SUPPOSITORIA

Lidya Ameliana
Menurut FI V
• Sediaan padat dalam berbagai bobot dan bentuk, yang
diberikan melalui rektal, vagina atau urethra
• Umumnya meleleh, melunak, atau melarut pada suhu
tubuh
• Sbg pelindung jaringan setempat, sebagai pembawa zat
terapetik yang bersifat lokal dan sistemik
Kelebihan
• untuk obat yang tidak bisa diberikan secara oral pada
pasien tidak sadar, mual, gangguan pencernaan, saat
pembedahan, gangguan jiwa.
• Menghindari FPM
• Untuk obat yang tidak dapat diberikan melalui oral karena
efek samping pada saluran cerna, rusak oleh cairan GIT
dan enzym GIT, rasa yang tidak enak
• Onset >> oral karena absorbsi obat melalui rektal mukosa
secara langsung sampai ke sirkulasi darah
• Suppo vaginal dan uretral karena perfusi darah di vagina
dan uretral rendah efek yang ditimbulkan lokal
mengurangi sistemik sirculation (reduksi toksisitas)
Kekurangan
• Daerah absorbsinya lebih kecil
• Bis terjadi iritasi mukosal
• Absorbsi hanya melalui difusi pasif
• Jika penggunaan terlalu dalam mengalami FPM
• kurang praktis
• Tdk dapat digunakan untuk zat-zat yang rusak oleh pH
rektum
Efek lokal : wasir, konstipasi, infeksi dubur.
• Anastetik lokal (benzokain, tetrakain)
• Adstringent (ZnO, Bi-subgalat, Bi-subnitrat)
• Vasokonstriktor (efedrin HCl)
• Analgesik (turunan salisilat)
• Emolien (balsam peru untuk wasir)
• Konstipasi (glisin bisakodil)
• Antibiotik (infeksi)

Efek sistemik
- Asma (efedrin, teofilin, aminofilin)
- Analgetik dan antiinflamasi (turunan salisilat, parasetamol)
- Antiartritis (fenilbutazon, indometasin)
- Hipnotik & sedatif (turunan barbiturat)
- Trankuilizer dan anti emetik (fenotiazin, klorpromasin)
- Kemoterapi (antibiotik, sulfonamid)
Faktor yang Mempengaruhi Absorpsi
Obat dari Rektum
A. Faktor Fisiologi
• Isi Kolon  obat diabsorpsi >> ketika rektum dalam keadaan
kosong.
• Rute sirkulasi  jika obat diabsorpsi dari pembuluh darah
hemorrhoidal akan langsung menuju vena cava inferior,
sehingga absorpsi akan cepat dan efektif.
• pH cairan rektum asam dan basa lemah lebih mudah
diabsorbsi
 8

B. Faktor Fisika Kimia Obat

• Konsentrasi bahan aktif

• Derajat ionisasi bahan aktifobat takterion lebih mudah diabsorpsi
• Kelarutan dalam lipid-water  obat lipofil jika diberikan dengan basis
lemak tidak dapat dikeluarkan dengan mudah, sehingga absorpsi
obat terganggu.
• Ukuran partikel  semakin kecil partikel semakin besar kelarutannya.
• Sifat basis  jika basis berinteraksi dengan obat atau mengiritasi
membran mukosa akan menurunkan absorpsinya.
 FORMULASI SUPPOSITORIA
• Obat
• Basis
• Bahan tambahan:
- Antioksidan
- Emulsifying agent
- Hardening agent
- Preservatif
- Thickening agent
- Plasticizer
Suppository bases
Melt at, or just below body temperature or dissolve in body
fluids.
Solidify quickly after melting.
Be easily moulded and removed from the mould.
Be chemically stable even when molten.
Release the active ingredient readily.
Be easy to handle.
non-toxic and non-irritant.
Jika basis tersebut berlemak, basis suppositoria
memiliki persyaratan tambahan sebagai berikut :
“Angka asam” dibawah 0,2.
“Angka penyabunan” berkisar dari 200-245
“Angka iod” kurang dari 7.
Interval antara titik leleh dan titik memadat
kecil
• Angka asam jumlah mg KOH (Potassium hydroxide) yg
dibutuhkan utk menetralisir asam lemak bebas dalam 1 g
lemak nilai yg rendah penting utk basis suppo yg bagus

