Yoga Windhu Wardhana

 Zat aktif sulit untuk langsung digunakan (krn. dosis

sangat rendah)
 Pemberian dosis obat yang akurat sangat sulit
 Supaya zat aktif dapat memberi efek terapi perlu
diberikan dengan rute yang memadai
 Beberapa zat aktif berkurang khasiatnya saat
terpapar lingkungan (cahaya, lembab, dll) sehingga
diperlukan penstabil agar efek terapi tercapai
 Zat aktif dapat terurai di tempat pemberian
 Kadangkala zat aktif dapat mengiritasi atau
melukai tempat dimana ia diberikan
 Kebanyakan zat aktif memiliki persepsi
organoleptis yang tidak menyenangkan (pahit,
rasa atau bau yang kurang enak)
 Rute pemberian zat aktif tidak mungkin
dimodifikasi agar sesuai dengan profil
farmakokinetik
 Gaseous dosage forms
 Liquid dosage forms
 Semisolid dosage forms
 Solid dosage forms
 Medicinal gases, inhalation/volatile
anaesthetics (vaporised before
administration by inhalation)
 Aerodispersions of solid particles (e.g.,
antiasthmatic inhalations) or liquid particles
(antiasthmatic inhalations or sprays)
 Solutions – one homogenous phase, prepared by dissolving one or more
solutes in a solvent
 Suspensions
▪ A dispersion system where solid particles (dispersed phase) are
dispersed in liquid phase (dispersion medium)
▪ According to the size of dispersed particles (1 nm - 0,5 mm) a
molecular, colloidal and coarse dispersions can be distinguished
▪ May require shaking before administration
▪ Not intended for systemic administration of drugs with high potency
 Emulsions
▪ a dispersion system consisting of two immiscible liquids
▪ o/w or w/o
▪ cloudy appearance
 Pharmaceutical Solutions

Aqueous Sweet &/or Viscid Nonaqueous

1. Douches 1. Syrups 1. Elixirs

2. Enemas 2. Honeys 2. Spirits
3. Gargles 3. Mucilages 3. Collodions
4. Mouthwashes 4. Jellies 4. Glycerins
5. Nasal washes 5. Liniments
6. Juices 6. Oleo Vitamin
7. Sprays
8. Otic solutions
9. Inhalations
1- Unshaped (without specific physical shape)

▪ Ointments – semisolid dosage forms with the oleaginous

(hydrocarbon), water-soluble or emulsifying base
 Oleaginous (hydrocabon) base: Petrolatum (Vaseline –
white, yellow)
 Water-soluble base: Polyethylenglycol (PEG)- ointment –
syn. macrogol ointments

▪ Pastes – semisolid dispersion system, where a solid particles

(> 25%, e.g. ZnO) are dispersed in ointments – mostly
oleaginous (Petrolatum)
2- Shaped
▪Suppositories (for rectal administration)
o different shapes
o Melting/dissolving at body temperature
o Oleaginous (cacao butter, adeps neutralis) or
aqueous (PEGs, glycerinated gelatine)

▪Pessaries (vaginal suppositories)

• Similar as above, PEGs or glycerinated gelatine
are often used as base.
for systemic administration for local administration
▪ Peroral (p.o) ▪ Topical (on the skin or mucosa)
▪ Sublingual (S.L) and buccal. Into/onto - the eye, nose, ear
▪ Rectal - the oral cavity
▪ Parenteral - the vagina, rectum
▪ Transdermal - the brochi
- the skin
▪ Inhalation
▪ Local parenteral (viz Parenteral
above)
▪ Oral (local effect within GIT;
antacids, adsorbents)
 DEFINISI CPOB

