S. B. Thoke [M. pharm]

TABLET

WHAT IS TABLET …..?

DEFINITION

Tablets are solid preparations

consisting of one or more active ingredient

obtained by compressing uniform volumes of particles into

. various

shapes and sizes.

THE INGREDIENT CLASSIFICATION USED IS:

Fillers- Lactose, Starch, Dextrose, Mannitol, Sorbitol, Maltodextrin,

Sucrose, Cellulose etc.

Binders- acacia, gelatin, liquid glucose, sucrose syrup, starch paste,

methyl cellulose, CMC, PVP, EC, HPMC etc.

Disintegrates

Lubricants, Glidants, Anti-adherents

Wetting agents

Colors and flavors

Preservatives

LIST OF DISINTEGRANTS

DISINTEGRANTS CONC.  IN GRANULES(%)

SPECIAL COMMENTS

Starch USP 5-20 Higher amount is required, poorly compressible

Starch 1500 5-15

Avicel®(PH 101, PH 102)

10-20 Lubricant properties and directly compressible

Cross-linked starchExplotab®

2-8 Sodium starch glycolate, superdisintegrant.

Crosscarmellose sodium AC-Di-Sol®

1-3 Direct compression

LUBRICANTS

In tablet manufacturing one faces the problem of flow of granules from the

hopper into the die cavity, sticking of material to the punches and die walls

and release free movement of the compressed tablets from the die cavity.

To overcome these difficulties

Lubricants- prevent adhesion of the tablet material to the surface of the

dies and punches, reduce interparticle friction, facilitate an easy ejection of

tablets from the die cavity and improves rate of flow of tablet granulation.

Eg. Talc, magnesium stearate, calcium stearate, stearic acid, hydrogenated

vegetable oil and PEG.

The quantity of lubricant significantly varies from 0.1 to 5%.

LIST OF LUBRICANTS

Lubricants Conc. Comments

Stearates(Magnesium Stearate, Calcium Stearate, Sodium stearate)

0.25 -1 Reduce tablet strength; prolong disintegration; widely used.

Talc 1 -2 Insoluble but not hydrophobic; moderately effective.

Glyceryl behapate (Compritol®888)

1 - 5 Both lubricant and binder;

GLIDANTS

Glidant-

Improves the flow characteristics of a powder mixture.

Always added in the dry state just prior to compression.

Eg. colloidal silicon dioxide (Cabosil®, Cabot®) and asbestos free talc etc.

They are used in concentration less than 1%.

Talc is also used and may serve the dual purpose of lubricant/glidant.

Glidants Range

Colloidal silica i.e. syloid, pyrogenic silica 0.25%

Hydrated sodium silioaluminate 0.75%

ANTIADHERENTS

Some material have strong adhesive properties towards the metal of

punches and dies or the tablet formulation containing excessive moisture

which has tendency to result in picking and sticking problem.

Antiadherent prevent sticking to punches and die walls.

Eg. Talc, magnesium stearate and corn starch etc.

Antiadherants Range Comments

Talc 1 – 5 Lubricant with excellent antiadherents properties

Cornstarch 3 –10 Lubricant with excellent antiadherents properties

Sodium lauryl sulfate <1 Antiadherents with water soluble lubricant

Colloidal silica 0.1 – 0.5 Does not give satisfactory results due to small surface area. Cab-O-Sil® and Syloid®

Stearates <1 Antiadherents with water insoluble lubricant

COLORS

Natural vegetable colors – limited availability & unstable

FD&C and D&C approved dyes are used.

Either added in dry granulation mix or in vehicle used for wet

granulation.

Lake dyes ( dyes absorbed on alumina or aluminium hydroxide) are used

in dry granulation.

Dyes tend to fade on standing and exposure to light leads to mottling.

Eg. FD&C approved lakes and dyes – lake sunset yellow, brilliant blue,

ferric oxide.

FLAVORS

Flavor's are usually limited to tablets intended to dissolve in the mouth.

In generally water soluble

Little acceptance in manufacturing due to poor stability.

Do not affect any physical characteristics of the tablet granulation.

Incorporated by spraying them on to the granules in the form of solutions

in some volatile organic solvent.

Also can be incorporated with lubricants

Proportion limited to 0.5 %

Excess quantity will interfere with free flow of granules

e.g. Raspberry, Pineapple, Peppermint, Blackcurrant, Orange, Mango,

Strawberry etc.

SWEETENERS

Use is primarily limited to tablets meant to dissolve in oral cavity

Mannitol – 72% as sweet as sucrose

Earlier saccharin was the only artificial sweetener used. It is 500 times

sweeter than sucrose but has a bitter aftertaste and also carcinogenic

properties.

Aspartame is the new sweetener- disadvantage is its instability in the

presence of moisture.

Three main manufacturing methods are used to prepare the running

powder:

1. Wet granulation

2. Direct compression

3. Dry granulation or slugging

Content uniformity

Uniform chemical composition.

Good mixing is essential, and segregation during the process

should be prevented.

WET GRANULATION

Wet granulation is a process of dry mixing, wet mixing, and particle size enlargement, and is a process of particle attachment (agglomeration).

It consists of six steps:

1. Dry mixing

2. Wet mixing

3. Milling of the wetted mass

4. Drying

5. Milling of the dried mass

6. Final blending

Wet Granulation

Mix powders

Add binder

Mill coarsely

Dry

Mill

Blend & lubricate

Compress or

fill into capsules

ADVANTAGES OF WET GRANULATION

Physical characteristics of the drug are usually not important.

