ABUSE RESISTANT MELT EXTRUDED FORMULATION HAVING REDUCED ALCOHOL INTERACTION

• US 20100172989A1
• Filed: 12/04/2009
• Published: 07/08/2010
• 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), Abbott Laboratories
• Inventors: Roth, Wolfgang, Burst, Alexander, Zietsch, Martina, Liu, Wei, Dutta, Sandeep
• Application Number:
  US12/631,010
• Publication Number:
  US 20100172989A1
• Time in Patent Office: Days
• US Class Current: 424/484
• 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 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 25/04 Centrally acting analgesics, e.g. opioids

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) a drug comprising an opioid or salt, hydrate or mixture thereof having potential for dose dumping in alcohol, and a non-opioid analgesic or salt, hydrate or mixture thereof having a 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 the matrix is melt extruded;

wherein the dosage form provides a controlled dissolution rate of the drug that is sufficient to prevent dose dumping of the drug when the dosage form is co administered to the patient with up to about 40% alcohol; 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 comprises a salt or an ester of an opioid 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

a non-opioid analgesic 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 opioid is hydrocodone and the non-opioid analgesic is acetaminophen.

4. The melt-extruded dosage form of claim 3 wherein when co administered to the human patient with up to about 40% Ethanol, the dosage form produces an AUC for hydrocodone that is equivalent to the AUC for hydrocodone when the dosage form is administered with 0% Ethanol.

5. The melt-extruded dosage form of claim 3 wherein when co administered to the human patient with up to about 40% Ethanol, the dosage form produces an AUC for acetaminophen that is equivalent to the AUC for acetaminophen when the dosage form is administered with 0% Ethanol.

6. The melt-extruded dosage form of claim 3 wherein when co administered to the human patient with up to about 20% Ethanol, the dosage form produces a mean Cmax for hydrocodone that is equivalent to a mean Cmax for hydrocodone when the dosage form is administered with 0% Ethanol.

7. The melt-extruded dosage form of claim 3 wherein when co administered to the human patient with up to about 20% Ethanol, the dosage form produces a mean Cmax for acetaminophen that is equivalent to a mean Cmax for acetaminophen when the dosage form is administered with 0% Ethanol.

8. The melt-extruded dosage form of claim 3 wherein when the dosage form is co administered to the human patient with up to about 40% Ethanol, the plasma concentration of hydrocodone at 12 hours does not differ from the plasma concentration of hydrocodone when the dosage form is administered with 0% Ethanol.

9. The melt-extruded dosage form of claim 3 wherein when the dosage form is co administered to the human patient with up to about 40% Ethanol, the plasma concentration of acetaminophen at 12 hours does not differ from the plasma concentration of acetaminophen when the dosage form is administered with 0% Ethanol.

10. The melt-extruded dosage form of any one of claims 1-9, wherein the polymer or copolymer comprises at least one dissolution 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.

11. The melt-extruded dosage form of any one of claims 1-9, wherein the polymer or copolymer comprises hydroxypropylcellulose or hydroxyethylcellulose.

12. The melt-extruded dosage form of any one of claims 1-9, wherein the polymer or copolymer comprises hydroxypropylmethylcellulose.

13. The melt-extruded dosage form of any one of claims 1-9, wherein the opioid comprises about 15 mg of hydrocodone.

14. The melt-extruded dosage form of any one of claims 1-9, wherein the non-opioid analgesic comprises about 500 mg of acetaminophen.

15. A method for preventing dose dumping of a drug in a human subject when the drug is co-administered to the subject with alcohol, the method comprising orally administering to the human subject the dosage from of any one of claims 1-12.

16. The method of claim 13 wherein the dosage form is co administered to the patient with up to about 40% alcohol.