“ Cara Pembuatan Obat yang Baik (CPOB)

bertujuan untuk menjamin obat dibuat
secara konsisten, memenuhi persyaratan
yang ditetapkan dan sesuai dengan tujuan
penggunaannya. CPOB mencakup seluruh
aspek produksi dan pengendalian mutu”
 cG M P
GMP is also sometimes referred to as
"cGMP". The "c" stands for "current,"
reminding manufacturers that they must
employ technologies and systems which are up-to-
date in order to comply with the regulation.
Systems and equipment used to prevent
contamination, mix-ups, and errors, which
may have been "top-of-the-line" 20 years
ago, may be less than adequate by
today's standards.
 Other GMPs
The formalization of good manufacturing practices commenced in the
1960s and they are now in effect in over 100 countries ranging from
Afghanistan to Zimbabwe. Many countries have not developed local
requirements and rely on the World Health Organization Good
Manufacturing Practices for Pharmaceutical Prodducts. Regional
requirements have also appeared with application to several countries.
Examples of these inciude :
a) Pharmaceutical Inspection Convention (PIC) Guide to Good Manufacturing Practice
for Pharmaceutical Products – Austria, Denmark, Finland, Hungary, Ireland,
Liechtenstein, Norway, Portugal, Romania, Sweden, Switzerland, and United
Kingdom.
b) Association of South – East Asia Nations (ASEAN) – Good Manufacturing Practice :
General Guidelines – Brunei, Indonesia, Malaysia, Vitnam, Fhilippines, Singapore,
and Thailand.
c) European Economic Community (EEC) – Guide to Good Manufac-turing Practice for
Medicinal Products-Belgium, Denmark, France, Germany, Greece, Ireland, Italy,
Luxembrueg, the Netherlands, Portugal, Spain, the United Kingdom, and more
recently Austria, Finland, and Sweden.
QM, QS, QA, GMP and QC Inter-relationships
Quality Management Policy, Objective,
Committent & Direction

Organization Structure,
Quality System Responsibility, Accoutability

External QA Quality Assurance Internal QA

GMP
Operational & Technical
Quality Activities on Fulfilling Quality
QC
Control Requirements
 QA
It is the sum total of the
organized arrangements with
the objective of ensuring that
products will be of the quality
required for their intended use
 GMP
Is that part of Quality
Assurance aimed at
ensuring that products
are consistently
manufactured to a
quality appropriate to
their intended use
 QC
Is that part of GMP concerned
with sampling, specification
& testing, documentation &
release procedures which
ensure that the necessary &
relevant tests are performed
& the product is released for
use only after ascertaining
it’s quality
 WEWENANG DAN TANGGUNG
JAWAB:
1. Melaksanakan pengawasan & pengujian
terhadap
seluruh bahan awal
2. Melakukan pengawasan selama proses
produksi
3. Melakukan pengujian terhadap produkjadi
4. Melakukan pengujian stabilitas produk
terhadap produk yang telah dan akan
diedarkan
 Operational  All those planned or
laboratory techniques systematic actions
and activities used to necessary to provide
fulfill the requirement adequate confidence
of Quality that a product will
satisfy the
 QC is lab based requirements for
quality

 QA is company
based
Aspek /hal yang harus diperhatikan dalam
pelaksanaan CPOB :
 Karyawan
 Bangunan
 Peralatan
 Sanitasi dan hygiene
 Produksi
 Pengawasan Mutu
 Penanganan keluhan, recall
dan produk kembalian
 Dokumentasi
 A poor quality medicine may contain toxic
substances that have been unintentionally
added.

 A medicine that contains little or none of

the claimed ingredient will not have the
intended therapeutic effect.
 A basic principle of GMP is that quality cannot
be tested into a batch of product but must be
built into each batch of product during all stages
of the manufacturing process.

 It is designed to minimize the risks involved in

any pharmaceutical production that cannot be
eliminated through testing the final product.
 unexpected contamination of products, causing
damage to health or even death.

 incorrect labels on containers, which could mean that

patients receive the wrong medicine.

 insufficient or too much active ingredient, resulting in

ineffective treatment or adverse effects.
 Kontaminasi adalah masuknya pengotor atau
impurities yang dapat berupa bahan kimia,
mikroba dan partikel asing kedalam bahan
awal atau produk antara

 Kontaminasi dapat terjadi selama

proses produksi, pengambilan contoh,
pengepakan, penyimpanan atau transport.
 Dalam CPOB dikenal 3 jenis penyebab
kontaminasi :

 Bahan kimia

 Mikroba

 Partikel asing
 Pelanggaran dapat mengakibatkan :
 Teguran

 Penarikan kembali obat yang

beredar (recall)

 Penutupan pabrik
 Sanksi tersebut dikenakan karena pemerintah
bertanggung jawab untuk melindungi
kesehatan masyarakat pemakai obat kita.

