TSF Steril Pertemuan 7

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Teknologi Farmasi Steril

Rumpun Teknologi Farmasi
Institut Sains & Teknologi Al-Kamal

Genap 2021/2022
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Pertemuan 7
Eksipien dalam Sediaan Steril
POKOK BAHASAN
• Eksipien
• Karakteristik Eksipien
• Tujuan Penggunaan Eksipien
• Manfaat Penggunaan Eksipien
• Jenis Sediaan Farmasi Steril
• Karakteristik Sediaan Farmasi Steril
• Tujuan Penggunaan Eksipien pada Sediaan
Farmasi Steril
• Komponen Eksipien dalam Sediaan Farmasi
Steril
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Principle
Parenteral drugs are formulated as solutions,
suspensions, emulsions, liposomes, microspheres,
nanosystems, and powders to be reconstituted as
solutions.
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Components of parenterals
• Active pharmaceutical ingredients
• Vehicle
• Added substances
• Primary container
• Closure
Eksipien
• Eksipien adalah zat yang digunakan sebagai
bahan tambahan/ pendukung suatu formula
sediaan, berssifat inert dan tidak memiliki
efek farmakologi
Karakteristik Eksipien yang Baik
• Inert
• Stabil secara fisik dan kimia
• Bebas mikroorganisme patogen
• Dapat mendukung bioavaibilitas
• Tersedia dalam perdagangan
• Harganya terjangkau
• Biokompatibel
• Kompatibel dengan Obat dan Eksipien lainnya
• Kompatibel dengan Pengemas
Tujuan Penggunaan Eksipien
• Bahan pembantu selama proses pembuatan
sediaan berlangsung
• Mencegah, mendukung atau meningkatkan
stabilitas dan bioavaibilitas
• Membantu identifikasi produk
• Meningkatkan keamanan, efektivitas produk
obat selama penyimpanan atau penggunaan
Manfaat Penggunaan Eksipien
• Dapat memberi nilai tambah pada sediaan
▫ Lebih stabil secara fisik dan kimia
▫ Memperbaiki tampilan fisik
▫ Mempengaruhi sifat lepasnya obat
• Oleh sebab itu mendesain suatu sediaan perlu
pengetahuan mengenai eksipien yang
digunakan dalam formula agar dihasilkan
produk yang bermutu, aman, menarik dan
memberikan efek terapi yang diinginkan
Sediaan Farmasi Steril
Sediaan Sediaan
Parenteral Parenteral
Volume Besar Volume Kecil
Sediaan Sediaan Nasal

Oftalmik dan Otik
Karakteristik
Sediaan Farmasi Steril
Penggunaan eksipien harus dapat mendukung pembuatan

sediaan farmasi steril yang memiliki 7 karakteristik dasar
sediaan farmasi steril
Eksipien Sediaan Farmasi Steril
Sediaan Sediaan
Parenteral Parenteral
Volume Besar Volume Kecil
Sediaan Sediaan Nasal

