STERILIZATION
Prof. Dr. Gülgün Yener
Department of Pharmaceutical Technology
CONTAMINATION (Pollution)
1. Active agents and excipients
2. Air
3. Employees
4. Solvents used
5. Equipments and materials previously used
Causes CONTAMINATION in drug
preparation
Types of Contamination
1.Chemical (Naturally originated
substances)
2.Mechanical (Outdoor, equipments)
3.Microbiological
Expression of the degree of
contamination
Matter
- If gas, is the number of particles per m3
- If liquid, is the number of particles per
cm3 or ml
- If surface, is the number of particles
per dm2
- If solid, the number of particles per g
1.Chemical Contamination
-Comes from natural substances
- Some substances may remain after drug
synthesis
-Plastic containers can take material from
outside to inside or other wise
2. Mechanical Contamination
Foreign material may come from external
environment.
Rubber part, hair, bristle, starch, talc
impurity
Especially, ophthalmic preparations should
be free of foreign particles
2. Mechanical
Contamination
There should be no metal, glass, plastic
material, pyrogenic material, textile
residue.
Insecticide (Lanolin is obtained from
sheep, should be removed when used in
treatment)
3.Microbiological
Contamination
-Injectable preparations
Should be absolutely sterile, free of
microorganisms
- Ophthalmic preparations
- - Preparations applied to the skin with
burns and ulcers
Should not contain any microorganisms in
ml or g
- Otic, nasal, pharyngeal preparations
can carry 100 microorganisms / g or ml.
3.Microbiological
Contamination
- Other preparations (oral, topical)
can contain microorganism up to
1000 / g or ml
- Baby powder, lipstick, ophthalmic
preparations can contain less than 100
microorganism / g.
STERILIZATION
It is the process of completely destroying the
microorganisms and spores in the
environment.
Refers to any process that effectively kills or
eliminates transmissible agents (microorganisms)
such as,
fungi,
bacteria,
viruses,
Protozoa and helminths,
prions and
spore forms,
from a surface, equipment, foods, medications,
or biological culture medium.
Disinfection
Refers to any process that effectively kills or
eliminates microorganisms from in-animate
(non-living) objects -
surface,
equipment,
Disinfectants are antimicrobial agents that are
applied to non-living objects to destroy
microorganisms, the process of which is known
as
disinfection.
Antisepsis
Removal of microorganisms from living
(animate)
tissue
Antiseptics are antimicrobial agents that
are
applied to living tissue to destroy
microorganisms, the process of which is
known as
antisepsis.
History
It has been known since the early ages.
Aristotle suggested drinking water after
boiling,
Hippocrates proposed the use of wine,
sulfur and burned wood products (cedar)
in wounds and operations.
History
Medieval
-Lister- (1827-1921)
Used phenol
Potassium permanganate, iodine,
eucalyptus essence, sublimation, silver
nitrate were used
-
History
Scheel A (1872)
Heat sterilization (heating vinegar-
increases stability)
-Pasteur (1847)
Sterilization methods of cotton, surgical
dressing material, surgical instruments
History
- Pasteur(1878)
Discovered microorganisims
- Loffler(1884)
Sterilization with vapour
- Tyndall(1881)
Tyndalization(heating at 100 0C for short
time fractionally)
History
- Koch
Sterilization with dry or moist heat
- Ehrlich(1906)
Chemical disinfectants
Membrane filter (1913)
History
Sterile filtration
Ancient Egyptian Civilization
Filtration of water
- 19. Century London (cholera outbreak)
- Pasteur (1884)
Chamberland filter
- Berkefeld (1891)
Wax and Seitz filter
Glass Filter
STERILIZATION PROCESS
It’s purpose is to deliver the sterile final
product to final user
Raw materials
Method selection
Water
Equipment Validation
Packing material
Enough space
Qualified staff
VALIDATION
These are processes that create results designed
under all possible conditions.
Control of sterilization results
Number of live microorganisms
Proper storage of sterile products
Reliability during storage
Distribution, opening and use of sterile
products
PURPOSE:
Obtaining a product with minimum
and consistent bioburden
To achieve a better safety level with
the latest sterilization procedures
BIOBURDEN
The number of viable microorganisms
in or on the substance or preparation
to be sterilized.
FINAL STERILIZATION
It is the application that ensures that
no living microorganisms remain in
the packaged finished product.
STERILITY SAFETY LEVEL
The term refers to the probability of a
non-sterile unit following the
sterilization step.
