Combination of active loaded granules with additional actives

摘要

Disclosed is a process for the manufacture of oral prolonged release tablets comprising an opioid antagonist such as naloxone and an opioid agonist such as hydromorphone, hydrocodone bitartrate or morphine sulphate. Particularly described is a method of manufacturing an oral prolonged release pharmaceutical tablet composition, comprising at least the steps of: a) producing granules comprising at least one prolonged release material and at least one first pharmaceutically active agent (preferably selected from oxycodone, hydromorphone, hydrocodone, tramadol or oxymorphone or their pharmaceutically acceptable salts, hydrates and solvates thereof); b) optionally selecting granules of step a) of substantially uniform size, such as wherein granules of a mean size in the range of about 100 microns to about 2.0 mm are selected in step b); c) blending said granules of step a) or step b) with at least one additional pharmaceutically active agent (preferably selected from naloxone, naltrexone or nalmephene or their pharmaceutically acceptable salts, hydrates and solvates) which is provided as such that it is not combined with an additional prolonged release material and not comprised within granules; d) compressing said blended granules of step c) to obtain an oral prolonged release pharmaceutical composition in the form of a tablet; wherein either the first pharmaceutically active agent is an opioid agonist and the additional pharmaceutically active agent is an opioid antagonist, or the first pharmaceutically active agent is an opioid antagonist and the additional pharmaceutically active agent is an opioid agonist. Also disclosed is an oral prolonged release pharmaceutical composition in tablet form obtained by the method as defined above.