INFLUENCE OF IRRADIATION STERILIZATION ON A SEMISOLID POLY(ORTHO ESTER)

Viscous poly(ortho ester) (POE), a promising polymer for controlled re lease is being investigated as an injectable drug delivery system for peptides, for antiproliferative agents after glaucoma filtering surger y and for antibiotics in the treatment of periodontitis. Due to the ch emical lability of POE, the strategies for obtaining a sterile product are limited to aseptic processing and terminal sterilization using hi gh energy radiation. In the first part of the present investigation, w e used electron-paramagnetic-resonance (EPR) spectroscopy to evaluate radical formation and radical-induced polymer degradation after irradi ation treatment. Due to the viscous nature of POE, radicals were only found at low temperatures or by using the method of 'spin-trapping'. S everal radical species could be distinguished by a variation of the mi crowave power and the differences of the thermal stability of the radi cals. The incorporation of 5-fluorouracil accelerates the degradation of the polymer. In the second part, we have compared the effects of th e two commonly applied methods for irradiation sterilization (i.e. gam ma and beta rays) on POE and on POE with incorporated 5-fluorouracil a nd compared these methods to aseptically prepared devices. In addition , we have checked the possibility of preventing radical-induced degrad ation using two different protecting agents: a-tocopherol at a concent ration of 0.1% (w/w) and sterilization under nitrogen monoxide. The we ight and number average molecular weight of POE decreased drastically after irradiation treatment and subsequent to irradiation, an accelera ted degradation was observed. Generally it was found that higher molec ular weight polymers are more affected and that gamma irradiation lead s to more degradation than beta treatment. Also, the addition of prote cting agents did not significantly prevent polymer degradation. Theref ore, we have concluded that irradiation sterilization of POE is not a viable process and aseptic preparation is preferred. Without steriliza tion POE is stable for about 1 year when kept as monodoses at low temp eratures. (C) 1998 Elsevier Science B.V. All rights reserved.