Abstract
Radiation sterilization is becoming increasingly popular for the sterilization of many pharmaceutical products. Although this technique is not limited to the sterilization of polymers, it is probably the most suitable method for such materials. This method however suffers several drawbacks. The sterilization of a product must lead to a safety level of 10−6, i.e. one chance in a million to find a contaminated sample. In many cases, this assurance of sterility can be achieved by using a uniform treatment dose of 2.5 Mrad, recommended by the pharmacopeia. We investigated the possibility of using doses of radiation inferior to 2.5 Mrad to sterilize a semi-solid poly(ortho ester) (POE) developed for use as carrier in controlled drug delivery. After determination of the initial bioburden, the polymer was intentionally contaminated with the bioindicator Bacillus pumilus E 601. Following exposure to gamma irradiation, the D10 value of the radio resistant bioindicator was determined. Using the initial contamination value, the reduction factor D10 and the safety level, it is possible to calculate an optimal sterilizing dose for POE. All polymers are affected by ionizing radiation and the amount of radiation which produces a significant change in properties may vary from one polymer to the other. A molecular weight and dynamic viscosity decrease resulting from backbone cleavage was observed for this POE at a dose lower than 2.0 Mrad. Evaluation of the structure using 1H-NMR, 13C-NMR and IR analysis shows that for doses higher than 2.0 Mrad, another degradation process takes place. Formation of two isomeric esters of the triol used for the synthesis was identified by these methods. Cleavage of the monomer cycle is believed to be the main cause of the degradation observed. A radiation dose of not less than 7 times the D10 value but less than 2.0 Mrad was used for this semi-solid biodegradable poly-(ortho ester) in order to ensure its sterility and avoid an excessive formation of degradation products.
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Merkli, A., Heller, J., Tabatabay, C. et al. Gamma Sterilization of a Semi-Solid Poly(ortho ester) Designed for Controlled Drug Delivery—Validation and Radiation Effects. Pharm Res 11, 1485–1491 (1994). https://doi.org/10.1023/A:1018964511053
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DOI: https://doi.org/10.1023/A:1018964511053