Effects of Thermal Neutron Irradiation on Some Potential Excipients for Colonic Delivery Systems

Abstract

Different excipients, which are currently being studied for colon delivery systems, were examined with respect to their stability toward neutron irradiation as a potential method of radiolabeling the formulations for γ-scintigraphic studies. Three different pectin and four different hydroxypropyl methylcellulose (HPMC) types, in addition to two types of polymethacrylate films, were exposed to 1, 2, and 3 min of thermal neutron irradiation in a flux of 1.1 × 10¹³ n cm⁻² s⁻¹. The physicochemical characteristics of pectins and HPMCs and the mechanical properties of the polymethacrylate films were examined after the radioactivity of the samples had declined to background levels. Methods included ultraviolet (UV) and Fourier transform infrared (FTIR) spectroscopy, pH measurements, loss on drying, thermogravimetric analysis (TGA), viscosimetry, gas chromatographic (GC) analysis of pectin monosaccharides, and tensile strength testing of the films. The results suggest that pectins and HPMCs undergo degradation, as expressed by a significant reduction in the dynamic and intrinsic viscosities of the samples. Generally, HPMCs were more sensitive than pectins to neutron irradiation. However, calcium pectinate proved to be the most sensitive among all the investigated polymers. Both polymethacrylate films (Eudragit® L and S) resisted loss of mechanical properties following 1 and 2 min of neutron irradiation, whereas irradiation for 3 min implied significant changes in the appearance and the mechanical properties of Eudragit L films. As a conclusion, neutron irradiation results in dose-dependent degradation of the investigated polysaccharides and polymethacrylates. The consequences on the in vitro behavior of a formulation containing such polymers are discussed.