STERILIZATION METHODS
1. PHYSICAL METHOD
2. CHEMICAL METHOD
3. MECHANICAL METHOD
Methods of sterilization
1. PHYSICAL METHODS
A. BY HEAT
a. DRY HEAT
b. MOIST HEAT
B. BY UV RAYS
C. BY RADIATION
STERILIZATION BY UV RAYS
Effective wavelength 2100 - 3300 A0
Optimum effect 2650 A0
Death of bacteria
Easy to absorb
Risk of changing structure
Usage in room and air sterilization
UV rays kill bacterias.
It is adsorbed by medium easily.
It does not effect deep liquids.
To sterilize sheets with 3 mm thickness it
is sufficient to apply 1-10 sec of UV rays.
STERILIZATION BY RADIATION
Irradiation: gamma radiation / ionization
Cobalt 60 - radioisotope
Product - ionized radiation
Penetration to product
Leaves no residue
Applicable to many products
STERILIZATION BY RADIATION
Subjecting the product to ionized radiation
at controlled levels.
STERILIZATION BY RADIATION
Radiation kills germs that can cause
disease and neutralizes other harmful
organisms. Sterilization with
ionizing radiation inactivates
microorganisms very efficiently and, when
used for product wrapping, ensures that
healthcare products are safe and can be
relied upon.
Medical Products
Disposable gloves
Plastic syringes
Infusion sets
Surgical laps
Sets for blood collecting
Cannula and drainage tubes
Pharmaceutical Products
Drug containers
Gelatin capsules
Aluminum tubes and caps
Membrane filters
Dry powders
Ophthalmic pomades
Antibiotics
Parenteral preparations
Aerosols
Advantages of Sterilization by
Radiation
Product formulation/packing
Simplicity of validation (sole variable is
time)
Warranty after application (Dosimeter)
Decreasing endotoxin level
Power of penetration
Selection of Radiation Dosage
Depends on the
Number of the microorganisms sensitive
to radiation
Intended level of sterilization to be
achieved
Product’s sensitivity to radiation
2. CHEMICAL METHOD
Sterilization with Vapours
Ethylene oxide,
Chlorine dioxide,
Propylene oxide,
Hydrogen peroxide
Gas penetration and purification
No toxic residues in product
2. CHEMICAL METHOD
CHEMICAL AGENTS
Alcohols
-Ethyl,
-Isopropyl,
Trichlorobutanol
Aldehydes
– Formaldehyde,
- Glutaraldehyde
Dyes
CHEMICAL AGENTS
Halogens
Phenols
Surface active agents
Metallic salts
Gases
– Ethylene oxide,
- Formaldehyde,
- Betapropiolactone.
Alcohols
Ethanol (80% v/v ethyl alcohol) or 2-
propanol (60-70% v/v iso- propyl alcohol)
solutions are used to disinfect skin and
decontaminate clean surfaces. Spectrum:
Effective against fungi, vegetative
bacteria, Mycobacterium species and some
lipid-containing viruses.
Alcohols
11. Limitation: Not effective against
spores.Concentration: Most effective at
70% inwater
.Caution: Do not use near flames due
toflammability.May swell rubber or harden
plastics.
Formaldehyde
Precautions are required when handling
formaldehyde Formalin is 37% w/v
formaldehyde gas in water.
Spectrum: Active against most microorganisms.
Bactericidal, sporicidal, virucidal.
13% v/v formalin is a good decontaminant
(but has an irritating odour).
8% v/v formalin in 80% v/v alcohol is effective
against vegetative bacteria, spores and viruses.
Does not corrode stainless steel.
Formaldehyde
Formaldehyde is used to preserve
anatomical specimens, and for destroying
anthrax spores in hair and wool. 10%
formalin containing 0.5% sodium
tetraborate is used to sterilize clean metal
instruments.
Formaldehyde
Formaldehyde gas is used to sterilize
instruments, heat sensitive catheters and
for fumigation of wards, sick rooms and
laboratories. It can also be used for
clothing, bedding, furniture and books.
To disinfect equipment such as centrifuges
or biosafety cabinets.
Fumigation Technique
After sealing the windows and other
outlets, formaldehyde gas is generated by
adding 250g of KMnO4 to 500 ml formalin
for every 1000 cu.ft of room volume.
Caution: The reaction produces
considerable heat, and so heat resistant
vessels should be used.
Fumigation Technique
After starting generation of formaldehyde
vapour, the doors should be sealed and
left unopened for 48 hours. Caution:
Formaldehyde can react with free chlorine
to produce toxic gas. Remove hypochlorite
solutions and hydrochloric acid from
spaces to be decontaminated. Irritant
vapours are released hence Neutralise
with ammonia following decontamination.
