J P Basly1, I Longy, M Bernard. 1. Laboratoire de Chimie Analytique et Bromatologie, UFR de Pharmacie, Limoges, France. Basly@alpha1.unilim.fr
Abstract
PURPOSE: As an alternative to heat and gas exposure sterilization, ionizing radiation is gaining interest as a sterilization process for medicinal products. The aim of this work was to develop equations to describe the ESR curves versus dose and storage time after gamma irradiation of ascorbic acid. Several ESR data sets previously acquired in this laboratory were adopted to check the performance of the models. RESULTS: Limit of detection and limit of discrimination are respectively 0.5 kGy and 2 kGy for ascorbic acid. Linear regression is applicable for doses lower than 25 kGy. Since the radiation dose selected must always be based upon the bioburden of the products and the Degree of Sterility required (ANSI/AAMI/ISO 11137), doses in the range 5-25 kGy could be investigated and linear regression would appear to be the least expensive route to follow and gives good results. Quadratic fit, power function, exponential function and bi-exponential functions are of more general applicability to predict irradiation dose. Decay kinetics for radicals versus storage were considered. Nonhomogeneous kinetics with time-dependent rate (diffusion-controlled second-order reaction) and bi-exponential function appeared valid to reproduce the experimental data. Discrimination between irradiated and unirradiated ascorbic acid is possible after a storage of 800 days. CONCLUSIONS: It is worth noting that, at present, ESR is the only technique which proves to be suitable for identification and quantification purposes in irradiated pharmaceuticals. Moreover, other features such as sensitivity, precision, ease and non-destructive readout make ESR superior to other proposed analytical techniques.
PURPOSE: As an alternative to heat and gas exposure sterilization, ionizing radiation is gaining interest as a sterilization process for medicinal products. The aim of this work was to develop equations to describe the ESR curves versus dose and storage time after gamma irradiation of ascorbic acid. Several ESR data sets previously acquired in this laboratory were adopted to check the performance of the models. RESULTS: Limit of detection and limit of discrimination are respectively 0.5 kGy and 2 kGy for ascorbic acid. Linear regression is applicable for doses lower than 25 kGy. Since the radiation dose selected must always be based upon the bioburden of the products and the Degree of Sterility required (ANSI/AAMI/ISO 11137), doses in the range 5-25 kGy could be investigated and linear regression would appear to be the least expensive route to follow and gives good results. Quadratic fit, power function, exponential function and bi-exponential functions are of more general applicability to predict irradiation dose. Decay kinetics for radicals versus storage were considered. Nonhomogeneous kinetics with time-dependent rate (diffusion-controlled second-order reaction) and bi-exponential function appeared valid to reproduce the experimental data. Discrimination between irradiated and unirradiated ascorbic acid is possible after a storage of 800 days. CONCLUSIONS: It is worth noting that, at present, ESR is the only technique which proves to be suitable for identification and quantification purposes in irradiated pharmaceuticals. Moreover, other features such as sensitivity, precision, ease and non-destructive readout make ESR superior to other proposed analytical techniques.