Affordable Access

Publisher Website

The influence of thermal neutron irradiation on the in vitro characteristics of ASA oral dosage forms validation of neutron activation

European Journal of Pharmaceutics and Biopharmaceutics
Publication Date
DOI: 10.1016/s0939-6411(96)00008-2
  • Paracetamol Crystals
  • Acetylsalicylic Acid Crystals
  • Ethyl Cellulose


Abstract This paper deals with the effects of the neutron irradiation procedure on the in vitro performance of various commercially available products on the Scandinavian market: paracetamol crystals coated with ethyl cellulose, acetylsalicylic acid (ASA) crystals coated with ethyl cellulose and compressed into tablets, and ASA crystals coated with ethyl cellulose (raw product). The primary objective of the work was to observe the impact of irradiation on complex formulations, manufactured under industrial scale conditions. All formulations, without any incorporation of lanthanide isotope, were irradiated in the JEEP II reactor (Institute of Energy Technology, Kjeller, Norway) and subjected to several in vitro tests. The irradiation was performed in a neutron flux of 1.1 × 10 13n/cm per s for 2, 4, 7 or 15 min. Irradiation of the microencapsulated paracetamol crystals up to 4 min caused no significant damage as compared with the reference. An increase in the exposure time, however, tends to decrease the dissolution rate. In spite of that, the changes were too small to conclude nonequivocally that radiation damage had occurred. Distinct differences of disintegration time and dissolution rate after irradiation were found in the formulation of ASA crystals microencapsulated with ethyl cellulose compressed in rapidly disintegrating tablets. Irradiation up to 7 min prolonged the disintegration time, but unexpectedly accelerated the dissolution. A 15 min exposure caused severe radiation effects, inhibiting drug release almost totally. Tablet hardness increased considerably after irradiation for 15 min, as compared with tablets not irradiated. Based on the present findings and subsequent work, it was concluded that irradiation damage was probably due to degradation of the ethyl cellulose and changes in the crystalline structure of the ASA. Unlike the tablets, drug release of the corresponding granules was accelerated after exposure to the neutron beam for 15 min. This behaviour was attributed to the different density of the materials. Irradiation of the granules for 15 min appeared to cause similar damage as irradiating tablets for 2 min, since the extent of interaction between exposed material and neutron particles depends directly on the density.

There are no comments yet on this publication. Be the first to share your thoughts.


Seen <100 times