Extruded extended release abuse deterrent pill

• US 10,172,797 B2
• Filed: 12/17/2014
• Issued: 01/08/2019
• Est. Priority Date: 12/17/2013
• Status: Active Grant

• Current Assignee: Pharmaceutical Manufacturing Research Services, Inc.
• Original Assignee: Pharmaceutical Manufacturing Research Services, Inc.
• Inventors: Thompson, Edwin R., Thompson, Eric R., Myslinski, Nicholas R., Kemeny, Steven F.
• Primary Examiner(s): Richter, Johann R
• Assistant Examiner(s): Alley, Genevieve S
• Application Number:
  US15/105,027
• Publication Number:
  US 20160317448A1
• Time in Patent Office: 1,483 Days
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• 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 9/2095 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

Abstract

The present disclosure relates to an oral, extended release, abuse deterrent pill containing at least one active pharmaceutical ingredient susceptible to abuse which is homogenously spread throughout a matrix used to deter abuse. The pill can be prepared using a hot melt extrusion process and a forming unit. The formed pill meets regulatory guidelines for extended release formulations and is abuse deterrent to parenteral administration due at least to particle size, viscosity, or purity limitations.

Claims

1. An oral, extended release, abuse deterrent pill comprising:

(i) 4 wt % to 40 wt % oxymorphone HCl or a pharmaceutically acceptable salt thereof;

(ii) 38 wt % to 42 wt % polyethylene oxide (PEO) having an average molecular weight between 50K Daltons and 150K Daltons;

(iii) a controlled release agent selected from either 15 wt % to 45 wt % hydroxypropyl methylcellulose or 29 wt % to 60 wt % combination of polyvinyl acetate and polyvinylpyrrolidone; and

,

(iv) 0.25 wt % to 20 wt % polyethylene glycol;

wherein the oxymorphone HCl or pharmaceutically acceptable salt thereof has an extended release profile,

wherein the pill exhibits less than a 10% increase in the release of the oxymorphone HCl or pharmaceutically acceptable salt thereof in a simulated alcoholic gastric fluid environment,

wherein the pill has at least 50 wt % of particles with a particle size greater than 0.5 mm following physical or mechanical manipulation of the pill, and

wherein the pill is a formed, uniform extrudate having a uniform blend of said oxymorphone HCl or pharmaceutically acceptable salt thereof, said polyethylene oxide, said controlled release agent and said polyethylene glycol, and is directly formed from an extrusion process.

2. The oral, extended release, abuse deterrent pill of claim 1,

wherein the oxymorphone HCl or pharmaceutically acceptable salt thereof is present at 5 to 200 mg.

3. The oral, extended release, abuse deterrent pill of claim 1, wherein the polyethylene glycol has an average molecular weight of less than 10K Daltons.

4. The oral, extended release, abuse deterrent pill of claim 1, wherein the pill further comprises at least one preservative or antioxidant selected from the group consisting of silica, sodium laurel sulfate, citric acid, butylated hydroxytoluene (BHT), ascorbic acid, ascorbyl palmitate, butylated hydroxyanisole (BHA), erythorbic acid, hypophosphorous acid, lactobionic acid, monothioglycerol, potassium metabisulfite, propyl gallate, racemethionine, sodium bisulfite, sodium formaldehyde sulfoxylate, sodium metabisulfite, sodium sulfite, sodium thiosulfate, stannous chloride, sulfur dioxide and tocopherols.

5. The oral, extended release, abuse deterrent pill of claim 1, further comprising one or more FD&

C dyes.

6. The oral, extended release, abuse deterrent pill of claim 1, wherein the extended release profile of the oxymorphone HCl or a pharmaceutically acceptable salt thereof passes the criteria for the USP monograph or passes the criteria for the matching reference listed drug for extended release oxymorphone HCl or a pharmaceutically acceptable salt thereof.

7. The oral, extended release, abuse deterrent pill of claim 1,

wherein the purity of the oxymorphone HCl or a pharmaceutically acceptable salt thereof following alcohol extraction is <

40%.