 Hal tersebut sebenarnya merupakan

tanggung jawab kita juga.

 Pelanggaran akan merusak reputasi

perusahaan, dan mempengaruhi kelangsungan
hidup perusahaan.
 ALL aspects of production; from the starting
materials, premises and equipment to the training
and personal hygiene of staff.

 Detailed, written procedures are essential for each

process that could affect the quality of the finished
product.

 There must be systems to provide documented

proof that correct procedures are consistently
followed at each step in the manufacturing process -
every time a product is made.
1. Design and construct the facilities and equipments
properly
2. Follow written procedures and Instructions
3. Document work
4. Validate work
5. Monitor facilities and equipment
6. Write step by step operating procedures and work
on instructions
7. Design ,develop and demonstrate job competence
8. Protect against contamination
9. Control components and product related processes
10. Conduct planned and periodic audits
[1] Tulislah prosedur kerja anda
▪ Pastikan untuk memiliki prosedur
sebelum mulai bekerja

[2] Kerjakanlah sebagaimana prosedur

yang ditulis
▪ Tanyakanlah apabila merasa ragu
atau tidak mengerti
[3] Catat /dokumentasikan hasil kerja
anda
▪ Lakukan pencatatan pada saat bekerja, bukan setelah
(sebelum) bekerja Validasi pekerjaan anda

[4] Validasi pekerjaan anda

▪ Validasi adalah tindakan pembuktian

33
[5] Gunakan fasilitas dan alat yang
memadai
▪ Untuk mendapatkan hasil optimum
▪ Menghindari kesalahan dan kecelakaan

[6] Pelihara fasilitas dan peralatan

▪ Pemeliharaan yang baik akan
membuat alat selalu berfungsi baik
dan siap digunakan
[7] Berlatihlah agar tetap terkini dan
berkembang

[8] Biasakan untuk bersih

dan rapi X
▪ Kebiasaan bersih dan cara kerja
yang cermat dapat menghindarkan
terjadinya kontaminasi dan
kesalahan
[9] Perhatikanlah kualitas
▪ Kualitas yang baik akan
meningkatkan kepercayaan pemakai
terhadap obat kita

[10] Lakukan audit untuk mengecek

kesesuaian
▪ Laksanakan program inspeksi diri
 In fact Cost benefits – positive cost benefits of
GMP/QA
 Good plant lay out, Smooth work flows, Efficient
documentation systems, well controlled process,
good stores lay outs and stores records- These
are Good manufacturing practices
 Reduction in work in process and inventory
holding costs
 Avoidance of cost of Quality failure ( cost of
waste, of rework, of recall, of consumer
compensation and of loss of company
reputation)
 Aman bagi konsumen

cGMP
PRODUKSI

Sesuai
PROMOSI kebutuhan
konsumen

Peningkatan
pangsa pasar
 MUTU PRODUK

 Peningkatan keamanan  Mengurangi risiko

konsumen produk tidak memenuhi
syarat mutu
 Peningkatan company
 Mengurangi risiko
image ketidak sesuaian
 Peningkatan pangsa dengan peraturan
pasar  Mengurangi stres dan
frustrasi
 Inspeksi 1
CPOB ed 3
Operational
Manual Sertifikasi I CPOB
Op. Manual Suplement
CPOB ed 1
Op. Manual
CPOB ed 2
In process
WH0-GMP
voluntary

1971 1989 1990 1990 1990 2001 2001 2006 2007 2009

Badan Pengawas Obat dan Makanan RI………………………..

 1971 : Penerapan CPOB dimulai secara sukarela
(berdasarkan standar WHO)
 1988 : Pedoman CPOB edisi I mulai diwajibkan untuk
diterapkan
 1989 – 1994 : Waktu penyesuaian pemenuhan CPOB
 1990 : Inspeksi CPOB pertama
 2001 : Pedoman CPOB edisi 2
 2005 : CPOB untuk produk Darah
 2006 : Revisi Pedoman CPOB  edisi 3
- 2008 : Petunjuk Operasional CPOB
- 2009 : Suplement CPOB
- 2012 : Revisi Pedoman CPOB  edisi 4
 Ditetapkan melalui surat keputusan menteri
kesehatan 43/Menkes/SK/II/1988-Tgl.2 Peb
1988

