Outline

I. Introduction to Ionizing RadiationII. Manufacture of RadiopharmaceuticalsIII. Radiation as Means of SterilizationIV. Radiation MonitoringV. Guidelines for Using Radiation in the

Manufacture of Drugs

Definition of Terms

• Radiation– energy transmitted from a source– 2 types:• Non-ionizing radiation• Ionizing radiation

Ionizing Radiation Non-ionizing Radiation

Definition of Terms

• Radioactivity– the process in which an unstable isotope

undergoes changes until a stable state is reached and in the transformation emits energy in the form of radiation

• Radioisotope– radioactive atoms of an element with different

number of neutrons

Definition of Terms

• Radioactive Decay– the process in which an unstable atomic nucleus

spontaneously loses energy by emitting ionizing particles and radiation

– parent nuclide transforming to an atom of a different type, named the daughter nuclide

– Types of emitted radiation:• Alpha• Beta• Gamma

Definition of Terms

• Radiopharmaceuticals– A preparation, intended for in vivo use, that

contains a radionuclide in the form of an element, simple salt or a complex

– Used for diagnosis and therapy• Radiopharmacy– also known as nuclear pharmacy– specialty area of pharmacy practice dedicated to

the compounding and dispensing of radioactive materials for use in nuclear medicine procedures

Ionizing Radiation

• Alpha– 2 protons, 2 neutrons– completely blocked when it

hits matter

Ionizing Radiation

• Beta– Negatron or positron– Used more commonly than

alpha

Ionizing Radiation

• Gamma– Electromagnetic– Radiated as photons of energy– Most penetrating type

MANUFACTURE OF RADIOPHARMACEUTICALS

Ideal Radionuclides

• Readily Available, Easily Produced & Inexpensive• High Target to Non target Ratio– maximize the efficacy of diagnosis– minimize the radiation dose to the patient

• Effective Half-life– It should be short enough to minimize the radiation dose

to patients and long enough to perform the procedure. Ideally 1.5 times the duration of the diagnostic procedure.

Production of Radiopharmaceuticals

• Preparation of Radiopharmaceuticals– Reconstitution of reagent kits

Production of Radionuclides

• Preparation of Radionuclides– Radionuclide generators– Charged particle bombardment– Neutron Bombardment

Production of Radionuclides

• Radionuclidegenerators– A long-lived parent

radionuclide is allowed to decay to its short-lived daughter radionuclide and the latter is chemically separated in a physiological solution.

Production of Radionuclides

• Charged ParticleBombardment– bombarding target

materials with charged particles in particle accelarators such as cyclotrons.

Production of Radionuclides

Production of Radionuclides

• Neutron Bombardment– bombarding target materials with neutrons in nuclear

reactors– majority of radiopharmaceuticals are produced by this

process

IONIZING RADIATION AS MEANS OF STERILIZATION

Sterilization

• Sterilization – Complete destruction or removal of all forms of

contaminating microorganisms– Methods of Sterilization• Steam Sterilization• Dry-heat Sterilization• Filtration Sterilization• Exposure to Ionizing Radiation• Gas Sterilization

Sterilization by Radiation

Advantages• Gamma radiation easily reaches all

parts of the object to be sterilized• Permits sterilization of heat-

sensitive materials• Relatively low chemical reactivity• Instantaneous and simultaneous

sterilizing effect

Disadvantages• very dangerous • only well-trained and

experienced staff should decide upon the desirability of their use

• should ensure monitoring of the processes

• specially designed and purpose-built installations and equipment must be used

Sterilization by Radiation

• Sterilization of certain active ingredients, drug products, and medical devices in their final container

• exposure to gamma radiation (60Co) or of electrons energized by a suitable electron accelerator

Sterilization by Radiation

• Principle Involved– effect ionization of the molecules in organisms– mutations are thus formed in the DNA and these

reactions alter replication

Sterilization by Radiation

Sterilization by Radiation

RADIATION MONITORING

Radiation Monitoring

• Dosimeters– used to monitor radiation– monitors dose distribution of the product– exposure time required to achieve a required

specified dose

Radiation Monitoring

• Dosimeters– only measures external radiation exposure– offers no protection from radiation– Types• Ring dosimeter• Whole body dosimeter

GUIDELINES FOR USING RADIATION IN THE MANUFACTURE OF DRUGS

Guidelines

• Requires well-planned techniques and procedures

• Requires the use of personal film badges or thermoluminescent dosimeters (TLDs) must be worn at all times

• Suitable electronic radiation detector should always be available when radioactive materials are manipulated

Guidelines

• Required radiation monitoring– External radiation– Air contamination– Personnel Monitoring

• Appropriate shielding• Radioactive waste disposal procedures• Necessary decontamination methods

References

ALLEN, LV, Popovich, NG, Ansel, HC. 2005. Ansel's pharmaceutical dosage forms and drug delivery systems. Philadelphia: Lippincott Williams & Wilkins.

GENNARO, AR. 2000. Remington: the science and practice of pharmacy. Philadelphia: Lippincott Williams & Wilkins.

HARVARD CAMPUS SCIENCES. Dosimetry. [online]. [Accessed 22 September 2012]. Available from World Wide Web: <http://www.uos.harvard.edu/ehs/radiation/dosimetry.shtml>

INSTITUTE OF MEDICINE. Radiation in Medicine: A Need for Regulatory Reform. [online]. [Accessed 22 September 2012]. Available from World Wide Web: <http://www.nap.edu/openbook.php?record_id=5154&page=R1>

MUKHERJEE, RN. Radiation: a means of sterilization. [online]. [Accessed 22 September 2012]. Available from World Wide Web: <https://docs.google.com/viewer?a=v&q=cache:7FEpgTLvrsQJ:www.iaea.org/Publications/Magazines/Bulletin/Bull176/17605882837.pdf+&hl=en&gl=ph&pid=bl&srcid=ADGEESgU6o8M7BzzHZV1w1XhFAT7x-4-IBcRBSN0Fd7MoNUd96nshS4KxRa_HgUz5158MEUDwPH3ALPJ9yDB-414BHFcOs-OhAbQvPia>

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY. 2012. Radiation Protection. [online]. [Accessed 22 September 2012]. Available from World Wide Web: <http://www.epa.gov/rpdweb00/sources/food_irrad.html>

US DEPARTMENT OF ENERGY. Radioisotopes: What Are They and How Are They Made? [online]. [Accessed 22 September 2012]. Available from World Wide Web: <http://hss.energy.gov/healthsafety/ohre/roadmap/achre/intro_9_4.html>

WORLD HEALTH ORGANIZATION. 2012. Ionizing Radiation. [online]. [Accessed 22 September 2012]. Available from World Wide Web: <http://www.who.int/ionizing_radiation/about/what_is_ir/en/index.html>

WORLD HEALTH ORGANIZATION. Methods of Analysis: Methods of sterilization. [online]. [Accessed 22 September 2012]. Available from World Wide Web: <http://apps.who.int/phint/en/p/docf/>

WORLD NUCLEAR ASSOCIATION. What is radiation? [online]. [Accessed 22 September 2012]. Available from World Wide Web: <http://www.world-nuclear.org/how/radiation.html>