PROBLEMS IN TABLET MANUFACTURING

SUTRIYO

TABLETTING STAGES

THE INSIDE STORY

PENYELESAIAN MASALAH

IDENTIFIKASI PENYEBAB

IDENTIFIKASI MASALAH

TABLET DOSAGE FORM

1. An ideal tablet should be free from any visual defect or functional defect.

2. Majority of visual defects are due to :

a. inadequate fines (d50 : 125-180µm)

b. inadequate moisture in the granules ready for compression

c. faulty machine setting

3. Functional defects are due to faulty formulation

CAPPING

LAMINATION

CHIPPING

CRACKING

STICKING

FILMING

PICKING

BINDING

MOTTLING

PROBLEMS IN TABLET

MANUFACTURING

CAPPING

Pemisahan sebagian atau seluruhnya mahkota tablet

bagian atas atau bawah dari bagian

utama tablet.

LAMINATION

Pemisahan tablet menjadi dua atau

lebih bagian/lapisan

The Causes Of Capping and Lamination

FOR

MU

LATI

ON

Air-entrapment in the granular material

Large amount of fines in the granulation ( ± 20 %)

Too dry or very low moisture content (leading to loss of proper binding action)

Insufficient amount of binder or improper binder

Insufficient or improper lubricant

Too much of hydrophobic lubricant (e.g.: Magnesium-stearate)

The Causes Of Capping and Lamination

MA

CH

INE

Poorly finished dies

Deep concave punches or beveled edge faces of punches

Too much pressure during compression

Lower punch remains below the face of die during ejection

GRANULATION FLOW

CONCAVITY OF PUNCH

STANDARD

DEEP CONCAVE

EXTRA DEEP CONCAVE

MODIFIED BALL

SHALLOW

Round Tablet, Flat with beveled edge

PUNCHES

Oval Convex

Round Convex Oblong Convex

Round Convex Coating

• Remove some or all fines through 100 to 200 mesh screen

• Moisten the granules suitably. Add hygroscopic substance e.g.: sorbitol, methyl- cellulose or PEG-4000.

• Increasing the amount of binder or adding dry binder (such as pre-gelatinized starch, gum acacia, powdered sorbitol, PVP, hydrophilic silica or powdered sugar).

• Increase the amount of lubricant or change the type of lubricant.

• Polish dies properly. (Investigate other steels or other materials).

• Use flat punches • Make proper setting of lower punch during ejection.

REMEDIES

STICKING, PICKING AND FILMING

Sticking : Tablet surface to stick to

the punch face or adhesion of

granulation to the die wall

Cause :

improperly dried or

lubricated granulation.

The Causes Of Sticking FO

RM

ULA

TIO

N

Granules not dried properly

Too little or improper lubrication

Too much binder

Hygroscopic granular material

Oily or waxy materials

Too soft or weak granules

The Causes Of Sticking M

AC

HIN

E Concavity too deep

Too little pressure

Too little pressure

Picking sticking, grows with each revolution of

the press (a small amount of material from a tablet is sticking to and being removed off from the tablet-surface by a punch face. ) when punch tips have engraving or embossing letters, as well as the granular material is improperly dried.

Cause of picking (formulation)

• Excessive moisture in granules.

• Too little or improper lubrication.

• Low melting point substances, may soften from the heat of compression and lead to picking.

• Low melting point medicament in high concentration.

• Too warm granules when compressing.

• Too much amount of binder.

Cause of picking (machine)

• Rough punch faces.

• Embossing or engraving letters on punch faces (such as B, A, O, R, P, Q, G.)

• Bevels or dividing lines too deep.

• Pressure applied is not enough; too soft tablets.

Filming : a slow form of picking and is largely due to excess moisture in the granulation. (excess moisture in the granulation,

high humidity, high temperatur, loss of

polished punch faces)

CHIPPING

• Chipping : tablets having pieces

broken out. (damaged tooling,

improperly set take of station)

• Incorrect machine settings, specially miss-set ejection take-off

CHIPPING

Tablets having pieces broken

out

The Causes Of Chipping FO

RM

ULA

TIO

N

Sticking on punch faces

Too dry granules

Too much binding

REMEDIES

• Dry the granules properly or increase lubrication.

• Moisten the granules to plasticize. Add hygroscopic substances.

• Optimize binding, or use dry binders.

CRACKING

• Cracking : cracked in the center of

the top

• It is observed as a result of rapid expansion of tablets, especially when deep concave punches are used.

CRACKING

The Causes Of Cracking FO

RM

ULA

TIO

N

Large size of granules

Too dry granules

Granulation too cold

Tablets expand

remedies

• Reduce granule size. Add fines.

• Moisten the granules properly and add proper amount of binder.

• Improve granulation. Add dry binders.

• Compress at room temperature.

BINDING

Binding : difficult ejection

(insufficient lubrication)

The Causes Of binding FO

RM

ULA

TIO

N

Too moist granules and extrudes around lower punch

Insufficient or improper lubricant.

Too coarse granules

Too hard granules for the lubricant to be effective

Granular material very abrasive and cutting into dies

Granular material too warm, sticks to the die.

Remedies

• Dry the granules properly. • Increase the amount of lubricant or use a more

effective lubricant. • Reduce granular size, add more fines, and

increase the quantity of lubricant. • Modify granulation. Reduce granular size. • If coarse granules, reduce its size. • Use wear-resistant dies. • Reduce temperature. • Increase clearance if it is extruding.

The Causes Of binding M

AC

HIN

E

Poorly finished dies

Rough dies due to abrasion, corrosion

Undersized dies

Too little clearance

Too much pressure in the tablet press

Remedies

• Polish the dies properly.

• Investigate other steels or other materials or modify granulation.

• Rework to proper size.

• Increase clearance.

• Reduce pressure. OR modify granulation.

MOTTLING

Unequal distribution of colour on the surface of the tablet

Causes of Mottling

A drug that differs in color from its excipients

A dye migrates to the surface of granulation while drying

Improperly mixed dye, especially during ‘Direct Compression

Improper mixing of a colored binder solution

degradation products are highly colored

Remedies

Use appropriate colorants.

Change the solvent system, Change the binder, Reduce drying temperature and Use a smaller particle size.

Mix properly and reduce size if it is of a larger size to prevent segregation

Incorporate dry colour additive during powder blending step, then add fine powdered adhesives such as acacia and tragacanth and mix well and finally add granulating liquid.