ABUSE-DETERRENT PHARMACEUTICAL COMPOSITIONS OF OPIOIDS AND OTHER DRUGS

• US 20160074326A1
• Filed: 11/19/2015
• Published: 03/17/2016
• Est. Priority Date: 07/05/2002
• Status: Active Grant

• Current Assignee: Collegium Pharmaceutical Incorporated
• Original Assignee: Collegium Pharmaceutical Incorporated
• Inventors: Hirsh, Jane, Klibanov, Alexander M., Rariy, Roman V., Fleming, Alison B.
• Granted Patent: US 9,592,200 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/13 Amines A61K31/04 takes precedence
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/20 having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
• CPC Class Codes: A61K 31/4458 only substituted in position 2, e.g. methylphenidate
• 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 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61K 9/148 with compounds of unknown constitution, e.g. material from plants or animals with oils, fats, waxes, shellac A61K9/145
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1664 Compounds of unknown constitution, e.g. material from plants or animals oils, fats, waxes, shellac A61K9/1617
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/50 Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals A61K9/2081 takes precedence; particles with a single coating comprising drug A61K9/167
• CPC Class Codes: A61K 9/5015 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61K 9/5042 Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/36 : Opioid-abuse
• CPC Class Codes: G06F 3/048 : Interaction techniques based on graphical user interfaces [GUI]
• CPC Class Codes: G06F 3/167 : Audio in a user interface, e.g. using voice commands for navigating, audio feedback
• CPC Class Codes: G06Q 20/209 : Specified transaction journal output feature, e.g. printed receipt or voice output
• CPC Class Codes: G06Q 20/3276 : using a pictured code, e.g. barcode or QR-code, being read by the M-device
• CPC Class Codes: G06Q 20/3278 : RFID or NFC payments by means of M-devices
• CPC Class Codes: G06Q 20/4014 : Identity check for transactions
• CPC Class Codes: G08C 19/00 : Electric signal transmission systems G08C17/00 takes precedence
• CPC Class Codes: G10L 15/00 : Speech recognition G10L17/00 takes precedence
• CPC Class Codes: H04N 21/2668 : Creating a channel for a dedicated end-user group, e.g. insertion of targeted commercials based on end-user profiles information retrieval from the Internet by querying with filtering and personalisation G06F16/9535; arrangements for replacing or switching information during the broadcast H04H20/10; push services over packet-switching network H04L12/1859; adaptation of message content in packet-switching networks H04L51/063
• CPC Class Codes: H04N 21/458 : Scheduling content for creating a personalised stream, e.g. by combining a locally stored advertisement with an incoming stream; Updating operations, e.g. for OS modules ; time-related management operations arrangements for replacing or switching information during the broadcast or during the distribution H04H20/10
• CPC Class Codes: H04W 12/50 : Secure pairing of devices
• CPC Class Codes: H04W 12/77 : Graphical identity
• CPC Class Codes: H04W 4/80 : Services using short range communication, e.g. near-field communication [NFC], radio-frequency identification [RFID] or low energy communication

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 tamper resistant pharmaceutical composition comprising a plurality of solid particles each particle comprising a solid solution comprising:

(a) one or more drugs prone to abuse; and

(b) one or more fatty acids;

wherein the one or more drugs interact ionically with the one or more fatty acids and the molar ratio of fatty acid to the drug is from about 6;

1 to about 15;

1.

31. The tamper resistant composition of claim 30, wherein said drug is soluble in said one or more fatty acids when the one or more fatty acids are in their molten state.

32. The tamper resistant composition of claim 30, wherein said drug prone to abuse is an opioid analgesic.

33. The tamper resistant composition of claim 30, wherein the composition retards the release of a portion of the drug prone to abuse even if the physical integrity of the composition is compromised and the compromised composition is exposed to water.

34. The tamper resistant composition of claim 30 further comprising one or more anti-oxidants.

35. The tamper resistant composition of claim 30, further comprising one or more excipients having a low peroxide content in order to reduce oxidation of the drug or excipients.