• Angka penyabunanjumlah mg KOH (Potassium hydroxide)

yg dibutuhkan utk menetralisir asam lemak bebas dan
menyabunkan ester yg mengandung 1 g lemak kita dpt
mengetahui type of glyceride present (mono-, di- or tri-) dan
jumlahnya

• Angka iodjumlah Iodine yg bereaksi dg 100 g lemak atau

bahan unsaturated lainnyaThe possibility of decomposition
by moisture, acids, oxygen (which leads to rancidity of fats)
increases with higher iodine value
Suppository bases

1- The fatty bases:

i. Theobroma oil (cocoa butter).
ii. Synthetic fats

2- Water-soluble and water-miscible bases:

i. Glycerol-gelatin bases
ii. Macrogols
Lemak coklat
• TL 30-36°C dan meleleh pada suhu tubuh
• Mudah mencair dengan pemanasan dan memadat jika
didinginkan.
• Memenuhi syarat sebagai basis
• Tidak mengiritasi
• Mempunyai bilangan iodin 34-38
• Memiliki nilai asam < 4

kerugian
• Polymorphism: Stable β form vs. unstable α and γ forms
• Pengerutannya sedikit butuh lubrikan pd cetakan
• Pengurangan TL dengan penambahan obat terlarut
 Note: addition of beeswax (up to 10%).
• Mudah teroksidasi
• Variasi antar batch
• Tdk campur dengan cairan tubuh dan absorbsi air rendah tdk
cocok untuk vaginal dan uretral
POLIMORFISME BASIS LEMAK CACAO
• Bentuk α (melebur suhu 24C) = tdk stabil
• Bentuk β’ (metastabil) (melebur 28-31C) = tdk stabil
• Bentuk β stabil (melebur 34-35C) = stabil
• Bentuk γ (melebur 18C) = tdk stabil
 Synthetic fats
• Terbuat dari vegetable oil yang dihidrogenasi

Disadvantages:
• Viskositas lemak yang dilelehkan lebih rendah dari ol cacao beresiko
sedimentasi bahan aktif iritasi lokal
• Jika didinginkan terlalu cepat akan “brittle” selama proses pembuatan
jangan didinginkan dulu
• There is a series of grades of synthetic fatty bases, each with different
hardness and melting point ranges resulting in a variety of drug
absorption and release profiles.
Glycerol-gelatin bases

• These bases are a mixture of glycerol and water stiffened with gelatin.
The commonest is Glycerol Suppositories Base BP, which has 14% w/w
gelatin, and 70% w/w glycerol. In hot climates the gelatin content can
be increased to 18% w/w.
• Gelatin is a purified protein produced by the hydrolysis of the
collagenous tissue, such as skins and bones, of animals.
• Two types of gelatin are used for pharmaceutical purposes, Type A,
which is prepared by acid hydrolysis and is cationic, and Type B, which
is prepared by alkaline hydrolysis and is anionic.
• Type A is compatible with substances such as boric acid and lactic acid
while Type B is compatible with substances like zinc oxide.
• The 'jelly strength' or 'Bloom strength' of gelatin is important, particularly
when it is used in the preparation of suppositories or pessaries.
 18

1-Glycerine Suppositories:
Glycerine 91 g
Sod. Stearate 4g
Purified water 5g
To make approximately l00g
2- Glycerated gelatin suppositories:
Drug & purified water 10g
Gelatin 20g
Glycerin 70g

- Because glycerin is hygroscopic, there suppositories are packed in

materials that protect them from environmental moisture.
- This base do not melt at body temp., but dissolve in the secretions of
the body cavity in which they are inserted.
Glycerol-gelatin bases

Disadvantages:
• Basis Glycerol-gelatin dpt menyebabkan iritasi rektal
• As they dissolve in the mucous secretions of the rectum,
osmosis occurs producing a laxative effect.
• Bersifat higroskopis penyimpanan harus tepat
• Mudah terkontaminasi mikroba karena ada kandungan
air butuh pengawet hati-hati inkompat
• Lebih sulit penanganannya dibanding basis lain
• The solution time depends on the content and quality of
the gelatin and also the age of the suppository.