 Dengan adanya ketentuan tersebut semua

industri farmasi di Indonesia harus mengacu
pada ketentuan CPOB dalam seluruh
rangkaian pembuatan
obat jadi
42
 GMP yang berlaku lokal:
 CPOB Indonesia
 CGMP (current GMP) : AS

 GMP yang berlaku regional - internasional

 ASEAN GMP
 WHO GMP Guideline

43
 Dilakukan oleh Badan POM
 Badan POM mendapatkan kewenangan dari Kemenkes

 Badan POM
 Memberikan panduan dan
memastikan pelaksanaan CPOB
di industri farmasi
 Dalam pembahasan pedoman
CPOB terdapat beberapa istilah
yang harus diketahui, karena
sering digunakan.

 Pemahaman terhadap istilah-

istilah tersebut penting, untuk
memudahkan memahami tentang
pedoman CPOB
 Produk Jadi:
Produk yang telah melalui seluruh tahap
proses pembuatan obat.

Telah selesai diolah dan dikemas,

siap dipasarkan.
 Produk ruahan:
Bahan yang telah selesai diolah, tinggal
dikemas.

Contoh: tablet yang telah dicetak, kapsul

yang sudah diisi.

47
 Produk antara:
Bahan atau campuran bahan yang masih
memerlukan tahapan pengolahan lebih lanjut
untuk menjadi produk ruahan.

Contoh: granul tablet yang belum dicetak,

granul kapsul yang belum diisikan.

48
 Bahan awal:
Semua bahan baku dan bahan pengemas
yang digunakan dalam produksi obat.

49
 Semua bahan aktif dan bahan tidak aktif
yang digunakan dalam pengolahan obat.

 Bahan baku aktif : Bahan yang memiliki efek

langsung terhadap tubuh.
Bahan yang memiliki khasiat.
 Bahan baku tidak aktif:
Bahan yang tidak memiliki efek langsung
terhadap tubuh pasien.

Tidak memiliki khasiat, digunakan untuk

membantu formulasi.
Contohnya : Air dan gula untuk pemanis
sirup.
 Bahan pengemas :
Semua bahan yang digunakan untuk
mengemas produk.
Untuk memudahkan distribusi produk dan
untuk melindungi produk dari pengaruh
lingkungan.

 Terdiri dari:
 Bahan pengemas primer
 Bahan pengemas sekunder
 Bahan pengemas primer :
Bahan pengemas yang berkontak langsung
dengan produk
 alufoil, blister, botol, vial dan ampul

 Karena berkontak langsung dengan produk,

proses pengemasan primer harus dilakukan
di area pengolahan, tidak boleh dilakukan di
area pengepakan.
 Bahan pengemas sekunder :
Bahan pengemas yang tidak berkontak
langsung dengan produk.
 Unit box, dus, corrugated box

 Proses pengemasan sekunder harus

dilakukan di area pengepakan, tidak boleh di
area pengolahan
 Sejumlah tertentu obat yang memiliki sifat dan
mutu yang seragam.
 Dibuat atas satu perintah produksi :
Batch record/ batch processing order

 Memiliki satu hasil pemeriksaan QC

yang tersendiri: COA

 Diolah dalam satu siklus pengolahan:

▪ satu kali mixing, satu kali coating, kecuali
apabila hasilnya dicampurkan
 Satu batch produk tidak boleh dicampurkan
dengan batch lain

 Kecuali ada persetujuan manager QC

dan disertai pencatatan yang jelas.

 Perlu didukung dengan alasan yang jelas, dan pembuktian

bahwa tidak terjadi penyimpangan mutu, dan stabilitas
produk
 Lot :
Bagian dari batch yang memiliki sifat dan
mutu yang seragam.