The coalescing of particles locks in blend uniformity.

A wide variety of powder materials can be processed into a uniform

mix with improved flow.

Optimum fill density can be achieved by adjusting the process to create

the optimum final particle size distribution.

Compressibility and consolidation are improved via the choice of the

correct binder and the moisture content of the granules.

Dissolution is modified through hydrophilization to improve wetting

or, with the choice of more insoluble binders, to obtain a modified

release pattern.

Dust and segregation tendencies are reduced.

DISADVANTAGES OF WET GRANULATION

Large number of process steps; each step requires qualification,

cleaning, and cleaning validation.

Long process time, particularly for drying.

High labor and manufacturing costs.

Some material loss during processing.

Problems associated with heat and solvent sensitive drugs.

Capital requirements for extra building space and equipment.

Upon aging, dissolution from granules can be slowed after tableting.

Assay problems may occur for low dosage drugs due to incomplete

extraction if the active ingredient is complexed by the binder, or

adsorbed onto one of the other excipients.

Still no exact way to determine granulation endpoint (torque, power

consumption, etc.).

SINGLE-STEP FLUID BED WET GRANULATOR

Fluid-bed granulator

Binder solution spray

Warm air flow

DIRECT COMPRESSION

This is, a two-step process involving screening and/or milling and final

mixing.

An effective binder is needed and should have good compression and

consolidation properties as a dry additive, even at low concentrations

(< 30%) in the formulation.

Good adhesive properties in the dry form are a combination of a rough

and porous surface combined with a van der Waal's and/or a hydrophilic

bonding mechanism to attach the active ingredient(s) to the excipient.

This feature is needed to assure good mixing of drug and excipients and

to prevent segregation.

ADVANTAGES OF DIRECT COMPRESSION

Economy in labor, time, equipment, operational energy, and space.

Problems due to heat and moisture eliminated.

Greater physical stability provided; hardness and porosity changes

less with time when direct compression is broadly compared to wet

granulation systems.

Extraction of the drug from the dosage form is not inhibited during

the assay procedure (polymer binding).

Choice of ingredients allows the formulator to improve or retard

dissolution rate.

DISADVANTAGES OF DIRECT COMPRESSION

Critical nature of the raw materials; need for greater quality control in

purchasing to assure batch uniformity.

Difficulty obtaining dense hard tablets for high-dose drugs.

Non-homogenous distribution of low-dose drugs due to segregation after

blending (content uniformity).

Sensitivity of direct compression 'running' blends to over lubrication.

Limitations in color variations.

Need for assisted feed and precompression for some high-dose drugs.

Need for commensurate particle size or particle size distribution between

drug and excipients.

DRY GRANULATION

1. Mixing

2. Roller compaction

3. Milling

4. Screening

5. Final blending

Roller CompactorIt consists of five steps:

Compact

Size reduction ofcompacts intogranules

Powder to becompacted

Roller compactor"Chilsonator”

FINAL BLENDING

Final blending is usually done in a cone or V-type blender,

To obtain the final blend, it is necessary to consider the objectives of the

mixing steps:

1. To achieve drug content uniformity

2. To obtain uniformity of flow and bulk density

3. To effect distribution of lubricant, color, and surface active agents

4. To reduce or eliminate segregation

FINAL BLENDING

Mill

Blend & lubricate

Compress or

fill into capsules

EQUIPMENT'S USED FOR MIXING, BLENDING AND LUBRICATION

High share mixers

Tumbling mixers

Y-cone

Rotating cube

Double cone

Fluidized bed

Agitator mixers

Ribbon blender

TUMBLEBLENDERS

DRY MIXING EQUIPMENT'S

Sigma blade mixer Planetary mixer

Littleford Lodige mixers

GRANULATOR MIXER

Diosna mixer

RMG

EQUIPMENT'S USED IN SIEVING

COMPRESSION

Tableting procedure Filling Compression Ejection

Tablet compression machines Hopper for holding and feeding granulation to be compressed Dies that define the size and shape of the tablet Punches for compressing the granulation within the dies Cam tracks for guiding the movement of the punches Feeding mechanisms for moving granulation from the hopper into the

dies

SINGLE PUNCH MACHINE

The compression is applied by the upper punch

Stamping press

Upper andLower Collar

Collar locker

Common stages occurring during compression

Stage 1: Top punch is withdrawn from the die by the upper cam. Bottom punch is low in the die so powder falls in through the hole and fil ls the die

Stage 2: Bottom punch moves up to adjust the powderweight-it raises and expels some powder

Stage 3: Top punch is driven into the die by upper cam. Bottom punch is raised by lower cam. Both punch heads pass between heavy rollers to compress the powder

Stage 4: Top punch is withdraw by the upper cam. Lower punch is pushed up and expels the tablet. Tablet is removed from the die surface by surface plate

Stage 5: Return to stage 1

MULTI-STATION ROTARY PRESSES

The head of the tablet machine that 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.

DIES & PUNCHES

Dies

Lower punchUpper punch

COMPRESSION CYCLE

Granules from hopper empty in the feed frame (A) containing several interconnected compartments.

These compartments spread the granulation over a wide area to provide time for the dies (B) to fill.

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

HIGH SPEED ROTARY MACHINE

MULTI ROTARY MACHINE

49

If any question or further clarifications write to

thokesagar7@gmail.com

Cell: +91 8275584727

Thanks

25-02-2013

49