Oftalmik dan Otik
Tujuan Penggunaan Eksipien pada Sediaan
Steril Farmasi
• Menjaga (mempertahankan) kelarutan obat
• Menjaga Stabilitas fisika dan kimia sediaan
• Menjaga Sterilitas Sediaan
• Memudahkan pemberian obat (misalnya parenteral
dengan cara mengurangi rasa nyeri atau iritasi pada
saat penyuntikan)
Sediaan Steril Oftalmik
• Bentuk Sediaan
▫ Tetes Mata
 Larutan
 Suspensi
 Emulsi
▫ Salep Mata (Semisolid)
▫ Larutan Pencuci Mata (Kolirium)
Eksipien
• Agen Pengisotonis
• Dapar (Buffering agents)
• Pembawa (Vehicles)
• Pengawet (Antimikrobia)
• Antioksidan
• Chelating Agent
• Agen Pengental (Viscosity Agent)
• Agen Pensuspensi (Suspending Agents)
• Solubilizing and Wetting Agent
Eksipien
• Pengawet
▫ Benzalkonium Klorida
 70% digunakan untuk tetes mata
 Jangan digunakan dengan lokal anastesi
▫ Klorheksidin Asetat / Glukonat
 Bakterisidal
 Aktivitas meningkat dengan adanya aromatik
alkohol dan EDTA
 Stabil pada pH 5-6, Kurang stabil pada proses
sterilisasi dengan Autoklaf
Eksipien
• Pengawet
▫ Thiomersal
 Bakteriostatik dan Fungistatik
▫ Klorbutol
 Aktif membunuh bakteri dan fungi
 Kompatibel dengan kebanyakan produk optalmik
 Kekurangan: kurang stabil pada proses sterilisasi
dengan autoklav, volatilitas , mudah terabsorbi
dengan wadah plastik
Eksipien
• Dapar :
▫ Buffer : Fosfat, Borat, Sitrat
• Agen Pengental:
▫ Metil selulosa
▫ Polivinil Alkohol
▫ Dektrosa
▫ NaCl
Eksipien
• Antioksidan :
▫ Physostigmine
▫ Na Metabisulfit , Na sulfit
• Chelating Agents :
▫ EDTA
• Wetting Agent and Solubilizing Agents
▫ Polysorbate 80
▫ Gliserin
▫ Propilen Glikol
Sediaan Steril Nasal dan Otik
• Telinga
▫ Tetes Telinga
▫ Bentuk Sediaan: Larutan , Suspensi
• Hidung
▫ Tetes Hidung
▫ Nasal Sprays
Eksipien
Sediaan Steril Nasal dan Otik
• Dapar
• Pengawet
• Pembawa
• Agen Pengental
• Chelating Agents
• Solubilizing Agent
• Suspending Agent
Eksipien
Sediaan Steril Nasal
• Dapar
▫ Asam Hidroklorat
▫ Potasium Sorbat
▫ Natrium Fosfat
▫ NaCl
▫ Dextrose
• Pembawa
▫ WFI
▫ Asam Oleat
• Pengawet
▫ Propyl dan Methyl Paraben
Eksipien
Sediaan Steril Nasal
• Solubilizing Agent
▫ Gliserin
▫ PEG 400
▫ EDTA
Eksipien
Sediaan Steril Otik
• Agen Pengental
• Solubilizing Agents
• Pengawet
• Pembawa (Vehicle)
• Dapar
Eksipien Sediaan Steril Otik
• Agen Pengental
▫ HEC ( Hydroxy Ethyl Cellulose)
• Solubilizing Agents
▫ Gliserin , Propylen Glycol
▫ Polysorbate 20 dan 80 ( dapat juga sebagai suspending agent)
▫ Air ,Mineral Oil
▫ NaCl
• Buffer
▫ Kalsium Karbonat , Asam Sitrat , Asam Hidroklorat , Sodium Asetat
• Pengawet
▫ Methyl Paraben
▫ Benzalkonium Klorida
▫ Benzil Alkohol
▫ Thimerosal
Eksipien Sediaan Steril Otik
▫ EDTA , Potasium Metabisulfit , Na Bisulfit
Sediaan Parenteral
• Sediaan Parenteral
▫ Infus
▫ Injeksi
▫ Serbuk untuk Injeksi
• Bentuk Sediaan Steril Parenteral
▫ Larutan
▫ Suspensi
▫ Emulsi
▫ Serbuk Kering (Dry Powder)
Eksipien Sediaan Steril Parenteral
• Bulking Agents (u/ sediaan parenteral serbuk injeksi)
• Lyoprotectants (u/ Sediaan parenteral serbuk injeksi)
• Dapar (Buffering Agents)
• Agen Pengisotonis (Tonicity Adjusting Agents)
▫ Pelarut (Minyak dan Air)
▫ Solubilizing agents
• Pengawet
• Agen Pengompleks dan Pendispersi (Complexing and
Dispersing Agents)
• Agen Pensuspensi (Flocculating/suspending agents)
• Antioksidan (Antioxidant And Reducing Agents)
• Chelating agents
• Wetting Agents
• Surfaktan
• Agen Pengental
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Bulking agent
• Bulking agent adalah bahan tambahan yang
menyebabkan tumpukan material menjadi
terlihat lebih besar/ mengembang (bulk)
• Bulking agent membentuk sebagian besar produk
lyophilized
• Liofilisasi adalah solusi farmasi untuk menghasilkan sebuah produk
bubuk yang stabil. Metode ini telah menjadi standar praktek dalam
memproduksi produk sediaan suntik di pasaran.
• Ini umumnya digunakan untuk obat dosis rendah (potensi tinggi) yang
tidak memiliki massa yang diperlukan untuk mendukung strukturnya
sendiri
• Bulking Agents
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Lyoprotectants
- Lyoprotectant didefinisikan sebagai zat yang digunakan untuk
stabilisasi dan pencegahan degradasi molekul baik selama
pengeringan beku dan setelah itu, selama penyimpanan. Di antara
disakarida, sukrosa dan trehalosa tampaknya yang paling umum
digunakan
- Dibandingkan dengan sukrosa, trehalosa tampaknya menjadi
lyoprotectant yang lebih disukai karena memiliki higroskopisitas yang
lebih rendah, reaktivitas kimia yang sangat rendah dan akhirnya, suhu
transisi gelas (Tg′) yang lebih tinggi.
• Suhu kritis adalah suhu di atas dimana produk beku-kering
kehilangan struktur makroskopik dan runtuh selama pengeringan
beku Oleh karena itu, eksipien yang memberikan suhu kritis lebih
tinggi lebih disukai untuk liofilisasi
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Lyoprotectants
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Lyoprotectants
Lyoprotectants
Lyoprotectants And Bulking Comments
Agents
Manitols Mannitol has a very high eutectic
melting temperature (-1.4°C) after
crystallization and is processed well in
lyophilization. Crystallization of the
bulking agent, however, might
adversely affect the physical stability
of the product in certain
instances, for which, an amorphous
bulking agent is preferred
Lactose it is a good bulking agent but is a

