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TRANSCRIPT
OBJECTIVES OF THE LECTURE
• At the end of this lecture, you will be aware of:• What are Sterile dosage forms?• What are various types of Sterile dosage forms?• What are the applications and rationale of Sterile
dosage forms?• What are advantages / disadvantages of Sterile dosage
forms?• How Sterile dosage forms are prepared?
All preparations that are free of viable microorganisms.
• Microrganism.
• Spores.
• Pathogens.
• Sterile products are mostly injected, applied onto eye
and administer intranasally.
• Parenteral products,
• Ophthalmic products,
• Implants,
• Intranasal & Pulmonary Drug Delivery systems,
• Others
• Solution for irrigation
• Radiopharmaceuticals
• Surgical
• Medicinal Devices
SELECTION OF THE STERILIZATION METHOD:
A. STEAM STERILIZATION (Autoclave)
a. Application of pressure:• Note that the temperature, not the pressure is destructive to the
microorganisms and that the application of pressure only for the purpose of increasing the temperature of the system, because it is not possible to raise the temperature of the steam above 100C. under atmospheric conditions.
• b. Time of application:• The usual conditions (time/pressure/temperature), are as follow:• 10 pounds pressure (115.50C) for 30 minutes• 15 pounds pressure (121.50C) for 20 minutes• 20 pounds pressure (126.50C) for 15 minutes• As can seen, the greater the pressure applied, the higher the
temperature obtainable and the less the time required for sterilization.
• c.The penetration time of the moist heat• It depends on the nature of the load/product.
A. STEAM STERILIZATION (Autoclave)..
•Applicable for pharmaceutical preparations and materials that can
withstand the required temperature and are penetrated by, but not
adversely affected by, moisture.
•In sterilizing aqueous solutions, the moisture is already present,
and all that is required is the elevation of the temperature of the
solution for the prescribed period of time. Thus solutions packaged
in sealed containers as ampules, are readily sterilized by this
method.
•Also applicable to bulk solutions, glassware and instruments.
AUTOCLAVE NOT APPLICABLE FOR:
•The sterilization of oils, fats, oleaginous preparations.
•Other preparations not penetrated by the moisture.
•Sterilization of exposed powders that may be damaged by
condensed moisture.
APPLICATION OF AUTOCLAVE
Mechanism: Dry heat kill microorganisms primarily through oxidation.
Hot air sterilization: Two principal methods of dry-heat sterilization are
infrared and convection hot air. (Infrared rays sterilize surfaces only.)
Dry heat sterilization is usually conducted at temperature of 160-1700C
for 2 hours or 2600C for 45 min.
Note1: If a chemical agent melts or decomposed at 170 °C, but is
unaffected at 140 °C, the lower temperature must be used and the
exposure time would be increased.
Note2: Individual unit to be sterilized should be as small as possible, and
the sterilizer should be loaded in such a manner as to permit free
circulation of heated air throughout the chamber.
Direct Flaming: Used to sterilize inoculating loops and needles. Heat
metal until it has a red glow.
Incineration: Effective way to sterilize disposable items (paper cups,
dressings) and biological waste.
B. DRY -HEAT STERILIZATION
Dry heat sterilization is generally employed for substances that are
not effectively sterilized by moist heat such as:
Fixed oils, Glycerin, Various petroleum products such as
petrolatum, liquid petrolatum (mineral oil).
Various heat-stable powders such as zinc oxide, kaolin and sulfur.
Dry heat transfers heat less effectively to a cool body, than moist
heat.
Higher temperature and longer period of exposure are required.
B. DRY -HEAT STERILIZATION..…..
Some moisture-sensitive and heat-sensitive materials can be
sterilized by exposure to ethylene oxide or propylene oxide gas.
Denature proteins by replacing functional groups with alkyl groups.
Several factors are important in determining whether ETO is effective
as a sterilizing gas, such as
a. Gas concentration (500mL/L),
b. Temperature (50-600C),
c. Humidity (60%),
d. Exposure time (4-16 hrs)
These gases are highly flammable when mixed with air but can be
employed safely when properly diluted with an inert gas such as
carbon dioxide or a suitable fluorinated hydrocarbon.
C. GAS STERILIZATION (ETHYLENE OXIDE)
The great penetration qualities of ETO make it a useful
sterilizing agent in special applications:
Sterilization of medical and surgical supplies such as
catheters, needles, and plastic disposable syringes in
their final plastic packaging.
Sterilize certain heat-labile enzyme preparations.
Certain antibiotics, and other drugs (with tests to assure
of the absence of chemical reactions).
Most hospitals have ethylene oxide chambers to sterilize
mattresses and large equipment.
C. GAS STERILIZATION (ETHYLENE OXIDE): APPLICATIONS
• Depends upon the physical removal of microorganisms by
adsorption on the filter medium or by sieving mechanisms.
