Cara Pembuatan Obat yang Baik (CPOB) untuk

sediaan Liquida – Semisolida

Yoga Windhu Wardhana

Mengapa dibuat sediaan farmasi ?

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

Mengapa dibuat sediaan farmasi ?

BENTUK PRODUK FARMASI

Gaseous dosage formsLiquid dosage formsSemisolid dosage formsSolid dosage forms

Gaseous 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)

Liquid dosage forms

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

1.Douches2.Enemas3.Gargles4.Mouthwashes5.Nasal washes6.Juices7.Sprays8.Otic solutions9. Inhalations

Sweet &/or Viscid

1.Syrups2.Honeys3.Mucilages4.Jellies

Nonaqueous

1.Elixirs2.Spirits3.Collodions4.Glycerins5.Liniments6.Oleo Vitamin

Semisolid dosage forms

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)

Semisolid dosage forms

2- Shaped

▪Suppositories (for rectal administration)o different shapeso Melting/dissolving at body temperatureo 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.

RUTE PEMBERIAN PRODUK FARMASI

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”

DEFINISI CPOB

Bagaimana membuat sediaan farmasi yang bermutu baik ?

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. 

c G M P

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.

Bagaimana membuat sediaan farmasi yang bermutu baik ?

Quality Management

Quality System

Quality Assurance

QualityControl

Policy, Objective,Committent & Direction

Organization Structure,Responsibility, Accoutability

Operational & TechnicalActivities on Fulfilling Quality

Requirements

External QAInternal 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

QA

QA, GMP & QC inter-relationship

Is that part of Quality Assurance aimed at

ensuring that products are consistently

manufactured to a quality appropriate to

their intended use

GMP

QA, GMP & QC inter-relationship

QA, GMP & QC inter-relationship

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

QC

QUALITY CONTROL ???

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:

QC and QA

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 based

GMP(Cara Pembuatan Obat yang Baik)

Aspek-aspek CPOB (1)

Aspek /hal yang harus diperhatikan dalam pelaksanaan CPOB :

Karyawan Bangunan Peralatan Sanitasi dan hygiene

Aspek-aspek CPOB (2)

Produksi Pengawasan Mutu Penanganan keluhan, recall

dan produk kembalian Dokumentasi

Why GMP is important

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.

Quality vs GMP

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.

Some of the main risks are

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.

Pengertian kontaminasi

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.

Penyebab kontaminasi

Dalam CPOB dikenal 3 jenis penyebab kontaminasi :

Bahan kimia

Mikroba

Partikel asing

Pelanggaran terhadap ketentuan CPOB (1)

Pelanggaran dapat mengakibatkan :

Teguran

Penarikan kembali obat yangberedar (recall)

Penutupan pabrik

Pelanggaran terhadap ketentuan CPOB (2)

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 reputasiperusahaan, dan mempengaruhi kelangsungan hidup perusahaan.

GMP Covers…

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.

Ten Principles of GMP

1. Design and construct the facilities and equipments properly

2. Follow written procedures and Instructions3. Document work4. Validate work5. Monitor facilities and equipment6. Write step by step operating procedures

and work on instructions7. Design ,develop and demonstrate job

competence8. Protect against contamination9. Control components and product related

processes 10. Conduct planned and periodic audits

Sepuluh aturan dasar CPOB (1)

[1] Tulislah prosedur kerja anda▪ Pastikan untuk memiliki prosedur

sebelum mulai bekerja

[2] Kerjakanlah sebagaimana prosedur yang ditulis

▪ Tanyakanlah apabila merasa raguatau tidak mengerti

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Sepuluh aturan dasar CPOB (2)

[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

Sepuluh aturan dasar CPOB (3)

[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 baikdan siap digunakan

Sepuluh aturan dasar CPOB (4)

[7] Berlatihlah agar tetap terkini dan berkembang

[8] Biasakan untuk bersihdan rapi

▪ Kebiasaan bersih dan cara kerjayang cermat dapat menghindarkan terjadinya kontaminasi dan kesalahan

X

Sepuluh aturan dasar CPOB (5)

[9] Perhatikanlah kualitas▪ Kualitas yang baik akan

meningkatkan kepercayaan pemakaiterhadap 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)

Cost of effective GMP

Manfaat Penerapan CPOB (1)

cGMPPRODUKSI

PROMOSI

Aman bagi konsumen

Sesuai kebutuhan konsumen

Peningkatan pangsa pasar

Manfaat Penerapan CPOB (2)

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

Sejarah CPOB di Indonesia

WH0-GMPvoluntary

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. ManualIn process

2007 2009

CPOBSuplement

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

PENERAPAN CPOB DAN PEMBARUAN PEDOMAN CPOB di INDONESIA

- 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

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Ketentuan CPOB di Indonesia (1)

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

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Ketentuan CPOB

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

GMP yang berlaku regional - internasional ASEAN GMP WHO GMP Guideline

Penegakan Pelaksanaan CPOB

Dilakukan oleh Badan POM Badan POM mendapatkan kewenangan dari

Kemenkes

Badan POM Memberikan panduan dan

memastikan pelaksanaan CPOBdi industri farmasi

Istilah-istilah CPOB (1)

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 Jadi:Produk yang telah melalui seluruh tahap proses pembuatan obat.

