SUSPENSI

• Suspensi adalah bentuk sediaan yang mengandung

bahan obat padat tidak larut dan terdispersi halus
dalam cairan pembawa.
• Suspensi adalah sistem terdispersi di mana padatan
yang terbagi halus terdispersi secara seragam dalam
medium dispersi cair (Nash 1988)
• Fase internal atau terdispersi terdiri dari bahan
partikulat, yang secara praktis tidak larut dalam fase
eksternal
• Fase eksternal, yang juga disebut sebagai fase
kontinu atau media dispersi, umumnya cair (mis.,
suspensi cair) atau setengah padat (mis., gel)
Alasan Formulasi Suspensi:
- Obat tidak larut dalam pembaw
- Untuk menutupi rasa pahit obat
- Untuk meningkatkan stabilitas obat
- Untuk mencapai pelepasan obat yang
terkontrol / berkelanjutan.
Classification
1. Based On General Classes
– Oral suspension
– Externally applied suspension
– Parenteral suspension
2. Based On Proportion Of Solid Particles
– Dilute suspension (2 to10%w/v solid)
– Concentrated suspension (50%w/v solid)
3. Based On Electrokinetic Nature Of Solid Particles
– Flocculated suspension
– Deflocculated suspension
4. Based On Size Of Solid Particles
– Colloidal suspension (< 1 micron)
– Coarse suspension (>1 micron)
– Nano suspension (10 ng)
 Keuntungan dan Kerugian
Keuntungan
• Suspensi dapat meningkatkan stabilitas kimiawi obat tertentu. E.g.Procaine
penicillin G
• Obat dalam suspensi menunjukkan tingkat ketersediaan hayati yang lebih
tinggi daripada bentuk sediaan lainnya. Solution > Suspension > Capsule >
Compressed Tablet > Coated tablet
• Onset dan Durasi dapat dikontrol E.g.Protamine Zinc-Insulin suspension
• Menutupi rasa obat yang tidak enak . E.g. Chloramphenicol

Kerugian
 Stabilitas fisik, sedimentasi dan pemadatan dapat menyebabkan masalah.
 Sulit diformulasikan
 Dosis yang seragam dan akurat tidak dapat dicapai kecuali suspensi
dikemas dalam bentuk unit dosis
 Karakter Suspensi
• Partikel tersuspensi tidak boleh mengendap
dengan cepat dan sedimen yg dihasilkan harus
dapat diresuspensikan kembali dengan
pengocokan sedang.
• Mudah dituang tapi juga tidak begitucair.
• Memiliki bau, rasa, dan warna yang
menyenangkan.
• Stabil secara fisik, kimia dan mikrobiologi.
• Suspensi parenteral/optalmik harus steril
 Aplikasi Suspensi
• Suspensi biasanya digunakan untuk bahan obat
yang tidak larut atau sukar larut. E.g.Prednisolone
suspension
• Untuk mencegah degradasi obat atau meningkatkan
stabilitas obat. E.g. Oxytetracycline suspension
• Untuk menutupi rasa tidak enak dari obat.
E.g. Chloramphenicol palmitate suspension
• Dapat diformulasikan untuk sediaan topikal e.g.
Calamine lotion
• Bisa untuk formulasi sediaan parenteral guna
mengontrol pelepasan obat.
• Vaksin juga sering diformulasikan dalam bentuk
suspensi. Cholera vaccine
• X-ray contrast agent are also formulated as
suspension. E.g. Barium sulphate for examination of
alimentary tract (Pemeriksaan saluran pencernaan)
 Flokulasi dan Deflokulasi
• Sistem flokulasi menghasilkan laju
pengendapan yang cepat karena setiap unit
terdiri dari banyak partikel dan ukuran
partikelnya lebih besar.
• Namun, karena jarak antar partikel yang
longgar pada gumpalan, sehingga mudah
terdispersi saat diguncang.
• Sistem deflokulasi terdiri dari partikel yang
lebih kecil yang laju pengendapannya lebih
lambat, tetapi partikel yang mengendap
cenderung membentuk kompleks yang
ireversibel dan sulit untuk didispersikan
kembali.
• Fenomena ini disebut caking
• suspensi deflokulasi akan memiliki
keseragaman dosis yang lebih baik tetapi
stabilitas lebih buruk karena pembentukan
sedimen
Hal yang perlu menjadi perhatianpembuatan suspensi
• Surfaktan dengan nilai HLB antara 7 dan 9 dapat berfungsi
sebagai agen pembasah.
• Sebagian besar surfaktan digunakan pada konsentrasi
hingga 0,1% sebagai bahan pembasah
• Zat pembasah yang umum digunakan untuk penggunaan
oral adalah ester polisorbat dan sorbitan. SDS adalah
contoh surfaktan yang digunakan secara eksternal
• Persiapan parenteral mungkin mengandung polisorbat,
beberapa poloxamers, dan lesitin
• Polimer hidrofilik Contohnya adalah akasia, tragacanth,
xanthan gum, bentonit, aluminium-magnesium silikat, silika
koloid, dan turunan selulosa, seperti natrium
karboksimetilselulosa. Polimer-polimer ini membentuk
lapisan hidrofilik di sekitar partikel padat sehingga
mendorong terjadinya pembasahan.
• a stable suspension is obtained by preparing a
partially flocculated suspension with controlled
viscosity so that settling is minimal.
• Controlled flocculation is achieved by a
combination of particle size control,electrolytes
to control zeta-potential and by the addition of
polymers.
• Inorganic electrolytes, added to an aqueous
suspension alter the zeta-potential of the
dispersed particle.
• Lowering the zeta-potential sufficiently will result
in flocculation.
• Some of the commonly used electrolytes include
sodium salts of acetates, phosphates, and citrates
• Use of ionic surfactants may also result in
flocculation by neutralization of particle charges.
• Starch, alginates, tragacanth, and cellulose
derivatives are sometimes added to control the
degree of flocculation so that the suspension is in
a flocculated state and the sedimentation volume
is large.
• Suspensions should exhibit high viscosity at low
shear rate