reducing sugar and may undergo
Maillard reaction with proteins
leading to instabilityof the
formulation(11). The critical
temperature of 1% lactose is
-32°
Lyoprotectants And Bulking Agents
Lyoprotectants And Bulking Comments
Agents
Sucrose It is having similar collapse
temperature i.e -31°C (2%)
as of lactose but it is not a reducing
sugar and does not undergo
Maillard reaction . Sucrose has a
higher density as compared to
lactose which can cause slight collapse
during drying.
PEG It provides good cake structure

and increases viscosity of water (13).
The 2% solution of PEG has
a critical temperature of -22°C. Apart
from lyophilization it is also
used as a co-solvent and viscosity
modifier in parenteral including
ophthalmics.
Lyoprotectants
Lyoprotectants Comments
Sucrose It is having similar collapse
temperature i.e -31°C (2%)
as of lactose but it is not a reducing
sugar and does not undergo
Maillard reaction (12). Sucrose has a
higher density as compared to
lactose which can cause slight collapse
during drying.
Polyethylene glycol (PEG) It provides good cake structure

and increases viscosity of water (13).
The 2% solution of PEG has
a critical temperature of -22°C. Apart
from lyophilization it is also
used as a co-solvent and viscosity
modifier in parenteral including
ophthalmics.
Lyoprotectants And Bulking Agents
Lyoprotectants Comments
Polyvinyl pyrollidone (PVP) The low-molecular grades,
Povidone K 12 and K 17 are used as
solubilizing agents, dispersants
and crystallization inhibitors,
particularly for injectables. This
application is used in particular for
antibiotics in solution or in
lyophilized form.
The povidone grades K12 and K 17 are
used as solubilizers in parenteral
applications. In addition Polyvinyl
pyrollidone also provides cryo-
protection to the product. The
C-grades are supplied with low
endotoxin levels (“pyrogen-free”)
Pengawet
• Pengawet Anti Mikrobial
Dapar ( Buffering Agents)
• Control of pH is critical to avoid degradation of drug during
processing, storage and reconstitution
• The choice of buffer depends on the pH stability profile of
active ingredient as drug needs to be reconstituted and
stored for some time before it could be administered to the
patient. For this purpose, the pH of maximum stability of
drug should be known and maintained.
• Selection of a suitable buffer and its concentration is
important for sensitive molecules.
• The buffering agent should have a high collapse
temperature, be non-volatile and have a high glass
transition temperature (Tg).
• A high collapse temperature would facilitate a faster
primary drying, and its non-volatile nature would prevent
pH drift, that might be detrimental to the product stability
• Commonly used buffers in the parenteral formulations are
Acetate, Citrate, Tartrate, Phosphate,Triethanolamine
(TRIS).
Agen Pengisotonis (Tonicity Adjusting Agents)
• Parenteral formulations should be isotonic with human

