PARENTERALS :

1. SMALL VOLUME PARENTERAL

(SMP)/ INJECTION
2. LARGE VOLUME PARENTERAL
(LVP)/ INFUS
 SVP - solutions LVP
Volume < 10 ml  10ml
Packaging single dose (ampul) Vial >10 mL, flacon, piggy
multiple dose (vial) back
pH & tonicity Isotonic, isohydric (im, iv, isotonic, isoosmoles, and
sc, intra dermal), iv : if it isohydric
is possible
Preservative (-) single dose (-)
(+) multiple dose
Buffer If it is needed (-)

Pyrogen Pyrogen free Pyrogen free

 SVP
Mixing room LAF
1. Dissolve active 2. Dissolve excipients in
ingredient in water and mixed up
aquabidest
Mix 1 & 2

Check pH/adjust pH if required

Add volume, minimize particulate matter

(0,45 m)

Packaging Bacterial membrane filtration

Autoclave  0,22 m
Aseptically filling
 LVP
Mixing room LAF

1. Dissolve active 2. Dissolve isotonic adjusting agent if

ingredient in required
aquabidest

Mix up 1 & 2, Check pH/adjust pH if required, add volume

Add activated carbon 0,1% w/v, heat 60-70oC for 15 min,

Filter using double filters

Minimize particulate matter using 0.45 m filter

Filling Bacterial membrane filtration  0,22 m

Autoclave Aseptically filling
 Tonicity calculation:

Calculation methods :

1. Freezing point depression (Tf)

2. Sodium chloride equivalent
3. Liso
 Liso method
 Liso value can be used to predict the freezing depression
of drug solution
Tf = Liso . C
 Liso value can be used to predict the NaCl equivalentof
drug solution
E = 17. Liso / MW
 Liso
Ion type Example
value
Sucrose, dextrose,
Non-electrolyte 1,9
gliserin
Weak electrolyte 2,0 Boric acid, citric acid
Divalent-divalent electrolyte 2,0 MgSO4, ZnSO4
Univalent-univalent electrolyte 3,4 NaCl, AgNO3
Atropin sulfate,
Univalent-divalent electrolyte 4,3
Na2CO3
Divalent-univalent electrolyte 4,8 CaCl2, Ca-gluconate
Univalent-trivalent electrolyte 5,2 Na-citrate, K-citrate
Trivalent-univalent electrolyte 6,0 AlCl3, FeCl3
Tetraborate 7,6 Na-borate, K-borate
 FOR INFUS
 Calculate both osmolarity and tonicity
mOsmole/L = [(g/L)/MW] x 1000 x ion numbers
 For electrolyte : calculate mEq

mEq/L = [(g/L)/MW] x 1000 x valence

 HIPERTONIC/HIPEROSMOLE ??
Use with local anesthetics for im, sc, id.
Injected to vena cava
Dilute with water for injection/infus
Slow injection / infus
 STERILIZATION METHOD

- Powder : melting point with decomposition?

- Heat stability in solution

AUTOCLAVE STERILIZATION only for solution

containing water!!!!!

Photodegraded drugs : amber glass vial/ampoule

 LVP:
 Make WATER FOR INJECTION: aquabidest and
eliminate pyrogen using carbon
 Rinse double filters, filtration using 0.45
m and 0,22 m and use pyrogen free containers

 To anticipate the reduction of drug concentration

due to adsorption into carbon = add 10%
 Evaluation:
1. pH
2. Clarity
3. Packaging integrity
4. Pyrogen content
5. Sterility test
6. Particulate matter
7. Concentration of drugs etc
 Labelling
 Label must not cover all the packaging surface to
leave a room for observing the content
 Registered name followed by generic name of the
drug, using the same font but 80% size
 Netto ……mL or gram
 Composition: every 1 mL contains: active ingredient
…… milligram
 Batch No., Registration no., Exp. date,
manufacturing date, use before:
 obat keras,
 Nama Pabrik dan alamat.
 Brosur, kardus
• Brosur: indikasi dan kontraindikasi
diterangkan lebih lengkap, tanpa no.
batch.
• Kardus: isi sama spt etiket. I & KI
bisa tidak dijelaskan secara lengkap,
diberi keterangan: Keterangan
lengkap lihat brosur di dalam.
 Penomoran
• DKL 00009315521A1
• No. registrasi: 15 digit

1 : D = dagang, G= Generik
2 : K = keras, T = bebas terbatas, B= bebas, P = psichotropik
3 : L = dalam negeri, A = PMA
4 & 5 : tahun registrasi
6,7,8 : no pendaftaran di POM
9, 10, 11, 12, 13 : jenis obat
14 & 15 kode pabrik: menyatakan isi/komposisi
14 : Huruf A
15 : angka 1
TERIMA KASIH