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EVALUASI TABLET

LIDYA AMELIANA
5/13/2015

EVALUASI???:
Monitoring kualitas produk
Untuk evaluasi kuantitatif & penilaian
sifat tablet.
Untuk mengecek kerusakan kimiawi
Mengecek adanya interaksi antar
komponen tablet

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a. Organoleptic properties
Color identitas dan acceptability must be
uniform within a single tablet, from tablet to
tablet and from lot to lot.spektrofotometer,
kolorimeter
Odor acceptability could indicate a
stability problem, such as the characteristic odor
of acetic acid in degrading aspirin tablets.
Taste acceptability, misal pd chewable tablet
3

b. Size & Shape micrometer


Kecuali dinyatakan lain diameter tablet
tidak boleh lebih dari 3x dan tidak
kurang dari 4/3 tebal tablet. Uji
diameter dan ketebalan tablet ini
dilakukan terhadap 20 tablet.

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c. KESERAGAMAN BOBOT
Di FI IIISebanyak 20 tablet ditimbang, lalu dihitung
bobot rata-ratanya .

Syarat :
2 tablet menyimpang kolom A & 1
tablet kolom B

Keragaman bobot dan keseragaman


kandungan
jika zat aktif merupakan bagian terbesar dari tablet
dan jika uji keragaman bobot dianggap cukup
mewakili keseragaman kandungan.
Keragaman bobot bukan merupakan indikasi yang
cukup dari keseragaman kandungan jika zat aktif
merupakan bagian kecil dari tablet atau jika tablet
bersalut gula. Oleh karena itu, umumnya
farmakope mensyaratkan bahwa tablet bersalut
dan tablet yang mengandung zat aktif 50 mg atau
kurang, dan bobot zat aktif lebih kecil dari 50%
bobot sediaan, harus memenuhi syarat uji
keseragaman kandungan seperti yang tertera pada
Keseragaman Sediaan <911> yang pengujiannya
dilakukan pada tiap tablet. (FI 5)
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d. Hardness (Fracture-resistance test):


1. Menahan goncangan mekanik pada saat pembuatan,
pengemasan dan distribusi
2. Mencegah kekeliruan penggunaan (abuse) saat d
tangan konsumen
3. Memiliki kaitan dgn disintegrasi dan disolusi

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Hardness Variation, dipengaruhi oleh:


- compression force,
- concentration and type of binding agent
Jika terlalu kerastdk terdisintegrasi pd waktu yg
dikehendaki
Jika terlalu lunakmudah rusak saat pembuatan,
pengemasan, dan peracikan

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Caranya : Ambil 20 tablet ukur


kekerasan menggunakan alat
hardness tester hitung rata-rata
dan Standard Deviation (SD)
Persyaratan : Ukuran yang didapat
per tablet minimal 4 kg/cm2,
maksimal 8 kg/cm2

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e. Friability
Why??
1. menurunkan acceptability
2. menyebabkan terlihat kotor pada saat pembuatan coating
dan kemasan
3. Dapat menambah bobot tablet atau content uniformity
% friability = (W0 Wf / W0) x 100 %.
W0 = initial weight,
Wf = final weight.
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Friability

Duapuluh tablet dibersihkan dari debu,


ditimbang, kemudian dimasukkan ke dalam alat
uji keregasan.
Alat diputar pada kecepatan 25 rpm selama 4
menit dan alat tersebut akan menjatuhkan tablet
sejauh 6 inci setiap putaran. Seluruh tablet
dikeluarkan, dibersihkan dari debu dan ditimbang
kembali. Dihitung kehilangan bobot dalam
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persentase.Syarat : lebih kecil dari 1 (%).

f. Disintegration Test (U.S.P.):


To test for disintegration time, one tablet is
placed in each tube and the basket rack is
positioned in a 1-L beaker of water, simulated
gastric fluid or simulated intestinal fluid at 37
0.5 C such that the tablet remain 2.5 cm
below the surface of liquid on their upward
movement and not closer than 2.5 cm from
the bottom of the beaker in their downward
movement.
Move the basket containing the tablets up and
down through a distance of 5-6 cm at a

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Floating of the tablets can be prevented by


placing perforated plastic discs on each tablet.
According to the test the tablet must
disintegrate and all particles must pass through
the 10 mesh screen in the time specified.
If any residue remains, it must have a soft
mass.
Syarat : - tablet 15 menit
- tablet salut 60 menit
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g. Dissolution
Dissolution is
substance that
unit time
conditions of
temperature
composition.