This type of base is commonly used for pessaries rather than

suppositories.
 Macrogols
• PEG dengan berbagai variasi bisa dikombinasi untuk menghasilkan
basis dengan berbagai TL, laju disolusi dan karakteristik fisik
• Pelepasan obat tergantung pada pelarutan basis daripada pelelehan
basis (TL nya sekitar 50°C).
• Higher proportions of high molecular weight polymers produce
preparations which release drug slowly and are also brittle.

Advantages:
1. They have no physiological effect.
2. Are not prone to microbial contamination.
3. Have a high water-absorbing capacity.
4. As they dissolve, a viscous solution is produced which means there is
less likelihood of leakage from the body.
 Macrogols

Disadvantages:
• They are hygroscopic which means they must be carefully
stored and this could lead to irritation of the rectal mucosa.
• They become brittle if cooled too quickly and also may
become brittle on storage.
• Incompatibility with several drugs and packaging materials,
e.g. benzocaine, penicillin and plastic, may limit their use.
• In addition crystal growth occurs with some drugs causing
irritation to the rectal mucosa and, if the crystals are large,
prolonged dissolution times.
METODE PEMBUATAN
• Pencetakan dengan tangan (Manual)
• Pencetakan dengan kompresi
• Pencetakan dengan penuangan
• Pencetakan dengan Mesin Otomatis
 23

Method Of Manufacture Of Suppositories:

1- Hand Molding:
It is the oldest and simplest method, by rolling the
suppository into the desired shape. The mass is then
rolled into a cylindrical rod of desire length and diameter.

2- Compression Molding:
Elegant suppository can be made by compression the
cold-grated mass into the desired shape .
It is simple and more elegant appearance than hand
molding.
It avoids the possibility of sedimentation of the insoluble
solids in the suppository base.
 24

3- Pour Molding:
Most commonly used method for production of
suppository on both small & large scale.
First, the base is melted on water bath, and then
the drugs are either emulsified or suspended in
it. Then, the mass is pour into cooled metal
molds, which are usually chrome or nickel plated.

4- Automatic Molding Machine:

The molding operation (pouring, cooling &
removal) can be performed by machine .
The output of a typical rotary machine, range from
3500 to 6000 suppositories per hour.
 25

SPECIFIC PROBLEMS IN FORMULATING SUPPOSITORIES

1- Water in suppositories:
Use of water as a solvent for drug should be avoided for the
following
Reasons:
a. Water accelerates oxidation of fats.
b. If water evaporates, the dissolved substance crystallizes out.
c. Unless H2O is present at level than that requires for dissolving the
drug, the water has little value in facilitating drug absorption.
Absorption from water containing suppository enhance only if an oil
in water emulsion exist with more than 50% of the water in the
external phase .
d. Reaction between ingredients (in suppository) are more likely to
occur in the presence of water.
e. The incorporation of water or other substances that might be
contaminate with bacteria or fungi necessitates the addition of
bacteriostatic agents (as parabens)
 26

2- Hygroscopicity:
a- Glycerinated gelatin suppositories lost moisture by
evaporation in dry climates and absorbed moisture under
conditions of high humidity
b- PEG bases are also hygroscopic.
 27

3- Incompatibilities:
a. PEG bases are incompatible with silver salt,
tannic acid, aminopyrine , quinine , icthammol,
asprine , benzoc.aine & sulphonamides .
b. Many chemicals have a tendency to crystallize
out of PEG, e.g.: sodium sarbital, salicylic acid
& camphor.
c. Higher concentration of salicylic acid softens
PEG to an ointment-like consistency, d- Aspirin
complexes with PEG.
d. Penicillin G , although stable in cocoa butter
and other fatty bases , was found to
decompose in PEG bases .
e. Fatty bases with significant hydroxyl values
may react with acidic ingredients.
 28

4- Viscosity:
The viscosity of the melted suppository base is important in the
manufacture of the suppository and to its behavior in the rectum after
melting.
Melted cocoa butter have low viscosity than glycerinated gelatin and
PEG type base in low viscosity bases, extra
Care must be exercised to avoid sedimentation of suspended particles.

