Opioid polymer release system

• US 9,707,179 B2
• Filed: 07/15/2014
• Issued: 07/18/2017
• Est. Priority Date: 09/21/2001
• Status: Expired due to Fees

• Current Assignee: Egalet, Ltd. (Assertio Holdings, Inc.)
• Original Assignee: Egalet, Ltd. (Assertio Holdings, Inc.)
• Inventors: Fischer, Gina, Andersen, Christine, Bar-Shalom, Daniel, Slot, Lillian
• Primary Examiner(s): ROGERS, JAMES WILLIAM
• Application Number:
  US14/331,833
• Publication Number:
  US 20150037417A1
• Time in Patent Office: 1,099 Days
• Field of Search: None
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/0092 Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• 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: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

A pharmaceutical composition for controlled release of an active substance is provided. The active substance is released into an aqueous medium by erosion of at least one surface of the composition. The composition comprises i) a matrix comprising a) polymer or a mixture of polymers, b) an active substance and, optionally, c) one or more pharmaceutically acceptable excipients, and ii) a coating.

Claims

1. A controlled release pharmaceutical formulation for oral delivery of hydrocodone or oxycodone consisting of a single injection molded matrix having a coating, wherein:

the single injection molded matrix has a cylindrical shape and comprises a therapeutically effective amount of hydrocodone or oxycodone or a pharmaceutically acceptable salt thereof and one or more polyethylene oxides, wherein the average molecular weight of the one or more polyethylene oxides present in the matrix is from about 200,000 to about 300,000 daltons; and

the coating on the matrix has at least one opening exposing an end surface of the matrix to permit release of the hydrocodone or oxycodone from the matrix by erosion of the matrix, and is insoluble and impermeable to body fluids during the intended hydrocodone or oxycodone release period;

wherein the coating and the matrix are formed by injection molding,

wherein the formulation exhibits zero order release of at least 60% of the hydrocodone or oxycodone from the formulation when subject to an in vitro dissolution test according to USP 24, NF 19, 711 Dissolution, employing Apparatus 2 equipped with a paddle using 1000 mL of 0.1 N hydrochloric acid dissolution medium and a paddle rotation of 120 rpm for the first 120 minutes, and a buffer solution having a pH of 6.8 and a paddle rotation of 50 rpm thereafter.

2. The pharmaceutical formulation of claim 1, wherein the one or more polyethylene oxides comprise at least two polyethylene oxides.

3. The pharmaceutical formulation of claim 1, wherein at least one polyethylene oxide has a molecular weight of about 200,000 or about 300,000 daltons.

4. The pharmaceutical formulation of claim 1, wherein the matrix further comprises a plasticizer.

5. The pharmaceutical formulation of claim 1, wherein the matrix further comprises a block copolymer of ethylene oxide and propylene oxide.

6. The pharmaceutical formulation of claim 1, wherein the matrix further comprises a block copolymer of ethylene oxide and propylene oxide having a molecular weight of from about 5,000 to about 30,000 daltons.

7. The pharmaceutical formulation of claim 1, wherein the matrix further comprises a poloxamer.

8. The pharmaceutical formulation of claim 1, wherein the matrix further comprises an antioxidant.

9. The pharmaceutical formulation of claim 8 wherein the antioxidant is butylhydroxytoluene.

10. The pharmaceutical formulation of claim 1, wherein the matrix further comprises hydroxypropylmethylcellulose.

11. The pharmaceutical formulation of claim 1, wherein the coating remains intact during release of the hydrocodone or oxycodone from the formulation following oral administration to a human.

12. The pharmaceutical formulation of claim 1, wherein the coating comprises a plasticizer.

13. The pharmaceutical formulation of claim 1, wherein the coating comprises one or more polylactic acid polymers.

14. The pharmaceutical formulation of claim 1, wherein the coating comprises a material selected from the group consisting of cellulose acetate, polyamide, polyethylene, polyethylene terephthalate, polypropylene, polyurethane, polyvinyl acetate, polyvinyl chloride, silicone rubber, latex, polyhydroxybutyrate, polyhydroxyvalerate, teflon, polylactic acid or polyglycolic acid and copolymers thereof, ethylene vinyl acetate (EVA), styrene-butadienestyrene (SBS), and styrene-isoprene-styrene (SIS).

15. The pharmaceutical formulation of claim 1, wherein the formulation is suitable for once-daily oral dosing.

16. The pharmaceutical formulation of claim 1, wherein the formulation is suitable for twice-daily oral dosing.

17. The pharmaceutical formulation of claim 1, wherein the formulation is prepared by injection molding the matrix inside the coating.

18. The pharmaceutical formulation of claim 1, wherein the coating and the matrix are each prepared by separate injection molding processes.

19. The pharmaceutical formulation of claim 1, wherein at least one end of the matrix is tapered and wherein at least one opening of the coating exposes the tapered end, to expose an increasing surface area during the first 1-3 hours of matrix erosion following oral administration to a human.

20. The pharmaceutical formulation of claim 1, wherein the matrix further comprises one or more methacrylic acid copolymers.