Polymers-gamma ray interaction. Effects of gamma irradiation on modified release drug delivery systems for oral administration.

摘要

The aim of this work is to verify the efficiency of two kinds of matrix tablets formulations containing PEO or PVA as retarding polymer. Moreover, since in the last years the exposure to ionizing radiation is a more and more used method to reduce bacterial charge in pharmaceutical products, the effects of gamma irradiation on these two kinds of polymers has been evaluated. The study is performed on matrix tablets containing diltiazem HCl, as model drug, and polyethylene oxides (PEO) of two different molecular weights or polyvinylalchool (PVA) of medium degree of hydrolysis, as drug release modulators. Dissolution of the matrices, release of diltiazem and morphological behaviour of the samples, before and after exposure to increasing doses of gamma irradiation, are investigated in order to verify their stability. The results show that the ionizing radiation does not modify significantly the dissolution trend of the PVA samples; on the contrary, the dissolution and the morphological behaviour of the PEO matrices is strongly affected by the radiation dose received. In particular, the dissolution rate of the irradiated PEO tablets dramatically increases as a function of the irradiation dose and the swelling process, which characterised the non-irradiated PEO samples, was replaced by a rapid erosion process responsible for the quickly dissolution of the matrices. The changes of the dissolution and morphological PEO tablets performances could be explained by a breaking of the polymeric chains (shown by EPR studies) as a consequence of the exposure to gamma rays. These chemical-structural modifications of the polymers are responsible for the reduced efficacy of the PEO systems in controlling the drug release rate.