Submitted by D. Srinivasa Rao M.

Pharmacy- Pharmaceutics

TABLET COMPRESSION

By Srinivas

CONTENTS
Introduction Different types of tablet compression machines Punches and dies Different shapes of tablets Compaction profile Effect of compaction on hardness Effect of compaction on friability Effect of compaction on lamination References

INTRODUCTION
What is a TABLET ?
A tablet is a pharmaceutical unit dosage form. It comprises a mixture of active substances and excipients, usually in powder form, pressed or compacted from a powder into a solid dose.

Powder compression
It is defined as the reduction in volume of a powder owing to the application of a forces. Because of the increased proximity of particle surfaces accomplished during compression, bonds are formed between particles which provide coherence to the powder i.e. compact is formed.

Effect of compression
When external mechanical forces applied to a powder mass there is reduction in bulk volume as follows
Repacking Particles deformation
Elastic deformation-e.g. acetyl salicylic acid, MCC Plastic deformation-at yield point of elastic.

Brittle fracture e.g. sucrose Microquashing-irrespective of larger particles, smaller particles may deform plastically.

Difference
Compaction It is defined as the formation of solid specimen of defined geometry by powder compression. The compression takes place in a die by the action of two punches, the lower and the upper by which compression force is applied. Consolidation It is in increase in mechanical strength of material from particle particle interactions.

Tablet production
Powders intended for compression into tablets must possess two essential properties
Powder fluidity
The material can be transported through the hopper into the die To produce tablets of a consistent weight Powder flow can be improved mechanically by the use of vibrators, incorporate the glidant

Powder compressibility
The property of forming a stable, intact compact mass when pressure is applied

Compression process
Filling
By gravitational flow of powder from hopper via the die table into die. The die is closed at its lower end by the lower punch.

Compression
The upper punch descends and enters the die and the powder is compressed until a tablet is formed. During the compression phase, the lower punch can be stationary or can move upwards in the die. After maximum applied force is reached, the upper punch leaves the powder i.e. the decompressed phase.

Ejection
During this phase, the lower punch rises until its tip reaches the level of the top of the die. The tablet is subsequently removed from the die and die table by a pushing device.

Tablet compression machine

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 (Tablets)

Upper and Lower Collar Collar locker

Tablet production methods

Dry methods
Direct compression Dry granulation

Wet methods
Wet granulation

Process Route for Tablet Manufacture

Direct compression
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 Advantages
Economy
Machine: fewer manufacturing steps and pieces of equipment Labor: reduce labor costs Less process vallidation Lower consumption of power

Cont..
Advantages
Elimination of granulation process
Heat (wet granulation) Moisture (wet granulation) High pressure (dry granulation) Processing without the need for moisture and heat which is inherent in most wet granulation procedures Avoidance of high compaction pressures involves in producing tablets by slugging or roll compaction

Elimination of variabilities in wet granulation processing

Binders (temp, viscous, age)
Viscosity of the granulating solution (depend on its temp), How long it has been prepared,

Cont..
Advantages
Rate of binder addition and kneading can affect the properties of the granules formed The granulating solution, the type and length of mixing and the method and rate of wet and dry screening can change the density and particle size of the granules, which can have a major effect on fill weight and compaction qualities Type and rate of drying
can lead not only to critical changes in equilibrium MC but also to unblending as soluble active ingredients migrate to the surfaces of the drying granules

More unit processes are incorporated in production, the chances of batch-to-batch variation are compounded

Cont..
Advantages
Prime particle dissociation
Each primary drug particle is liberated from the tablet mass and is available for dissolution Disintegrate rapidly to the primary particle state

Uniformity of particle size Greater stability of tablet on aging

Color Dissolution rate Fewer chemical stability problems would be encountered as compared to those made by the wet granulation process

Cont..
Concerns
Excipient available from only one supplier and often cost more than filler used in granulation Procedure conservation Machine investments Lack of material knowledge Physical limitation of drug
No compressibility No flow ability

