CPOB Liquid dan Semi Solid

Yoga Windhu Wardhana

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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

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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

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Medicinal gases, inhalation/volatile anaesthetics (vaporised before administration by inhalation)

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Aerodispersions of solid particles (e.g., antiasthmatic inhalations) or liquid particles (antiasthmatic inhalations or sprays)

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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 2. Enemas 3. Gargles 4. Mouthwashes 5. Nasal washes 6. Juices 7. Sprays 8. Otic solutions 9. Inhalations

1. Syrups 2. Honeys 3. Mucilages 4. Jellies

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 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 ▪ 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)

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-todate 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

Quality System External QA

Quality Assurance

Policy, Objective, Committent & Direction Organization Structure, Responsibility, Accoutability Internal QA

GMP

Quality QC Control

Operational & Technical Activities on Fulfilling Quality 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

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Operational laboratory techniques and activities used to fulfill the requirement of Quality

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QC is lab based

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All those planned or systematic actions necessary to provide adequate confidence that a product will satisfy the requirements for quality

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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.

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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.

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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.

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Kontaminasi adalah masuknya pengotor atau impurities yang dapat berupa bahan kimia, mikroba dan partikel asing kedalam bahan awal atau produk antara

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Kontaminasi dapat terjadi selama proses produksi, pengambilan contoh, pengepakan, penyimpanan atau transport.

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Dalam CPOB dikenal 3 jenis penyebab kontaminasi :  Bahan kimia  Mikroba

 Partikel asing

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Pelanggaran dapat mengakibatkan :  Teguran  Penarikan kembali obat yang

beredar (recall)  Penutupan pabrik

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Sanksi tersebut dikenakan karena pemerintah bertanggung jawab untuk melindungi kesehatan masyarakat pemakai obat kita.

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Hal tersebut sebenarnya merupakan tanggung jawab kita juga.

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Pelanggaran akan merusak reputasi perusahaan, dan mempengaruhi kelangsungan hidup perusahaan.

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ALL aspects of production; from the starting materials, premises and equipment to the training and personal hygiene of staff.

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Detailed, written procedures are essential for each process that could affect the quality of the finished product.

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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.

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.

[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

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[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

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[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

PROMOSI

Sesuai kebutuhan konsumen Peningkatan pangsa pasar

MUTU PRODUK

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Peningkatan keamanan konsumen Peningkatan company image Peningkatan pangsa pasar

 Mengurangi risiko

produk tidak memenuhi syarat mutu  Mengurangi risiko ketidak sesuaian dengan peraturan  Mengurangi stres dan frustrasi

Inspeksi 1 CPOB ed 3 Operational Manual

Sertifikasi I

Op. Manual

CPOB ed 1

Op. Manual In process

CPOB ed 2 WH0-GMP voluntary

1971 1989

1990

1990

1990

2001

2001

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

CPOB Suplement

2006

2007

2009

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1971

: Penerapan CPOB dimulai secara sukarela (berdasarkan standar WHO)

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1988

: Pedoman CPOB edisi I mulai diwajibkan untuk diterapkan

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1989 – 1994

: Waktu penyesuaian pemenuhan CPOB

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1990

: Inspeksi CPOB pertama

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2001

: Pedoman CPOB edisi 2

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2005

: CPOB untuk produk Darah

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2006

: Revisi Pedoman CPOB  edisi 3

-

2008

: Petunjuk Operasional CPOB

-

2009

: Suplement CPOB

-

2012

: Revisi Pedoman CPOB  edisi 4

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Ditetapkan melalui surat keputusan menteri kesehatan 43/Menkes/SK/II/1988-Tgl.2 Peb 1988

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Dengan adanya ketentuan tersebut semua industri farmasi di Indonesia harus mengacu pada ketentuan CPOB dalam seluruh rangkaian pembuatan obat jadi 42

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GMP yang berlaku lokal:  CPOB Indonesia  CGMP (current GMP) : AS

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GMP yang berlaku regional - internasional  ASEAN GMP

 WHO GMP Guideline

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Dilakukan oleh Badan POM  Badan POM mendapatkan kewenangan dari Kemenkes

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Badan POM  Memberikan panduan dan

memastikan pelaksanaan CPOB di industri farmasi

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Dalam pembahasan pedoman CPOB terdapat beberapa istilah yang harus diketahui, karena sering digunakan.

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Pemahaman terhadap istilahistilah tersebut penting, untuk memudahkan memahami tentang pedoman CPOB

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Produk Jadi: Produk yang telah melalui seluruh tahap proses pembuatan obat. Telah selesai diolah dan dikemas, siap dipasarkan.

