ABUSE RESISTANT MELT EXTRUDED FORMULATION HAVING REDUCED ALCOHOL INTERACTION

• US 20090317355A1
• Filed: 01/26/2009
• Published: 12/24/2009
• Est. Priority Date: 01/21/2006
• Status: Abandoned Application

• Current Assignee: Abbvie Deutschland GmbH & Company KG (Abbvie Incorporated)
• Original Assignee: Abbott GmbH & Company KG (Abbott Laboratories Incorporated)
• Inventors: Burst, Alexander, Roth, Wolfgang, Zietsch, Martina
• Application Number:
  US12/359,788
• Publication Number:
  US 20090317355A1
• Time in Patent Office: Days
• US Class Current: 424/78.310
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/277 having a ring, e.g. verapamil
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• 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 3/14 for calcium homeostasis vitamin D A61P3/02; parathyroid hormones A61P5/18; calcitonin A61P5/22; osteoporosis A61P19/10; bone metastasis A61P35/04

Abstract

The present invention relates to compositions for oral administration. The invention preferably comprises at least one abuse-resistant drug delivery composition for delivering a drug having potential for dose dumping in alcohol, related methods of preparing these dosage forms, and methods of treating a patient in need thereof comprising administering the inventive compositions to the patient. Most preferably, the dosage form includes verapamil. These formulations have reduced potential for abuse. In another formulation, preferably the abuse relevant drug is an opioid and the non-abuse relevant drug is acetaminophen or ibuprofen. More preferably, the opioid is hydrocodone, and the non-abuse relevant analgesic is acetaminophen. In certain preferred embodiments, the dosage forms are characterized by resistance to solvent extraction; tampering, crushing or grinding. Certain embodiments of the inventions provide dosage forms that provide an initial burst of release of drug followed by a prolonged period of controllable drug release.

Claims

1. A melt-extruded dosage form having reduced drug-alcohol interaction, comprising:

(a) An abuse relevant drug or a drug having potential for dose dumping in alcohol; and

(b) a matrix having a polymer, copolymer or combinations thereof wherein the monomer is selected from a group consisting of cellulose ether, cellulose ester, acrylic acid ester, methacrylic acid ester, vinyl alcohol, ethylene oxide and natrium-alginate.

wherein said matrix is melt extruded;

wherein the dosage form has reduced drug-alcohol interaction; and

wherein the dosage form is adapted so as to be useful for oral administration to a human 3, 2, or 1 times daily.

2. The melt-extruded dosage form of claim 1, wherein the drug is a salt or an ester of verapamil, gammahydroxybutyrate, flunitrazepam or an opioid wherein the opioid is selected from the group consisting of alfentanil, allylprodine, alphaprodine, anileridine, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, cyclazocine, desomorphine, dextromoramide, dezocine, diampromide, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazene, fentanyl, heroin, hydrocodone, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, levallorphan, levophenacylmorphan, levorphanol, lofentanil, meperidine, meptazinol, metazocine, methadone, metopon, morphine, myrophine, nalbulphine, narceine, nicomorphine, norpipanone, opium, oxycodone, oxymorphone, papvreturn, pentazocine, phenadoxone, phenazocine, phenomorphan, phenoperidine, piminodine, propiram, propoxyphene, sufentanil, tilidine, and tramadol, and salts, hydrates and mixtures thereof and the non-opioid analgesic is selected from the group consisting of acetaminophen, aspirin, fentaynl, ibuprofen, indomethacin, ketorolac, naproxen, phenacetin, piroxicam, sufentanyl, sunlindac, interferon alpha, and salts, hydrates and mixtures thereof.

3. The melt-extruded dosage form of claim 1, wherein the polymer or copolymer comprises at least one rate altering pharmaceutically acceptable polymer, copolymer, or a combination thereof, having a monomer selected from the group consisting of hydroxyalkylcellulose, hydroxyalkyl alkylcellulose, natrium-alginate, methyl methacrylate, ammonio methacrylate, butylated methacrylate, vinyl alcohol, ethylene oxide, and acrylate.

4. The melt-extruded dosage form of claim 3, wherein the hydroxyalkylcellulose is hydroxypropylcellulose or hydroxyethylcellulose.

5. The melt-extruded dosage form of claim 3, wherein the hydroxyalkyl alkylcellulose is hydroxypropylmethylcellulose.

6. The melt-extruded dosage form of claim 1, wherein the drug is a salt or an ester of verapamil.

7. The melt-extruded dosage form of claim 1, wherein the drug comprises 1 mg to 1000 mg of a salt or an ester of verapamil.

8. The melt extruded formulation of claim 7, wherein less that 40% of the verapamil in the dosage form is dissolved in 40% ethanol solution using USP dissolution method.

9. The melt-extruded formulation of claim 8, wherein the dissolution profile for verapamil from the dosage form in 5% or 40% ethanol at eight hours does not differ from the dissolution profile for verapamil from the dosage form in 0% ethanol at eight hours.

10. The melt-extruded dosage form of any one of the claims 1-9, wherein the drug comprises 240 mg of a salt or an ester of verapamil.

11. The melt-extruded dosage form of any one of the claims 1-9, wherein the drug is an opioid and a non-opioid analgesic, further wherein the opioid is hydrocodone and the non-opioid analgesic is acetaminophen or ibuprofen.

12. The melt-extruded dosage form of any one of the claims 1-11, wherein the reduced in vitro drug alcohol interaction correlates to reduced in vivo drug alcohol interaction.

13. The melt-extruded dosage form of any one of the claims 1-12, wherein the dosage form is manufactured by melt-extrusion followed by direct shaping of the drug-containing melt.

14. A method for treating a human patient in need thereof, comprising orally administering to the human patient the dosage from of any one of the claims 1-13.