the amount of drug


goes into solution per
under standardized
liquid/solid interface,
and
solvent

16

Dissolution a tool for predicting


bioavailability

determine
bioequivalence.
Dissolution behavior of drugs has a
significant
effect
on
their
pharmacological activity. In fact, a direct
relationship between in vitro dissolution
rate of many drugs and their
bioavailability has been demonstrated
and is generally referred to as in vitro-in
vivo correlation, IVIVC

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h. CONTENT UNIFORMITY:
Faktor yg mempengaruhi:
- non-uniform distribution of drug
substance throughout the powder
mixture or granulation.
- segregasi.
- Variasi berat tablet

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PROCESSING PROBLEMS IN
TABLETS:
Tableting process (Capping, Lamination
& cracking).
Excipients (Picking, Sticking, Mottling &
Binding).
Machine related (Double impression).

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CAPPING:
Capping : pemisahan sebagian atau
keseluruhan bagian atas/bawah tablet
dari badan tablet

CAPPING RELATED TO FORMULATION


(GRANULATION)
Sr.No.

CAUSES

REMEDIES

1.

Large amount of fines in


the granulation

Remove some or all fines through 100 to 200


mesh screen

2.

Too dry or very low


moisture content (leading
to loss of proper binding
action).

Moisten the granules suitably. Add hygroscopic


substance e.g.: sorbitol, methyl- cellulose or PEG4000.

3.

Not thoroughly dried


granules.

Dry the granules properly.

4.

Insufficient amount of
binder or improper binder.

Increasing the mount of binder OR


Adding dry binder such as pre-gelatinized starch,
gum acacia, powdered sorbitol, PVP, hydrophilic
silica or powdered sugar.

5.

Insufficient or improper
lubricant.

Increase the amount of lubricant or change the


type of lubricant.

6.

Granular mass too cold to


compress firm.

Compress at room temperature.

CAPPING RELATED TO MACHINE (DIES, PUNCHES


AND TABLET PRESS)
Sr.No

CAUSES

REMEDIES

1.

Poorly finished dies

Polish dies properly. Investigate other


steels or other materials.

2.

Deep concave punches or


beveled-edge faces of punches.

Use flat punches.

3.

Lower punch remains below the Make proper setting of lower punch
face of die during ejection.
during ejection.

4.

Incorrect adjustment of sweepoff blade.

Adjust sweep-off blade correctly to


facilitate proper ejection.

5.

High turret speed.

Reduce speed of turret (Increase


dwell time).

Lamination / Laminating
Laminasi : pemisahan tablet menjadi dua
bagian atau lebih
Reason: Airentrapment during
compression and subsequent release
on ejection.

LAMINATION RELATED TO FORMULATION (GRANULATION)


Sr. No

CAUSES

REMEDIES

1.

Oily or waxy materials in


granules

Modify mixing process. Add adsorbent


or absorbent.

2.

Too much of hydrophobic


lubricant e.g.:
Magnesium-stearate.

Use a less amount of lubricant or


change the type of lubricant.

Lamination related to MACHINE (Dies, Punches and Tablet Press)


Sr. No.

CAUSES

REMEDIES

1.

Rapid relaxation of the


Use tapered dies, i.e. upper part of
peripheral regions of a
the die bore has an outward taper
tablet, on ejection from a die. of 3 to 5.

2.

Use pre-compression step. Reduce


turret speed and reduce the final
compression pressure.

Rapid decompression

Chipping

Chipping : keadaan dimana bagian


bawah tablet terpotong
Reason: Incorrect machine settings,
specially mis-set ejection take-off.

CHIPPING RELATED TO FORMULATION (GRANULATION)


Sr. No

CAUSES

REMEDIES

1.

Sticking on punch faces

Dry the granules properly or


increase lubrication.

2.

Too dry granules.

Moisten the granules to plasticize.


Add hygroscopic substances.

3.

Too much binding causes chipping at


bottom.

Optimize binding, or use dry


binders.

CHIPPING RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS)


Sr. No

CAUSES

REMEDIES

1.

Groove of die worn at compression


point.

Polish to open end, reverse or


replace the die.

2.

Barreled die (center of the die wider


than ends)

Polish the die to make it cylindrical

3.