 Dalam proses pengolahan suatu produk dapat ditemui tahapan

yang mengharuskan untuk membagi batch kedalam beberapa
bagian
 Misalnya: karena kapasitas mesin yang kecil: mixer, coating
dan autoclave
 Batch tidak dibagi kedalam Lot apabila hasil
akhirnya dicampurkan.
 Sebelum bagian-bagian batch dapat dicampurkan, harus
dipastikan bahwa semua bagian memiliki sifat mutu yang
seragam
Misal : hasil pengeringan FBD

 Apabila bagian batch tidak dijamin memiliki mutu seragam,

harus dibagi kedalam lot-lot, dan masing-masing lot
diperiksa.
Misal : hasil autoclave, coating, mixing
BANGUNAN
1. PEMILIHAN LOKASI
• Tidak dilingkungan perumahan
• Sebaiknya dikawasan Industri
• Bebas pencemaran : udara, tanah, air, lingkungan
2. RANCANG BANGUN DAN PENATAAN GEDUNG
Berdasarkan Kontak dengan luar
• Tempat penerimaan & penyimpanan : Bahan baku, bahan
pengemas, dan produk jadi.
• Tempat ganti pakaian
• Tempat pembersihan diri & Toilet
Berdasarkan Jenis produksi
• Bangunan terpisah : Produksi  - Laktam ; non  - Laktam:
Sefalosporin; Hormon estrogen.
• Ruang terpisah : Produk steril & non steril
 Kelas ruangan di industri farmasi ada 3 :
 Kelas hitam
 Kelas abu-abu
 Kelas putih

 Kelas ruangan disesuaikan dengan tujuan

pemakaiannya.
 Pembagian kelas berdasarkan :
 Jumlah partikel (terutama)
 Tingkat kebersihan
 Jumlah mikrobanya

 Secara teknis tiap kelas berbeda pada:

 Konstruksi
 Material
 Sistem pengendalian udara
Kelas hitam digunakan untuk:
Penanganan produk ruahan yang sudah tertutup kemasan
primer: pengepakan
Wadah tertutup rapat : gudang

Kegiatan di kelas hitam :

- Gudang
- Pengemasan sekunder

 Pakaian kerja
 Baju, celana sepatu
 Tutup kepala, masker
 Digunakan untuk
 Pengolahan
 Pengambilan contoh
bahan baku
 Pengemasan primer

 Pakaian kerja
 Baju, celana sepatu
 Tutup kepala, masker
 Digunakan untuk pengolahan
produk steril

 Merupakan kelas yang tertinggi tingkat

kebersihannya, baik dari segi partikel
ataupun jumlah mikrobanya.

 Pakaian kerja (khusus)

 Baju, celana, sepatu
 Tutup kepala, masker
 Sarung tangan, goggle (kaca mata)
 Temperature

Humidity

Air Cleanliness

Room Pressure

Air movement

Lighting
65
 Ref. PICS GMP 2006 WHO TRS 902

AS PICs FDA At rest In operation

EA Maximum permitted number of particles/m3 equal to or above
N
0,5 mm 5mm 0,5mm 5mm

I A 100 3 500 0 3 500 0

(UDAF)
I B 100 3 500 0 350 000 2000
(Turb.)
II C 10 000 350 000 2 000 3 500 000 20 000

III D 100 000 3 500 000 20 000 Not Not

defined defined
IV NC NC Not defined Not defined Not Not
defined defined

(LAF/UDAF) = laminar air flow or uni-directional air flow

(Turb.) = turbulent or non-uni-directional air flow
Rekomendasi Jumlah Partikel di Lingkungan Produksi
Nonsteril.
Jumlah maksimum partikel /m³ yang
diperbolehkan
Keterangan
Kelas At Rest Operasional
0,5µm 5µm 0,5µm 5µm
Jumlah mikroba ditetapkan oleh
E Tidak di- Tidak di- masing-masing industri farmasi,
ruang 3.500. 20.
000 000 tetapkan tetapkan misal: ruang pengolahan dan
proses
pengemasan primer.

Ruang pengemasan sekunder tidak

F berhubungan langsung dengan
ruang
Tidak di- Tidak di- Tidak di- Tidak di- area luar; untuk memasuki ruang
penge-
tetapkan tetapkan tetapkan tetapkan ini disarankan melewati suatu
masan
ruang penyangga udara (airlock)
sekunder
atau ruang antara (ante- room).

