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Teknologi Sediaan Steril For Mhs
Teknologi Sediaan Steril For Mhs
http://www.free-powerpoint-templates-design.com
Learning Outcomes
Sterile Dosage Forms
01
and calculation
02 Preformulation
03 Formulation
Pro active!!
References
Armstrong, N.A., and James, K.C., 1996, Pharmaceutical Experimental Design and
Interpretation. Taylor and Francis, Bristol.
Banker, G.S. and Rhodes, C.T. 2002, Modern Pharmaceutics, 3rd. Ed., MNarcel-Dekker Inc.,
New York.
Gennaro A.R, 2013, Remington : :The Sience and Practice of Pharmacy, 22nd Ed., Mack
Publ. Co., Pensylvania.
Lachman, 1986, The Theory and Practice of Industrial Pharmacy, 2nd, Ed., Lea & Febiger,
Philadelphia.
Sterile dosage Forms
Q Q
Sterile? Sterilization? Dosage form of sterile
Q product?
Administration?
Why should be sterile?
Q
How to make sure the
sterility?
Q
Production facility?
Sterile Products
01 Sterile 02 Why? 03 So, why?? 04 What?
Free of viable Injected through the skin
As first line of body - Starting material
microorganism or mucous membranes
defense - Production facility
into internal body
compartments - Manufacturing
Absolute condition process
(Relative - Person
connotation and
probability) of a total
destruction or
elimination of all
living microorganism
REMEMBER SAL!
06 Administration 05 How?
- Biovalaibility Sterilization ?
- Fast effect
- Targeted
Sterile
Dosage Forms Administration
Dosage - Small volume injection - Intravenous
Water or non water based - Intraspinal
Forms Oil
Suspension
Reconstitution powder
-
-
-
Intramuscular
Subcutaneous
Intradermal
- Ophthalmic preparation
- Large volume injection
Water based
- Semisolid
Ointment
Cream
Gel
- Ophthalmic preparation
- Solid
Pellets
Implantation tablet
Administration route
Intravascular Nonvascular injection
Solution Solution
Suspension (particle size?, %) Suspension 5%
Emulsion
ACHTUNG!! Blockage of fine capillaries
Nonvascular
Intramuscular, Intracutaneous Intraspinal
Subcutaneous
Solution
Suspension Less than 0.2 mL tissue
10 mL or less
Emulsion volume
Solid pellets
Intravitreal injection
Implants
Specification
Example Text :
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Sterility Tonicity
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Template will your Time,
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molds and viruses. The gram or filtration procedure? MoneyHealthy
and Reputation.
human body : -0.52ºC
negative bacteria produce the most
potent pyrogenic substance as 2. Sodium
Example Text : chloride equivalent
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Calculation of tonicity
1 2
3
Thermal
Physical
Non
Thermal
Sterilization
technique
Gas
sterilization
Chemical
Surface
disinfection
Manufacturing Process of Sterile Products
CPOB 2012
Isolator
technology and Terminal vs Building and
Principle
Blow, Fill and Aseptic process facility
seal tech
Processing
Principle
Special req minimize risks contamination of micro, particulate and pyrogen, depends on sktll, training and personnel
General Grade A:
• Airlocks The local zone for high risk operations.
• Preparation in separate area Provided by a laminar air flow work station
• In operation and at rest states (air speed in a range of 0.36 – 0.54 m/s
(guidance value) at the working position. The
maintenance of laminarity should be
demonstrated and validated.
• Routinely monitored
• Class A during critical process
• Class B frequency less than A
• C and D areas accordance with priciples of quality risk
management
• Preparation of components and most products should • Components after washing Grade D
be done in at least a Grade D. Where there is unusual
risk Grade C • Handling of sterile starting materials and components,
unless subjected to sterilization or filtration Grade A
• Filling of products for Grade C. Where the product is environment with Grade B background.
at unusual risk Grade A zone
• Preparation of solutions which are to be sterile filtered
Grade C
• Conveyor belt should not pass through a • Accordance with a written programme.
partition between a Grade A or B area
and a processing area of lower air • More than one type disinfectant . In Grades A
cleanliness and B areas should be sterilized prior to
use
• Equipment used can be effectively sterilized
• UV light should not be used as a substitute
• Equipment and services operations,
maintenance and repairs can be carried out • Levels (limits) of detection of microbiological
outside the clean area contamination should be established for alert
and action purposes, and for monitoring the
• All equipment should be subject to validation trends in air quality in the facility
and planned maintenance; their return to use
following maintenance should be approved
and recorded
Water Processing
Forms Oil
Suspension
Reconstitution powder
-
-
-
Intramuscular
Subcutaneous
Intradermal
- Ophthalmic preparation
- Large volume injection
Water based
- Semisolid
Ointment
Cream
Gel
- Ophthalmic preparation
- Solid
Pellets
Implantation tablet
STEP PREFORMULATION
1. Physicochemical properties
1.Preformulation 2. Pharmacology & Pharmacokinetics
3. Supplier
2.Formulation trial Lab Scale 4. Cost
5. Compatibility with excipient
3.Pilot Scale 6. Market
4.Production FORMULATION
1. Hypothesis
2. Excipient selection (quality and
quantity)
Formulation process is same, the different only req for sterile
3. Process optimization
and ‘place’ for manufacturing process & grade starting
material
Basic in formulation :
1. Dose
2. Goal of treatment
Material should be able to sterilize 3. Route of adm
1. Starting material aseptic without filtration 4. Patient
2. Bulk of finished product aseptic with filtration
3. Finished product (in final prim pack) terminal sterilization
Physicochemical properties
Solvent Solutes
• Aqueous • Antioxidant
• Non aqueous • Buffer
• Miscible w/ water • Tonicity agent
• Immiscible w/water • Preservative
• Solubilizer
Solvent
When we are using aq or no aq?