Edge of punch face turned


inside/inward.

Polish the punch edges

4.

Concavity too deep to compress


properly.

Reduce concavity of punch faces.


Use flat punches.

Cracking
Cracking : keadaan dimana tablet pecah, lebih
sering di bagian atas-tengah
Reason: It is observed as a result of rapid
expansion of tablets, especially when deep
concave punches are used.

CRACKING RELATED TO FORMULATION (GRANULATION)


Sr. No.

CAUSES

1.

Large size of granules.

Reduce granule size. Add fines.

Too dry granules.

Moisten the granules properly and add


proper amount of binder.

3.

Tablets expand.

Improve granulation. Add dry binders.

4.

Granulation too cold.

Compress at room temperature.

2.

REMEDIES

CRACKING RELATED TO MACHINE (DIES, PUNCHES AND TABLETPRESS)


Sr. No.

CAUSES

REMEDIES

1.

Tablet expands on ejection due


to air entrapment.

Use tapered die.

2.

Deep concavities cause cracking


while
removing tablets

Use special take-off.

Sticking
Sticking : keadaan dimana granul
menempel pada dinding die (ada adhesi)
Reason: Improperly dried or improperly
lubricated granules.

STICKING RELATED TO FORMULATION


(GRANULATION)
Sr. No.

CAUSES

REMEDIES

1.

Granules not dried


properly.

Dry the granules properly. Make moisture


analysis to determine limits.

2.

Too little or improper


Increase or change lubricant.
lubrication.

3.

Too much binder

Reduce the amount of binder or use a different


type of binder.

4.

Hygroscopic
granular material.

Modify granulation and compress under


controlled humidity.

5.

Oily or way materials Modify mixing process. Add an absorbent.

6.

Too soft or weak


granules.

Optimize the amount of binder and granulation


technique.

STICKING RELATED TO MACHINE (DIES,


PUNCHES AND TABLET PRESS)

Sr. No.

CAUSES

REMEDIES

1.

Concavity too deep for granulation.

Reduce concavity to optimum.

2.

Too little pressure.

Increase pressure.

3.

Compressing too fast.

Reduce speed.

Picking
Picking : perpidahan bahan dari permukaan
tablet dan menempel pada permukaanpunch
Reason: Picking is of particular concern when
punch tips have engraving or embossing
letters, as well as the granular material is
improperly dried.

PICKING RELATED TO FORMULATION


(GRANULATION)
Sr.No

CAUSES

REMEDIES

1.

Excessive moisture in granules.

Dry properly the granules, determine


optimum limit.

2.

Too little or improper


lubrication.

Increase lubrication; use colloidal silica


as a polishing agent, so that material
does not cling to punch faces.

3.

Low melting point substances,


may soften from the heat of
compression and lead to
picking.

Add high melting-point materials. Use


high meting point lubricants.

4.

Low melting point medicament


in high concentration.

Refrigerate granules and the entire


tablet press.

5.

Too warm granules when


compressing.

Compress at room temperature. Cool


sufficiently before compression.

6.

Too much amount of binder.

Reduce the amount of binder, change


the type or use dry binders.

PICKING RELATED TO MACHINE (DIES,


PUNCHES AND TABLET PRESS)
Sr.No

CAUSES

REMEDIES

1.

Rough or scratched punch faces.

Polish faces to high luster.

2.

Embossing or engraving letters


on punch faces such as B, A, O,
R, P, Q, G.

Design lettering as large as possible.


Plate the punch faces with chromium
to produce a smooth and non-adherent
face.

3.

Bevels or dividing lines too deep.

Reduce depths and sharpness.

4.

Pressure applied is not enough;


too soft tablets.

Increase pressure to optimum.

Mottling
Mottling : keadaan dimana distribusi zat
warna pada permukaan tablet tidak
merata
Reason: One cause of mottling may be a
coloured drug, whose colour differs from
the colour of excipients used for
granulation of a tablet.

Causes And Remedies Of Mottling:


Sr.No.

CAUSES

REMEDIES

1.

A coloured drug used


along with colourless or
Use appropriate colourants.
white-coloured
excipients.

2.

A dye migrates to the


surface of granulation
while drying.

Change the solvent system,


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

3.

Improperly mixed dye,


especially during
Direct Compression.

Mix properly and reduce size if it is of a larger


size to prevent segregation.

4.

Improper mixing of a
coloured binder
solution.

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.