Pharmaceutical Tablet

Tablet

Tablet may be defined as solid dosage forms containing drug substances with or without suitable diluents and prepared either by compression or molding methods.

Advantages of Tablet dosage form

⇨ Low cost

⇨ Easiest and cheapest to package and strip

⇨ Easy to swallowing with least tendency for hang-up

⇨ Objectionable odour & bitter taste can be masked.

⇨ Greatest chemical & microbial stability

⇨ Product identification become easy.

Tablet Shapes

The ideal shape is Spherical shape.

The worst shape is Square flat-faced tablet.

Classification of Tablets

A. According to method of preparation:

⇨ Molded tablet

⇨ Compressed tablet (For large scale production)

B. According to BP

⇨ Coated tablet

⇨ Uncoated tablet

⇨ Film coated tablet

⇨ Sugar coated tablet

⇨ Soluble tablet

⇨ Dispersible tablet

⇨ Effervescent tablet

⇨ Chewable tablet

⇨ Sublingual tablet

⇨ Buccal tablets

⇨ Modified release tablets

⇨ Delayed release tablet

⇨ Sustained release tablet

C. According to USP

⇨ Immediate tablet

⇨ Disintegrating tablet

⇨ Chewable tablet

⇨ Sublingual tablet

⇨ Buccal tablet

⇨ Effervescent tablet

Classigication of Modified release tablet

⇨ Exrended release tablet

⇨ Delayed release tablet

Compressed tablet

Compressed tablets are manufactured by the three basic methods:

1. Wet granulation

2. Dry granulation

3. Direct compression

Film coated tablet

Film coated tablets are compressed tablets coated with a thin layer of a water insoluble or water soluble plasticizer.

Effervescent tablets

Effervescent tablets are prepared by compressing granular effervescent salts or other materials having the capacity to release gas (CO2) when contact with water.

Here the active ingredients are mixed with organic acids such as citric acid or tartaric acid and Sodium bi-carbonate (NaHCO3)

Hypodermic Tablet

Hypodermic tablets are composed of one or more drugs, with other readily water soluble ingredients and are intended to be added to sterile water or water for injection.

Tablet Excipients

⇨ Adsorbents (Silicon di oxide)

⇨ Antiadherents

⇨ Anticaking agents

⇨ Antioxidants

⇨ Binders

⇨ Buffers

⇨ Chelating agents

⇨ Coloring agents

⇨ Diluents

⇨ Disintegrants

⇨ Super disintegrants

⇨ Dissolution enhancers

⇨ Dissolution retardants

⇨ Fillers

⇨ Flavouring agents

⇨ Glidants

⇨ Lubricants

⇨ Preservatives

⇨ Sweetening agents

⇨ Wetting agents

Compression Machine

Tablet compresion machine is the device that compresses the powder into tablet of uniform size with different shape and uniform weight.

Basic components of compression machine

⇨ Hopper (Hold the materials to be compressed)

⇨ Dies (Defines the shapes and size of the tablet)

⇨ Punches (Used for compressing of the materials within the dies)

⇨ Cam Crack (Used for guiding the movement of the punches,)

⇨ Feeding mechanism

Types of Compression machine/ Tableting machine

A. On the basis of Feed system:

⇨ Single hopper compression machine 

⇨ Double hopper compression machine

B. On the basis of tooling:

⇨ Single punch/single station/ Eccentric presses compression machine

⇨ Multi punch machine/ Rotary tablet machine/ High speed rotary tablet machine/ Multi layer rotary tablet machine

C. On the basis of number of punches:

⇨ 17 punch compresdion machine

⇨ 19 punch compression machine

⇨ 23 punch compression machine

⇨ 33 punch compression machine

⇨ 37 punch compression machine

Compression machine capacity calculation (Number of tablet production in min or in a hour)

Machine capacity (in min) = Number of punch × Number of feeding system (number of hopper) × rpm

Machine capacity (in hour) = Number of punch × Number of feeding system (number of hopper) × rpm × 60

* In two feeding system (two hopper),  Each punch can compress 2 tablets. So 33 punchs can compress 66 tablets in a round.

* rpm means rotation per minute. 

Example: If two feeding system compression machine with 33 punchs is rotated under 60 rpm,  

then number of tablet production is = 33×2×60×60 ⇨ 2,37,600 pieces tablet in one hour

Compression machine tooling

⇨ The setup of dies and punches for the compression of tablets on the compression machine is called tooling.

⇨ Tooling determine the shape, size and identification marking of the tablets.