8. The oral, extended release, abuse deterrent pill of claim 1,

wherein between 20% and 40% of the oxymorphone HCl or a pharmaceutically acceptable salt thereof is released from the pill after 1 hour of exposure to simulated gastric fluid,

wherein between 35% and 55% of the oxymorphone HCl or a pharmaceutically acceptable salt thereof is released from the pill after 2 hours of exposure to simulated gastric fluid,

wherein between 55% and 75% of the oxymorphone HCl or a pharmaceutically acceptable salt thereof is released from the pill after 4 hours of exposure to simulated gastric fluid,

wherein between 70% and 90% of the oxymorphone HCl or a pharmaceutically acceptable salt thereof is released from the pill after 6 hours of exposure to simulated gastric fluid, and

wherein not less than 80% of the oxymorphone HCl or a pharmaceutically acceptable salt thereof is released from the pill after 8 hours of exposure to simulated gastric fluid.

9. The oral, extended release, abuse deterrent pill of claim 1 formed using a tablet press and cured using preceding, simultaneous, or subsequent heat.

10. The oral, extended release, abuse deterrent pill of claim 1 formed using a hot melt extrusion process and a forming unit.

11. The oral, extended release, abuse deterrent pill of claim 1, comprising:

(i) 4 wt % to 6 wt % of the oxymorphone HCl or a pharmaceutically acceptable salt thereof;

(iii) 36 wt % to 39 wt % of hydroxypropyl methylcellulose; and

(iv) 14 wt % to 17 wt % of polyethylene glycol.

12. The oral, extended release, abuse deterrent pill of claim 1, comprising:

(i) 32 wt % to 35 wt % of the oxymorphone HCl or a pharmaceutically acceptable salt thereof;

(iii) 18 wt % to 22 wt % of hydroxypropyl methylcellulose; and

(iv) 4 wt % to 6 wt % of polyethylene glycol.

13. The oral, extended release, abuse deterrent pill of claim 1, comprising:

(i) 6 wt % to 9 wt % of the oxymorphone HCl or a pharmaceutically acceptable salt thereof;

(iii) 31 wt % to 38 wt % of hydroxypropyl methylcellulose; and

(iv) 16 wt % to 19 wt % of polyethylene glycol.

14. The oral, extended release, abuse deterrent pill of claim 1, comprising:

(i) 8 wt % to 12 wt % of the oxymorphone HCl or a pharmaceutically acceptable salt thereof;

(iii) 29 wt % to 35 wt % of hydroxypropyl methylcellulose; and

(iv) 16 wt % to 19 wt % of polyethylene glycol.

15. The oral, extended release, abuse deterrent pill of claim 1, comprising:

(i) 13 wt % to 17 wt % of the oxymorphone HCl or a pharmaceutically acceptable salt thereof;

(iii) 27 wt % to 31 wt % of hydroxypropyl methylcellulose; and

(iv) 13 wt % to 16 wt % of polyethylene glycol.

16. The oral, extended release, abuse deterrent pill of claim 1, comprising:

(i) 18 wt % to 22 wt % of the oxymorphone HCl or a pharmaceutically acceptable salt thereof;

(iii) 27 wt % to 31 wt % of hydroxypropyl methylcellulose; and

(iv) 8 wt % to 11 wt % of polyethylene glycol.

17. The oral, extended release, abuse deterrent pill of claim 1, comprising:

(i) 28 wt % to 32 wt % of the oxymorphone HCl or a pharmaceutically acceptable salt thereof;

(iii) 26 wt % to 30 wt % of hydroxypropyl methylcellulose; and

(iv) 0.2 wt % to 5 wt % of polyethylene glycol.

18. The oral, extended release, abuse deterrent pill of claim 1, comprising:

(i) 28 wt % to 32 wt % of the oxymorphone HCl or a pharmaceutically acceptable salt thereof;

(iii) 26 wt % to 30 wt % of hydroxypropyl methylcellulose; and

(iv) 0.2 wt % to 0.3 wt % of polyethylene glycol.

19. The oral, extended release, abuse deterrent pill of claim 1, comprising:

(i) 6 wt % to 9 wt % of the oxymorphone HCl or a pharmaceutically acceptable salt thereof;

(iii) 31 wt % to 38 wt % of hydroxypropyl methylcellulose; and

(iv) 10 wt % to 20 wt % of polyethylene glycol.

20. The oral, extended release, abuse deterrent pill of claim 1, comprising:

(i) 8 wt % to 12 wt % of the oxymorphone HCl or a pharmaceutically acceptable salt thereof;

(iii) 29 wt % to 35 wt % of hydroxypropyl methylcellulose; and

(iv) 10 wt % to 20 wt % of polyethylene glycol.