Telah selesai diolah dan dikemas, siap dipasarkan.

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Produk ruahan

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

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

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Produk antara

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

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

Bahan baku (1)

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 (2)

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 (1)

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 (2)

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 (3)

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

Batch (1)

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

Batch (2)

Satu batch produk tidak boleh dicampurkan dengan batch lain

Kecuali ada persetujuan manager QCdan disertai pencatatan yang jelas.

Perlu didukung dengan alasan yang jelas, dan pembuktian bahwa tidak terjadi penyimpangan mutu, dan stabilitas produk

Lot (1)

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

Lot (2)

Batch tidak dibagi kedalam Lot apabila hasil akhirnya dicampurkan. Sebelum bagian-bagian batch dapat

dicampurkan, harus dipastikan bahwa semua bagian memiliki sifat mutu yang seragamMisal : 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-kelas ruangan (1)

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

Kelas ruangan disesuaikan dengan tujuan pemakaiannya.

Kelas-kelas ruangan (2)

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

Secara teknis tiap kelas berbeda pada: Konstruksi Material Sistem pengendalian udara

Kelas hitam

Pakaian kerja Baju, celana sepatu Tutup kepala, masker

Kelas hitam digunakan untuk:

Penanganan produk ruahan yang sudah tertutup kemasan primer: pengepakanWadah tertutup rapat : gudang

Kegiatan di kelas hitam :- Gudang- Pengemasan sekunder

Kelas abu-abu

Digunakan untuk Pengolahan Pengambilan contoh

bahan baku Pengemasan primer

Pakaian kerja Baju, celana sepatu Tutup kepala, masker

Kelas putih

Digunakan untuk pengolahanproduk steril

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

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

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Facility Parameters That Need To Be Controlled

Temperature

Humidity

Air Cleanliness

Room Pressure

Air movement

Lighting

ASEAN

PICs FDA At rest In operationMaximum 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

Ref. PICS GMP 2006 WHO TRS 902

Jumlah maksimum partikel /m³ yang diperbolehkan

KeteranganKelas At Rest Operasional

0,5µm 5µm 0,5µm 5µm

Eruang 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.

Fruang 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).

Ggudang, 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 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

Alur Pengolahan Sediaan Liquida - Semisolida

Dispensing

Pengolahan

Liquida - Semisolida

Pencampuran

Akhir

Pengisian

Pengemasan Primer

Pengemasan Sekunder/Tersi

er

Produk Jadi

Release

Gudang

IPCIPC

InspeksiAkhir (QA)

Bahan Awal Produk AntaraProduk Ruah

Produk JadiMonitoring

Alur Proses

Pengolahan Sediaan Liquid

Automatic Liquid Mfg. Plant

Flow pattern on Mixing Liquid

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 pengadukDiameter

daun pengaduk Jenis aliran

Putaran lambat

Pengaduk SangkarP. BingkaiP. PalletP. Impeller

Besar Tangensial

Putaran cepat

P. PropellerP. CakramP. Cakram+gigi Kecil Axial+Radial

Pengaruh pengaduk pada pola aliran

Beberapa contoh tipe mixer

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 – RadialHigh 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

Powder/ Liquid Mixing - MHD 2000

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

Pengolahan Sediaan Semisolida

CONTOH VESSEL UNTUK SEMISOLIDA

COLLOID MILL

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

Liquid – Semisolid Filling

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.

Liquid - Semisolid Filling

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.

Liquid – Semisolid Filling (cont’d)

Overflow liquid filling machinesFor 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

Overflow liquid filling machines

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.

Servo pump liquid filling machines

Servo pump liquid filling machines

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.

Peristaltic filling machines

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.

Peristaltic filling machines

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.

Gravity Liquid Filling

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.

Gravity Liquid Filling

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.

Piston liquid filling machines

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.

Piston liquid filling machines

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.

Net weight liquid filling machines

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 Filling

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.

Liquid Filling

KLIK LINK INI

Semisolid Filling

KLIK LINK INI

Kemasan Sediaan Liquid & Semisolid

Presentation Identification Protection Convenience Containment during storage

Primary Package Secondary Package Tertiary Package

Primary Packaging

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

Primary Package Materials

Glass Metals Rubber Plastics Foil, film & laminating

Secondary & Tertiary Packaging Materials

Fibrous material such as : paper, cartons, boxes

STORAGE 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

Terms employed for the desired conditions as defined by the USP:

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)

Terms employed for the desired conditions as defined by the USP:

Signs of degradation of the specific dosage forms must be observed and reported

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.

Signs of degradation of the specific dosage forms must be observed and reported

TERIMAKASIH

ATAS

ATENSINYA