Several types of radiation find a sterilizing application in the manufacture of pharmaceutical and medical products, principal among which are accelerated electrons (particulate radiation), gamma rays and UV light (both electromagnetic radiations).
RADIATION STERILIZATION
Several types
of radiation find
a sterilizing application in the manufacture of pharmaceutical and medical products,
principal among which
are accelerated electrons (particulate radiation), gamma rays and UV light (both
electromagnetic radiations). The major target
for these radiations is believed
to be microbial DNA, with
damage occurring as a consequence of ionization and free-radical
production (gamma rays
and electrons) or excitation (UV light). This
latter process is less damaging
and less lethal than ionization, and so UV irradiation is not as efficient a sterilization method as electron
or gamma irradiation. Vegetative bacteria generally prove
to be the most sensitive to irradiation (with
notable exceptions, e.g. Deinococcus (Micrococcus) radiodurans), followed
by moulds and yeasts, with bacterial spores and viruses as the most resistant (except
in the case of UV light,
where mould spores
prove to be most resistant). The extent of DNA damage required
to produce cell death
can vary and this, together
with the ability to carry out effective repair, probably
determines the resistance of the organism
to radiation. With ionizing radiations (gamma ray and accelerated electrons), microbial resistance decreases with the presence of moisture or dissolved oxygen (as a result of increased free-radical production) and also with
elevated temperatures.
Radiation sterilization with high-energy gamma rays or accelerated electrons has proved to be a useful method for the industrial sterilization of heat-sensitive products. However, undesirable changes can occur in irradiated preparations, especially those in aqueous solution where radiolysis of water contributes to the damaging processes. In addition, certain glass or plastic (e.g. polypropylene, PTFE) materials used for packaging or for medical devices can also suffer damage. Thus, radiation sterilization is generally applied to articles in the dried state; these include surgical instruments, sutures, prostheses, unitdose ointments, plastic syringes and dry pharmaceutical products . With these radiations, destruction of a microbial population follows the classic survivor curves and a D-value, given as a radiation dose, can be established for standard bacterial spores (e.g. B. pumilus) permitting a suitable sterilizing dose to be calculated. In the UK it is usual to apply a dose of 25 kGy (2.5 Mrad) for pharmaceutical and medical products, although lower doses are employed in the USA and Canada.
UV light, with its much lower energy, causes
less damage to microbial DNA. This, coupled
with its poor penetrability of normal packaging materials,
renders UV light unsuitable for sterilization of pharmaceutical dosage forms. It does find applications, however, in the sterilization of air, for the surface
sterilization of aseptic
work areas, and for the treatment of manufacturing-grade water.
a) Sterilizer Design And Operation
i) Gamma ray sterilizers
Gamma rays for sterilization are usually derived
from a cobalt-60 (60Co) source (caesium-137 may also be used), with a half-life of 5.25 years,
which on disintegration emits radiation at two energy
levels of 1.33
and 1.17 MeV. The isotope
is held as pellets packed
in metal rods,
each rod carefully arranged
within the source
and containing up to 20 kCi (740
× 1012 Bq) of activity; these rods are replaced or rearranged as the activity of the source
either drops or becomes
unevenly distributed. A typical 60Co installation
may contain up to 1 MCi (3.7
× 1016 Bq) of
activity. For safety reasons,
this source is housed within
a reinforced concrete building with walls
some 2 m thick, and it is raised from a sunken
water-filled tank only when
required for use. Control
devices operate to ensure that the
source is raised
only when the chamber is locked and that it is immediately lowered if a malfunction occurs. Articles being sterilized are passed through
the irradiation chamber
on a conveyor belt
or monorail system
and move around the raised source,
the rate of passage regulating the dose absorbed (Figure
21.9).
Radiation monitors are
continually employed to detect any radiation leakage during operation or source storage,
and to confirm a return to satisfactory background levels
within the sterilization chamber following
operation. The dose
delivered is dependent upon source
strength and exposure period, with
dwell times typically up to 20 hours. The
difference in radiation susceptibilities of microbial cells and humans
may be gauged from the fact that a lethal
human dose would
be delivered by an exposure of seconds or minutes.
ii)
Electron accelerators
Two types of electron
accelerator machine exist,
the electrostatic accelerator and the microwave linear accelerator,
producing electrons with maximum energies
of 5 MeV and 10 MeV, respectively. Although higher energies
would achieve better penetration into the product,
there is a risk
of induced radiation and so they
are not used.
In the first, a high-energy electron beam is generated by accelerating electrons from a hot
filament down an evacuated
tube under high potential difference, while in
the second, additional energy
is imparted to this beam in a pulsed
manner by a synchronized travelling microwave. Articles for treatment
are generally limited
to small packs and are arranged on a horizontal conveyor belt,
usually for irradiation from one side but sometimes from both. The sterilizing dose is delivered more rapidly in an
electron accelerator than
in a 60Co plant, with exposure times for sterilization usually
amounting to only a few seconds or minutes. Varying extents
of shielding, depending upon the size of the accelerator, are necessary to protect operators from X-rays generated
by the bremsstrahlung effect.
iii)
Ultraviolet irradiation
The optimum wavelength for UV sterilization is around 260 nm.
A suitable source
for UV light
in this region
is a mercury lamp giving
peak emission levels at 254 nm.
These sources are generally wallor
ceiling-mounted for air disinfection, or fixed to vessels for water treatment. Operators present in an
irradiated room should wear appropriate
protective clothing and eye shields.
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