression: Compression is the process of applying pressure to a material with the

help of a Tablet punching machine.

Transitional repacking/particle rearrangement

Deformation at point of contact

Fragmentation and deformation

Bonding

• Mechanical Theory

• Inter molecular theory

• Liquid –Surface film Theory

Decompression

Ejection

TABLET COMPRESSION

Single punch machine The compression is applied by the upper punch making the single punch machine a

“stamping press.”

Multi-station rotary presses• The head of the tablet machine 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

• 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.

• 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.

• 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.

Single punch tablet machine (left) & 16 station rotary tablet machine(R)

Processing Problems

• Capping & Lamination: Complete or partial loss of top and bottom

crowns of a tablet from the main body is called capping.

• The separation of a tablet into two or more distinct layers is called lamination.

Causes: Air entrapment , Deep concave punch ,Incorrect setting of the press ,

Compression of too dry material .

Remedy: By precompression ,Slowing Tableting ,Reducing final compression force ,

Using flat punch ,Using hygroscopic materials to maintain proper moisture level

eg. - PEG-4000 and Methyl Cellulose

capping. lamination.

• Picking & Sticking: Surface materials from a tablet that is sticking to the punch and

being removed from the tablet surface is picking. Sticking refers to tablet materials

adhering to the die wall.

Causes: Picking occurs when punch tips are engraving or embossing. Small enclosed

areas in letters A.

• Mottling: It is an unequal distribution of colors on a tablet with light and dark areas

on tablet surface.

Cause: 1. Use of a drug whose color differs from tablet excipients

2. Use of a drug whose dehydration products are colored Remedy: 1. The use of colorant2. Disperse a dry colour additive during powder binding steps.

• Weight Variation: Variation of tablet weight also causes variation of active medicament

which change the bioavailability.

Cause: (a) Granule size & size distribution: Variations in the ratio of small to large granules

and difference in granule size determine the void space between particles are filled.

(b) Poor Flow: The die fill process in based on a continuous and uniform flow of granules from the hopper through the feed frame.

Bridging (1) Arching or Bridging: Granules separate at the neck of the hopper and flow stops completely..

Rat holling

(2) Rat Holling: In this case particles segregate near the wall of the hopper and at the centre flow continues forming hole. In rat holling flow rate decreases. Addition of glidant can overcome these problems.

(c) Punch Variation: When length of lower punches is unequal, the fill in each die

varies which causes weight variations of tablet.

(d) Poor Mixing: Some times lubricants and glidants are not thoroughly distributed.

The flow of particles then impaired and the granules do not move efficiently into

the dies.

• Hardness Variation: Hardness depends on the weight of materials and space

between upper and lower punch at the moment of compression.

• Double Impression: This involves only punches that have monogram or engraving.

If the monogram present in upper punch, slight rotation of punch after

precompression produce double impression and vice versa.

Evaluation of Tablet

1.GENERAL APPEARANCE: The general appearance of a tablet, its identity and general

elegance is essential for consumer acceptance. The control of general appearance

involves the measurement of size, shape, colour, presence or absence of odour, taste etc.

Size & Shape: Tablet thickness can be measured by micrometer or by other device. Tablet

thickness should be controlled within a ± 5% variation of standard value.

Unique identification marking: These marking utilize some form of embossing, engraving

or printing. These markings include company name or symbol, product code, product

name etc.

Organoleptic properties: Color distribution must be uniform with no mottling. For visual

color comparison compare the color of sample against standard color.

• The presence of odour in a batch of tablet indicates a stability problem Presence of odour

could be characteristic of the drug (Vitamin), added ingredients (flavouring agent).

2.Weight variation test: weigh randomly 20 tablets individually in a batch.

Determine the average weight of 20 tablets.

Compare individual tablet weight to average weight

• As per I.P. ,

If the tablet weight is, < 80mg , % deviation allowed up to 10%

> 80mg , % deviation allowed up to 7.5%

> 250mg , % deviation allowed up to 5%

If any of the tablet from the batch deviates from the above specifications,

another 10 tablets are selected from the same batch and the procedure is

repeated. Of 30 tablets , not more than 1 tablet should deviate.

