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Chapter: Pharmaceutical Engineering: Sterilization

Ultraviolet (UV) light is frequently employed to reduce airborne microbial contamination and for surface sterilization.


Ultraviolet (UV) light is frequently employed to reduce airborne microbial contamination and for surface sterilization. This is usually achieved by utilizing mercury vapor lamps with an emitted light of 2.537 x 10-7 m.

Radiation sterilization includes the use of the ionizing radiation of X rays and γ rays. X rays are derived from bombardment of a heavy metal target with electrons. γ Rays are obtained from atomic nucleus decay from the excited state to the ground state.

The energy evolved from radiation can be equated to photon behavior as follows:

E = hv


v = C/λ

where E and v are the energy and frequency of a photon, respectively, h is Planck’s constant, and C and λ are the speed and wavelength of light, respectively.

The energy absorbed from the radiation sources equates to the dose.

1 rad = 100 ergs/g of material absorbing

= 6.24 x 1013 eV/g

= 2.4 x 10-6 cal/g

There are a variety of radiation sources. 60Cobalt (60Co) decays to 59Co in the core of a nuclear reactor to emit two photons (1.17 x 106 eV and 1.33 x 106 eV) and an electron (0.31 x 106 eV). The halftime for decay is 5.3 years. 137Cesium (137Cs) decays emitting one photon (0.661 x 106 eV). Cesium has a 33-year half-life. An electron beam can be accelerated to energy equivalent to 5 x 106 to 10 x 106 eV. At energies below 5 x 106 eV, penetration is insufficient for sterilization. Energy above 10 MeV may induce untoward effects of radioactivity. The depth of penetration of radiation can be correlated with energy levels. For example, materials with density equivalent to water (ρ = 106 g/m3) are penetrated 5 x 107 m/eV. 60Co gives rise to radiation that penetrates 0.3 m through water. Accelerating electrons have high dose rate, and exposure is only required for seconds. 60Co has a lower dose rate, so an exposure for hours is required.

Ionizing radiation arises from the photoelectric effect, the Compton effect, or ion pair production. γ Radiation causes local and intense damage and may break chemical bonds. The primary target is the deoxyribonucleic acid (DNA) of the microorganism. In addition, free radicals may be formed, that is, peroxides that result in intracellular and extracellular peroxides by a chain reaction that cause damage.

Resistance to Damage

Damage depends on the amount of energy absorbed relative to the number and resistance of the microorganisms being irradiated. Unicellular organisms have greater resistance than multicellular ones. Gram-positive bacteria have greater resistance than gram-negative bacteria. Finally, bacterial spores have greater resistance than vegetative forms. Viruses are more resistant than bacteria. The energy required to reduce the population of viruses by 90% (D-value) is 5 x 105 rad. Fungi are equivalent to bacterial spores in their resistance.

To evaluate the dose, a number of parameters must be known. What magnitude of source (e.g., 60Co) is available? A typical source ranges between 500,000 and 2 million curies (Ci) where 1 Ci is 3.7 x 1010 disintegrations/sec. The product geometry and the speed of the conveyor carrying it to the source must be known. The dose can be evaluated by a variety of dosimetric techniques. In bulk or ampules containing liquids, ferric ammonium sulfate and ceric sulfate can be used to show an absorbance change, evaluated by UV spectrophotometry. This is only accurate for 60Co and 137Cs.

Radiochromic solids can be utilized and evaluated by visible spectrophotometry. Amber and red polymethylmethacrylate are used to evaluate 0.1 x 106 to 1.0 x 106 or 0.5 x 106 to 5.0 x 106 rad, respectively. Nylon film is examined for opacity following exposure and may be used to evaluate exposures of 0.1 x 106 to 5.0 x 106 rad.

Validation requires the determination of the bioburden and the D-value. These represent the dose required to achieve sterilization and the estimated dose.

The dose may be regarded as overkill if low D-values are obtained. Bacillus pumulis exhibits inherently high resistance to γ-ionization radiation with D-values of 0.15 x 106 to 0.22 x 106 rad. The Food and Drug Administration would like a 12-log reduction in microorganisms. The dose required is approximately 2.6 x 106 rad.

Product Development

The product, container, and closure must be evaluated for physical and chemical stability. A number of radiation-induced changes can potentially occur. The product may change in color, odor, flavor, potency, biocompatibility, and tox-icity. The container may lose rigidity, become brittle, label adhesion, and become leachable. The product and container may be assessed by exposure to multiple doses and single high doses of radiation. The long-term stability can then be evaluated under ambient storage conditions, at elevated temperatures, and under worst-case shipping conditions.

Dose mapping can be performed by determining the minimum radiation point in the load. Multiple dosimeters can be used to view vertical quadrant through the load. Dosimeters are routinely set to measure the minimum dose.

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