BYARJUN NARALA

M.PHARMACY, I SEM

DEPARTMENT OF PHARMACEUTICSUNIVERSITY COLLEGE OF PHARMACEUTICAL SCIENCES

KAKATIYA UNIVERSITYWARANGAL.

CONTENTS

Introduction

Defects in Tablets

Defects in sugar coated tablets

Defects in film coated tablets

Conclusion

References

INTRODUCTION In the normal process of developing formulations,

and in the routine manufacture of tablets, variousdefects are observed. Sometimes, the source of theproblem or the defect is the formulation, thecompression equipment, or a combination of the two.

Some defects are noticed immediately duringmanufacturing but others may be noticed duringstorage as in the case of capping.

DEFECTS IN TABLETS

CAPPING AND LAMINATION

PICKING AND STICKING

MOTTLING

DOUBLE IMPRESSIONS

BLACK SPECKS

CHIPPING AND SPLITTING

CAPPING AND LAMINATION

Capping is defined as the partial or complete separation of thetop or bottom crowns of a tablet from the main body of thetablet.

Lamination is the separation of a tablet into two or moredistinct layers.

These processing problems are readily apparent immediatelyafter compression or may occur hours or even days later.

Subjecting tablets to the friability test is the quickest way ofrevealing such problems.

CAPPING AND LAMINATION

CAUSES AND CORRECTIVE ACTIONS

Air entrapment

Reduce press speed

Precompress granulation

Reduce quantity of fine particles in the granulation

Taper dies

Ensure that punch-to-die clearance is correct

Excessive pressure

Reduce tablet weight and/or increase its thickness withinallowable tolerances

Adjust pressure

CAUSES AND CORRECTIVE ACTIONSToo rapid expansion of tablet upon ejection

Taper dies

Poor granulation

Increase quantity of binder; use strong binder

Excessively dry granulation

Increase lubricant

Excessive lubrication of granulation

Decrease lubricant; blend all ingredients before addinglubricant

CAUSES AND CORRECTIVE ACTIONSPunch cavity too deep

Use punches with less concave depth

Punch tips worn

Refurbish or replace punches

Lower punch set too low at tablet take-off

Set lower punch tip flush with top of die

Tablet take-off bar set too high

Adjust take-off bar

PICKING AND STICKING Picking refers to a tablet material

being removed from the tabletssurface by a punch.

It is of particular concern whenpunch tips have engraving orembossing.

Tablet materials adhering topunches can accumulate to thepoint of obliterating the tipdesign.

Sticking refers to a tablet materialadhering to the die wall.

It results in the buildup ofmaterial on punch faces.

CAUSES AND CORRECTIVE ACTIONSExcessive moisture

Check moisture content of granulation; drying

Check room humidity

Presence of low-melting-point substances

Dilution with higher-melting-point materials

Insufficient compaction force

Reduce tablet weight and/or increase its thickness withinallowable tolerances

Inadequate lubrication of granulation

Check and/or adjust level of lubricant used

CAUSES AND CORRECTIVE ACTIONSPunch face condition: pits on punch faces and/or improper draft

on embossing

Try repolishing punch faces

Try chrome-plating of punch faces

Poor embossing design

Redesign embossing per TSM guidelines, or consult toolingsupplier

MOTTLING

Unequal distribution of color on a tablet, with light or darkareas standing out in an otherwise uniform surface.

Causes and corrective actions:

Drug whose color differs from the tablet excipients or a drugwhose degradation products are colored.

Use of colorants

Migration of dyes to the surface of granulation during drying

Change the solvent system

Reduce the drying temperature

Grind to a small particle size

CAUSES AND CORRECTIVE ACTIONS

High moisture content of granulation Dry granulationOversized granulation particles Reduce particle sizeContamination of granulation, usually by grease or oil Check oil seals on upper punch guides Fit oil/dust caps to upper punches Reduce lubrication of upper punches to an acceptable levelContamination of granulation from chutes or feed hoppers Clean and reset components correctly

DOUBLE IMPRESSION

This problem is encountered with punches that have amonogram or other engraving on them.

