There is described a
prolonged release pharmaceutical
dosage form comprising a plurality of coated beads, each of the coated beads comprising: (a) a granule; (b) a first layer coated on the granule, the first layer comprising: (i)
hydromorphone or a pharmaceutically acceptable salt thereof, (ii) naloxone or a pharmaceutically acceptable salt thereof, (iii) an
antioxidant compound, and (iii) a chelating compound; and (c) a second layer coated on the first layer, the second layer comprising a
prolonged release agent. The
dosage form has improved stability and
dissolution properties. Another aspect of the invention relates to use of a combination of an
antioxidant (such as
sodium metabisulfite) and a chelating agent (such as ethylenedinitrotetraacetic acid disodium salt dihydrate) to improve the stability and / or
dissolution properties of a
prolonged release dosage form comprising (i)
hydromorphone or a pharmaceutically acceptable salt thereof and (ii) naloxone or a pharmaceutically acceptable salt thereof.