Types of Tooling

⇨ D tooling

⇨ DB Tooling

⇨ B tooling

⇨ BB Tooling

Types of Tablet size

⇨ 25 mm

⇨ 19 mm

⇨ 16 mm

⇨ 13 mm

Types of Punch Barrel diameter

⇨ 25.40 mm

⇨ 19.05 mm

Types of Die outer Diameter

⇨ 38.10 mm

⇨ 30.16 mm

⇨ 24 mm

Relationship among tooling, punch barrel diameter, Die outer diameter, Punch length and Tablet size

Types of Tooling/ Tablet size/ Punch Barrel diameter/ Die outer diamter/ Punch length

D tooling/ 25 mm/ 25.40 mm/ 38.10 mm/133.60 mm

DB tooling/ 19 mm/ 25.40 mm/ 30.16 mm/133.60 mm

B tooling/ 6 mm/ 19.05 mm/ 30.16 mm/ 133.60 mm

BB tooling/ 13 mm/ 19.05 mm/ 24 mm/ 133.60 mm

Function of tablet press during compressing

⇨ Filling of empty cavity during compression

⇨ Precompression of granulation

⇨ Compression of granulation

⇨ Easily ejection of tablet from die cavity 

Problems of Tableting Problems & Remedies (11)

⇨ Binding

⇨ Capping

⇨ Chipping

⇨ Cracking

⇨ Double impression

⇨ Hardness variation

⇨ Lamination

⇨ Mottling

⇨ Picking

⇨ Sticking

⇨ Weight variation

Tableting Problems-Causes & Remedy

Capping

Capping is the partial or complete separation of the top or bottom crowns of a tablet from the main body of the tablet.

Causes & remedies of capping problem

Cause-1: Large amount of fine powders

Remedy-1: Remove some or all fines through 100 to 200 mesh screen

Cause-2: Too dry or very low moisture content

Remedy-2: Moisten the grangules suitable/ Add hygroscopic substance e.g., Sorbitol, methyl cellulose,  poleethylene glycol-4000

Cause-3: Insufficient amount of binder

Remedy-3: Increasing the amount of binder/ adding dry binder such as pre-gelatinized starch, gum acacia

Cause-4: Insufficient lubricant

Remedy-4: Increase the amount of lubricant/ Change the type of lubricant

Cause-5: Tablet tooling can also be a cause of capping

Cause-6: Incorrect setup at the press

Lamination

Lamination is the separation of tablet into two or more distinct layer.

Causes & Remedies of Lamination problem

Cause-1: Rapid stress relaxation of tablet from die wall

Remedy-1: Use tapered dies, i.e. upper part of the die bore has an outward taper of 3° to 5°

Cause-2: Rapid decompression

Remedy-2: Precompression before final compression

Cause-3: Air entrapment

Remedies:

⇨  A granulation that is too dry trends to cap or lamination for lack of cohesion

⇨ For moisture-critical granulations, the addition of a hygroscopic substances can help to maintain a proper moisture level.

Chipping

The breaking of tablet after press leaves or during subsequent handing and coating operation.

Causes & Remedies of Chipping problem

C-1: Too dry granules

R-1: Moisten the granules to plasticize/ Add hygroscopic substances

C-2: Too much binding

R-2: Optimize binding/ Use dry binders

C-3: Sticking on punch faces due to improper lubrication

R-3: Dry the granules properly/ Increase lubrication

Cracking

Small fine cracks observed on the upper & lower central surface of tablets or very rarely on the die wall.

Causes & Remedies of Cracking problem

C-1: Large size of granules

R-1: Reduce granule size. Add fines

C-2: Too dry granules

R-2: Moisten the granules properly and add proper amount of binder.

C-3: Granulation too cold

R-3: Compress at room temperature

R-4: Tablet expands on ejection due to air entrapment

R-4: Use tappered die

Sticking (Adhere to die wall)

Granules adhere to the die wall and thereby lower punch can not move freely.

Causes & Remedies of Sticking problem

C-1: Insufficient lubrication

R-1: Increase the lubricant/ Change the lubricant

C-2: Granules not dried properly

R-2: Dry the granules properly. Make moisture analysis to determine limits.

C-3: Too much binder

R-3: Reduce the amount of binder/ Use a different type of binder

C-4: Hygroscopic granular materials

R-4: Modify granulation and compress under controlled humidity.

Picking (Adhere to punch)

A small surface of the tablet material is removed by the punches and adhere to the punches therefore the resulting show a pitted surface instead of smooth surface.

Causes & Remedies of Picking problem

C-1: Excessive moisture in granules.

R-1: Dry properly the granules, determine optimum limit.

C-2: Insufficient lubrication added

R-2: Increase lubrication; use colloidal silica as a polishing agent.

