CPOB Liquid dan Semi Solid

 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

 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}

 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

Pharmaceutical Solutions Aqueous 1. Douches 2. Enemas 3. Gargles 4. Mouthwashes 5. Nasal washes 6. Juices 7. Sprays 8. Otic solutions 9. Inhalations

Sweet &/or Viscid 1. Syrups 2. Honeys 3. Mucilages 4. Jellies Nonaqueous 1. Elixirs 2. Spirits 3. Collodions 4. Glycerins 5. Liniments 6. Oleo Vitamin

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

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 ▪ Peroral (p.o)

▪ Sublingual (S.L) and buccal.

▪ Rectal

▪ Parenteral

▪ Transdermal

▪ Inhalation

for local administration

▪ Topical (on the skin or mucosa)

Into/onto - the eye, nose, ear - the oral cavity - the vagina, rectum - the brochi

- the skin

▪ Local parenteral (viz Parenteral above)

▪ Oral (local effect within GIT; antacids, adsorbents)

“ 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”

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.

Quality Management Quality System Quality Assurance Quality Control Policy, Objective, Committent & Direction Organization Structure, Responsibility, Accoutability

Operational & Technical Activities on Fulfilling Quality

Requirements External QA

Internal QA

QM, QS, QA, GMP and QC Inter-relationships

QC GMP

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

Is that part of Quality Assurance aimed at ensuring that products

are consistently manufactured to a quality appropriate to

their intended use

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

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

WEWENANG DAN TANGGUNG JAWAB:

 Operational

laboratory techniques and activities used to fulfill the requirement of Quality

 QC is lab based

 All those planned or systematic actions necessary to provide adequate confidence that a product will

satisfy the

requirements for quality

 QA is company

Aspek /hal yang harus diperhatikan dalam pelaksanaan CPOB :

 _Karyawan  Bangunan

 _Peralatan

 _Produksi

 _{Pengawasan Mutu}

 _{Penanganan keluhan, recall}

dan produk kembalian

 _{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

 _{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,

 Dalam CPOB dikenal 3 jenis penyebab

kontaminasi :

 _{Bahan kimia}  _Mikroba

 Pelanggaran dapat mengakibatkan :

 _Teguran

 _{Penarikan kembali obat yang}

beredar (recall)

 _{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

33

[3] Catat /dokumentasikan hasil kerja anda

▪ Lakukan pencatatan pada saat bekerja, bukan setelah (sebelum) bekerja Validasi pekerjaan anda

[4] Validasi pekerjaan anda

[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

▪ 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

 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)

cGMP

PRODUKSI

PROMOSI

Aman bagi konsumen

Sesuai kebutuhan

konsumen Peningkatan

 Mengurangi risiko

produk tidak memenuhi syarat mutu

 Mengurangi risiko

ketidak sesuaian dengan peraturan

 Mengurangi stres dan

frustrasi MUTU PRODUK  Peningkatan keamanan konsumen  Peningkatan company image  Peningkatan pangsa pasar

WH0-GMP voluntary CPOB ed 3 Op. Manual Operational Manual CPOB ed 1 Inspeksi 1 Sertifikasi I 1971 1989 1990 1990 1990 2001 2006 CPOB ed 2 2001 Op. Manual In process 2007 2009 CPOB Suplement

 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

42

 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

43

 GMP yang berlaku lokal:

 _{CPOB Indonesia}

 _{CGMP (current GMP) : AS}

 GMP yang berlaku regional - internasional

 _{ASEAN GMP}

 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.

47

 Produk ruahan:

Bahan yang telah selesai diolah, tinggal dikemas.

Contoh: tablet yang telah dicetak, kapsul yang sudah diisi.

48

 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.

49

 Bahan awal:

Semua bahan baku dan bahan pengemas yang digunakan dalam produksi obat.

 Semua bahan aktif dan bahan tidak aktif

yang digunakan dalam pengolahan obat.

 Bahan baku aktif : Bahan yang memiliki efek

langsung terhadap tubuh.

 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.

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.