To overcome the problems caused by use of low viscosity bases:

a. Use base with a more narrow melting rang that is closer to body
temperature.
b. The inclusion of approximately 2% aluminum monostearate not
only increase the viscosity of the fat base but to maintain
homogenous suspension of insoluble material.
c. Cetyl , stearyl or myristyl alcohols or stearic acid are added to
improve the consistency of suppositories .
 29

5- Brittleness :
Suppositories made from cocoa butter are elastic
and don't fracture readily.
Synthetic fat base with high degree of
hydrogenation and high stearate content and a
higher solids content at room temperature are
usually more brittle.
To overcome,
1. the temperature difference between the melted
base & the mold should be minimal.
2. Addition of small amount of Tween 80, castor
oil, glycerin imparts plasticity to a fat
 30

6- Volume contraction:
Occurs in many melted suppository base after cooling the
mold, result in:
a. Good mold release (contraction facilitate the removal of
the suppository from the mold , eliminating the need for
mold release agents).
b. Contraction hole formation at the open end of the mold,
this will lowered suppository . The contraction can be
eliminated by pouring a mass slightly above its
congealing temperature into a mold warmed at about
the same temperature or the mold is overfilled so that
the excess mass containing the contraction hole can be
scraped off.
 31

Lubricant or mold releasing agent:

Cocoa butter adhere to suppository molds
because of its low volume contraction. A various
mold lubricants or release agents must be used
to overcome this difficulty (mineral oil , aqueous
solution of sodium lauryl sulfate , alcohol ,
silicones , soap). The release of suppository from
damaged mold was improved by coating the
cavities with polytetrofluoroethylene (Teflone).
 32

7- Rancidity and Antioxidant:

Rancidity results from the autoxidation and subsequent
decomposition of unsaturated fats into low & medium
molecular weight saturated & unsaturated aldehydes ,
ketones and acids , which have strong unpleasant odor.
Example of effective antioxidant are phenols such as "
hydroquinone or B-naphtholquinone.
PERHITUNGAN SUPPOSITORIA
• DENSITY FACTORjumlah g zat aktif yang
setara 1 g basis
Contoh: dibuat 12 suppo mengandung aspirin
300 mg dengan ol cacao, berat sediaan 2 g.
(dilebihi 1)
- Aspirin : 13x0,3 g=3,9 g
- Faktor densitas aspirin : 3,9/1,1=3,55 (3,9 g
aspirin setara 3,55 g ol. Cacao)
- Ol. Cacao teoritis : 13 x 2 g = 26 g
- Ol. Cacao sebenarnya : 26 g-3,55 g = 22,45 g
• REPLACEMENT FACTORjumlah basis yg dapat
digantikan B.O (ol cacao yg punya vol = 1 g B.O)

( E  G)
f  100 x 1
(GxN )
• f: 0,81 artinya 0,81 g basis dapat digantikan
dengan 1 g B.O
• E: berat suppo hanya basis
• G: berat suppo dengan zat aktif x%
• N:% B.O
• G.N : jumlah bahan obat dalam suppositoria
Contoh:
Suppositoria mengandung 100 mg fenobarbital
menggunakan ol cacao sbg basis, bobot suppo
menggunakan basis ol cacao 2 g. Berapa bobot suppo yg
mengandung 100 mg fenobarbital?
• DISPLACEMENT VALUEjumlah zat aktif yg dpt
menggantikan ol. Cacao
- Contoh:buat 6 suppo ol cacao tanpa bahan aktif,
misal:6 g
- Buat suppo 40% bahan aktif, bobot 8,8 g
- Jumlah ol cacao: 60%x8,8 g = 5,28 g
- Jumlah bahan aktif: 40% x 8,8 g = 3,52 g
- Jadi jumlah ol cacao yang dpt digantikan 3,52 g
bahan aktif adalah : 6-5,28 g =0,72 g
- Displacement value = 3,52/0,72 = 5
 39