Causes and corrective actions:

Rotation of punches

Adjust antiturning devices

Use keyed punches

DIRT IN PRODUCT (BLACK SPECKS) :

Dust,dirt,or press lubrication in the granulation

Clean press more frequently

Excessive or wrong press lubrication

Use proper punch dust caps

Rubbing of feeder components

CHIPPING OR SPLITTING

Poor surface finish on punch tips; worn punches and dies

Poor tooling design (e.g., sharp embossing or bisect lines)

Polish punch tips; replace punches and dies

DEFECTS IN SUGAR COATED TABLETS

CHIPPING OF COATINGS:

Sugar coatings are inherently brittle and thus prone to chipping ifmishandled.

Excessive use of insoluble fillers and pigments tends to increasethe brittleness of sugar coatings.

Avoid them where ever it is possible

Addition of small quantities of polymers(such ascellulosics,polyvinylpyrrolidine,acacia,or gelatin) to improvestructural integrity.

CRACKING OF COATINGS:

Tablet cores that expand, either during or after coating, arelikely to cause the coating to crack. Such expansion may result from

1.Moisture absorption by the tablet core.2.By stress relaxation of the core after compaction.

Moisture sorption can be minimized by appropriate use ofseal coat.

Expansion due to post compaction stress relaxation can beresolved by extending the time between the compaction eventand commencement of sugar coating.

TWINNING (OR BUILD OF MULTIPLES)

By their very nature, sugar-coatingformulations are very sticky,particularly as they begin to dry, andallow adjacent tablets to stick together.

Build up of multiples really becomes aproblem when the tablets being coatedhave flat surface which can easily comeinto contact with one another.

Troublesome with high-dose, capsule-shaped tablets that have high edgewalls.

Appropriate choice in tablet punchdesign can be effectively used tominimize the problem.

UNEVEN COLOR

Uneven distribution of color, particularly with the darkercolors, is often visually apparent, and thus a major cause ofbatch rejection.Poor distribution of coating liquids during application Uniform mixing of tablets in the coating process Addition of sufficient coating liquidsColor migration of water-soluble dyes while the coating is

drying Change the solvent system Reduce the drying temperature Grind to a small particle size

Unevenness of the surface of the subcoat

Achieve desired surface smoothness

Washing back of pigment-colored color coatings

Replace aluminium lakes

Use combinations of dyes and pigments

Excessive drying between color applications

Reduce rate of drying

Reduce drying temperature

BLOOMING AND SWEATING

Residual moisture in finished sugar-coated tablets can oftenbe a problem. over a period of time, this moisture can diffuseout and affect the quality of the product.Moderate levels of moisture egress cause the polish of the

product to take on a fogged appearance, a phenomenon oftentermed blooming.At higher levels of moisture egress, the moisture may appear

like beads of perspiration on the tablet surface, a phenomenonoften termed sweating.Sweating can be much more serious, since tablets stored in

closed containers will ultimately stick together. Obtain appropriate levels of moisture.

MARBLING

To achieve a high-quality, sugar coated product it is importantto ensure that color is uniformly distributed in the color layer,and at the end of the application of the color coating that asmooth coating surface is obtained.

Failure to achieve the requisite smoothness often results in amarbled appearance on polishing.

This problem occurs as the result of the collection of wax in thesmall surface depressions of a rough coating and is particularlyevident with darker colors.

Check for smooth surface at the end of color coating.

DEFECTS IN FILM COATED TABLETSPICKING:

It results when the coating on two adjacent tablets is notsufficiently dry before contact between them occurs.

As the partially dried coating is extremely tacky, once the twotablets make contact they adhere to one another.

Once the coating has dried they break apart later under theinfluence of attrition.

In extreme cases the tablets may become permanently gluedtogether so that twinning occurs.

Over wetting typically occurs when the spray rate is excessivefor the drying conditions in the process.