Physical characteristics of materials (both drug and excipient)

Size and size distribution Moisture Shape and surface Flowability Density

Lot to lot variability Dusting problem Coloring

Direct compression fillers

Common materials that have been modified in the chemical manufacturing process to improve fluidity and compressibility

Soluble fillers
Lactose
Spray dried lactose

Sucrose
Nutab: 95.8% sucrose, 4% convert sugar Di-Pac: cocrystallization of 97% sucrose and 3% modified dextrin

Dextrose
Emdex: spray crystallized

Sorbitol Mannitol Maltodextrin

Maltrin

Insoluble fillers
Starch
Starch 1500 Spray dried starch

Celulose
Microcrystalline cellulose (Avicel)

Inorganic calcium salts

Dicalcium phosphate (Emcompress or DiTab) Tricalcium phosphate (TriTab)

Heckel equation
Heckel plot is density Vs applied pressure. Follows first order kinetics. As the porosity increases the compression force will increase. The Heckel equation is described as follows. It is based on the assumption that powder compression follows first-order kinetics, with the interparticulate pores as the reactant and the densification of the powder bed as the product. Where
D= relative density of a powder P=compact at pressure P. Constant k = measure of the plasticity of a compressed material. Constant A =die filling and particle rearrangement before deformation and bonding of the discrete particles.

Thus, a Heckel plot allows for the interpretation of the mechanism of bonding.

DIFFERENT TYPES OF TABLETTING MACHINES

Single punch press Rotatory tablet press Computerised tablet press

Single punch press

It posses a die and a pair of punches. The amount of powder fill in to the die is controlled by the position of the lower punch. After ejection of tablet it is displaced by the shoe of the hopper.as it moves back to the die for next tablet. OUTPUT:200 TABS per minute Used in production of small batches.

ROTATORY PRESS
Developed to increase the out put. It operates with a number of dies & sets of punches which can vary considerably. Both the dies & punches rotate during the operation. The vertical movement of the punches is controlled by tracks that pass over cams and rolls used to control the volume of powder fed in to the die and the pressure applied during compression.

Computerised hydraulic press

In these the movement of the punches can be controlled and varied considerably. Thus the tablet can be prepared under controlled conditions with respect to loading pattern and loading rate. Applications: to predict the sensitivity of the drug to such variations, to mimic the loading pattern of production presses to predict scale up problems. Because of the later application this is also called as compaction simulator

International Standards
BB tool B tool D tool

Type of Tools D tools B tools BB tools

Punch Body (mm) 25.35 19 19

Diameter (mm) 38.10 30.16 24

PUNCHES AND DIES

General Terminology of Tooling Different shapes of dies and punches International Standards Materials For Construction Coating of Dies and Punches Quality Control Maintenance of Dies and Punches New Developments

GENERAL TERMINOLOGY OF TOOLING Upper punch Lower punch Die Keying

KEYS ON PUNCHES TERMINOLOGY

Different shapes of tablets

Different Shapes of punches and Dies

Round shape punch die set Oval shape punch die set Capsule shape punch die set Geometric shape punch die set Irregular shape punch die set Core rod tooling punch die set

Round shape Punch Die Set

Used by pharmaceutical and veterinary industry. Can manufacture following type of tablets:

Shallow Concave Ball Shape Deep Concave Flat Faced Concave with Edges Flat with Bevel Edges Normal Concave.

Oval Shape Punch Die Set

Applicable to pharmaceutical and ayurvedic industries. Can manufacture following types of tablets:
Flat Faced Flat with bevel edges Concave/Deep/Deep Concave with bevel edges.

Capsule shape punch die set

Applicable to pharmaceutical and ayurvedic industries. Can manufacture following types of tablets:
Concave with Edges Deep Concave Flat Faced Normal concave Flat with Bevel Edges.