• It Is used for sterilization of heat-sensitive solutions.
• Millipore filters are thin plastic membranes of cellulosic
esters with millions of pores/square inch of filter surface
• The pores are extremely uniform in size and occupy
approximately 80% of the filter membrane's volume.
• They are available in pore size from 14-0.025μm where the
smallest bacteria, about 0.2μm, and viruses about 0.025μm
can be trapped.
D. STERILIZATION BY FILTRATION
• Its speed in the sterilization / filtration.
• Its ability to sterilize thermo labile materials.
• Inexpensive equipment required.
• The complete removal of living and dead microorganism as
well as other particulate matter from the solution.
• DISADVANTAGES
The membrane is fragile thus it is essential to be sure that the
membrane is not ruptured.
Filtration of large volumes of liquids would require more
time (particularly if the liquids were viscous).
D. STERILIZATION BY FILTRATION: ADVANTAGES
• Three types of radiation kill microbes:
• Ionizing Radiation (X rays, GAMMA rays)
• Dislodge electrons from atoms and form ions.
• Cause mutations in DNA and produce peroxides.
• Used to sterilize pharmaceuticals and disposable medical
supplies.
• Penetrates human tissues. May cause genetic mutations in
humans.
• Nonionizing Radiation (Ultraviolet light)
• Damages DNA by producing thymine dimers, which cause
mutations.
• Used to disinfect operating rooms.
E. STERILIZATION BY RADIATION
• Microwave Radiation.
• Heat is absorbed by water molecules.
• May kill vegetative cells in moist foods.
• Bacterial endospores, which do not contain water, are not
damaged by microwave radiation.
• Solid foods are unevenly penetrated by microwaves.
E. STERILIZATION BY RADIATION
E. STERILIZATION BY RADIATION
Testing of Sterilization Process
Two types are performed to test the efficiency of sterilization:
1. Testing the sterility of the final product
2. Testing the sterilization process (by physical, chemical and biological
methods) to confirm that the equipment is working satisfactory.
PHYSICAL TEST
Thermocouples test: is used to measure the temperature at selected sites
in the chamber or within the load of a dry heat, steam or gas
sterilizer.
In case of sterilization by radiation: A measurement of radiation dose
i.e. the amount of energy absorbed by the material tested.
In case of sterilization by filtration: A bubble pressure test is used to
determine the pore size of filters.
Types that cannot indicate time of exposure:
Klintex papers:
• These are paper strips or stickers attach to each object to be
sterilized.
• The word (sterile) is written on the strip (colorless) but after
exposure to the sterilizing agent as steam the word (sterile)
will be cleared.
• Klintex test tablets:
• These contain 75% lactose, 24% starch and 1% magnesium
trisilicate.
• They are hard and white but after steam sterilization they
become brown and gelatinous.
Testing of Sterilization Process: Chemical indicator tests
C) Autoclave test tape (Bowie – Dick test):
• This is a valuable test for confirming that
the steam has displaced all the air from a
porous load (i.e. air removal test).
• The tape carries heat sensitive bars which
become colored if steam has full penetrated
the pack.
• If air remains, the bars in the centre are
lighter in color.
Testing of Sterilization Process: Chemical indicator tests
Types that indicate time of exposure:Browne’ tubes:
• Each tube consists of a sealed glass tube which
contains a red fluid (an ester and acid - base
indicator) that changes to yellow, brown and finally
green on heating (the ester undergoes heat
hydrolysis to form an acid + alcohol. The acid will
change the color of the indicator).
• Browne’s tube type I: Suitable for ordinary steam
sterilizers
• Browne’s tube type II: Suitable for high vacuum
sterilizers
• Browne’s tube type III: Suitable for hot air oven
• Browne’s tube type IV: Suitable for I.R conveyer oven.
Testing of Sterilization Process: Chemical indicator tests
• At the end of the process,
the bacteria are transferred
to a nutrient medium which
is incubated and the
presence or absence of
growth is noted.
• Biological indicators consist of bacterial cultures
which are usually used in the form of impregnated
strips e.g. paper and metal foil and are placed in
different sites in the sterilizer.
Testing of Sterilization Process: Biological indicator
• The bacterial species to be used must be carefully
selected, since it must possess high resistance to the
particular process.
• The following types of bacteria are commonly used in
the different sterilization process.
• Moist heat (autoclave): Standardized preparation of
Bacillus strearothermophilus spores.
• Hot air oven & Ethylene oxide sterilizer: Standardized
preparation of Bacillus globigii spores.
• Gamma radiation: Standardized preparation of
Bacillus pumilus spores.
• Filtration: Serratia marcescens is used.
Testing of Sterilization Process: Biological indicator
THANK YOU FOR ATTENTION