ABUSE-DETERRENT PHARMACEUTICAL COMPOSITIONS OF OPIOIDS AND OTHER DRUGS

• US 20140105987A1
• Filed: 10/15/2013
• Published: 04/17/2014
• Est. Priority Date: 07/05/2002
• Status: Active Grant

• Current Assignee: Collegium Pharmaceutical Incorporated
• Original Assignee: Collegium Pharmaceutical Incorporated
• Inventors: RARIY, Roman V., FLEMING, Alison B., HIRSH, Jane, KLIBANOV, Alexander M.
• Granted Patent: US 9,248,195 B2
• Time in Patent Office: Days
• US Class Current: 424/490
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/46 Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates

Abstract

An abuse-deterrent pharmaceutical composition has been developed to reduce the likelihood of improper administration of drugs, especially drugs such as opioids. In a preferred embodiment, a drug is modified to increase its lipophilicity. In some embodiments the modified drug is homogeneously dispersed within spherical microparticles composed of a material that is either slowly soluble or not soluble in water. In some embodiments the drug containing microparticles or drug particles are coated with one or more coating layers, where at least one coating is water insoluble and/or organic solvent insoluble. The abuse-deterrent composition retards the release of drug, even if the physical integrity of the formulation is compromised (for example, by chopping with a blade or crushing) and the resulting material is placed in water, snorted, or swallowed. However, when administered as directed, the drug is slowly released from the composition as the composition is passes through the GI tract.

Claims

1-29. -29. (canceled)

30. A method of administering an abuse-deterrent pharmaceutical composition comprising orally administering to a patient in need thereof an abuse-deterrent oral dosage form comprising a plurality of microparticles, where each microparticle comprises:

a fatty acid salt of one or more drugs prone to abuse; and

one or more carrier material(s) comprising fats, fatty substances, waxes, wax-like substances or mixtures thereof

wherein the oral dosage form retards the release of the one or more drugs prone to abuse, even if the physical integrity of the dosage form is compromised and the compromised dosage form is placed in water.

33. The method of claim 30 or 31, wherein the one or more drugs prone to abuse is an opioid.

34. The method of claim 33, wherein the opioid is an opioid agonist.

35. The method of claim 34, wherein the opioid agonist is hydrocodone, hydromorphone, morphine, oxycodone, oxymorphone or tramadol.

36. The method of claim 30 or 31, wherein the fatty acid salt is the stearate, palmitate or the myristate fatty acid salt.

37. The method of claim 30 or 31, wherein the one or more carrier materials comprise myristic acid, stearic acid, palmitic acid, beeswax, carnauba wax, hydrogenated oil or mixtures thereof.

38. The method of claim 30 or 31, wherein the oral dosage form is a capsule or a tablet.

39. The method of claim 30 or 31, wherein the oral dosage form further comprises an antioxidant.

40. The method of claim 39, wherein the antioxidant comprises butylated hydroxytoluene (BHT);

ascorbic acid, its salts and esters;

Vitamin E, tocopherol and its salts;

sodium metabisulphite;

cysteine;

citric acid;

propyl gallate;

butylated hydroxyanisole (BHA);

or combinations thereof

41. The method of claim 30 or 31, wherein each microparticle further comprises an enteric coat.

42. The method of claim 30 or 31, wherein the oral dosage form is a controlled-release oral dosage form.

43. The method of claim 30 or 31, wherein each microparticle further comprises a pharmaceutically acceptable surfactant.

44. The method of claim 30 or 31, wherein the microparticles are spherical.

45. The method of claim 30 or 31, wherein the one or more drugs prone to abuse is a stimulant.

46. The method of claim 45, wherein the stimulant is amphetamine, methamphetamine or methylphenidate.

31. A method of administering an abuse-deterrent pharmaceutical composition comprising orally administering to a patient in need thereof an abuse-deterrent oral dosage form comprising a plurality of microparticles, where each microparticle comprises:

a solidified solution of a fatty acid salt of one or more drugs prone to abuse; and

one or more carrier material(s) comprising fats, fatty substances, waxes, wax-like substances or mixtures thereof.

32. The method of claim 31, wherein the oral dosage form retards the release of the one or more drugs prone to abuse, even if the physical integrity of the dosage form is compromised and the compromised dosage form is placed in water.

47. The method of claim 31, wherein the one or more drugs prone to abuse is uniformly dispersed in the carrier material of each microparticle.

48. The method of claim 31, wherein each microparticle comprises one or more fatty acids as carrier materials in an amount sufficient to solubilize the one or more drugs prone to abuse in the carrier material(s).

49. A method for the management of pain comprising administering to a patient in need thereof an abuse-deterrent oral dosage form comprising a plurality of microparticles, where each microparticle comprises:

a fatty acid salt of one or more drugs prone to abuse; and

one or more carrier material(s) comprising fats, fatty substances, waxes, wax-like substances or mixtures thereof

wherein the oral dosage form retards the release of the one or more drugs prone to abuse, even if the physical integrity of the dosage form is compromised and the compromised dosage form is placed in water; and

wherein the one or more drugs prone to abuse is an opioid.

50. The method of claim 49, wherein the opioid is an opioid agonist.

51. The method of claim 50, wherein the opioid agonist is hydrocodone, hydromorphone, morphine, oxycodone, oxymorphone or tramadol.