 Kelas ruangan di industri farmasi ada 3 :

 _{Kelas hitam}  _{Kelas abu-abu}  _{Kelas putih}

 Kelas ruangan disesuaikan dengan tujuan

 Pembagian kelas berdasarkan :

 Jumlah partikel (terutama)

 _{Tingkat kebersihan}  Jumlah mikrobanya

 Secara teknis tiap kelas berbeda pada:

 Konstruksi

 _Material

 Pakaian kerja

 Baju, celana sepatu

 Tutup kepala, masker

Kelas hitam digunakan untuk:

Penanganan produk ruahan yang sudah tertutup kemasan primer: pengepakan

Wadah tertutup rapat : gudang

Kegiatan di kelas hitam :

- Gudang

 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

65  Temperature Humidity Air Cleanliness Room Pressure Air movement Lighting

AS EA N

PICs FDA _{At rest In operation}

Maximum permitted number of particles/m3 _{equal to or above}

0,5 mm 5mm 0,5mm 5mm I A 100 (UDAF) 3 500 0 3 500 0 I B 100 (Turb.) 3 500 0 350 000 2000 II C 10 000 350 000 2 000 3 500 000 20 000 III D 100 000 3 500 000 20 000 Not defined Not defined

IV NC NC Not defined Not defined Not defined

Not defined

(LAF/UDAF) = laminar air flow or uni-directional air flow (Turb.) = turbulent or non-uni-directional air flow

Jumlah maksimum partikel /m³ yang diperbolehkan

Keterangan Kelas At Rest Operasional

0,5µm 5µm _{0,5µm 5µm} E ruang proses 3.500. 000 20. 000 Tidak di- tetapkan Tidak di- tetapkan

Jumlah mikroba ditetapkan oleh masing-masing industri farmasi, misal: ruang pengolahan dan pengemasan primer. F ruang penge-masan sekunder Tidak di- tetapkan Tidak di- tetapkan Tidak di- tetapkan Tidak di- tetapkan

Ruang pengemasan sekunder tidak berhubungan langsung dengan area luar; untuk memasuki ruang ini disarankan melewati suatu ruang penyangga udara (airlock) atau ruang antara (ante- room).

G gudang, tehnik, lab, kantin Tidak di- tetapkan Tidak di- tetapkan Tidak di- tetapkan Tidak

di-tetapkan Ruang penyimpanan (gudang).

Rekomendasi Jumlah Partikel di Lingkungan Produksi Nonsteril.

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

Diferensial Pressure / perbedaan Tekanan (∆P)

Bertujuan untuk meniadakan kemungkinan terjadi Cross

Contamination/kontaminasi silang antara ruangan pengolahan, koridor &

udara luar.

“One way air lock” =

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 :

Dispensing Pengolahan Liquida - Semisolida Pencampuran Akhir Pengisian Pengemasan Primer Pengemasan

Sekunder/Tersier Produk Jadi

Release Gudang IPC IPC Inspeksi Akhir (QA)

Bahan Awal Produk Antara Produk Ruah

Produk Jadi Monitoring

 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

Jenis pengaduk

Diameter

daun pengaduk Jenis aliran

Putaran lambat Pengaduk Sangkar P. Bingkai P. Pallet P. Impeller Besar Tangensial Putaran cepat P. Propeller P. Cakram

Jenis pengaduk _{ukuran putaran Pola aliran}

P. jangkar Øblade = 95% x Øbejana

lambat tangensial P. Gate paddle Øblade = 2/3 x

Øbejana lambat tangensial P. leaf+pallet Øblade = ½ x Øbejana lambat tangensial P. 3leaf bended impeller Øblade = ½ - 2/3 x Øbejana 100-200 rpm Axial – Radial High shear stress 2-3 leaf propeller Øblade = 1/3 -1/10 x

Øbejana

cepat Axial - Medium shear stress turbin Øblade kecil cepat Axial - Radial Cakram + gigi Øblade = 1/6-1/2 x

Øbejana

cepat Axial - Radial Rotor + stator Øblade = 1/6 – ½ x

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 Rotor+stator

Sgt cocok utk suspensi/emulsa yang viskos, dpt dgunakan 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

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

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

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

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

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

 Presentation  Identification  Protection

 Convenience

 Containment during storage

 Primary Package

 Secondary 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}

 Glass

 Metals

 Rubber

 Plastics

 Fibrous material

 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

 Cold

- any temp not exceeding 8o_{C (46}o_F)

- a refrigerator is a cold place where the

temp. is maintained bet. 2o and 8oC (36o and 46oF)

 Cool

 Room Temp.

- temp prevailing in a working area

- 20o _{to 25}o_{C (68}o_{F to 77}o_{F) but also allows for temp variations}

bet 15o _{and 30}o_{C (59}o _{and 86}o_{F) experienced in pharmacies,}

hospitals, and drug warehouses

 _Warm

- any temp bet 30o _{and 40}o_{C (86}o _{and 104}o_F)

 Excessive Heat

 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

ATAS