Abuse-resistant pharmaceutical compositions

• US 8,623,412 B2
• Filed: 09/23/2003
• Issued: 01/07/2014
• Est. Priority Date: 09/23/2002
• Status: Active Grant

• Current Assignee: Elan Pharma International Limited (Perrigo Company PLC)
• Original Assignee: Elan Pharma International Limited (Perrigo Company PLC)
• Inventors: Liversidge, Gary G., Ruddy, Stephen B., Cooper, Eugene R., Farid, Vaghefi
• Primary Examiner(s): Draper, L. R.
• Application Number:
  US10/528,727
• Publication Number:
  US 20060104909A1
• Time in Patent Office: 3,759 Days
• Field of Search: None
• US Class Current: 424/484
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 9/16 Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction A61K9/20 takes precedence if the final form is a tablet; microspheres with drug-free outer coating, microcapsules A61K9/50; mixture of different granules, microcapsules, (coated) microparticles A61K9/5084; nanoparticles A61K9/51
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/1664 Compounds of unknown constitution, e.g. material from plants or animals oils, fats, waxes, shellac A61K9/1617
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 25/36 Opioid-abuse
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

An abuse-resistant controlled release pharmaceutical composition comprising a pharmaceutically effective amount of discrete particles of an active capable of abuse, wherein surfaces of said particles are wetted with a water insoluble coating material, and preferably wherein said composition comprises a matrix, in which said particles are distributed, and which renders the abuse-capable compound within the matrix difficult to separate from the matrix; and a method for the preparation of a controlled release pharmaceutical composition having a reduced potential for abuse, comprising applying a pressure force to a mixture comprising a water insoluble material, and particles of a pharmaceutically active compound capable of inducing in a subject a reaction that is physiologically or psychologically detrimental if administered in an immediate release dosage form, thereby resulting in surface coated particles, and incorporating said surface coated particles into a pharmaceutical composition.

Claims

1. An abuse-resistant controlled-release pharmaceutical composition comprising a plurality of microspheres, each microsphere comprises:

(i) a water insoluble matrix material, and

(ii) a plurality of discrete particles distributed throughout the water insoluble matrix material, each particle comprises a pharmaceutically effective amount of an active water soluble compound capable of abuse and having surfaces that are wetted with a coating of the water insoluble matrix material,

wherein said water insoluble matrix material is present in an abuse-reducing amount whereby crushing, compressing, fracturing, tumbling, rolling, or milling of said controlled-release pharmaceutical composition results in an increase in the aqueous dissolution of said active water soluble compound by less than about 15% of the total pharmaceutically effective amount of the active water soluble compound in the composition in the first hour of in vitro dissolution testing,

wherein the water soluble compound capable of abuse is an opioid agonist, and

wherein the composition does not include an antagonist of the water soluble compound capable of abuse.

2. The abuse-resistant composition according to claim 1 wherein said matrix material is non-erodable at pH less than about 6.

3. The abuse-resistant composition according to claim 2 wherein said matrix material is erodable in the presence of bile salts and lipase.

4. The abuse-resistant composition according to claim 1 wherein crushing said matrix before contacting with water increases the aqueous dissolution of active water soluble compound in said composition by less than about 10% of the total pharmaceutically effective amount of the active water soluble compound in the composition in the first hour of in vitro dissolution testing.

5. The abuse-resistant controlled-release pharmaceutical composition according to claim 1 for administration to a subject in need thereof from once to four times a day.

6. The dosage form according to claim 1 wherein said opioid agonist is selected from the group consisting of fentanyl, sufentanil, carfentanil, lofentanil, alfentanil, hydromorphone, oxycodone, hydroxycodone, propoxyphene, methadone, tilidine, butorphanol, buprenorphine, levorphanol, codeine, oxymorphone, meperidine, dihydrocodeinone and cocaine.

7. The abuse-resistant composition of claim 1, wherein the matrix material is a triglyceride wax selected from the group consisting of a hydrogenated cottonseed oil wax, a partially hydrogenated soybean oil, carnuba wax or a mixture thereof.