3.Content uniformity test:

It is used to ensure that every tablet contains the amount of drug substance intended

with little variation.

Procedure:

o 10 tablets are assayed,

o 9 tablets should have % limit of 85-115%.

o If more than 1 tablet deviates from 85-115%,

o 20 tablets are assayed

o Not more than 1 tablet should have the % limit of 75-125%

4. Hardness test:

• It is defined as the force required to break a tablet in a diametric compression test.

Tablet requires a certain amount of strength or hardness and resistance to friability

to withstand mechanical shocks of handling in manufacture, packaging and

shipping

. Types of hardness testers are used.

1. Monsanto hardness tester .

2. Strong cob tester.

3. Pfizer tester.

• For, Conventional tablets hardness : 2.5- 5 kg/cm2

Dispersible/ chewable tablets hardness: 2.25- 2.5 kg/cm2

Extended release tablets hardness : 5- 7.5 kg/cm2

5. Friability test:

• The instrument used is Roche friabilator.

• It consists of a acrylic drum having 280-290mm diameter with a

thickness of 30mm. Acrylic drum is mounted on a horizontal axis

of a drive motor.

• Drum is operated at a speed of 25rpm.&Allowed revolutions

for each tablet is 100.

• Allowable range: loss 0.5 - 1% weight

hardness tester

Disintegration test:

Disintegration is the breakdown of tablet crust in to finely divided particulate matter or into granules once the tablet is exposed to the gastric fluids .

• For enteric coated tablets:

Disintegration fluid for first 2hrs- 0.1NHcl.

After 2hrs, replace with 6.8pH phosphate buffer

Disintegration time – 60 min .

Type of tablets Time Of disintegration

uncoated conventional tablets 15min

sugar coated tablets 60 min.

film coated tablets 30 min

• For dispersible tablets:

Temperature – 22-240c

Disintegration time < 5min.

Uniformity of dispersion: place 2 tablets in 100ml of water and stirr gently .the

tablet should undergo dispersion within 5 min, which should pass through a sieve

screen of 22 mesh.

• For effervescent tablets:

Temperature- 200-300c

Place one tablet in a 250ml beaker containing water, numerous gas bubbles are

evolved.

Disintegration time- 3min.

Dissolution Test (U.S.P.): It is the solubilization of the drug or active moiety in to the

dissolution media.

Different types of dissolution apparatus:

Apparatus -I-Rotating Basket type.

Apparatus -II- Rotating Paddle type.

Apparatus-3-Reciprocating cylindrical type.

Apparatus-4-Flow through cell.

Apparatus-5-Paddle over disk.

Apparatus-6-Cylindrical apparatus.

Apparatus-7-Reciprocating disc apparatus.

• Procedure:

Acceptance criteria:

S1= 6 tablets are taken

Acceptable: If all of the

tablets are not less than

Q ±5%

If S1 fails

S2=S1+6 tablets are taken

Acceptable: If average of 12

tablets is ≥Q and no tablet is

less than Q-15%

If S2 failsS3= 12+12 tablets are taken

Average of 24 ≥ Q% not

more than 2 tablets should

be less than Q-15% and

None should be less than

Q-25%

The theory and practice of Industrial pharmacy, by Leon Lachmann and

Herbert .A.Lieberman,3rd edition. Page no: 294 to 336.

Pharmaceutical dosage forms tablet volume-1 edited by Herbert A.Liberman, Leon

Lachman, and Joseph B. Schwartz, page no:88 to 121.

Pharmaceutical dosage forms tablet volume-2 edited by Herbert A.Liberman, Leon

Lachman, and Joseph B. Schwartz, page no :201 to 211

Indian pharmacopoeia 2010 vol-2, page No: 751 to 754

The science and practice of pharmacy by Remington Volume I -905 to 916.

www.google.com

www.wikipidia .com