Sterile Dosage Forms and Technology

http://www.free-powerpoint-templates-design.com
Learning Outcomes
Sterile Dosage Forms
01
and calculation

02 Preformulation

03 Formulation

Sterility Test and

04
pyrogenetic test
 Class Rules
Time Evaluation
1 SKS Theory : 50/45 minutes Mid exam : 35%
2 SKS Practice : 2 x 160/145 minutes Final exam : 35%
200 minutes practice lab Task + soft skill (include quiz) : 30%
120/90 minutes yaitu pre dan post practice
UP I : 30%
Late maximum : 10 minutes? UP II : 35%
UP III : 35%
No eat and snacking, No SLEEP!
Keep the camera ON during class Final score : ((NT X SKS) + (NP X SKS))/Total SKS
Drink is allowed

Keep the class comfortable for everyone

Pro active!!
 References
Armstrong, N.A., and James, K.C., 1996, Pharmaceutical Experimental Design and
Interpretation. Taylor and Francis, Bristol.

Aulton,M.E., 1988, The Science of Dosageform Design, Churchil Livingstone, Edinburgh.

Avis, K.E., Lachman, L, and Lieberbamn, H.A., 2000, Pharmaceutical Dosageform :

Parenteral, Tablet, Disperse System, vol I, II, III, Marcel dekker Inc., New York.

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?

How to make sterile dosage

Q
Q forms?

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

Absorption, passive diffusion

Absorption affected by :
Isotonic
1. PSD
2. Blood supply
3. Movement of tissue
4. Physicochemical properties
Has lipophilic and hydrophilic properties (Why?) 5. Dosage forms

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

Intramuscular < 2 mL Absorption slow  lack of Absorption?

Subcutaneous < 1 mL blood vessels

Hypertonic for rapid Example? Example?

absorption
 Ophthalmic preparation
Location Dosage forms (conventional) Dosage form (new)

External surfaces (topical) Solution Gel

Inside (intraocular) Suspension Gel forming solution

Adjacent (periocular) Ointment Ocular inserts

Intravitreal injection

Implants
Specification
Example Text :
Get a modern PowerPoint Presentation
Sterility Tonicity
that is beautifully designed. You can simply
Pyrogens impress your audience and add a unique
zing−and appeal to your Presentations.
Osmosis phenomena
- Lipid substances associated with a − Make sure using validated sterilization Easy− For ophthalmicphotos
to change colors, and Text. I
: irritation
carrier molecule, which is usually procedure hope and I believe that this Template will
− For parenteral : depend on site
polysaccharide or peptide − Final package or bulk your Time, Money and Reputation. I hope
adm, quantity and method adm
− Tube inoculation and filtration and I believe that this Template will your
Time, Money and Reputation. Easy to
- Products of metabolisms of procedures  USP
− Calculation
change colors, photos and Text. I hope and
microorganism. Most bacteria and − Which one are using tube inoculation I believe that this freezing
Template will your Time,
1. Concept points
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
endotoxin Get a modern
methodPowerPoint Presentation
Leakage test that is beautifully
Defined as designed.
weightYou can simply
of NaCl that
- 1 h injection  fever, chills, body impress your audience and add a unique
produces the same osmotic effect
aches, cutaneous vasoconstriction Clarity Test zing and appeal to your Presentations.
Easy toas 1 g ofcolors,
change givenphotos
substances inI 100
and Text.
hope andmLI of solution
believe that this Template will
- Source : solutes, water, containers your Time, Money and Reputation. I hope
water : distillated and3.I believe
V-valuethat this Template will your
method
containers : 210ºC, 3-4 h Time, Money
Volume andofReputation.
the water Easy
to betoadded
solution : adsorption, change colors, photos and Text. I hope and
to a certain quantity of drug
ultrafiltration I believe that this Template will your Time,
Money and Reputation.
 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

Personnel Equipment Sanitation Waters

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.

Grade B: For aseptic preparation and filling,

this is the background environment for Grade
A zone.

