parenteral preparation

zulfiayu,S1UNG,may 2012

parenteral
Parenteral (Gk, para enteron= beside the
intestine)
Parenteral administration of drugs involves
the injection of therapeutic agents, in the
form of solutions, suspensions or
emulsions, into the body.
In so doing, one of the major barriers to
drug entry (the skin) is breeched.

5 general categories of
injection

1. Solution ready for injection

2. Dry, soluble products ready to be
combined with a solvent just prior to
use
3. Suspensions ready for injection
4. Dry, insoluble products ready to be
combined with a vehicle just prior to
use
5. Emulsions

Route of administration

Intravenous
Subcutaneous
Intradermal
Intramuscular
Intraarticular
Intrathecal

Macam cara penyuntikan

Injeksi intravena (i.v)
Injeksi iv yg diberikan dlm dosis tunggal dgn
volume >10 ml disebut infus
intravena/infus/infundabilia. Infus harus bebas
pirogen, tdk boleh mengandung bakterisida,
jernih, dan isotonis.
Injeksi i.v dgn volume 15 ml atau lbh tdk boleh
mengandung bakterisida. Inj.i.v dgn volume 10
ml atau lebih harus bebas pirogen.

Macam cara penyuntikan

Inj. Intraarterium (i.a)
Disuntikkan ke dlm pembuluh darah
arteri/perifer/tepi, volume 1-10 ml, tdk boleh
mgndung bakterisida

Injeksi intrakordal/intrakardiak (i.kd)

Disuntikkan langsung ke dlm otot jantung atau
ventrikel, tdk boleh mgandung bakterisida,
disuntikkan hanya dlm keadaan gawat

Macam cara penyuntikan

Inj.intratekal (i.t), intraspinal,
intrasisternal (i.s),intadural (i.d),
subaraknoid
Disuntikkan lgsung ke dlm saluran sumsum
tulang belakang di dasar otak (antara 3-4 atau 56 lumbar vertebrata) tempat terdapatnya cairan
cerebrospinal. Larutan harus isotonis krn sirkulasi
ciaran serebrospinal lambat, meskipun
lar.anestetik u sumsum tulang sering hipertonis.
Jar saraf di daerah anatomi ini sangat peka

Macam cara penyuntikan

Intraartikular
Disuntikkan ke dalam cairan sendi di dalam
rongga sendi. Benutknya suspensi atau alrutan
dlm air.

Injeksi subkonjungtiva
Disuntikkan ke dalam selaput lendir di bawah
mata. Berupa suspensi atu larutan, tidak lebih
dari 1 ml

Macam cara penyuntikan

Inj.intrabursa
Disuntikkan ke dlm bursa subcromillis atau bursa
olecranon dlm bentuk lar.suspensi dlm air

Inj.intraperitoneal (i.p)
Disuntiikan langsung ke dalam rongga perut.
Penyerapan berlangusng cepat, namun bahaya
infeksi besar

Macam cara penyuntikan

Inj.peridural (p.d), ekstradural,
epidural
Disuntikkan kedalam ruang epidural, terletak di
atas durameter, lapisan penutup terluar dari otak
dan sumsum tulang belakang

Advantages
Immedidiate physiological action is
nedded
Patient cant not be given orally
because of the unconscious or
uncooperative state of the patient, or
because of inactivation or lack of
absorption in the intestinal tract.

Disadvantages
The requirement of aseptis at administation
The risk of tissue factor and difficulty in
correcting an error
If a direct pharmacological antagonist is
immediately available, correction of an error
may be impossible
Daily or frequent administration poses
difficulties, either for the patient to visit a
professionally trained person or to learn to
inject oneself

pH optimal
pH optimal u darah atau cairan tubuh
yg lain ad 7,4 dan disebut isohidri.
Krn tdak semua bahan obat stabil pd
pH cairan tubuh, injeksi sering dibuat
di luar pH cairan tubuh dan berdasar
kestabilan bahan tsb.

Pengaturan pH lar injeksi

diperlukan u :
1. Menjamin stabilitas obat, mis
perubahan warna, efek terapi optimal
obat,menghindari kemungkinan
terjadinya reaksi dr obat tsb.
2. Mencegah terjadinya rangsangan
atau rasa sakit sewaktu disuntikkan.
pH>>> : nekrosis jaringan
pH<<< : rasa sakit jika disuntikkan

Isotonis
1. Punya tek.osmosis yg sama dgn
tekanan osmosis cairan tubuh (darah,
cairan lumbar, air mata) bernilai sama
dgn tekanan osmosis lar.NaCl 0,9% b/v
2. Mempunyai titik beku yg sama dgn
titik beku cairan tubuh, yi -0,52C
<<< NaCl 0,9% b/v : hipotonis
>>> NaCl 0,9% b/v : hipertonis

 Hipotonis disuntikkan : air dr lar.inj akan

diserap dan masuk ke dalam sel, akibatnya sel
akan mengembang dan pecah (haemoolisis),
bersifat tetap. Pecah sel ini akan dibawa aliran
darah dan dpt menyumbat pembuluh darah yg
kecil
Hipertonis disuntikkan : air dlm sel akan ditarik
keluar dr sel shg sel akan mengerut, bersifat
sementara dan tdk menimbulkan kerusakan
sel.

 Hipotonis disuntikkan : air dr lar.inj akan

diserap dan masuk ke dalam sel, akibatnya sel
akan mengembang dan pecah (haemoolisis),
bersifat tetap. Pecah sel ini akan dibawa aliran
darah dan dpt menyumbat pembuluh darah yg
kecil
Hipertonis disuntikkan : air dlm sel akan ditarik
keluar dr sel shg sel akan mengerut, bersifat
sementara dan tdk menimbulkan kerusakan
sel.