• Also, the viscosity should be low enough to be

poured from the container but should spread
evenly, if it is intended for external application.

• Suspensions for injection should be able to

pass through hypodermic needles.
 Commonly Used Excipients
in Pharmaceutical Suspensions
• The suspension must be physically stable, chemically
stable over the required time, possess a viscosity that
allows it to be used for its intended purpose, be easily
reconstituted (redispersible) upon shaking, easy to
manufacture and be acceptable in use to the patient,
care-giver or other user.
• water soluble hydrocolloids such as acasia, agar,
dextrin, gellatin, hidroxyethyl cellulosa, etc. act as
suspending. water-soluble hydrophilic colloids work by
increasing the viscosity of the aqueous continuous
phase, and thereby hindering the sedimentation of the
disperse phase.
• Microcrystalline cellulose, calcium carbonate, silica,
magnesium carbonate are suitable as bulking
agent/auxiliary suspending agent.
• The group of Non-ionic surfactants such as Polysorbate,
Tween, Polyoxyethylene stearates, Polyoxyethylene alkyl
ethers is the largest group of surfactants used in the
formulation of pharmaceutical suspensions.
• Buffers are included in suspensions to maintain chemical
stability and control tonicity. The better buffer systems
use salts of weaker polyvalent acids, e.g. sodium salts of
citric acid, or combinations of sodium salts of citric acid
with sodium salts of phosphoric acid
• Antioxidant molecules which themselves are
preferentially oxidized can be included in the
formulation to reduce the degradation of other
components.
• Addition of preservatives is important, particularly
when using naturally occuring adjuvants.
• Flavors, colors, and perfumes may be added to
improve palatability and appearance of the product.
• In some situations sweeteners may be added but
their affect on final product viscosity and degree of
flocculation should be well understood.
 Manufacture of Suspensions
• Suspensions are normally manufactured using colloidal
mills.
• Definition of the dispersion procedure:
The powder is dispersed in a liquid such that every particle
is completely surrounded by the liquid. The solid/air
interfaces are exchanged for solidlliquid interfaces.
• The procedure of dispersion can be split into three steps,
though these generally overlap:
- wetting of the powder
- comminution and distribution of the particles
(deagglomeration)
- stabilization of the particles
 Wetting of the Powder
• For optimal dispersion, the powder from
which the dispersion is to be manufactured
must be completely wetted.
• Good wetting agents must cause complete
wetting and they must adsorb onto the
particle surface if possible.
Comminution and Distribution of the Particles
in the Liquid
• When a substance is ground, an equilibrium is
achieved: the fine particles produced gather
together into agglomerates or flocs because of
their increased surface energy.
• Deflocculants or dispersants must be added to
stabilize the ground powder.
• The primary particles or fragments thus
formed must be prevented from
reagglomerating or flocculating; this is the