Req for non aq?
Reducing Chelating
Blocking agent Synergist
agent agent
• Oxidized first • H • Increasing • Complex with
merusak effectiveness catalyst
radikal of
antioxidants
Buffer
When we are using buffer?
1. Diff at freezing point (∆Tf) 0.52º Univalent-univalent electrolyte 3,4 NaCl, AgNO3
2. E NaCl 0.9% NaCl Univalent-divalent electrolyte 4,3 Atropin sulfate, Na2CO3
3. Liso
Divalent-univalent electrolyte 4,8 CaCl2, Ca-gluconate
Aseptic
Remove
microorganism
Bacteriostatic or
killing process
Latanoprost eye drop 0.005%, 2.5 mL 1. Indication, route adm, dose, patient information
(see brochure)
2. Physicochemical properties
Zink Sulphate eye drop 0.4%, 10 mL 3. Problem and conclusion stability, tonicity,
packaging or other
4. Formula material, Qty (%), function
5. Manufacturing process step, class
Dexamethasone suspension eye drop
1 mg/mL, 10 mL 6. Evaluation parameter
In PPT or PDF
Metode Sterilisasi
Akhir
Waktu Filtrasi
Aseptis
Tanpa filtrasi
Panas basah
Panas
Panas kering
UV
Metode Radiasi
Ionizing
Etilen oksida
Filtrasi
Preparation Sealing
Weighing Mixing B Filling
(A) (C)
Waktu A B C
Metode
Aseptis tanpa filtrasi A Class
Aseptis dengan filtrasi B Weighing C-A E-C E-C
Terminal sterilisasi C Preparation A C C
Mixing A C/A C
Metode
Filling A A C
Panas basah C
Sealing A A C
Panas kering A, C
Sterilization A A C
Radiasi UV -
Radiasi ionizing A
Etilene Oxide A
Filtrasi B
Sterilisasi Panas
• Diutamakan
Sterility After
Wet condition
SAL condition
Sterilizer types :
(1) Natural convection: Rise of hot air and fall of cool air :
blocked, diff 20ºC ZAQ
(2) Forced convection : Blower
(3) Tunnel unit with moving belt : glass bottle
Mechanism
Passed matter
Energy liberated
Reactivity
Excitation and alteration activity of
essential atoms within molecules
microorganism or of their essential Maintenance
metabolites dies or unable to Free from dust, grease and scratches
reproduces emission intensity
Ionizing Radiations
Lethal action
Transfer of radiation beam
energy lethal mutation (direct,
indirect)
Gas Sterilization
05
04
03 -
02 +
• Double filter
• Free asbes
+ -
Accumulate then stop • Integritas filter : bubble point, diffusive flow atau
pressure hold
Removing dirt particles
as well as Flow rate
microorganism- • Tidak digunakan lebih dr 2 hari kerja kec telah
Filling speed divalidasi
1. Compatibility
2. Size
3. Cost
Bubble point test
SAL : probability of viable microorganism on the product after it has been sterilized
Dipengaruhi o/:
1. Karakteristik container : ukuran, geometric, heat transfer
coefficient
2. Product vol dan ɳ
3. Ukuran dan konfigurasi ‘load’ dlm sterilizer
Tahapan validasi
Tentukan
Tentukan penterasi
Lakukan heat
panas kedalam Ulangi
pengujian distribution Evaluasi
Kualifikasi produk pd coolest proses
Pilih utk pd efek dr Monitoring
dan point dan hingga
indikator menentuka keadaan cycle : t, T, scr
pengeceka ‘suspected location’ didapt
biologi n D value kosong, load dan periodik
n sterilizer dmn heat hasil
dan Z identifikasi Fo
penetration sesuai
value coolest
‘slowest’
point
Pilih
sensitive
microbial Jika
Evaluasi
Air and growth Sterilisasi Tentukan >0.1%
fasilitas Inkubasi
surfaces medium groeth Lakukan level Ulangi perlu
dan filled
microbial dan medium simulasi kontamina proses dilakukan
critical container
test microorga dan filter si review
area
nism kembali
‘challenge
’
Indikator Biologi
• To monitor sterilizers Pengujian : min 3 lot spore, prepared from different
• Microbiological test system providing a defined spore crops. Pengujian :
resistance to a specific sterilization process 1. Viable spore population assay
• BI is the most resistance to the process 2. Resistance characteristic study (resistometer) : D,
Z, survival/Kill window
3. Carrier and prim pack material evaluation
4. Holding time assessment
5. Recovery protocol 7 days
6. Mail in protocols
CPOB
• Indikator biologis dan kimiawi bukan utk pembuktian proses sterilisasi telah efektif, tapi menunjukan
kegagalan proses
• Indikator kimia : pita atau lembaran adhesive, kartu bercak warna dll. Indikator tsb dapat berubah
warna krn reaksi kimia saat proses sterilisasi
Practice Steril A
Topic 1 Topic 2 Topic 3