Grade C and D: Clean areas for carrying out

less critical stages in processing of sterile
products.
Clean rooms and clean air device classification Clean rooms and clean air device monitoring

• Routinely monitored
• Class A  during critical process
• Class B  frequency less than A
• C and D areas  accordance with priciples of quality risk
management

• Aseptic operation : settle plates, volumetric air, surface

sampling (swab and contact plates)
 Isolator Technology Blow/Fill/Seal Technology

• Minimize human interventions  decrease in

the risk of microbiological contamination
• The transfer of materials into and out of the unit
is one of the greatest potential sources of
contamination
 Terminally Sterilized Products
• Preparation of components and most products should
be done in at least a Grade D. Where there is unusual
risk  Grade C
• Filling of products for  Grade C. Where the product is
at unusual risk  Grade A zone
Aseptic Products
• Components after washing Grade D
• Handling of sterile starting materials and components,
unless subjected to sterilization or filtration  Grade A
environment with Grade B background.
• Preparation of solutions which are to be sterile filtered 
Grade C
• Handling and filling of aseptically  Grade A
environment with a Grade B background
• Transfer of partially closed containers, as used in
freeze drying  Grade A with Grade B background
• Preparation and filling of sterile ointments, creams,
suspensions and emulsions should be done in a Grade A
with a Grade B background,
Building and Facility

• Can be observed from outside

• Surfaces should be smooth, impervious

and unbroken

• No un-cleanable recesses and a minimum

of projecting ledges, shelves, cupboards
and equipment

• Sinks and drains should be prohibited in

Grade A/B areas

• Changing room should be for personnel only

• Airlock doors should not be opened

simultaneously, pressure differential of 10 - 15
pascals
 Personnel

• Minimum number Clothing A B C D

Hair cover V V
• Selected Beard cover V V
Face mask
• Receive regular training Headgear V V
Coverall Single or two-piece The clothing V
• Outdoor clothing and regular working trouser should shed
clothes should not be brought into suit, gathered at the virtually no
changing rooms leading to Grade B and C wrists and with a fibres or
high neck, particulate
rooms
matter

• Gloves should be regularly disinfected

Gloves V V
• Masks and gloves should be changed at least Booties V V V V
at every working session

• Wristwatches, make-up and jewellery

should not be worn in clean areas.
 Equipment
• Conveyor belt should not pass through a
partition between a Grade A or B area
and a processing area of lower air
cleanliness
• Equipment used can be effectively sterilized
• Equipment and services  operations,
maintenance and repairs can be carried out
outside the clean area
• All equipment should be subject to validation
and planned maintenance; their return to use
following maintenance should be approved
and recorded
Sanitation
• Accordance with a written programme.
• More than one type disinfectant . In Grades A
and B areas  should be sterilized prior to
use
• UV light should not be used as a substitute
• Levels (limits) of detection of microbiological
contamination should be established for alert
and action purposes, and for monitoring the
trends in air quality in the facility
 Water
• Controlled , as a starting material
• WFI produced either by distillation or other
• WFI  produced, stored and distributed in a
manner which prevents microbial growth
• WFI  stored in clean, sterile, non-reactive,
nonabsorptive, non-additive containers and
protected from contamination
• Water sources, water treatment equipment
and treated water should be monitored
regularly
• Recording devices should be used to
monitor storage temperature
Processing
• Microbiological origin  different areas,
except vaccines consisting of dead
organisms or of bacterial extracts after
validated inactivation and validated cleaning
procedures
• Validation of aseptic  include (media fill),
three consecutive satisfactory simulation tests
per shift
• Microbiological contamination of starting
materials should be minimal
• Containers and materials liable to generate
particles should be minimized and avoided
completely
• The bioburden should be monitored before
sterilization
 Praktikum
Topic 1 Topic 2 Topic 3

• Filomena • Nada • Selvina

• Fika • Rifa • Afifah
• Erika • Herlinda • Luly
• Shinta • Tri Dewi • Denanda
 Practice

Before Spec Olopatadin ISDN Dexametha

Olopatadine eye drop autoclave e eye drop Injection sone
suspension
eye drop
ISDN Injection Assay (%) 90-115% 101 105 102

Impurity (%) NMT 1.0% BDL BDL BDL

Dexamethasone
suspension eye drop After Spec Olopatadin ISDN Dexametha
autoclave e eye drop Injection sone
suspension
eye drop
Assay (%) 90-115% 100 103 103

Impurity (%) NMT 1.0% BDL 1.2% BDL

1. Tipe sterilisasi
2. Jalur personalia dan barang
3. Jelaskan tiap step nya

Step Class Reason

Weighing
Mixing
Filling
Sterilization
Weighing Preparation Mixing Filling Sealing