3. Define Sterilization
is a process of achieving sterility or a
process where viable life forms are killed or
removed or
process of killing or removing mos or
destruction of all living organisms and their
spores or their complete removal from a
preparation
may be effected by killing mos by physical
and chemical means
4. parenteral pdts can be sterilized in their
final containers or as bulky solution or by
sterilization of the components whc are
mixed aseptically
Sterilization in final container is referred to
as “ Terminal sterilization and whc is the
preferred method of sterilizing parenteral
pdts since they are more easily controlled,
monitored, and quantified than aseptic
processes
5. Pdts not terminally sterilized must be
transferred aseptically to their final
containers whc must also be sterile
(aseptic filling)
Process involving heat is the most reliable
Aseptic processes involve risks of
contamination upon the env’t, processing
operators, processing time, and most
importantly the operators
6. What is sterility?
Total absence of viable mos
An absolute term( there no degrees of sterility,
something is either sterile or not)
7. Critical important factors in the
determination of conditions) of any
sterilization method chosen are:
• time and temperature
• Nature and amount of pdt bioburden in
pdt before sterilization)
• Whether the pdt & container-closure will
be predominantly moist or dry
environment during sterilization
8. Five general methods used to sterilize
pharmaceutical products:
Steam
Dry-heat
Filtration
Gas
Ionizing radiation
all are commonly used for parenteral pdts
except gas & ionizing used for devices
and surgical materials
9. Five general methods used to sterilize
pharmaceutical products
• Method is determined largely by the nature
of the preparation and its ingredients
• Regardless of method used ,the resulting
pdt must pass a test for sterility as a proof
of effectiveness of the method and the
performance of the equipment and
personnel
10. • For sterilization purposes, mos are
categorized into three general categories:
Easy to kill with either dry or moist heat
Susceptible to moist heat but resistant to dry
heat (e.g. Bacillus sublitis),
Resistant to moist heat but susceptible to dry
heat (e.g. Clostridium sporogenes)
11. Steam sterilization
Is conducted in an autoclave
Types of autoclaves:
Portable
Steam jacketed
Air Ballasted
Continuous sterilizers
Employs steam under pressure
Usually method of choice if pdt can with
stand it
12. Most pharmaceutical pdts are adversely
affected by heat and cannot be safe to the
temperature required for dry heat sterilization
(about 150°-170°, or 302°-338°F)
With the presence of moisture, bacteria is
coagulated and destroyed at considerably
lower temperature than when moisture is
absent
bacteria cells with a large percentage of
moisture are generally killed easily
spores that containing a relatively low
percentage of water are comparatively difficult
to destroy
13. MOA :
Microbial destruction in moist heat is by
denaturation and coagulation of some
organism’s essential proteins
Hot moisture in the microbial cells permits the
destruction at relatively low temperatures
Because its not possible to raise temperature
above 100°C(212 F°) under atmospheric
conditions, pressure is employed to achieve
higher temperatures
It’s the temperature not pressure that destroys
the mos and the application of pressure is
solely to increase the temp of the system
14. Time is another important factor in destruction
of mos by heat
Most modern autoclaves have gauges to
indicate to the operator the internal conditions
of temperature and pressure and timing device
to permit the desired exposure time for the load
Usual steam pressures ,and the temperatures
obtainable under these pressures, and the
approximate length of time required for
sterilization after the system reaches the
indicated temps are as follows:
15. Pressure (lb)
Pounds per in² or
kPa
Temperature (°C
or °F)
Time (minutes)
10 Or 68.91 115 Or 240 30
15 or 103.4 121.5 or 250 15 -20
20 126.5 or 260 15
16. The greater the pressure applied, the higher the
temperature obtainable and the less the time
required for sterilization
Most autoclaves routinely operate at 121°C
(250°F), as measured at the steam discharge
line from the autoclave
Temp in the chamber of the autoclave must
also be reached by the interior of the load being
sterilized , and the temp must be maintained fro
adequate time
Penetration time of moist heat into the load
varies with the nature of the load, and the
exposure time must be adjusted to account for
this latent period
17. For example,
A solution packaged in a thin-walled 50 -mL ampoule
may reach 121°C ,6-8 minutes after that temp is
registered in the steam discharge line, whereas 20
minutes or longer may be required to reach that temp
within a solution packaged in a complete filled thick
walled 1000-mL glass bottle
An estimate of these latent periods must be added to
the total time to ensure adequate exposure times