36. The tamper resistant composition of claim 35, wherein the one or more excipients comprises carnauba wax having a peroxide value of less than 25 ppm.

37. The tamper resistant composition of claim 36, wherein the carnauba wax has a peroxide value of less than 5 ppm.

38. The tamper resistant composition of claim 36, wherein the carnauba wax has a peroxide value of less than 3 ppm.

39. The tamper resistant composition of claim 30, further comprising one or more substances used to change the dissolution behavior or the physical and/or chemical stability of the composition.

40. The tamper resistant composition of claim 39, wherein the one or more substances change the dissolution behavior of the composition.

41. The tamper resistant composition of claim 39, wherein the one or more substances comprises rate-controlling materials.

42. The tamper resistant composition of claim 41, wherein said rate-controlling materials comprise starch derivatives, cellulose derivatives, acrylic polymers, polyvinyl pyrrolidone, alginic acid, lactose, or mixtures thereof.

43. The tamper resistant composition of claim 41, wherein said rate-controlling materials comprise one or more pharmaceutically acceptable surfactants.

44. The tamper resistant composition of claim 43, wherein the one or more pharmaceutically acceptable surfactants comprise lecithin, sodium dodecyl sulfate, sodium salts of fatty acids, potassium salts of fatty acids, poloxamer, polyethoxylated castor oil, polyoxylglycerides, polysorbates, sorbitan stearate, or mixtures thereof.

45. The tamper resistant composition of claim 43, wherein the one or more pharmaceutically acceptable surfactants are applied to the surface to the particles, or are blended with the particles.

46. The tamper resistant composition of claim 30, wherein the particles are combined with one or more excipients and encapsulated into hard or soft shell capsules.

47. The tamper resistant composition of claim 46, wherein the one or more excipients are selected from the groups consisting of diluents, lubricants, gel forming excipients, and combinations thereof.

48. The tamper resistant composition of claim 46, wherein the hard shell capsules comprise hydroxypropylmethylcellulose.

49. A method of making the tamper resistant pharmaceutical composition of claim 30, comprising:

(a) dispersing or dissolving a drug prone to abuse in one or more fatty acids; and

(b) forming a plurality of particles comprising a solid solution comprising the drug in the one or more fatty acids via a spray congealing process from the material obtained in step (a)

wherein the molar ratio of fatty acid to the drug is from about 6;

1 to about 15;

1.

50. The method of claim 49, wherein the dissolving of said drug comprises a hot melt process.

51. The method of claim 49, wherein the dissolving of said drug comprises the use of a solvent or co-solvent.

52. The method of claim 49, wherein said spray congealing process comprises a spinning disc atomization process.

55. The tamper resistant pharmaceutical composition of claim 30, wherein the drug prone to abuse is selected from the group consisting of oxycodone, oxymorphone, hydrocodone, morphine, and pharmaceutically acceptable salts thereof.

53. A tamper resistant pharmaceutical composition comprising a plurality of particles made by a process comprising forming a plurality of particles via a spray congealing process from a solution comprising:

a drug prone to abuse; and

(ii) one or more fatty acids;

wherein the drug prone to abuse interacts ionically with the one or more fatty acids and the molar ratio of fatty acid to the drug is from about 6;

1 to about 15;

1.

54. A tamper resistant pharmaceutical composition made by a process comprising the steps of:

(a) dissolving a drug prone to abuse in one or more fatty acids; and

(b) forming a plurality of particles comprising a solid solution comprising the drug in the one or more fatty acids via a spray congealing process from the material obtained in step (a) wherein the molar ratio of fatty acid to the drug is from about 6;

1 to about 15;

1.

54-1. A method of treating pain comprising administering to a human subject in need thereof, a therapeutically effective amount of a tamper resistant pharmaceutical composition comprising a plurality of particles, each particle comprising a solid solution comprising:

(a) one or more drugs prone to abuse; and

(b) one or more fatty acids;

wherein the drug prone to abuse interacts ionically with the one or more fatty acids and the molar ratio of fatty acid to the drug is from about 6;

1 to about 15;

1.