Extended Release, Abuse Deterrent Pharmaceutical Compositions

• US 20140017310A1
• Filed: 07/11/2013
• Published: 01/16/2014
• Est. Priority Date: 07/12/2012
• Status: Active Grant

• Current Assignee: SpecGx LLC (Mallinckrodt plc)
• Original Assignee: Mallinckrodt LLC (Mallinckrodt plc)
• Inventors: Park, Jae Han, Herman, Clifford J., Gower, Brad L., Castaneda, Carlos H.
• Granted Patent: US 9,730,885 B2
• Time in Patent Office: Days
• US Class Current: 424/474
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/0002 Galenical forms characterised by the drug release technique; Application systems commanded by energy
• 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 9/28 Dragees; Coated pills or tablets , e.g. with film or compression coating A61K9/2072 takes precedence, e.g. partially coated tablets A61K9/2072, coated multilayer tablets A61K9/2086, tablets with drug-coated core A61K9/209
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/36 Opioid-abuse

Abstract

The present disclosure provides pharmaceutical compositions comprising at least one active pharmaceutical ingredient or a pharmaceutically acceptable salt thereof, at least one hydrophilic plastomer, optionally at least one hydrophilic elastomer, and at least one deliquescent plasticizer, wherein the pharmaceutical compositions provide extended release of the API and have abuse deterrent properties. Also provided are methods for preparing the pharmaceutical compositions in which the components of the composition are humidified such that the deliquescent plasticizer deliquesces, thereby plasticizing the hydrophilic polymers.

Claims

1. A pharmaceutical composition, the composition comprising at least one active pharmaceutical ingredient (API) or a pharmaceutically acceptable salt thereof, at least one hydrophilic plastomer, optionally at least one hydrophilic elastomer, and at least one deliquescent plasticizer.

2. The pharmaceutical composition of claim 1, wherein the composition provides extended release of the API and has abuse deterrent properties.

3. The pharmaceutical composition of claim 1, wherein the hydrophilic plastomer is a cellulose ether, a polyalkylene oxide, a polyalkylene glycol, a polyolefinic alcohol, a polyvinyl lactam, a polycarboxylic acid, a polysaccharide, a polypeptide, or a combination thereof, and is present in an amount from about 10% to about 90% by weight of the pharmaceutical composition.

4. The pharmaceutical composition of claim 3, wherein the hydrophilic plastomer is hydroxypropyl cellulose, hydroxypropylmethyl cellulose, polyethylene oxide, or a combination thereof.

5. The pharmaceutical composition of claim 1, wherein the hydrophilic elastomer is an acrylate polymer, a methacrylate polymer, or a combination thereof, and, when present, is present in an amount from about 0.5% to about 40% by weight of the pharmaceutical composition.

6. The pharmaceutical composition of claim 5, wherein the hydrophilic elastomer is a carbomer, a polycarbophil, or a combination thereof.

7. The pharmaceutical composition of claim 1, wherein the deliquescent plasticizer is an organic acid, a sugar alcohol, a co-processed mixture of an organic acid and/or a sugar alcohol and a liquid plasticizer, or a combination thereof, and is present in an amount from about 2% to about 50% by weight of the pharmaceutical composition.

8. The pharmaceutical composition of claim 1, wherein the composition is a solid dosage form, and optionally comprises a film coating.

9. The pharmaceutical composition of claim 1, wherein after the composition is milled for about 12 minutes to form particles, more than about 30% of the particles have an average diameter of greater than about 250 microns.

10. The pharmaceutical composition of claim 9, wherein more than about 60% of the particles are greater than about 250 microns in diameter.

11. The pharmaceutical composition of claim 1, wherein the hydrophilic plastomer comprises hydroxypropyl cellulose, hydroxypropylmethyl cellulose and polyethylene oxide and is present in an amount from about 50% to about 80% by weight of the composition;

the optional hydrophilic elastomer, if present, is a carbomer and is present in an amount from 0.5% to about 10% by weight of the composition; and

the deliquescent plasticizer comprises citric acid and sorbitol and is present in an amount from about 10% to about 30% by weight of the composition.

12. The pharmaceutical composition of claim 11, wherein the API is oxycodone, oxymorphone, hydrocodone, hydromorphone, codeine, or morphine.

13. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is a solid dosage form prepared by a process comprising:

a) forming a mixture comprising the API, the plastomer, the optional hydrophilic elastomer, and the deliquescent plasticizer, wherein the mixture is a powder, a granulate, or a solid dosage unit;

b) humidifying the mixture of (a) to form a humidified powder, a humidified granulate, or a humidified solid dosage unit;

c) optionally forming the humidified powder or the humidified granulate of (b) into a treated solid dosage unit;

d) optionally coating the humidified solid dosage unit of (b) or the treated solid dosage unit of (c) to form a coated solid dosage unit; and

e) heating the humidified solid dosage unit of (b), the treated solid dosage unit of (c), or the coated solid dosage unit of (d) to form the solid dosage form of the pharmaceutical composition.

14. A process for preparing a solid dosage form, the process comprising:

a) forming a mixture comprising at least one hydrophilic plastomer, optionally at least one hydrophilic elastomer, and at least one deliquescent plasticizer, wherein the mixture is a powder, a granulate, or a solid dosage unit;

b) humidifying the mixture of (a) to form a humidified powder, a humidified granulate, or a humidified solid dosage unit;

c) optionally forming the humidified powder or the humidified granulate of (b) into a treated solid dosage unit;

d) optionally coating the humidified solid dosage unit of (b) or the treated solid dosage unit of (c) to form a coated solid dosage unit; and

e) heating the humidified solid dosage unit of (b), the treated solid dosage unit of (c), or the coated solid dosage unit of (d) to form the solid dosage form.

15. The process of claim 14, wherein the humidifying step (b) occurs at a temperature and at a relative humidity such that the deliquescent plasticizer undergoes deliquescence.

16. The process of claim 15, wherein the relative humidity at 25°

C. is from about 40% to about 100%.

17. The process of claim 14, wherein the heating step (e) occurs at a temperature greater than about 50°

C.

18. The process of claim 14, wherein the hydrophilic plastomer is a cellulose ether, a polyalkylene oxide, a polyalkylene glycol, a polyolefinic alcohol, a polyvinyl lactam, a polycarboxylic acid, a polysaccharide, a polypeptide, or a combination thereof, and is present in an amount from about 10% to about 90% by weight of the solid dosage form;

the hydrophilic elastomer is an acrylate polymer, a methacrylate polymer, or a combination thereof, and, when present, is present an amount from about 0.5% to about 40% by weight of the solid dosage form; and

the deliquescent plasticizer is an organic acid, a sugar alcohol, a co-processed mixture of an organic acid and/or a sugar alcohol and a liquid plasticizer, or a combination thereof, and is present in an amount from about 2% to about 50% by weight of the solid dosage form.

19. The process of claim 14, wherein the solid dosage form further comprises at least one active pharmaceutical ingredient (API) or a pharmaceutically acceptable salt thereof.

20. The process of claim 19, wherein the API is chosen from oxycodone, oxymorphone, hydrocodone, hydromorphone, codeine, and morphine.