Diversion- and/or abuse-resistant aompositions and methods for making the same

• US 20110207761A1
• Filed: 02/24/2010
• Published: 08/25/2011
• Est. Priority Date: 02/24/2010
• Status: Active Grant

• Current Assignee: Invincible Biotechnology LLC, Medical Biological Union LLC
• Original Assignee: Invincible Biotechnology LLC
• Inventors: Libman, Michael, Losev, Mikhail Viktorovich, Troisky, Alexandr Vasilievich, Zolotarsky, Vadim
• Granted Patent: US 9,125,867 B2
• Time in Patent Office: Days
• US Class Current: 514/282
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/59 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• CPC Class Codes: A61K 47/6921 the form being a particulate, a powder, an adsorbate, a bead or a sphere
• 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: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/30 for treating abuse or dependence

Abstract

A composition formulated for diversion- and/or abuse-resistance, includes at least one active pharmaceutical ingredient (API), each present in an acidic form, a first compound capable of coupling to the acidic form of the API to form a complex, where the resulting complex is resistant to separation by conventional separation methods, and a second compound capable of preferentially coupling to the first compound to thereby release the API from the complex.

Claims

1. A composition comprising:

(a) at least one active pharmaceutical ingredient (API), each present in an acidic form;

(b) a first compound capable of coupling to the acidic form of the API to form a complex, said complex being resistant to separation by conventional separation methods; and

(c) a second compound capable of preferentially coupling to the first compound to thereby release the API from the complex.

2. The composition of claim 1 wherein the first compound is capable of undergoing autooxidation and forming a suspension of fine particles in the presence of the API upon exposure to an increase in the pH.

3. The composition of claim 1 wherein the first compound is astringent.

4. The composition of claim 1 wherein the API is an alkaloid.

5. The composition of claim 1 wherein:

said first compound is at least one polyphenol; and

said second compound is at least one water soluble polymer.

6. The composition of claim 1 wherein the sum of the amounts of the first compound and the second compound exceed the amount of the API.

7. The composition of claim 1 wherein the weight ratio of the (a):

(b);

(c) is in the range of from about 1;

1-10;

1-30.

8. The composition of claim 7 wherein the weight ratio is from about 1:

1-3;

5-10.

9. The composition of claim 8 wherein the weight ratio is about 1:

1;

7.

10. The composition of claim 4 wherein the alkaloid is a nitrogenous organic molecule or a precursor thereof, having a nitrogen-containing base.

11. The composition of claim 10 wherein the alkaloid is selected from the group consisting of opiates, ephedrine, pseudoephedrine, phenyl propanol amine, and combinations thereof.

12. The composition of claim 4 wherein the alkaloid is natural, synthetic, semi-synthetic or combinations thereof.

13. The composition of claim 11 wherein the opiates are selected from the group consisting of oxycodone, morphine, hydrocodone, oxymorphone, and combinations thereof.

14. The composition of claim 5 wherein the polyphenol is selected from the group consisting of hydrolyzable tannins, phenylpropanoids, compounds having at least one phenolic subcomponent selected from the group consisting of phenols, pyrocatechols, pyrogallols, resorcinol, phloroglucinol, and hydroquinone, and combinations thereof.

16. The composition of claim 5 wherein the polyphenol is astringent.

17. The composition of claim 5 wherein the polyphenol is natural, synthetic, semi-synthetic or combinations thereof.

18. The composition of claim 14 wherein the hydrolyzable tannins are selected from the group consisting of gallic acid esters of sugars.

19. The composition of claim 14 wherein the phenylpropanoids are selected from the group consisting of lignins, flavonoids, condensed tannins, and combinations thereof.

20. The composition of claim 19 wherein the flavonoids are selected from the group consisting of flavonols, flavones, catechins, flavanones, anthocyanidins, isoflavanoids, and combinations thereof.

21. The composition of claim 5 wherein the polyphenol is selected from the group consisting of tannins, tannic acid, gallic acid, and combinations thereof.

22. The composition of claim 5 wherein the water soluble polymer is selected from the group consisting of polyalkyleneoxides, polyvinyl pyrrolidone, and combinations thereof.

23. The composition of claim 22 wherein the polyalkyleneoxides are selected from the group consisting of polyethylene glycol, polypropylene glycol, and combinations thereof.

24. The composition of claim 23 wherein the polyethylene glycol has a molecular weight of from about 400 Da to 400,000 Da.

25. A pharmaceutical composition for administration to a warm-blooded animal for release of an active pharmaceutical active (API) for a therapeutic purpose, comprising:

(a) a therapeutically effective amount of at least one API, each present in acidic form;

(b) a first compound capable of coupling to the acidic form of the API to form a complex, said complex being resistant to separation by conventional separation methods;

(c) a second compound capable of preferentially coupling to the first compound within the warm-blooded animal to thereby release the API from the complex; and

(d) a pharmaceutically acceptable carrier.