G Tidak di- Tidak di- Tidak di- Tidak di-

gudang,
tetapkan tetapkan tetapkan tetapkan Ruang penyimpanan (gudang).
tehnik, lab,
kantin
Differential Pressure / perbedaan tekanan
 Ruang produksi non-betalaktam
Tekanan udara dalam ruang pengolahan liquid > tekanan
udara di koridor
Tekanan udara dalam ruang pengolahan solida < tekanan
udara di koridor ( ∆ P = 10-15 Psi)
Tekanan udara dalam ruang produksi > tekanan udara di
koridor ( ∆ P = 10-15 Psi)

Ruang produksi betalaktam (dry sirup, kapsul, tablet)

Tekanan udara dalam ruang pengolahan < tekanan
udara di koridor ( ∆ P = 10-15 Psi)
Tekanan udara dalam ruang produksi < tekanan udara
luar ( ∆ P = 10-15 Psi)
Diferensial Pressure / perbedaan Tekanan (∆P)
Bertujuan untuk meniadakan kemungkinan terjadi Cross
Contamination/kontaminasi silang antara ruangan pengolahan, koridor &
udara luar.

“One way air lock” =

Ruang antara yang pintunya hanya bisa dibuka salah satu saja
1. Tekanan ruang pengolahan sediaan solid < tek. di ruang koridor
(bertujuan agar debu yang dihasilkan di ruang pengolahan solid
tidak menyebar ke ruang lain via koridor)
2. Tekanan ruang pengolahan sediaan Liquid > tek. di ruang
koridor/solid (bertujuan agar debu yang berasal dari solid tidak
pindah ke ruang pengolahan liquid yang relatif tidak berdebu)
3. Tekanan diruang produksi non-betalaktam > tekanan udara luar
(bertujuan agar debu yang berasal luar gedung tidak dapat masuk
ke dalam gedung melalui aliran udara luar)
Kesimpulan :
P. ruang liquid > P. ruang koridor > P. ruang solid > P. ruang luar
 Pengolahan
Dispensing Liquida - Pengemasan
Produk Jadi
Semisolida Sekunder/Tersier
Inspeksi
IPC Akhir (QA)
IPC
Pencampuran Pengemasan
Akhir Primer Release

Pengisian Gudang

Bahan Awal Produk Antara Produk Ruah

Produk Jadi
Monitoring
Alur Proses
Automatic Liquid Mfg. Plant
 Radial movement, acting in a direction
vertical to the impeller shaft

 Longitudinal / axial movement, acting

parallel to the impeller shaft

 Tangential movement, acting in direction

that is a tangent to circle of rotation round
the impeller shaft
 PENGADUK
Diameter
Jenis pengaduk daun pengaduk Jenis aliran

Putaran lambat
Pengaduk Sangkar
P. Bingkai
P. Pallet Besar Tangensial
P. Impeller

Putaran cepat
P. Propeller
P. Cakram
P. Cakram+gigi Kecil Axial+Radial
Jenis pengaduk ukuran putaran Pola aliran

P. jangkar Øblade = 95% x lambat tangensial

Øbejana
P. Gate paddle Øblade = 2/3 x lambat tangensial
Øbejana
P. leaf+pallet Øblade = ½ x lambat tangensial
Øbejana
P. 3leaf bended Øblade = ½ - 2/3 x 100-200 rpm Axial – Radial
impeller Øbejana High shear stress
2-3 leaf propeller Øblade = 1/3 -1/10 x cepat Axial - Medium
Øbejana shear stress
turbin Øblade kecil cepat Axial - Radial
Cakram + gigi Øblade = 1/6-1/2 x cepat Axial - Radial
Øbejana
Rotor + stator Øblade = 1/6 – ½ x cepat Radial
Øbejana
Jenis pengaduk Aplikasi
3leaf impeller Melarutkan solute dlm solvent, membuat suspensi/ emulsa

