Oral dosage form comprising a therapeutic agent and an adverse-effect agent

Abstract

The present invention provides an oral dosage form comprising a first composition and a second composition. The first composition comprises an effective amount of a therapeutic agent and the second composition comprises an effective amount of an adverse-effect agent. The adverse-effect agent is covered with a coating that is substantially insoluble in the gastrointestinal tract. In one embodiment, the adverse-effect agent is coated with an outer base-soluble layer and an inner acid-soluble layer. The therapeutic agent can be uncoated or can be coated with a coating having an outer acid-soluble layer and an inner base-soluble layer. The dosage form discourages administration of the therapeutic agent by other than oral administration.

Description

[0001] This application claims the benefit of U.S. Provisional Application No. 60 / 309,791, filed Aug. 6, 2001, the disclosure of which is incorporated by reference herein in its entirety.1. FIELD OF THE INVENTION[0002] This invention relates generally to an oral dosage form comprising a therapeutic agent and an adverse-effect agent.[0003] 2. BACKGROUND OF THE INVENTION[0004] 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.[0005] 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.[0006] There have been previous attempts in the art to ...

AI Technical Summary

Benefits of technology

0044] The adverse-effect agent can be an agent that reduces or eliminates the therapeutic agent's pharmacological activities including, but not limited to: (1) the capacity of the drug to produce the kind of physical dependence in which drug withdrawal causes sufficient distress to bring about drug-seeking behavior; (2) the ability to suppress withdrawal symptoms caused by withdrawal from the drug; and (3) the induction of euphoria similar to that produced by morphine and other opioids. Adverse-effect agents that reduce or eliminate the pharmacological effects of the therapeutic agent include, but are not limited to, antagonists of the therapeutic agent agonist. When an opioid agonist is used as the therapeutic agent in the oral dosage form of the present invention, an opioid antagonist can be used as the adverse-effect agent. Likewise, when a benzodiazepine is used as the therapeutic agent in the oral dosage form of the present invention, a benzodiazepine antagonist can be used as the adverse-effect agent. When a barbiturate is used as a therapeutic agent in the oral dosage form of the present invention, a barbiturate antagonist can be used as the adverse-effect agent. When an amphetamine is used as a therapeutic agent in the oral dosage form of the present invention, an amphetamine antagonist can be used as the adverse-effect agent. When the therapeutic agent is toxic when dosed above its normal therapeutic range, i.e., there is a potential for an overdose, then an antidote of the toxic therapeutic agent can be used as the adverse-effect agent.

0045] The phrase "adverse-effect agent" is also meant to encompass all pharmaceutically acceptable salts of the adverse-effect agent. Pharmaceutically acceptable salts include, but are not limited to, metal salts, such as sodium salts, potassium salts, and lithium salts; alkaline earth metals, such as calcium salts, magnesium salts, and the like; organic amine salts, such as triethylamine salts, pyridine salts, picoline salts, ethanolamine salts, triethanolamine salts, dicyclohexylamine salts, N,N'-dibenzylethylenediamine salts, and the like; inorganic acid salts such as hydrochloride salts, hydrobromide salts, sulfate salts, phosphate salts, and the like; organic acid salts such as formate salts, acetate salts, trifluoroacetate salts, maleate salts, tartrate salts, and the like; sulfonate salts such as methanesulfonate salts, benzenesulfonate salts, p-toluenesulfonate salts, and the like; and amino acid salts, such as arginate salts, asparginate salts, glutamate salts, and the like.

0046] Opioid antagonists that can be used as the adverse-effect agent of the present invention include, but are not limited to, naloxone, naltrexone, nalmefene, cyclazacine, levallorphan, and mixtures thereof. In certain embodiments, the opioid antagonist is naloxone or naltrexone.

0047] Benzodiazepine antagonists that can be used as the adverse-effect agent of the present invention include, but are not limited to, flumazenil.

0048] Barbiturate antagonist which can be used as the adverse-effect agent of the present invention include, but are not limited to, amphetamines, described herein.

0049] Stimulant antagonists that can be used as the adverse-effect agent of the present invention include, but are not limited to, benzodiazepines, described herein.

Problems solved by technology

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.

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.

When administered parenterally, however, the antagonist can be profoundly antagonistic to the opioid.

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