Geometric Shape Punch Die Set

Applicable to pharmaceutical, confectionery, chemical, industrial powder metallurgy industries. Can manufacture following types of tablet:

Triangular Benzene Rhombus Rectangular Square.

Irregular Shape Punch Die Set

Are applicable to confectionery industries. Available with different size, concavity, and flat in plain or engraved break line.

Core Rod Tooling Punch Die Set

Applicable in confectionery and ceramic industries. Can manufacture following types of tablets:
Tablet with hole in center & concave rib Tablet with hole in center & flat rib.

Materials For Construction

Dies- HCHC (High carbon High chromium steel ) Punches- OHNS (Oil Hardened Nitride steel) Different types of steel standards:
For dies:- AISI-01 For punches:- AISI-S7, AISI-S1, D2(HCHC-D2), SUS 440C.

Coating of Dies and Punches

Why coating is required?
Sticky material Corrosive material Abrasive material

Different Types of Coatings

Titanium Nitride Coating Electroless Nickel Plating (ENI) Chromium Nitride Coating (CrN) Chromium Carbon Nitride (CrCN) Coating Diamond Coating of Diamond like Carbon (DLC) Cr-CrN-Cr Multilayer Coating (Nano Coating)

Quality Control
Visual Inspection Dimensional Inspection Punches:
Overall length Working length Cup depth Tips round and capsule Tip and Barrel concentricity Head, Head flat and Neck Barrel
Dies: Height and outside

diameter Die bore diameter using expandable, small bore gauges Die bore major and minor axis using Vernier caliper and expandable, small bore gauges Die Bore concentricity Squareness

Maintenance of Dies and Punches

Why is it required?
To improve the lifespan of toolings.

How are they Maintained? Fitting instructions usually as per the manual given. Warm soap water and a soft brush are suitable for thorough cleaning Not to be touched by bare fingers Thoroughly coated with an acid-free oil in order to prevent corrosion.

Contd..
Toolings should be regularly checked. Polishing
By hand Drag Finishing machine

Storage cabinets for tooling

Clashing Dusting Humidity

New Developments
Multi-tip punches Development in manufacturing different shapes of tablets
Polo Teddy Beer, Lion, etc.

Tablets which can be broken into 4 equal halves

Multi-tip Punches

COMPACTION PROFILE

EFFECT OF COMPACTION ON HARDNESS OF TABLET

It has the same causes as weight variations. Hardness depends on weight of the material and the space between the upper and lower punch at the moment of compression. If the distance between the punches varies hardness is like in consistent.

Effect of Compaction on Friability of Tablet

When the punches are in poor condition or worn at their surface edges this problem arises. Less compression pressure also leads to increased friability.

Effect of compaction on lamination

Rapid relaxation of the peripheral region of a tablet,on ejection from a die. This can be prevented by using tappered dies Rapid decompression also causes lamination. This can be prevented by doing pre compression step. And decreasing the final compression pressure.

Kawakita equation
The Kawakita equation is described as follows. This equation describes the relationship between the degree of volume reduction of the powder column and the applied pressure. The basis for the Kawakita equation for powder compression is that particles subjected to a compressive load in a confined space are viewed as a system in equilibrium at all stages of compression, so that the product of the pressure term and the volume term is a constant.

where
C = degree of volume reduction of a powder compact at pressure P. constants (a and b) =evaluated from a plot of P/C versus P. a= total volume reduction for the powder bed [carrs index] b= constant that is inversely related to the yield strength of the particles.

The data from this study were modeled via the Kawakita equation in an attempt to evaluate the relationship between the volume reduction and applied pressure for each studied DC binder.

References:
www.google.com Parle-Elizabeth Tools Pvt Ltd. Encyclopedia of Pharmaceutical Technology, second and third volumes http//www.thomaseng.compresstooling. pdf www.vmindustries.com Pharmaceutics by Aulton Pharmaceutical technology by Libermann and laitman.