Abuse-deterrent drug formulations

• US 8,758,813 B2
• Filed: 04/25/2013
• Issued: 06/24/2014
• Est. Priority Date: 06/12/2004
• Status: Active Grant

• Current Assignee: Collegium Pharmaceutical Incorporated
• Original Assignee: Collegium Pharmaceutical Incorporated
• Inventors: Hirsh, Jane, Fleming, Alison, Rariy, Roman, Klibanov, Alexander M.
• Primary Examiner(s): CLAYTOR, DEIRDRE RENEE
• Application Number:
  US13/870,690
• Publication Number:
  US 20130310413A1
• Time in Patent Office: 425 Days
• Field of Search: 424/458, 424/476, 514/282
• US Class Current: 424/458
• 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 one embodiment, the drug is modified to increase its lipophilicity by forming a salt between the drug and one or more fatty acids wherein the concentration of the one or more fatty acids is one to 15 times the molar amount of the active agent. The abuse-deterrent composition prevents the immediate release of a substantial portion of drug, even if the physical integrity of the formulation is compromised 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 broken down or dissolved gradually within the GI tract by a combination of enzymatic degradation, surfactant action of bile acids, and mechanical erosion.

Claims

1. A method for the management of pain comprising administering to a patient in need thereof a therapeutically effective pharmaceutical composition comprising solid microparticles, wherein the microparticles comprise:

a) an active agent,

b) one or more fatty acids, and

c) one or more carrier materials selected from the group consisting of waxes or wax-like substances and mixtures thereof;

wherein the active agent comprises a fatty acid salt of oxycodone, and the one or more fatty acids are present in an amount ranging from 6.9 to 15 times the molar amount of the active agent.

2. The method of claim 1, wherein the molar concentration of the one or more fatty acids in the microparticle is 6.9 to 10 times the molar amount of the active agent.

3. The method of claim 1, wherein the one or more fatty acids is one or more C₅ to C₃₀ monovalent fatty acids, one or more C₈ to C₄₀ divalent fatty acids, or mixtures thereof.

4. The method of claim 2 wherein the one or more fatty acids is one or more C₅ to C₃₀ monovalent fatty acids, one or more C₈ to C₄₀ divalent fatty acids, or mixtures thereof.

5. The method of claim 3, wherein the one or more fatty acids is one or more C₅ to C₃₀ monovalent fatty acids selected from the group consisting of pentanoic acid, hexanoic (caproic) acid, heptanoic acid, octanoic (carylic) acid, nonanoic acid, decanoic (capric) acid, undecanoic acid, dodecanoic (lauric) acid, tridecanoic acid, tetradecanoic (myristic) acid, pentadecanoic acid, hexadecanoic (palmitic) acid, heptadecanoic (margaric) acid, octadecanoic (stearic) acid, nonadecanoic acid, eicosanoic (arachidic) acid, heneicosanoic acid, docasanoic (behenic) acid, tricosanoic acid, tetracosanoic (lignoceric) acid, pentacosanoic acid, hexacosanoic acid, heptacosanoic acid, octacosanoic acid, nonacosanoic acid, triacontanoic acid, linoleic acid, oleic acid, and mixtures thereof.

6. The method of claim 4, wherein the one or more fatty acids is one or more C₅ to C₃₀ monovalent fatty acids selected from the group consisting of pentanoic acid, hexanoic (caproic) acid, heptanoic acid, octanoic (carylic) acid, nonanoic acid, decanoic (capric) acid, undecanoic acid, dodecanoic (lauric) acid, tridecanoic acid, tetradecanoic (myristic) acid, pentadecanoic acid, hexadecanoic (palmitic) acid, heptadecanoic (margaric) acid, octadecanoic (stearic) acid, nonadecanoic acid, eicosanoic (arachidic) acid, heneicosanoic acid, docasanoic (behenic) acid, tricosanoic acid, tetracosanoic (lignoceric) acid, pentacosanoic acid, hexacosanoic acid, heptacosanoic acid, octacosanoic acid, nonacosanoic acid, triacontanoic acid, linoleic acid, oleic acid, and mixtures thereof.

7. The method of claim 5, wherein the one or more fatty acids is myristic acid.

8. The method of claim 6, wherein the one or more fatty acids is myristic acid.

9. The method of claim 1, wherein the one or more carrier materials are present in an amount of from 0.25 to 8 times the weight of the amount of active agent.

10. The method of claim 2, wherein the one or more carrier materials are present in an amount of from 0.25 to 8 times the weight of the amount of active agent.

11. The method of claim 9, wherein the one or more carrier materials are present in an amount of from 2 to 6 times by weight of the amount of active agent.

12. The method of claim 10, wherein the one or more carrier materials are present in an amount of from 2 to 6 times by weight of the amount of active agent.

13. The method of claim 1, wherein the carrier material is a wax selected from the group consisting of carnauba wax, beeswax, microcrystalline wax, and mixtures thereof.

14. The method of claim 2, wherein the carrier material is a wax selected from the group consisting of carnauba wax, beeswax, microcrystalline wax, and mixtures thereof.

15. The method of claim 13, wherein the carrier material is a mixture of beeswax and carnauba wax.

16. The method of claim 14, wherein the carrier material is a mixture of beeswax and carnauba wax.

17. The method of claim 1, wherein the active agent comprises a myristic acid salt of oxycodone, the one or more fatty acids is myristic acid, and the carrier comprises beeswax and carnauba wax.

18. The method of claim 2, wherein the active agent comprises a myristic acid salt of oxycodone, the one or more fatty acids is myristic acid, and the carrier comprises beeswax and carnauba wax.

19. The method of claim 1, wherein the active agent is prepared by contacting a molar excess of one of the one or more fatty acids with the free base form of the active agent.

20. The method of claim 2, wherein the active agent is prepared by contacting a molar excess of one of the one or more fatty acids with the free base form of the active agent.