Abuse resistant opioid drug-ion exchange resin complexes having hybrid coatings

• US 8,202,542 B1
• Filed: 05/28/2008
• Issued: 06/19/2012
• Est. Priority Date: 05/31/2007
• Status: Active Grant

• Current Assignee: Tris Pharma Incorporated
• Original Assignee: Tris Pharma Incorporated
• Inventors: Mehta, Ketan, Tu, Yu-Hsing, Chaudhuri, Alivia, Perumal, Ashok
• Primary Examiner(s): Tran, Susan
• Application Number:
  US12/154,970
• Publication Number:
  US 20120135077A1
• Time in Patent Office: 1,483 Days
• Field of Search: None
• US Class Current: 424/489
• CPC Class Codes: A61K 47/52 the modifying agent being an inorganic compound, e.g. an inorganic ion that is complexed with the active ingredient
• CPC Class Codes: A61K 47/585 Ion exchange resins, e.g. polystyrene sulfonic acid resin
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61K 9/2081 with microcapsules or coated microparticles according to A61K9/50
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids

Abstract

A sustained release formulation for opioid drugs is described. The formulation contains an opioid-ion exchange resin complex having a hybrid coating. The hybrid coating contains a cured polyvinylacetate polymer and a pH-dependent enteric coating layer mixed therein. Also provided are methods of making and using same.

Claims

1. A solid oral dose tablet, powder or granular formulation having modified release characteristics comprising at least one hybrid coated opioid-ion exchange resin complex and pharmaceutically acceptable excipients, said at least one hybrid coated opioid-ion exchange resin complex comprising:

a pharmaceutically effective amount of an opioid bound to a pharmaceutically acceptable ion exchange resin; and

a cured hybrid modified release coating layer over the opioid-ion exchange resin complex, said hybrid coating comprising;

a pH-independent, high tensile strength, water insoluble, water-permeable, diffusion barrier coating forming component comprising about 70% to about 90% w/w polyvinylacetate (PVA) and about 3 to about 10% w/w of a plasticizer; and

an enteric coating forming component having pH-dependent solubility in an aqueous system which is non-reactive with said barrier coating forming component, said enteric coating forming component comprising polyvinylacetate phthalate,

wherein said barrier coating forming component and said enteric coating forming component are present in a weight ratio of about 20;

1 to about 3;

1.

2. The solid dose formulation according to claim 1, wherein the opioid is morphine or morphine sulfate.

3. The solid dose formulation according to claim 1, wherein the solid formulation is a tablet.

4. The solid dose formulation according to claim 1, wherein the solid formulation is granules in a capsule.

5. The solid dose formulation according to claim 1, wherein said barrier coating forming component and said enteric coating forming component are present in a ratio of about 6:

1 to 4;

1 wt/wt.

6. The solid dose formulation according to claim 1, wherein the plasticizer in said barrier coating forming component is selected from the group consisting of dibutyl sebacate, propylene glycol, polyethylene glycol, polyvinyl alcohol, triethyl citrate, acetyl triethyl citrate, acetyl tributyl citrate, tributyl citrate, triacetin, Soluphor P, and mixtures thereof.

7. The solid dose formulation according to claim 6, wherein the plasticizer is triacetin.

8. The solid dose formulation according to claim 1, wherein the hybrid coating comprises 25% to 50% by weight of the complex.

9. The solid dose formulation according to claim 8, wherein the hybrid coating comprises 30% to 45% by weight of the complex.

10. The solid dose formulation according to claim 1, wherein said enteric coating forming component comprises polyvinylacetate phthalate and 10% titanium dioxide.

11. The solid dose formulation according to claim 1, wherein the enteric coating component comprises a polyinylacetate phthalate, at least one plasticizer, and one or more selected from the group consisting of a detackifier, a lubricant, an alkalizing agent, a viscosity modifier, and an anti-caking agent.

12. The solid dose formulation according to claim 11, wherein the at least one plasticizer in the enteric coating component comprises a liquid plasticizer and a solid plasticizer.

13. The solid dose formulation according to claim 12, wherein the liquid plasticizer is triethylcitrate.

14. The solid dose formulation according to claim 12, wherein the solid plasticizer is polyethylene glycol 3350.

15. The solid dose formulation according to claim 1, wherein the resin further comprises a release retardant which forms a matrix with the resin complex, wherein said hybrid coating is over said opioid-ion exchange resin complex-matrix.

16. The solid dose formulation according to claim 15 wherein the release retardant is selected from the group consisting of a polyvinyl acetate polymer, ethyl cellulose, cellulose acetate, acrylic based polymers or copolymers, cellulose phthalate, and mixtures thereof.

17. The solid dose formulation according to claim 1, wherein said opioid drug-ion exchange resin complex is in a matrix which further comprises a solvating agent and wherein said hybrid coating is over said opioid-ion exchange resin complex matrix.

18. The solid dose formulation according to claim 17, wherein said hybrid coating is present in an amount which provides a 40% weight gain over the opioid-drug ion exchange resin complex-matrix.

19. The solid dose formulation according to claim 17, wherein the solvating agent is polyvinyl pyrrolidone.

20. The solid dose formulation according to claim 1, wherein the barrier coating forming component comprises PVA, a stabilizer, a surfactant and a plasticizer.

21. The solid dose formulation according to claim 20, wherein the stabilizer is a polyvinylpyrrolidone.

22. The solid dose formulation according to claim 21, wherein the polyvinyl pyrrolidone comprises about 5 to about 10% w/w of the barrier coating component.

23. The solid dose formulation according to claim 20, wherein the surfactant is sodium lauryl sulfate.

24. The solid dose formulation according to claim 1, wherein the opioid drug is selected from the group consisting of opioid analgesics drugs selected from the group consisting of hydrocodone, morphine, hydromorphone, oxycodone, codeine, levorphanol, meperidine, methadone, oxymorphone, buprenorphine, fentanyl, dipipanone, tramadol, etorphine, dihydroetorphine, butorphanol, levorphanol, or salts thereof or mixtures thereof.

25. The solid dose formulation according to claim 20, wherein the opioid is selected from morphine or morphine sulfate.