Process depend on moisture ands elevated
temperature, so air is removed from the chamber as
sterilization begins because a combination of air and
steam yields a lower temp than does steam under
same pressure
18. at 15 lb pressure, the temp of saturated steam
is at 121.5°C, but a mixture of equal parts of air
and steam will reach only about l12°C(234°F)
Principal uses of Moist-heat sterilization:
To sterilize materials that are thermostable
(within the conditions of sterilization cycle) and
through whc moisture can perfuse whc include:
Glass apparatus, and equipment, rubber parts
Surgical dressings and fabrics at 134°C for
3min
Plastic and rubber closures
Aqueuos parenteral solutions & suspension at
19. Disadvantages of autoclaving:
Unsuitable for thermolabile preparations
Unsuitable for oils, oleaginous preparations
Cannot be used for assembled equipment
where moisture cannot enter every part
Cause damage to glass because of repeated
exposure (clouds the glass, and alkali
extraction)
Cannot be used for exposed powders (may be
damage by condensed moisture)
20. DRY HEAT STERILIZATION
• Carried out in Hot Air Oven designed for that
purpose
• Is simplest method
• Dry heat has the advantage of penetrating power
and lack of corrosive properties
• Oven may be heated by either gas or electricity
• Thermostatically controlled
Are two in principal
• Infrared
• Convectional hot air
21. Infra-red rays –sterilize only surfaces
Sterilization of internal portions rely on
conduction
Convection hot air oven are normally heated
electrically (and are gravity or mechanically)
A fan is thus used to promote uniformity of heat
distribution throughout the chamber
MOA: dry- heat process kill mos primarily though
oxidation
• Amount of moisture available to assist
sterilization in dry- heat units varies
considerably at different locations within the
chamber and time interval within the cycle
22. • The amount of heat available , its diffusion , and
the env’t at the spore/air interface all influence
the microorganisms kill rate
• Consequently, cycles tend to be longer and
hotter than would be expected from
calculations to ensure that varying conditions
do not invalidate a run
• Generally , convection dry- heat sterilization
cycles run above 160°C
23. • Because dry heat is less effective in killing mos
than moist heat, higher temps and longer period
of exposure are required
• Determination of each pdt is considered in
accordance with the size and type of product,
container, and its heat distribution
characteristics
• Individual units to be sterilized shd be as small
as possible
• Sterilizer shd be loaded so as to permit free
circulation of heated air throughout the chamber
• Is conducted at 150-170°C for not less than 2
hrs
24. • Dry heat has also limited application in
parenteral manufacture
• Various combinations of temps and time are
recommended depending on the material to be
sterilized
• BP recommends cycles of:
Minimum of 180° for not less than 30 min
Minimum of 170° for not less than 1 hour
Minimum of 160° for not less than 2 hours and
other combinations are recommended
25. • But whatever combination is selected, the
process must be fully validated both for
efficiency of sterilization and for pdt stability
• USP requires manufacturers to challenge dry
heat sterilization cycles with resistant spores
such as Bacillus subtilis
• A 12 log reduction in number of spores is
desirable
(validation of sterility will be met later during the
course)
26. • Higher temps-shorter exposure for a given
article
• Lower temps –longer exposure times,
i.e. if a particular chemical agent melts or
decomposes at 170°C but is unaffected at
140°C(284°F), the lower temp is used and
exposure time increased
Dry heat sterilization is generally employed
for substances not affectively sterilized by moist
heat (paraffin; and various heat stable powders,
such as zinc oxide)
27. Oily and fats ; oily injections and implants
(processed aseptically)
Glassware (sterilized up to 250° for 2 hours to
effect depyrogenation)
Fixed oils ( ethyl oleate, glycerin; petroleum
pdt such as petrolatum, liquid petrolatum
(mineral oil ) require lower temps
Dry heat sterilization isn't suitable for injection
formulated in an aqueous base or cosolvent
system
28. • is an effective method for sterilizing glassware
and surgical instruments
• method of choice when dry apparatus or dry
containers are required , as in handling of
packaging of dry chemicals or non aqueous
solutions
Disadvantages of dry heat sterilization:
• long exposure at high temp make it unsuitable
for many medications and equipment
containing rubber
• unsuitable for surgical dressings because the
natural moisture vaporizes and therefore there
29. • prolonged heating up times and cooling times
make it time consuming and energy intensive
but the tunnel stererilizer overcomes these
problems
• cannot be used for assembled equipment into
which moisture cannot penetrate but the time
lag time must be carefully adhered to and is
long