propeller Dgunakan dlm proses fluidisasi, cocok utk cairan bviskositas

rendah,mmiliki efek kavitasi shg efektif utk proses aerasi

Cakram+gigi Sgt cocok utk suspensi/emulsa yang viskos, dpt dgunakan

Rotor+stator sbg disolver/disperser, karena shear stress tinggi mnimbulkan
efek pengecilan ukuran partikel
Pencampur getar digunakan pada suspensi/emulsa bviskosita rendah, guna
memperhalus ukuran partikel. kerja alat menimbulkan
turbulensi tinggi akibat getaran vertikal yang kuat, sehingga
bahan dipaksa mlewati lubang2 krucut. Utk mhindari aerasi,
gunakan vakum tinggi, efek samping mnimbulkan
bising+klelahan pd alat.
In-line mixer Digunakan dalam proses homogenisasi kontinu thd produk
bkuantitas besar dalam waktu relatif singkat. Alat mencampur
produk dalam pipa dengan sdikit resirkulasi dan dalam
ruangan dmana hambatan+ resirkulasi terjadi, adanya fluktuasi
mnimbulkan turbulensi+resirkulasi
The colloid mill is a fluid ultramicro
smashing machinery. It performs the
functions of smashing, emulsification,
dispersing, homogen, milling and so on.

 Chemical industry: grease, paint,

emulsified bitumen, detergent,
leather dyestuff
 Medicine industry: Biological
products, vaccine, medicinal
ointment, each kind of oral liquid
 Daily expenses industry: washing
floods, toothpaste, shoe polish, jacket
oil, cosmetics
The Choice of Filling Machine Depends on:
 The range of viscosity of the liquid
 Temperature
 Chemical compatibility
 Particulate size
 Foam characteristics and
 Hazardous environment considerations.
Commonly Used Filling Machines
 Overflow liquid filling machines: These are
commonly used in small bottle filling operations and
the machine is also able to handle liquids with
medium viscosity.
 Servo pump liquid filling machines: These
machines are very versatile liquid filling machine
capable of filling nearly any type of product that can
be pumped.
 Peristaltic filling machines: This specially designed
filler machine is used to fill liquids of high value and
small volume of liquids fills with high accuracy.
Commonly Used Filling Machines
 The gravity liquid filling machines: This is the
most economical type of liquid filling machine
for a limited range of applications.
 Piston liquid filling machines: These machines
are one of the oldest and most reliable types
that are used in the packaging industry.
 Net weight liquid filling machines: This type of
filler is best suited for liquids that are required to
fill in bulk quantities.
For liquids with low to medium viscosity. liquids with
solid particulates not exceeding 1/16" can also be filled.
Note that overflow fillers are the machine of choice in
handling very foamy products at higher speeds.
Examples:
Sauces, syrups, light gels and shampoos, foamy
cleansers and chemicals, water and other non
carbonated aqueous beverages.
Adv. : High performance, easy to clean, easy to operate,
expandable at low cost. Offers greatest flexibility at
lowest cost
The supply side (dark blue) of a two part nozzzle is used to pump product into the
container. When the container fills up to the target fill height, the excess product
and foam is forced out of the container (red arrows) via the return side to the
original product source tank.
Both thin and thick products, and also very large
particulates can all be filled on this machine. Cosmetic
creams as well as thick, chunky sauces at pasteurized
temperatures can all be filled.

Adv. : Fill size changeovers are practically infinite and are

instantaneous by computer control. Operator setup is
greatly simplified. The design also lends itself very well to
sanitary applications due to the ease of automatic
cleaning.
The filler's master computer
independently tracks the rotation
of each pump head so that it
knows precisely how much
product has been delivered. When
the target fill volume is reached,
each pump and nozzle is instantly
shut off, resulting in high accuracy
fills of your valuable products. The
computer stores all fill parameters
in memory for fast changeovers.
Specifically designed for high value, small volume fills at
very high accuracy. Suitable for aqueous and other light
viscosity products.

Examples:
Pharmaceutical preparations, fragrances, essential oils,
reagents, inks, dyes, and specialty chemicals.