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Produk ruahan: Bahan yang telah selesai diolah, tinggal dikemas. Contoh: tablet yang telah dicetak, kapsul yang sudah diisi.

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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.

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

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

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

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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.

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Bahan pengemas : Semua bahan yang digunakan untuk mengemas produk. Untuk memudahkan distribusi produk dan untuk melindungi produk dari pengaruh lingkungan.

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Terdiri dari:  Bahan pengemas primer  Bahan pengemas sekunder

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

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Karena berkontak langsung dengan produk, proses pengemasan primer harus dilakukan di area pengolahan, tidak boleh dilakukan di area pengepakan.

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Bahan pengemas sekunder : Bahan pengemas yang tidak berkontak langsung dengan produk.  Unit box, dus, corrugated box

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Proses pengemasan sekunder harus dilakukan di area pengepakan, tidak boleh di area pengolahan

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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

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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

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Lot : Bagian dari batch yang memiliki sifat dan mutu yang seragam.

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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

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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

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Kelas ruangan di industri farmasi ada 3 :  Kelas hitam  Kelas abu-abu  Kelas putih

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Kelas ruangan disesuaikan dengan tujuan pemakaiannya.

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

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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

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Pakaian kerja  Baju, celana sepatu  Tutup kepala, masker

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Digunakan untuk  Pengolahan  Pengambilan contoh

bahan baku  Pengemasan primer 

Pakaian kerja  Baju, celana sepatu  Tutup kepala, masker

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Digunakan untuk pengolahan produk steril

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Merupakan kelas yang tertinggi tingkat kebersihannya, baik dari segi partikel ataupun jumlah mikrobanya.

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Pakaian kerja (khusus)  Baju, celana, sepatu  Tutup kepala, masker  Sarung tangan, goggle (kaca mata)

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Temperature Humidity

Air

Cleanliness

Room

Air

Pressure

movement

Lighting 65

Ref. PICS GMP 2006

AS PICs FDA EA N

At rest

WHO TRS 902

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

IV

NC

NC

Not defined

Not defined

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

Rekomendasi Jumlah Partikel di Lingkungan Produksi Nonsteril. Jumlah maksimum partikel /m³ yang diperbolehkan Kelas

At Rest 0,5µm

E ruang proses

3.500. 000

5µm 20. 000

Operasional 0,5µm Tidak ditetapkan

5µm Tidak ditetapkan

Jumlah mikroba ditetapkan oleh masing-masing industri farmasi, misal: ruang pengolahan dan pengemasan primer. 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).

F ruang pengemasan sekunder

G gudang, tehnik, lab, kantin

Keterangan

Tidak ditetapkan

Tidak ditetapkan

Tidak ditetapkan

Tidak ditetapkan

Tidak ditetapkan

Tidak ditetapkan

Tidak ditetapkan

Tidak ditetapkan

Ruang penyimpanan (gudang).

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

Dispensing

Pengolahan Liquida Semisolida

Pengemasan Sekunder/Tersier

Produk Jadi Inspeksi Akhir (QA)

IPC

IPC

Pencampuran Akhir

Pengemasan Primer

Pengisian Bahan Awal

Gudang

Produk Antara Produk Ruah

Monitoring Alur Proses

Release

Produk Jadi

Automatic Liquid Mfg. Plant

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Radial movement, acting in a direction vertical to the impeller shaft

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Longitudinal / axial movement, acting parallel to the impeller shaft

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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

Besar

Tangensial

Kecil

Axial+Radial

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

Putaran cepat P. Propeller P. Cakram P. Cakram+gigi

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

cepat

Radial

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. 



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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.

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Presentation Identification Protection Convenience Containment during storage

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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

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Glass Metals Rubber Plastics Foil, film & laminating

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Fibrous material such as : paper, cartons, boxes

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product must be stored under proper conditions - to ensure the stability of a pharmaceutical prepn for the period of its intended shelf life

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Labeling of each product - includes the desired conditions of storage

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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)

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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

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

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Excessive Heat - any temp above 40oC (104oF)

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Oral Solutions and Suspensions: Appearance, precipitation, pH, color, odor, dispersibility (suspension) and clarity (solutions)

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Topical creams: ointments, lotions, solutions, and gels. Appearance, color, homogeneity, odor, pH, resuspendability (lotions), consistency, particle size, distribution strength, weight loss.

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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.

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