26. The pharmaceutical composition of claim 25 wherein the first compound is capable of undergoing autooxidation and forming a suspension of fine particles in the presence of the API upon exposure to an increase in the pH.

27. The pharmaceutical composition of claim 25 wherein the first compound is astringent.

28. The pharmaceutical composition of claim 25 wherein the API is an alkaloid.

29. The pharmaceutical composition of claim 25 wherein the first compound is at least one polyphenol.

30. The pharmaceutical composition of claim 25 wherein the second compound is at least one water soluble polymer.

31. The pharmaceutical composition of claim 25 further comprising at least one additive selected from the group consisting of surfactants, gel forming compounds, and combinations thereof.

32. The pharmaceutical composition of claim 25 in the form of a gel.

33. The pharmaceutical composition of claim 25 wherein the insoluble complex is formed in an acidic or slightly basic environment.

34. The pharmaceutical composition of claim 25 in the form of tablets, soft capsules, hard capsules, gels, and liquid formulations.

35. A pharmaceutical composition for administration to a warm-blooded animal for release of an active pharmaceutical ingredient (API) for a therapeutic purpose comprising a complex of an API present in an acidic form bound to a polyphenol and a water soluble polymer capable of preferentially binding to the polyphenol in said warm-blooded animal to thereby release the API from the complex.

36. The pharmaceutical composition of claim 35 wherein the polyphenol is capable of undergoing autooxidation and forming a suspension of fine particles in the presence of the API upon exposure to an increase in the pH.

37. The pharmaceutical composition of claim 35 wherein the polyphenol is astringent.

38. The pharmaceutical composition of claim 35 wherein the API is an alkaloid.

39. The pharmaceutical composition of claim 35 wherein the water soluble polymer preferentially binds to the polyphenol in an acidic or slightly basic environment.

40. A method for administering an active pharmaceutical ingredient (API) to a warm-blooded animal comprising the step of administering a pharmaceutical composition comprising:

(a) a therapeutically effective amount of at least one API, each present in an acidic form;

(b) a first compound capable of coupling to the acidic form of the API to form a complex, said complex being resistant to separation by conventional separation methods; and

(c) a second compound capable of preferentially coupling to the first compound within the warm-blooded animal to thereby release the API from the complex.

41. The method of claim 40 wherein the first compound is astringent.

42. The method of claim 40 wherein the API is an alkaloid.

43. The method of claim 40 wherein the first compound is capable of undergoing autooxidation and forming a suspension of fine particles in the presence of the API upon exposure to an increase in the pH.

44. A method for preventing diversion and/or abuse of an active pharmaceutical ingredient (API), comprising the steps of:

obtaining a first compound capable of coupling to an API present in an acidic form to form a complex, said complex being resistant to separation by conventional separation methods;

obtaining a second compound capable of preferentially coupling to the first compound to thereby release the API from the complex; and

admixing the first and second compounds with the API.

45. The method of claim 44 wherein the first compound is astringent.

46. The method of claim 44 wherein the API is an alkaloid.

47. The method of claim 44 wherein the first compound is capable of undergoing autooxidation and forming a suspension of fine particles in the presence of the API upon exposure to an increase in the pH.

48. An additive for preventing diversion and/or abuse of an active pharmaceutical ingredient (API), comprising:

(a) a first compound capable of coupling to an API present in an acidic form to form a complex, said complex being resistant to separation by conventional separation methods; and

(b) a second compound capable of preferentially coupling to the first compound to thereby release the API from the complex.

49. The additive of claim 48 wherein the first compound is astringent.

50. The additive of claim 48 wherein the API is an alkaloid.

51. The additive of claim 48 wherein the first compound is capable of undergoing autooxidation and forming a suspension of fine particles in the presence of the API upon exposure to an increase in the pH.

52. A method for making an additive for preventing diversion and/or abuse of an active pharmaceutical ingredient (API), comprising the steps of:

obtaining a first compound capable of coupling to an API present in an acidic form to form a complex, said complex being resistant to separation by conventional separation methods;

obtaining a second compound capable of preferentially coupling to the first compound to thereby release the API from the complex; and

admixing the first and second compounds together.

53. The method of claim 52 wherein the first compound is astringent.

54. The method of claim 52 wherein the API is an alkaloid.

55. The method of claim 52 wherein the first compound is capable of undergoing autooxidation and forming a suspension of fine particles in the presence of the API upon exposure to an increase in the pH.