WEIGHT AND VOLUME CONTROLE:

The amount of active ingredient in each suppository
depends on:
1 . Its concentration in the mass.
2. The volume of the mold cavity.
3. The specific gravity of the base.
4. The volume variation between molds (within 2% of the
desired value).
5. Weight variations between suppositories due to
inconsistencies in the manufacturing process. e.g.
incomplete closing of molds, uneven scrapings (variations
in weight should be within ± 5%)
10/8/2019 BA-FP-JU-C
EVALUASI
• Organoleptis
• Keseragaman bobot??
• Test Jarak Leleh (Melting Range Test) --Menunjukkan
waktu yang diperlukan suppo untuk leleh bila dicelup
dalam air yang dipertahankan suhunya 37C--
Menggunakan USP Tablet Disintegrating Apparatus
• Liquefaction time / softening time -- Mengukur waktu
suppo menjadi lunak dalam kondisi in vitro 37C Alat yang
digunakan adalah U tube dan celophan tube
• Breaking test (Hardness)
• Uji Disolusi suppo dapat menggunakan perangkat uji
disolusi basket atau menggunakan tube dialisis
• Uji stabilitas
 42

Quality Control of Suppository

1) Surface appearance and shape:
to evaluate: absence of fissuring – absence of migration of
active ingredient, absence of pitting, absence of fat
blooming (dullness of surface)
 43

2) MELTING RANGE TEST:

Macromelting range: measures the time it takes for the
entire suppository to melt when immersed in a constant
temperature (37C) water bath.
Micromelting range: is the melting range measured in
capillary tubes for the fat base only.

The apparatus used for measuring the melting range of the

entire suppository is a USP tablet disintegration apparatus.
The suppository is completely immersed in the constant
temperature water bath, and the time for the entire
suppository to melt or dispense in the surrounding water is
measured. The in-vitro drug release pattern is measured
by using the same melting range apparatus.
 44

3) LIQUIFACTION OR
SOFTENING TIME TESTS OF
RECTAL SUPPOSITORIES:
The "softening test" measures the
liquefaction time of rectal
suppositories are an apparatus
that simulate in-vitro conditions
(at 37oC).
 45

4) BREAKING TEST:
- It is designed as a method for
measuring the fragility or
brittleness of suppositories.
- The apparatus consists of
double-wall chamber in which the
test suppository is placed. Water
at 37C is pumped through the
double walls of the chamber, and
the suppository, contained in the
drug inner chamber, supports a
disk to which a rod is attached.
The outer end of the rod consists
of another disc to which weights
are applied.
 46

• 5) Mechanical strength: It is a force necessary to

break a supp. And indicate whether supp is brittle
or elastic. ( not less than 1.8-2 Kg) by Erweka
method

• 6) Melting & solidification

• Solidification can be determine by using
evacuated flask into which the melt is placed, the
temp of cooling is noted to determine the
solidification point.
 47

7) DISSOLUTION TESTING:
The patterned is measured by using the same melting
range apparatus. If the volume of water surrounding the
suppository is known, then by measuring aliquots of the
water for drug content at various intervals within the
melting period. A (time versus drug release) curve could
be established and can be plotted.
 48

PACKAGING OF SUPPOSITORY
Suppository must be placed in a container in such
a manner that they do not touch each other.

• Staining, breakage or deformation by melting

caused by adhesion can result from poorly
wrapped packaged suppository. Suppository is
foiled in tin or Al paper and plastic.
• Over wrapping is done by hand or machine.
Many suppositories are not individually, wrapped.
In such cases, they are placed into cardboard
boxes or plastic containers that have been
molded to provide compartment for 6 or 12
suppositories.
 49

STORAGE
Suppository should be protected from heat, preferably
stored in the refrigerator.
Glycerinated gelatin suppositories should be protected from
heat, moisture, and dry air by packaging in well-sealed
containers and storing in a cool place.