Adv. : Fluid path is disposable; easy cleanup and

elimination of cross contamination problems. Accuracies
of 0.5% are achievable for fill volumes less than 1 ml.
The peristaltic pump makes
intermittent contact on only the
outside of the surgical (product)
tubing so that the product only
touches the inside of the tubing. The
filler's master computer
independently tracks the # of
rotations of the peristaltic pump head
so that it knows precisely how much
product has been delivered. When
the target fill volume is reached, the
pump stops and the remaining
product fluid does not drip out due to
pipette action. The computer stores
all fill parameters in memory for fast
changeovers.
For liquids with very thin viscosities that do not change with
ambient temperature or with batch variation. This machine is also
suited for applications where recirculation of the liquid in the
fluid path is not desireable. Although this type of filler is used
predominantly on products that do not foam, foam may be
limited and controlled by subsurface/bottom-up-fill capability.
Examples:
Water, solvents, alcohol, specialty chemicals, paint, inks, corrosive
chemicals i.e. acids and bleach.
Advantages:
This is the most economical type of filling machine for a limited
range of applications. It is especially well suited for corrosive
chemicals.
The product bulk supply is pumped into a holding tank above a set of pneumatically
operated valves. Each valve is independently timed by the filler's master computer so
that precise amounts of liquid will flow by gravity into the container. Gravity fillers
built with bottom up fill capability can handle a wide range of flowable liquids
including foamy products.
This type of piston filler is best suited for viscous products
that are paste, semi paste, or chunky with large particlates.
Examples: Heavy sauces, salsas, salad dressings, cosmetic
creams, heavy shampoo, gels, and conditioners, paste
cleaners and waxes, adhesives, heavy oils and lubricants.
Adv. : This lower cost conventional technology is easy to
understand for most users. Fast fill rates are achievable
with fairly thick products. Warning: this technology is
nearly obsolete with the advent of servo positive
displacement fillers.
The piston is drawn back in its
cylinder so that the product is sucked
into the cylinder. A rotary valve then
changes position so that the product
is then pushed out of the nozzle
instead of back into the hopper.
For liquids filled in bulk quantities e.g. 5 gallon pails, etc. or products
that have a very high manufactured value.
The product bulk supply is
pumped into a holding tank
above a set of pneumatically
operated valves. Each valve is
independently timed by the
filler's master computer so
that precise amounts of liquid
will flow by gravity into the
container. Gravity fillers built
with bottom up fill capability
can handle a wide range of
flowable liquids including
foamy products.
Volumetric Fillers are ideal for filling liquids with low to
medium viscosity. There are tube filling machines used for
filling viscous and semi viscous products.

Types of Volumetric Filling Machines

 Pnematic Volumetric Filling Machines: These machines
are operated using volumetric displacement pump
based filling system.
 Manual Volumetric Filling Machines: As the name
suggests, they are operated manually.
KLIK LINK INI
KLIK LINK INI
 Presentation
 Identification
 Protection
 Convenience
 Containment during storage

 Primary Package
 Secondary Package
 Tertiary Package
Liquid
 Generally glass has been the material of
choice for the packaging of liquid
 Variety plastics used they have little or no
permeability to the liquid

Semisolid
 flexible tubes
 made from aluminium or plastic such as PE
 Glass
 Metals
 Rubber
 Plastics
 Foil, film & laminating
 Fibrous material
such as : paper, cartons, boxes
 product must be stored under proper
conditions
- to ensure the stability of a pharmaceutical
prepn for the period of its intended shelf life

 Labeling of each product

- includes the desired conditions of storage
 Cold
- any temp not exceeding 8oC (46oF)
- a refrigerator is a cold place where the
temp. is maintained bet. 2o and 8oC (36o and
46oF)
 Cool
- any temp bet. 8o and 15oC (46o and 59oF)
 Room Temp.
- temp prevailing in a working area
- 20o to 25oC (68oF to 77oF) but also allows for temp variations
bet 15o and 30oC (59o and 86oF) experienced in pharmacies,
hospitals, and drug warehouses

 Warm
- any temp bet 30o and 40oC (86o and 104oF)

 Excessive Heat
- any temp above 40oC (104oF)
 Oral Solutions and Suspensions: Appearance,
precipitation, pH, color, odor, dispersibility
(suspension) and clarity (solutions)

 Topical creams: ointments, lotions, solutions,

and gels. Appearance, color, homogeneity,
odor, pH, resuspendability (lotions),
consistency, particle size, distribution
strength, weight loss.
 Opthalmic and Nasal and Oral inhalation
preparations: Appearance, color consistency,
pH, clarity (solutions), particle size, and
resuspendability (suspensions, ointments),
strength and sterility.
 Suppositories: Softening range; appearance
and melting.
 Emulsions: Appearance (such as phase
separation) color, odor, pH, and viscosity.
 ATAS

ATENSINYA