plasma so as to avoid damage to the tissues. However, not
all drugs at their recommended dosage are isotonic with
blood, thus requiring the addition of a tonicity adjusting
agent to the formulation.
• The most commonly used tonicity agent is dextrose, while
others such as glycerol and sodium chloride are less
commonly used. Other commonly used tonicity adjusting
agents are: Glycerin and Mannitol
Pengawet
• Pengawet Anti Mikrobial
Pengawet Antimikobial
• Antimicrobial agents are required for parenteral products that

are intended for multiple dosing, in order to protect the product from
accidental microbial contamination during clinical usage & maintain
sterility.
• Some typical preservative used in parenteral suspensions
and their commonly used concentrations are as follows:
▫ Benzyl alcohol (0.9% to 1.5%)
▫ Methylparaben (0.18%to0.2%)
▫ Propylparaben (0.02%)
▫ Benzalkonium chloride (0.01% to 0.02%)
▫ Thiomersal (0.001% to 0.01%)
• Agen Pengkhelat (Chelating Agents)
▫ Chelating agents are used in formulations to aid in inhibiting free
radical formation and resultant oxidation of active ingredients caused
by trace metal ions such as copper, iron, calcium, manganese, and zinc .
▫ Ex: EDTA, Na Metabiulsfit
• Antioksidan (Antioxidants and Reducing Agents)
▫ The antioxidants and Reducing Agents are used to prevent/minimize
the oxidation reaction of the drug or excipients over the shelf life of the
product
▫ The mechanisms:
 Bind with free radical in the system
 Bind with heavy metals that contain in formula
 Prevent Reduction Oxidation Reaction
• Chelating Agent
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• Antioksidan
• VEHICLE
• Solubilizing agents
• The agents which help in dissolving or increase the
drug solubility into the formulation are known as
solubilizing agents, thesolubilising agents can be
broadly classified into :
▫ surfactants : The surfactants increase the dissolution
by reducing the surface tension of the drug substances
▫ co-solvents.: are defined as a solvent that in
conjunction with another solvent can dissolve a solute.
• VEHICLE
• Solubilizing agents
▫ Few examples of surfactants are: Polyoxyethylene
sorbitan monooleate (Tween 80), Sorbitan
monooleate Polyoxyethylene sorbitan monolaurate
(Tween 20), Lecithin, Polyoxyethylene
polyoxypropylene copolymers (Pluronics).
▫ Examples of co-solvents are: Propylene glycol,
Glycerin, Ethanol, Polyethylene glycol (300 and 400),
Sorbitol, Dimethylacetamide and Cremophor EL etc.
• VEHICLE
• Air
• Air sbg Pembawa (VEHICLE)
• Air Air
Air Steril Air Air Steril Air steril
Untuk Injeksi Bakteriostatik untuk Inhalasi untuk Irigasi
Untuk Injeksi
Disterilkan Ada 1 atau lebih Disterilkan Disterilkan
Dikemas dengan Agen Dimurnikan secara Dikemas dengan
Kontener dosis tunggal bakteriostatika destilasi/ osmosis dosis tunggal
kapasitas < 1000 ml (Benzil Alkohol , terbalik Tidak
Metil Paraben mengandung
Tidak Mengandung dan Propil Dosis Tunggal antimikroba atau
Zat Bakteriostatik Paraben) zat lain
Tidak mengandung Kapasitas < 1ltr
Kontener Antimikroba
Takaran Ganda Untuk
Untuk membersihkan
Dikemas dengan melembabkan luka
kapasitas < 30 ml udara atau alat yang
sama yang mungkin
terkontaminasi
• Minyak sbg Pembawa (VEHICLE)
• Minyak (Oil)
▫ Persyaratan monografi minyak untuk sediaan injeksi
( Farmakope Edisi III)
 Minyak lemak nabati atau ester asam, lemak tinggi alam
atau sintetik dan harus jernih pada suhu 10°C
 Bilangan Asam: 0,2< X<0,9
 Bilangan Yodium : 79 <X <128
 Bilangan Penyabunan: 185 <X <200
 Penyimpanan: Tertutup rapat, diisi penuh dan
terlindung dari cahaya
• Minyak sebagai Pembawa (VEHICLE)
• Minyak (Oil)
• Oily vehicles cannot be administered by the intravenous route
▫ For some oil or lipid soluble drugs such as some vitamins (Vitamin K,
Vitamin E) hormons (e.g., progesterone, testosterone,
deoxycorticicosterone), oily vehicle can be used:
 Soybean oil
 Olive oil
 Corn Oil
 Cottonseed Oil
 Sesame Oil
 Peach Oil
