Many therapeutic agents are highly effective for improving quality of life but, because of their abuse potential, may attract drug abusers. For example, opioids are excellent analgesic agents that can control severe and/or chronic pain, such as cancer pain and post-operative pain, but are also subject to abuse by drug users.
Opioids, also known as opioid agonists, are a group of drugs that exhibit opium- or morphine-like properties. Opioids are employed primarily as moderate to strong analgesic agents, but provide other pharmacological effects as well.
There have been previous attempts in the art to control the potential for abuse of opioid analgesics. For example, sustained release forms enable an active ingredient to work over many hours, and such slow release tends to deter illicit use of opioids because abusers tend to prefer the quick euphoric rush, also known as the “burst,” provided by immediate release opioids. Drug abusers, however, can defeat the controlled release design by crushing or dissolving the original drug form, for example a tablet, giving them access to snortable and/or injectable opioids that provide the burst. Accordingly, there is an important need for more effective methods of deterring opioid abuse while still keeping orally administered opioids available to patients who have a legitimate need for them.
Prior art approaches to this problem have involved combining an opioid with an opioid antagonist. When administered orally, these combinations provide the pharmacologic action of the opioid with minimal action of the antagonist. When administered parenterally, however, the antagonist can be-profoundly antagonistic to the opioid. Particular examples of such combinations include compositions comprising naloxone and morphine or oxymorphone (U.S. Pat. No. 3,493,657 to Lewenstein et al.); methadone and naloxone (U.S. Pat. No. 3,773,955 to Pachter et al.); methadol or acetyl methadol and naloxone (U.S. Pat. No. 3,966,940 to Pachter et al.); oxycodone and naloxone (U.S. Pat. No. 4,457,933 to Gordon et al.); and buprenorphine and naloxone (U.S. Pat. No. 4,582,835 to Lewis et al.). Also, the combination of pentazocine hydrochloride and naloxone has been marketed in the United States as TALWIN NX (Sanofi-Winthrop); VALORON N, a combination of tilidine and naloxone, has been available in Germany for the management of severe pain since 1978; and TEMGESIC NX, a combination of buprenorphine and naloxone, has been available in New Zealand since 1991.
U.S. Pat. No. 6,228,863 to Palermo et al. discloses an oral dosage form of an opioid agonist and an opioid antagonist that reduces the abuse potential of the opioid by combining the agonist and antagonist such that at least two steps are required to separate them.
U.S. Pat. No. 5,935,975 to Rose et al. discloses a method for treating drug dependency by the combined administration of the drug or an agonist of the drug and an antagonist of the drug.
There remains, however, a clear need in the art for more advanced oral dosage forms that are effective for preventing abuse and useful for delivering a therapeutic agent.