Drugs radiation sterilization

CFN Nonsterile bulk by fermentation crude drug RSP Radiation sterilization process... 

The irradiation of micellar solutions effects the phase behavior and the critical micelle concentration (CMC). Because radiation sterilization of biopharmaceutical products is a common routine it is important to investigate the influence of radiation on surfactants that are widely used in the pharmaceutical industry for formulations as wetting agents, emulsifiers, or solubilizers. In particular, in drug formulations... 

Manual on radiation sterilization of medical and biological materials (1973) Technical Reports Series No. 149. International Atomic Energy Agency, Vienna Hygiene Recommendations (1972) Drug manufacturers association, Stockholm (Dec. 1972)... 

M. A. Abuirjeie, A. A. Abdel-Aziz, and M. E. Abdel-Humid, Feasibility studies on radiation sterilization of cephradinq, Drug Dev. Ind. Phram. 16, 1661-1673(1990). 

Theoretically, it is unlikely that aqueous pharmaceutical formulations are going to be amenable to radiation sterilization. Consider the drug ranitidine (molecular weight of 314) in 1% aqueous solution ... 

In practical terms, terminal sterilization of liquid parenteral products means sterilizaticMi by saturated steam. Production of free radicals in water prohibits the application of radiation sterilization to aqueous products, but radiation sterilization may be suitable for some solid dosage forms. Dry heat and ethylene oxide are unlikely to be of any value. In the first instance, therefore, saturated steam should be the process of first choice for sterilization of thermally stable drug substances dosage forms should not be formulated in ways that compromise thermal stability. 

A new field of radiation application is the radiation sterilization of drugs. The requirement for sterility of drugs depends on type of administration. It concerns mostly ophthalmic preparations, sterile topical products, and injectable solutions. In some cases, radiation sterilization appears to be an attractive alternative to other types of sterilization, e.g., heat sterilization. For drugs the usual requirement (six orders of magnitude decrease in the microorganism level) is achieved by applying an absorbed dose of 25 kGy. 

On a large scale, chemotherapy and radiation may be effective on several levels. The concept of spatial interaction was devised to mean that chemotherapy and radiation act on spatially distinct compartments of the body, resulting in a net gain in tumor control. The concept of spatial interaction does not take into account any drug-radiation interaction on the level of the tumor itself, but rather assumes that radiation or chemotherapy would be active in different compartments, respectively. In a narrow sense, this concept describes the fact that chemotherapy would be employed for the sterilization of distant microscopic tumor seeding, whereas radiation... 

The results of Babanalbandi and co-workers (221), in which new aliphatic chains ends formed by cleavage of the main chain at the ester unit are observed, are in support of a mechanism in which chain scission dominates cross-linking. These authors reported G-values for the formation of chain end structures comparable with earlier study. Furthermore, the main volatile products of radiolysis of PLA and poly(glycolic acid) (GPA) are CO2 and CO, consistent with chain scission being the most important reaction. In addition, small amounts of hydrogen and ethane gas were observed on the radiolysis of PLA. Finally, Montanari and co-workers (226) have examined the effects of radiation sterilization on the stability of PLGA microparticles used for drug delivery. 

Current interest in radiation sterilization of pharmaceuticals led Fletcher and Davies [142] to investigate the sensitivity of benzocaine to irradiation in aqueous solution. Cetrimide and polysorbate 80 protect the drug from the deleterious effects of a Co source at doses up to 0.3 M rad. However, ethanol, glycerol and polyoxyethylene glycol 200 when used as co-solvents at concentrations up to 40% were more effective [142] (Fig. 11.23) (equal concentrations of surfactant and co-solvent were not compared). These results emphasize the need to compare critically the different approaches to both solubilization and stabilization. High concentrations of surfactant, even non-ionic surfactant, are usually impracticable on the grounds of toxicity and thus the choice of solubilization technique cannot always be made on the basis of the physical chemistry of the competing methods. 

Parenteral drug products are required to be sterile. There are principally five different ways to sterilize a product. These are steam, dry heat, radiation, gas. 

Manufacturing is performed in cleanroom conditions. Sterilization processes in the form of heat, steam, gas, or radiation are applied to ensure microorganisms are destroyed in the drug product. For protein-based drugs that can be damaged by the normal sterilization processes, the product is manufactured under aseptic conditions. Both sterility and pyrogen tests are performed to ensure parenteral drug products are safe to be injected. 

The yield of carbonyl and peroxy compounds (Table XV) is dose-dependent up to a limiting value of G (the number of reacting molecules), which is 12.6 and 3.5 per 100 eV of radiation energy absorbed, respectively. Estimation of total carbonyl compounds and peroxides may provide an appropriate indicator for irradiation control in the sterilization of foods and drugs containing starch. 

Terminal sterilization is most commonly accomplished by moist heat. Terminal sterilization by other means is certainly possible, and a very limited number of parenteral drugs are treated with dry heat or radiation after filling. There is growing interest in the use of radiation, including low-energy E-beam, as a terminal treatment suggesting more products will be processed in this manner. 

Ready to Sterilize (RtS) Typically components are washed, then rinsed with Water For Injection (WFI) to reduce bioburden and endotoxin levels, lubricated with silicone oil, and finally packaged in a classified area (Classes 100-10,000) in Tyvek bags that can be steam sterilized by the drug or device manufacturer before use. Alternately polyethylene bags may be used if the end user is utilizing gamma radiation for sterilization. 

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