Teknologi Farmasi Steril

Najma Annuria Fithri

Universitas Sriwijaya
Ganjil 2014/2015
Pertemuan 5
Eksipien dalam Sediaan Steril
Principle
Parenteral drugs are formulated as solutions,
suspensions, emulsions, liposomes, microspheres,
nanosystems, and powders to be reconstituted as
solutions.
Components of parenterals
• Active pharmaceutical ingredients
• Vehicle
• Added substances
• Primary container
• Closure
Vehicle
• Aqueous
• Non aqueous (miscible and immiscible)
Syarat Vehicle
• Mudah didapat harga murah
• Inert
• Dapat bercampur dengan cairan badan
• Tidak toksik
• Tidak mengiritasi
• Tidak bersifat pirogenik
• Stabil fisikokimiawi
• Tetap cair pada suhu tubuh
• Tidak dipengaruhi pH
• Efektik untuk melarutkan/menjadi pembawa zat
aktif dalam volume kecil
• Dapat disterilkan dengan autoklaf (lebih baik
hasilnya)
WFI
• Water for Injection can be prepared by
distillation or by membrane technologies (i.e.,
reverse osmosis or ultrafiltration). The EP
(European Pharmacopeia) only permits
distillation as the process for producing WFI.
The USP and JP (Japanese Pharmacopeia) allow
all these technologies to be applied.
Aqua pro injeksi
Aqua pi bebas CO2
Aqua pi bebas O2

?
Aqua pi bebas pirogen
Still
Several factors must be considered in selecting a still
to produce WFI:
• The quality of the feed water will affect the quality of
the distillate
• The size of the evaporator will affect the efficiency
• The baffles (condensing surfaces) determine the
effectiveness of refluxing
• Redissolving volatile impurities in the distillate
reduces its purity.
• Contamination of the vapor and distillate from the
metal parts of the still can occur. Constructed of
metal coated with pure tin, 304 or 316 stainless-
steel, or chemically resistant glass
Purity of WFI
• Total organic carbon (TOC), with a limit of 500
ppb (0.5 mg/L), and conductivity, with a limit of
1.3 μS/cm at 25°C or 1.1 μS/cm at 20°C.
Added substances function
• Increase and maintain drug solubility
Examples include complexing agents and surface active
agents. The most commonly used complexing agents are
the cyclodextrins, including Captisol. The most commonly
used surface active agents are polyoxyethylene sorbitan
monolaurate (Tween 20) and polyoxyethylene sorbitan
monooleate (Tween 80).
• Provide patient comfort
Reducing pain and tissue irritation, as do substances
added to make a solution isotonic or near physiological
pH. Common tonicity adjusters are sodium chloride,
dextrose, and glycerin
• Enhance the chemical stability of a solution, as do
antioxidants, inert gases, chelating agents, and
buffers.
• Enhance the chemical and physical stability of a
freezedried product, as do cryoprotectants and
lyoprotectants. Common protectants include sugars,
such as sucrose and trehalose, and amino acids,
such as glycine.
• Enhance the physical stability of proteins by
minimizing self-aggregation or interfacial induced
aggregation. Surface active agents serve nicely in
this capacity.
• Minimize protein interaction with inert surfaces,
such as glass and rubber and plastic. Competitive
binders, such as albumin, and surface active agents
are the best examples.
• Protect a preparation against the growth of
microorganisms. The term ‘preservative’ is sometimes
applied only to those substances that prevent the growth
of microorganisms in a preparation. However, such
limited use is inappropriate, being better used for all
substances that act to retard or prevent the chemical,
physical, or biological degradation of a preparation.
• Although not covered in this chapter, other reasons for
adding solutes to parenteral formulations include
sustaining and/or controlling drug release (polymers),
maintaining the drug in a suspension dosage form
(suspending agents, usually polymers and surface active
agents), establishing emulsified dosage forms
(emulsifying agents, usually amphiphilic polymers and
surface active agents), and preparation of liposomes
(hydrated phospholipids).