Extruded Immediate Release Abuse Deterrent Pill

• US 20190209481A1
• Filed: 12/05/2018
• Published: 07/11/2019
• Est. Priority Date: 08/12/2013
• 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.
• Granted Patent: US 10,639,281 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• 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
• 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: B29C 2043/463 corrugated, patterned or embossed surface
• CPC Class Codes: B29C 2043/483 cooperating with a second endless belt, i.e. double band presses
• CPC Class Codes: B29C 43/48 Endless belts
• CPC Class Codes: B29C 48/0011 combined with compression moulding
• CPC Class Codes: B29C 48/022 characterised by the choice of material
• CPC Class Codes: B29C 48/04 Particle-shaped making granules B29B9/00
• CPC Class Codes: B29C 48/05 Filamentary, e.g. strands
• CPC Class Codes: B29C 48/06 Rod-shaped
• CPC Class Codes: B29C 48/303 using dies or die parts movable in a closed circuit, e.g. mounted on movable endless support B29C48/35 takes precedence
• CPC Class Codes: B29K 2071/02 : Polyalkylene oxides, e.g. PEO, i.e. polyethylene oxide, or derivatives thereof
• CPC Class Codes: B29K 2105/0035 : Medical or pharmaceutical agents
• CPC Class Codes: B29K 2105/0038 : Plasticisers
• CPC Class Codes: B30B 11/02 : using a ram exerting pressure on the material in a moulding space
• CPC Class Codes: B30B 11/027 : Particular press methods or systems
• CPC Class Codes: B30B 11/14 : co-operating with moulds on a movable carrier other than a turntable or a rotating drum
• CPC Class Codes: B30B 11/16 : using pocketed rollers, e.g. two co-operating pocketed rollers
• CPC Class Codes: B30B 15/308 : in a continuous manner, e.g. for roller presses, screw extrusion presses

Abstract

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

Claims

1. A directly-formed oral, immediate release, abuse deterrent dosage form comprising an active substance susceptible to abuse, a matrix agent and a plasticizer, wherein the dosage form is directly formed from an extrusion process.

39. A method of treating pain comprising administering to an individual in need thereof a therapeutically effective amount of a dosage form of claim 1.

2-3. -3. (canceled)

4. An oral, immediate release, abuse deterrent dosage form comprising:

(i) an active substance susceptible to abuse;

(ii) a matrix agent, wherein the matrix agent has an average molecular weight between about 50K Daltons and 300K Daltons; and

(iii) a plasticizer,

wherein the active substance susceptible to abuse has an immediate release profile, and wherein the composition includes a physical barrier to reduce abuse.

5. The oral, immediate release, abuse deterrent pill of claim 4, wherein the active substance is Oxycodone HCl or Hydrocodone Bitartrate.

6. The oral, immediate release, abuse deterrent pill of claim 4, wherein the physical barrier reduces abuse by pulverizing and swallowing, pulverizing and snorting, or pulverizing and injecting.

7. The oral, immediate release, abuse deterrent pill of claim 4, wherein the physical barrier is 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.

8. The oral, immediate release, abuse deterrent pill of claim 4, wherein the physical or mechanical manipulation includes pulverizing, cutting, grating or grinding.

9. The oral, immediate release, abuse deterrent pill of claim 4, wherein the physical barrier is the pill forms a hydrogel upon exposure to an aqueous solution.

10. The oral, immediate release, abuse deterrent pill of claim 4, wherein the matrix agent is selected from the group consisting of agar, alamic acid, alginic acid, carmellose, carboxymethylcellulose sodium, chitosan, copovidone, dextrin, gelatin, hydroxyethyl cellulose, hydroxypropyl cellulose, hypromellose (HPMC), methylcellulose derivatives, microcrystalline cellulose, polyacrylic acid, polyalkalene oxide, polyvinyl acetate, polyvinyl alcohol, povidone, propylene glycol alginate, a polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer, pullulan, silicon dioxide, sodium alginate, starch, and vinylpyrrolidone-vinyl acetate copolymers.

11. The oral, immediate release, abuse deterrent pill of claim 4, wherein the pill contains about 10 Wt % to about 90 Wt % of matrix agent.

12. The oral, immediate release, abuse deterrent pill of claim 4, wherein the plasticizer is selected from the group consisting of polyalkalene glycol, acetyltributyl citrate, acetyltriethyl citrate, castor oil, diacetylated monoglycerides, dibutyl sebacate, diethyl phthalate, glycerin, propylene glycol, pullulan, sorbitol sorbitan solution, triacetin, tributyl citrate and triethyl citrate.

13. The oral, immediate release, abuse deterrent pill of claim 4, wherein the pill contains about 5 Wt % to about 60 Wt % of plasticizer.

14. The oral, immediate release, abuse deterrent pill of claim 4, further comprising a filler, a disintegrant, or an alcohol purity decreasing agent.

18. The oral, immediate release, abuse deterrent pill of claim 4, further comprising a FD&

C dye.

19. The oral, immediate release, abuse deterrent pill of claim 4, wherein greater than or equal to 75 Wt % of the active substance is released from the pill within 45 minutes following administration.

15-17. -17. (canceled)

20. An oral, immediate release, abuse deterrent dosage form comprising:

(i) about 0.5 Wt % to about 30 Wt % of an active substance susceptible to abuse;

(ii) about 10 Wt % to about 90 Wt % of a matrix agent having an average molecular weight of about 50K Daltons to about 300K Daltons; and

(iii) about 5 Wt % to about 60 Wt % of a plasticizer.

21-26. -26. (canceled)

27. An oral, immediate release, abuse deterrent dosage form comprising an active substance susceptible to abuse, wherein less than about 95% of the active substance is released from the dosage form within 20 minutes following administration, and wherein greater than or equal to 75% of the active substance is released from the dosage form within 45 minutes following administration.

28. A process for the production of an oral, immediate release, abuse deterrent dosage form containing at least one active substance susceptible to abuse comprising:

(i) processing a uniform blend of the at least one active substance susceptible to abuse, a matrix agent and a plasticizer by hot melt extrusion using an extruder to make an extrudate; and

(ii) forming the extrudate using a forming unit into the dosage form.

29-34. -34. (canceled)

35. A process for the production of an oral, immediate release, abuse deterrent dosage form, comprising:

(i) processing an analytically determined uniform blend of at least one active substance susceptible to abuse, a matrix agent and a plasticizer by hot melt extrusion using an extruder to make an extrudate and forming the dosage form.

36-37. -37. (canceled)

38. A process for the production of an oral, immediate release, abuse deterrent pill containing at least one active substance susceptible to abuse comprising:

(i) combining the at least one active substance susceptible to abuse, a matrix agent and a plasticizer in a hopper to form a mixture;

(ii) blending the mixture in the hopper until a uniform blend is achieved;

(iii) monitoring the mixture during blending using a process analytical technique to determine when a uniform blend is achieved;

(iv) feeding the uniform blend into an extruder;

(v) processing the uniform blend by hot melt extrusion in the extruder to make an extrudate;

(vi) transferring the extrudate to a forming unit using a transfer unit capable of controlling the temperature, pressure, environment or shape of the extrudate;

(vii) forming the extrudate using the forming unit into the pill; and

(viii) determining the quality, volume and weight of the pill using an optical inspection technique.