Adjust the spray rate

Adjust the temperature of drying

Check for the proper functioning of the spray guns

Certain types of coating formulations(e.g., those based onhydroxypropylcellulose, and several of the acrylic aqueouslatex coating systems) are inherently tackier during application.

Replace with other polymer systems.

ORANGE PEEL(ROUGHNESS) Inadequate spreading of the coating

solution before drying causes a bumpy ororange-peel effect on the coating.

This indicates that spreading is impededby too rapid drying or by high solutionviscosity.

This is caused by process conditionswhich include low spray rates coupledwith excessive drying conditions and useof excessive atomizing air pressures.

Adjust the spray rate and dryingconditions

Coating liquids with high viscosities Thinning the coating solution with

additional solventsIn brief optimize the coating process.

EDGE WEAR(CHIPPING)

Tablet edges are often exposedto attritional effects, so fractureat this point results in parts ofthe surface being exposed,referred as chipping.Seen with brittle film coatings

that offer insufficient protectionto tablet edges. Addition of small quantities of

polymers(such ascellulosics,polyvinylpyrrolidine,acacia,or gelatin) to improvestructural integrity.

FILM CRACKING

Cracking of film coating occurs when the internal stressexceeds the tensile strength of the coating.The problem is exacerbated when significant differences exist

between the thermal expansion coefficients for the core andcoating.Totally unacceptable for products where the applied coating is

a major factor in modifying drug-release characteristics. Minimize the internal stresses by adjusting the plasticizer type,

pigment type and their concentration. Increase the tensile strength of the film by using high

molecular-weight polymers or polymer blends.

FILM PEELING

During application of aqueouscoating formulations, cohesivefailure(cracking) of the coatingoccurs.This coating may peel back from

the surface of the substrate andresult in peeling.Cohesive and adhesive failure(

both linked to internal stress) Increase the tensile strength of

the film Decrease the internal stress

BRIDGING OF LOGOS(INTAGLIATIONS) This phenomenon occurs when a

component of the internal stressbecomes sufficiently high so as tocause partial or complete detachmentof the coating ( from the substrate) inthe region of logo.

As a result of such detachment, thefilm is able to shorten and thuspartially relieve the stress within thefilm.

This defect can be so severe that themonogram or bisect is completelyobscured.

Improve film adhesion by adjustingplasticizer content

Appropriate design of tablet puncheswith respect to logo

IN-FILLING OF LOGOS

In-filling of logos typically occurs during the spray applicationof aerated aqueous film-coating solutions.

When a foamy coating solution impinges on a regular part ofthe tablet surface it will, under the shear forces generated, forma film with normal characteristics.

Those droplets of coating liquid that reside in the logo, beingprotected from shear forces at the surface, gradually dry toform a solid foam that eventually obliterates the bisect.

Judicious monitoring of the fluid application rate and thoroughmixing of the tablets in the pan prevent filling.

BLISTERING

When coated tablets require further drying in ovens, too rapidevaporation of the solvent from the core and the effect of hightemperature on the strength, elasticity, and adhesion of the filmmay result in blistering.

Use milder drying conditions.

CONCLUSION Tablets are widely used dosage forms but defects in

aesthetic appearance may lead to the rejection of theiradministration by the patient.

From the manufacturer point of view these defects maylead to reworking or rejection of the batch.

Although many of these defects may be purely cosmeticsome of them are totally unacceptable.

So a proper attention by the manufactuer on the source ofdefects and their orderly corrections is required.

REFERENCES

Herbert A. Lieberman, Leon Lachman, Joseph B. Schwartz,Pharmaceutical dosage forms : Tablets, Second Edition,vol 3.

Herbert A. Lieberman Leon Lachman, Theory and Practice ofIndustrial Pharmacy, 2009.

James Swarbrick, James C. Boylan, Encyclopedia ofPharmaceutical technology, Volume 15, 1996.

James Swarbrick, Encyclopedia of Pharmaceutical technology,Third Edition, Volume 6, 2007.

Website:

www.pharmainfonet.com

THANK YOU