C-3: Too much amount of  binder added

R-3: Reduce the amount of binder/ Change the type of binders/ Use dry binders

C-4: Punch tips have engraving or embossing on punch faces such as B, A, O, R, P, Q, G

R-4: Design lettering as large as possible/ Plate the punch faces with chromium to produce a smooth and non-adherent face.

Mottling

An unequal distribution of colour on a tablet

Causes & Remedies of Mottling problem

C-1: A coloured drug used alongside with colourless or white-coloured excipients

R-1: Use appropriste colourants.

C-2: Improperly mixed dye, especially during direct compression

R-2: Mix properly.

Double impression

It is due to free rotation of the punches, which have some engraving on the punch faces.

Causes & Remedies of Double impression problem

C-1: Free rotation of either upper punch or lower punch during ejection of a tablet.

R-1: Use keying in tooling

R-2: Newer presses have anti-turning devices, which prevent punch rotation.

Binding

Binding to the die wall when the tablets adhere, seize or tear in the die.

As a result a film is formed in the die and ejection of tablet is hindered.

With excessive binding, the tablet sides are cracked and it may crumble apart.

Tablet Coating

Tablet coating is the application of a coating material to the exterior of a tablet with the intention of conferring benefits and properties to the dosage form over the uncoated variety.

Purpose of Tablet coating:

⇨ Protection from light and moisture

⇨ Mask unpleasant taste, odour, color

⇨ Improve pharmaceutical eleglance.

⇨ Proctect drug from gastric acid

⇨ To increase chemical & physical stability / protection

⇨ Coated tablets are easier to swallow than uncoated tablets

⇨ To provide sequential drug release/ to control the release of the drug from the tablet

Types of tablet coating

1. Film coating

2. Sugar coating

Film coating

Film coating process, which involves the deposition of a membrane, consisting of polymer, plasticizer, colorant and possibly other additives on to the surface of a pharmaceutical dosage form especially tablet of granule.

Reason for film coating

⇨ Intended to make the tablet to pass through the stomach intact to disintigrate and release their drug content for absorption along the intestines.

⇨ To protect acid liable drugs from the gastric fluid.

⇨ To protect tablet from heat, light and moistue.

⇨ To provide a delayed-release component for repeat action tablets.

⇨ To create modified relapse form

⇨ To improve product appearance, to mask odor and taste and to aid swallowing

Main purpose of Film coating

⇨™Film coating can control the drug release patterns of tablets in terms of site, rate and time.

⇨ Film coatng is used for control release 

Types of film coating

1. Non-enteric film coating

2. Enteric film coating

Non-enteric film coating

Non-enteric film coating is like sugar coating but film coating agents are used.

It is used to overcome the disadantages of sugar coating

Non-enteric film coating agents

⇨ Methyl cellulose

⇨ Hydropropyl methyl cellulose

⇨ Hydroxy propyl cellulose

⇨ Methylhydroxy  ethyl cellulose

⇨ Sodium carboxymethyl cellulose

⇨ Polyvinyl phthalate

⇨ Polyethylene glycol (PEG)

Enteric film coating

Enteric fim coating is a special type of coating which intended to make the tablet to pass through the stomach intact to disintigrate and release their drug content for absorption along the intestines.

Purpose of enteric film coating

⇨ Protect acid-liable drugs from the gastric fluid.

⇨ Prevent gastric distress nausea due to irritation from drug

⇨ To deliver drugs that is optimally absorbed in the small intestine.

⇨ To provide a delayed-release component for repeat action tablets.

Enteric film coating agents:

⇨ Cellulose acetate phthalate

⇨ Polyvinyl acetate phthalate

⇨ Hydroxypropyl methylcellulose phthalate

⇨ Acrylate polymers

Film coating Problems (17)

⇨ Blistering (Film becomes detached from substrate forming a blister)

⇨ Blooming ( Coating becomes dull immediately or after prolong storage.)

⇨ Blushing (Whitish specks or haziness in film occur)

⇨ Bridging (Films pulls out of intagliation forming bridge across the edges of the mark of a blister)

⇨ Chipping ( Film becomes chipped and dented, usually at the edges off the tablet)

⇨ Cracking (Film become cracks or spilts)

⇨ Cratering (Volcanic-like craters occurs in film exposing tablet surface

⇨ Flaking (Film become flake off exposing tablet surface)

⇨ Infilling (Intagliation filled with either particles of dried polymer or solidified foam)

⇨ Orange peel/ Roughness (Surface appear similar to that of an orange or lemon)

⇨ Peeling (Film peels off exposing the best tablet surface)

⇨ Picking (Isolated areas of film pulled off the surface)

⇨ Pimpling

⇨ Pitting (Pits occur in tablet surface but film surface not disrupted)

⇨ Pulling out

⇨ Scuffing problem of film coating (Gray to black marks on the surface of white or lighty colored film coated tablet appear)

⇨ Splitting (Film spilts usually around the edges of the tablet)

⇨ Wrinkling (Film has a wrinkled appearance)

Film coating problems & Remedies

Bridging

Films pulls out of intagliation forming bridge across the edges of the mark of blister.