 Peanut Oil
• Wetting Agents
▫ Various nonionic surfactants and non-aqueous
solvents like glycerin, alcohol & propylene glycol are
types of wetting agents commonly used in injectable
suspensions.
▫ Wetting agents reduce the contact angle between the
surface of the particle & the wetting liquid to obtain
maximum wetting efficiency; surfactants with
hydrophilic lipophilic balance (HLB) value in the
range of 7to 9 should be selected.
• Wetting Agents
▫ The usual concentration of surfactants varies from 0.05%
to 0.5% depending on the solid contents of the suspension.
▫ Care should be taken in terms of the amount
used;excessive amounts may cause foaming or caking or
provide an undesirable taste/odor to the product.
▫ Surfactants (wetting agent)
 Lecithin, Polysorbate 20, Polysorbate 80, Pluronic F-68,
Sorbitan
 trioleate (span 85) are used, as surfactants in injectable
suspensions
• Wetting Agents
▫ for e.g. in the preparation of a non-aqueous
suspension of Cefazolin
 sodium in peanut oil, addition of polysorbate 80 at
concentration greater than 0.17% resulted in
deflocculated suspension which was difficult to
redisperse.
 Microscopic examination revealed extensive
agglomeration and crystal growth of cefazolin sodium in
the presence of polysorbate 80
• Flocculating/suspending agents
▫ The controlled flocculation approach uses a flocculating agent(s) to
from loosely bound aggregate or flocs in a controlled manner that
settles rapidly but redisperses easily upon agitation. An appropriate
amount or flocculating agent is added that result in maximum
sedimentation volume & prevents cake formation.
▫ Electrolytes, surfactant and hydrophilic colloids have been typically
used as flocculating agents. Electrolytes & surfactants reduce the
electrical forces of repulsion between particles & allow the flocs to
form, which in turn is influenced by the surface charge on the
particles.
• E.g. Electrolytes used in Parenteral Suspensions.
▫ Potassium/sodium chloride
▫ Potassium/sodium citrate
▫ Potassium/sodium acetate
• Flocculating/suspending agents
▫ The surface charge of the system can be measured by the zeta
potential. The zeta potential must be controlled so as to lie
within a range (generally less than 25 mV) to obtain a
flocculated,noncaking suspension with maximum
sedimentation.
▫ Hydrophilic colloids (generally negatively charged) not
only affect the repulsive force but also provide mechanical
barrier to the particles.For e.g. a 25% PVP solution is used
in combination with polysorbate 80 (2%) acts as a
stabilizer to provide a stable injectable 30% aqueous
powder suspension.
• Viscosity Agents
▫ Some viscosity building agents used in formulation of injectable
suspension are:
 Sodium carboxymethyl cellulose
 Acacia
 Gelatin
 Methyl cellulose
 Polyvinyl pyrrolidone
• Complexing and Dispersing Agents
Complexation is sometimes used to improve the solubility of
drug in the solvent especially water.
▫ Cyclodextrins have emerged as very effective additive compounds for
solubilizing hydrophobic drugs.
 In the parenteral dosage form, modified cyclodextrins, such
as hydroxypropyl-b-cyclodextrin and sulfobutylether- b –
cyclodextrin have been reported to solubilize and stabilize many
injectable drugs, including dexamethasone, estradiol, interleukin-2,
and other proteins and peptides without apparent compatibility
problems
• Terima Kasih

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1

Teknologi Farmasi Steril

Institut Sains & Teknologi Al-Kamal

Sediaan Sediaan Nasal

Penggunaan eksipien harus dapat mendukung pembuatan

Sediaan Sediaan Nasal

Eksipien Sediaan Steril Parenteral

Lactose it is a good bulking agent but is a

PEG It provides good cake structure

Polyethylene glycol (PEG) It provides good cake structure

• Parenteral formulations should be isotonic with human

• Antimicrobial agents are required for parenteral products that

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