Cara mendapatkan isoioni

Isoioni : lar.inj tsb mengandung ionion yg sama dgn ion-ion yg terdapat
dlm darah, yaitu K+, Na+, Mg2+,
Ca2+, Cl-.
Isoioni diperlukan pd penyuntikan dlm
jumlah besar, mis: pd infus intravena

sterilization
The complete destruction or removal
of all forms of live from materials
The process by which living
organisms are removed or killed to
this extent that they are no longer
detectable in standard culture media
in which they have previously have
been found to proliferate

definition
Antiseptic : a substance which, when
aplied to microorganism, renders them
innocuous either by killing them or
preventing their growth
Asepsis : the prevention of access of
viable microorganism to materials or
process
Bactericide: a substance or process
thatt kills bacteria

 Disinfectant : agent that frees from

infection/chemical substance that
destroy pathogenic bacteria
Germicide : a chemical substance
which kills mo but not necessary
bacterial spores
Preservative : a chemical agent that
prevents microbial decomposition or
growth in the product

 Sanitizer : an agent or process that

produce the number of bacterial
contaminants to safe level as jugged
by public health requirements
Sporacide : a process or substance
that destroys microbial spores,
especially bacterial spores
Virucide : any process or substance
that destroys or inactivates viruses

Kind of sterilization
Sterilization by moist heat
Sterilization by dry heat
Sterilization by ionizing radiation
Gaseous sterilization with ethylene
oxide
5. Sterilization with liquid chemical
6. sterilization by uv radiation
7. Sterilization by filtation
1.
2.
3.
4.

Skema pembuatan secara

aseptik
Bahan Obat

Zat pembawa (steril)

Zat pembantu (steril)

Alat utk pembautan (gelas)

Dicuci
steril

disterilkan

dilarutkan (ruang

Wadah (ampul, vial)

Dicuci

disterilkan

diisi

ditutup kedap
dikarantina
Sibwei etiket dan dikemas

diperiksa

Skema pembuatan secara nonaseptik

Bahan Obat

Zat pembawa

Zat pembantu

Alat utk pembautan (gelas)

Dicuci

dilarutkan (ruang steril)

Wadah (ampul, vial)

disaring

Dicuci
kedap

diisi dan ditutup

disterilkan
dikarantina
Sibwei etiket dan dikemas

diperiksa

components

Vehicles
Solutes
Containers
Closures

production
Maintaining facilities and equipment
Preparing and controlling the
environment
Cleaning the containers and equipment
Preparing the product
Filtering the solution
Filling containers with the product
Sealing the containers

Control of quality
Evaluation of components
Validation of equipment and
processes
Determination with the prescribed
requirements
Performance of necessary evaluative
test on the finished product

Packaging and labelling

All steps necessary to identify the
finished product and enclose it in
manner that is safely and properly
prepared for sale and delivery to the
user

Component and
containers

Essential first step establishing

spesifications to insure the quality of
each of the components of an
injection

vehicle
Since most liquid injections are quite
dilute, the component present in the
highest proportion
No therapeutic activity and nontoxic
The vehicle of greatest importance
water
Prepared by distillation or by reserve
osmosis.

Types of vehicles
Aqueous vehicles isotonicc to
which a drug may be added at the
time of administration
Water miscible vehicles
Non aqueous vehicles effect
solubility and to reduce hydrolysis
Nonaqueous vehicles

solutes
Requirements for purity
Level of microbial and pyrogenic
contamination
Solubility characteristic as
determined by the chemical or
physical form of the compound
Freedom from the dirt

Added substances
Effect solubility
Provide patient comfort
Enhance the chemical stability of the
solution
Preserve a preparation against the
growth of microorganism

Antimicrobial agents
USP states that antimicrobial agents in
bacteriostatic or fungistatic concentrations
must be added to preparations contained
in multiple-dose containers
Adequate concentration at the of use to
prevent the multiplication of the
microorganisms inadvertently introduced
into the preparation while withdrawing a
portion of the contents with a hypodemic
needle and syringe

Antimicrobial agents
Phenylmercuric nitrate and thimerosal
0,01% (most frequently 0,002%)
Metil apraben and propyl paraben
(0,18%/0,02% in combination)
Benzethonium chloride and
benzalkonium chloride 0,01%
Phenol or cresol 0,05%
Chlorobutanol 0,5%

buffers
Used primarily to stabilize a solution
againts the chemical degradation that
might be occur if the pH changes
appreciably.
Buffer systems employed should normally
have as low a buffer cappacity as feasible
in order not to disturb significantly the
body buffer system when injected
Ex: acid salts (citrates, acetates,
phosphates)

antioxidants
To preserve products because of the
ease with the which many drugs are
oxidizes
Ex: sodium bisulfite 0,1%

PYROGENS
Anticipated contaminants in crude
drugs, such as antibiotics produced
by fermentation, or they may be
present as unexpected and
unwanted contaminants in a finished
product as result of inadvertent
contamination during processing.

process
The former must be:
eliminated during the purification
steps of the drugs
Eliminated best by prebventing their
introduction or development during
the process

 Pyrogens cause a febrile reaction in human

beings.
Symptoms : chills, pains in the back and
legs and malaise, if fatal : significant
discomfort for the patients
Recent findings indicate that bacterial
pyrogens, when introduced into the body,
stimulate the production of an endogenus
(leukocytic) pyrogen that causes the
familiar physological responses

 Pyrogens are products of the growth

of microorganism.
The most potent pyrogenic
substances are produced by gram
negative bacteri (endotoxins), but
gram positive bacteria and fungi also
produce pyrogenic substances of
lesser potential

containers
Plastic
Glass

Terima kasih