[ Intaglio ⇨ A design or piece of art which is engraved or etched into something.]

Causes of bridging

High internal stresses in film.

R-1: Increase the plasticizer content or changing plasticizer

Blushing

Whitist specks or haziness in film.

Causes of blushing

Precipitation of polymer due to high temparature or poor solvent.

R-1: Decrease the drying air temperature

Blistering

Film becomes detached from substrate forming a blister.

C-1: Overheating during spraying of at the end of coating run.

R-1: Milder drying condition

Blooming

Coating becomes dull immediately or after a prolong storage.

C-1: Due to low molecular weight plasticizers included in the coating formulation.

R-1: Decrease plasticizer concentrations and increase molecular weight of plasticizer.

Polymer

A polymer is a large molecule or macromolecule, composed of monomers.

In film coating formulations, the polymer is the major ingredients.

Polymers used in Film coating formulations:

⇨ Ethyl cellulose

⇨ Hydroxyethyl cellulose

⇨ Hydroxypropyl cellulose

⇨ Hydroxypropyl methylcellulose

⇨ Methyl cellulose

⇨ Methylhydroxy ethyl cellulose

⇨ Polyethylene glycol

⇨ Polyvinyl pyrolidone

Plasticizer

Plasticizer is a non-volatile, low molecular weight substance. When plasticizer added to a polymer, changes its physical properties in such a manner that the finished profuct is in a more useful form. Plasticers are used for increasing pliability (Flexibility)

Plasticizers used in film coating (8):

⇨ Polyethylene glycol

⇨ Propylene glycol

⇨ Glycerol

⇨ Glyceryl triacetate

⇨ Triethyl citrate

⇨ Diethyl phthalate

⇨ Castor oil

⇨Mineral oil

Sugar coating

It involves the successive application of sucrose-based solutions to tablet cores in suitable coating equipment.

Main purpose of sugar coating

Main purpose is to protect the drug inside the tablet and act as a barrier to external contaminants.

Sugar coating stages (6 stages)

1. Sealing of the tablet cores ( To prevent moisture penetration into tablet core)

2. Sub coating (to round the edge of tablet and build up the tablet size)

3. Smoothing/ Grossing

4.  Colouring

5. Polishing

6. Printing

Sealing materials used in sugar coating

⇨ Acetate phthalate

⇨ Polyvinyl acetate phthalate

⇨ Shellac

Materials used in subcoating 

⇨ Calcium carbonate

⇨ Cocoa powder

⇨ Talc

Sugar coating problens

1. Chipping of coating

2. Cracking of the coating

3. Non-drying coating

4. Twinning (Two tablets are stick together)

5. Uneven colour

6. Blooming & Sweating ( Coating becomes dull immediately or after a prolong storage.)

7. Marbling

1. Chipping of coating

C-1: Less or  absence of polymer

R-1: Add polymer

C-2: Excessive use of insoluble filler

R-2: Reduce quantity of fillers.

2. Cracking of the coating

C-1: Expansion of tablet core during or after coating by moisture absorption or stress relaxation

R-1: Extent the time between compaction and sugar coating

3. Non-drying coating

C-1: Excess level of invert sugar present.

R-1: Avoid excess heating of sucrose syrup under acidic condition.

4. Twinning

C-1: Flat surface / high edge punch walls

R-1: Modify tablet punch design

5. Uneven colour

C-1: Poor distribution of coating liquid

R-1: Improve mixing and add sufficient liquid

C-2: Excessive drying between color application (color layer erosion)

R-2: Optimize drying

6. Blooming & Sweating

C-1: Residual moisture present in finished coated tablets.

R-1: Dry to get appropriate label of moisture at each application and at the end.

7. Marbling (A mottled or streaky appearance)

C-1: Uneven coating surface

R-1: Achieve smooth coating surface prior to polishing

Process equipments of coating

1. The standard coating pan

2. The perforated coating pan

3. The fluidized bed coater (Air suspension)

Sugar coating vs Film coating

S: Appearence is rounded, with high degree of polish.

F: Retain contour of original core usually not as shiny as sugar coat types. (Contour = দেহরেখা)

S: Weight increase due to coating materials is about 30-50%

F: Weight increase due to coating materials is about 2-3%

S: Logo or breal lines is not possible.

F: Logo or breal lines possible

S: Involve multiple process stages

F: Involve usually single stage

S: Coating function usually not possible apart from enteric coating

F: Coating is easily adaptable for controlled release.