New abuse-resistant pharmaceutical composition for the treatment of opioid dependence

Abstract

There is provided pharmaceutical compositions for the treatment of e.g. opioid dependency comprising microparticles of a pharmacologically-effective amount of buprenorphine, or a pharmaceutically-acceptable salt thereof, in associative admixture with particles comprising a weak acid, or particles comprising weakly-acidic buffer forming materials. The composition may further comprise a disintegrant and / or particles of a pharmacologically-effective amount of naloxone, or a pharmaceutically-acceptable salt thereof. The compositions are useful in the treatment of opioid dependency / addiction and / or pain.

Description

[0001]The present application claims priority to U.S. Provisional Patent Application 61 / 536,180 filed on Sep. 19, 2011, which is hereby incorporated by reference herein in its entirety.[0002]This invention relates to new pharmaceutical compositions comprising opioids that are useful in the treatment of opioid / opiate dependency and / or pain, which compositions may be abuse-resistant, and may be administered transmucosally and, in particular, sublingually.[0003]Opioids are widely used in medicine as analgesics. Indeed, it is presently accepted that, in the palliation of more severe pain, no more effective therapeutic agents exist.[0004]Opioid agonist analgesics are used to treat moderate to severe, chronic cancer pain, often in combination with non-steroidal anti-inflammatory drugs (NSAIDs), as well as acute pain (e.g. during recovery from surgery and breakthrough pain). Further, their use is increasing in the management of chronic, non-malignant pain.[0005]A perennial problem with pot...

AI Technical Summary

Benefits of technology

The patent describes a new formulation of buprenorphine and naloxone tablets that have higher plasma buprenorphine and lower plasma norbuprenorphine concentrations compared to a comparator. The new formulation also disintegrates faster and has a slightly higher crushing strength. The patent also describes an in vivo experiment where the pH of saliva was measured after administering the tablets. The results showed that the pH decrease peaked at around 35-40 seconds, and the body rapidly compensates for the modified pH. The patent also describes a method for preparing the tablets using micronized buprenorphine hydrochloride and mannitol. The tablets were placed on a silica filter in a glass funnel and dried using a peristaltic pump.

Problems solved by technology

Indeed, it is presently accepted that, in the palliation of more severe pain, no more effective therapeutic agents exist.

A perennial problem with potent opioid agonists however is one of abuse by drug addicts.

Drug addiction is a worldwide problem of which opioid dependence, notably of heroin, is a major component.

Opioid dependence is a major health problem and long-term heroin use is connected to a substantially increased risk of premature death from drug overdoses, violence and suicide.

Furthermore, sharing of needles among addicts contribute to the spreading of potentially fatal blood infections such as HIV, and hepatitis C. In addition, opioid dependence often leads to difficulties with social relations, inability to manage a normal job and increased criminality to finance addiction, with severe implications for the opioid dependent person and his / her family.

With most commercially-available pharmaceutical formulations, this can be done relatively easily, which renders them unsafe or “abusable”.

Naloxone in particular has a poor bioavailability when administered transmucosally but is rendered fully bioavailable when administered by injection.

Nonetheless, when administered parenterally, naloxone's functional blockade of buprenorphine's action is also only partial and is short-lived in its nature.

Further, Suboxone has also been reported to have several other significant limitations.

Moreover, the taste is not well tolerated by all patients and the tablet has an unpleasant gritty mouthfeel.

A film-based product has recently been developed to counteract these problems, but the film formulation also does not dissolve particularly quickly.

Opioid agonist effects of buprenorphine are less than the maximal effects of other, “full” opioid agonists, such as morphine, and are limited by a “ceiling” effect.

It will be evident to the skilled person that “premature” hydration will dramatically decrease the performance of a tablet formulation in use and may result in premature dissolution of active ingredients.