purpose of deflocculants.
• Most deflocculants are charged tensides that
adsorb onto the particles and cause repulsion
between them.
• wet grinding is the most effective method for
the manufacture of liquid dispersions.
 Stabilization of the Dispersion
• A “stable dispersion is one in which the total number and
size of the particles in the dispersion does not change
over time.
• Dispersants are used to stabilize the dispersion.
• Selection of different dispersant based on the type and
electrical charge of the particles, and the nature of the
liquid medium (water, polar or nonpolar organic liquid).
• The dispersant must be adsorbed on the surface of the
solid. These create an energy barrier to attraction.
• Good dispersants are therefore molecules with both an
electrical charge and various hydrophobic groups, for
example high molecular mass hydrocarbon chains known
as polyelectrolytes.
PREPARATION OF SUSPENTION
(on laboratory or small pilot batch)
1. Drug dispersion
2. Preparation of structure vehicle and addition
of drug
3. Addition of other formula adjuncts
4. Deaeration, followed by making up to final
volume
5. Homogenization
6. In-process testing
7. Transfer and filling
1. Drug dispersion
Untuk memudahkan dispersi, bahan aktif ditambah
larutan pekat wetting agent dlm sedikit pembawa
gunakancolloid mill utk pembasahan optimal

Alkohol atau gliserin dapat digunakan pada tahap

awal pendispersian partikel untuk membantu penetrasi
pembawa kedalam massa serbuk

Atau bahan aktif didispersikan dgn cara menambahkan

perlahan-lahan kedalam air atau sistem air-gliserin
mengandung wetting agent
2. Preparation of structure vehicle and addition
of drug dispersion

structure vehicle : aqueous solution of suspending

agent ; hydrocolloid, polysaccharide, clay atau
kombinasinya
4. Deaeration, followed by making up to final
volume
Tiap bacth diproses melewati deaerating
equipment sblm diadkan.
Suspensi dgn udara yg terjebak dlm jumlah
besar tidak aseptabel secara farmasetik, dpt
mempengaruhi sifat reologi, dosis, warna, BJ,
volume
5. Homogenization
Terakhir, suspensi dilewatkan colloid mill atau
homogenizer untuk mengecilkan ukuran
partikel yang beraglomerasi

6. In-process testing
untuk menjamin kualitas produk pada setiap
langkah yang dilakukan
7. Transfer and filling

Sediaan dipindahkan ke storage /holding tank

untuk pengisian sesudah memenuhi in
process spesification.

Sediaan tidak boleh mengalami perubahan

kimia,fisika dan mikrobiologi setelah proses
pemindahan dan pengisian
3 Addition of other formula adjunct :
Bahan tambahan lain spt chelating agent, antioxidant,
humectan, preservative, color, fragrance:
- Dapat langsung ditambahkan kedlm pembawa atau
- Dilakukan presolubilized dlm cosolvent yg tepat
Waktu dan suhu pencampuran tgt sifat fisika-kimia
Fragrance ditambahkan terakhir dan suhu sudah dingin
 Kontrol kualitas
• Ukuran partikel dan distribusi ukuran partikel
• Homogenitas
• Viskositas
• pH
• Disolusi
• effectiveness of preservative
• Kecepatan pengendapan
• Kemudahan penuangan
• Redispersibilitas
• Sterilitas (untuk tujuan tertentu)
See you in the next lecture