Abuse resistant drug formulation

Abstract

A pharmaceutical composition may include a granulate which may include at least one active pharmaceutical ingredient susceptible to abuse by an individual mixed with at least two materials, a first material that is substantially water insoluble and at least partially alcohol soluble and a second material that is substantially alcohol insoluble and at least partially water soluble, wherein the active pharmaceutical ingredient and the two materials are granulated in the presence of water and alcohol. The composition may also include a coating on the granulate exhibiting crush resistance which may have a material that is deposited on the granulate using an alcohol based solvent. The composition further comprises a second particle comprising a fat / wax. The present invention also includes a coated granulate, various dosage forms of the composition, as well as methods of production and tableting.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of the filing date of U.S. Provisional Patent Application Nos. 60 / 845,128 filed Sep. 15, 2006, 60 / 845,127 filed Sep. 15, 2006, 60 / 845,126 filed Sep. 15, 2006, 60 / 845,151 filed Sep. 15, 2006, and 60 / 850,456 filed Oct. 10, 2006, the disclosures of which are hereby incorporated herein by reference.BACKGROUND OF THE INVENTION[0002]Some prescription drugs provide a controlled release of the active pharmaceutical ingredient (“API”) that they are intended to deliver. Controlled release can be a delayed release such as an enteric release in the intestines. It can be an extended release where release begins immediately or shortly after ingestion and continues, either at a constant rate or in some pattern, over an extended period of time, usually from about 6 to about 24 hours. Often this is accomplished using a controlled release coating. Not only are controlled release dosage forms, and especially extended rele...

AI Technical Summary

Benefits of technology

[0008]The present invention can be used in any number of contexts including improving manufacturing, storage, and use of dosage forms. However, one particular benefit that can inure from the use of the present invention is rendering an active pharmaceutical ingredient (“API”)-containing particle, a coated particle or a dosage form less capable of being crushed, dissolved, injected or otherwise abused.

[0009]Certain drugs, such as, for example, the opioid oxycodone, are administered to patients to reduce pain. Successful pain management in many of these patients requires maintenance of certain blood levels of the opioid throughout the day. One way of obtaining acceptable blood levels, used commonly in the pharmaceutical industry, is providing a dose which contains far more drug than is necessary to obtain the desired blood level. Blood levels shortly after the tablet is ingested reach a maximum or Cmax in a relatively short time, often within hours of ingestion (Tmax) and thereafter, as the body uses, processes and excretes drug from the blood system, the blood level drops. If the Cmax attained is sufficiently high, and the body's clearance of the drug is sufficiently slow, the blood levels may not fall to subtherapeutic levels for 4-12 hours or even longer. However, with drugs like oxycodone and indeed for many other drugs, this is an impractical and inefficient dosing system. In addition, there is a risk to the patient in that such high initial API levels can cause significant side effects.

[0010]Another method of administering drugs involves the use of an extended release mechanism. An extended release can be achieved in many different ways and there are many different release profiles that can be attained. For exemplification only, a granulate material can be produced with a material that when exposed to the digestive tract, swells with available fluids and either slowly erodes or slows the wetting and diffusion of API drug materials contained within the granulate, thus providing a much lower Cmax and often a much longer Tmax. Ideally, a zero order release is obtained whereby a constant release rate and a constant blood level is attained throughout an extended period of time often six hours or more, more preferably twelve hours or more, and most preferably over about 24 hours. Not only could this strategy reduce the number of doses that need to be taken in a day, it also may prevent one from being exposed to the side effects which can come from unnecessarily high initial blood levels.

Problems solved by technology

However, with drugs like oxycodone and indeed for many other drugs, this is an impractical and inefficient dosing system.

In addition, there is a risk to the patient in that such high initial API levels can cause significant side effects.

Those who seek to abuse these types of products to “get high” can be frustrated by such extended and indeed other controlled release strategies.

These strategies actively prevent one from obtaining high blood levels of the drug which can cause the euphoria or other physiologic effects which they are actually seeking, but which normal patients would consider an undesirable or even dangerous side effect.

This can cause the rupture or otherwise compromise the API particle and / or controlled release coating, exposing more of the API to digestion and absorption more quickly, allowing the abuser to achieve much higher blood levels.

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