Abuse-deterrent opioids

Patent metadata

Field	Value
Publication number	US-2016199368-A1
Application number	US-201514877208-A
Country	US
Kind code	A1
Filing date	Oct 7, 2015
Priority date	Jan 9, 2015
Publication date	Jul 14, 2016
Grant date	—

Abstract

Described herein are abuse deterrent controlled release oral pharmaceutical compositions comprising and methods for making the same. In particular, an abuse deterrent controlled release oral pharmaceutical composition comprising a soft capsule and an abuse deterrent controlled release matrix comprising an active pharmaceutical ingredient are described.

First claim

1 . An abuse deterrent oral pharmaceutical composition comprising a tamper resistant controlled release matrix comprising:
(a) at least one lipid or lipophilic vehicle; (b) at least one organogelator; (c) at least one hydrophilic polymer; (d) at least one hydrophilic vehicle; and (e) at least one active pharmaceutical ingredient;
wherein the matrix is resistant to tampering and is encapsulated in a soft capsule shell.

2 . The composition of claim 1 , wherein the tamper resistant controlled release matrix further comprises at least one antioxidant.

3 . (canceled)

4 . The composition of claim 1 , wherein the lipid or lipophilic vehicle comprises about 30% to about 85% of the total matrix mass.

5 . The composition of claim 1 , wherein the at least one organogelator comprises from about 0.5% to about 25% of the total matrix mass.

6 . The composition of claim 1 , wherein the at least one hydrophilic polymer comprises about 1% to about 30% of the total matrix mass.

7 . The composition of claim 1 , wherein the at least one hydrophilic vehicle comprises about 2% to about 40% of the total matrix mass.

8 . The composition of claim 1 , wherein the at least one active pharmaceutical ingredient comprises about 1% to about 35% of the total matrix mass.

9 . The composition of claim 2 , wherein the at least one anti-oxidant comprises about 0.05% to about 0.5% of the total matrix mass.

10 . (canceled)

11 . The composition of claim 1 , wherein the ratio of the active pharmaceutical ingredient percent mass to the matrix percent mass is about 1:100 to about 1:3.

12 - 13 . (canceled)

14 . The composition of claim 1 , wherein the liquid lipid or lipophilic vehicle comprises: olive oil, sunflower oil, canola oil, palmitoleic acid, oleic acid, myristoleic acid, linoleic acid, arachidonic acid, paraffin oil, or mineral oil.

15 - 18 . (canceled)

19 . The composition of claim 1 , wherein the organogelator forms a gel at a temperature of about 90° C. to about 120° C.

20 . (canceled)

21 . The composition of claim 1 , wherein the organogelator comprises ethyl cellulose having a viscosity value of about 3 cP to about 20 cP.

22 - 24 . (canceled)

25 . The composition of claim 1 , wherein the hydrophilic polymer comprises methylcellulose, hydroxypropylmethyl cellulose, a mixture of hydroxypropylmethyl cellulose and methylcellulose, polymethylmethacrylate, polyvinyl pyrrolidone, or a combination thereof.

26 . The composition of claim 1 , wherein the hydrophilic polymer comprises methylcellulose or hydroxypropylmethyl cellulose.

27 . (canceled)

28 . The composition of claim 26 , wherein methylcellulose has a viscosity value of about 50 to about 4,000 cP and hydroxypropylmethyl cellulose has a viscosity value of about 50 to about 100,000 cP.

29 . (canceled)

30 . The composition of claim 2 , wherein the anti-oxidant comprises butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), or a combination thereof.

31 . (canceled)

32 . The composition of claim 1 , wherein the active pharmaceutical ingredient comprises at least one of: hydrocodone, morphine, morphine analogues, or morphine antagonists, tapentadol, codeine, morphine, methadone, fentanyl and analogs, hydrocodone hydrochloride, hydrocodone bitartrate, hydromorphone, oxymorphone, oxycodone, meperidine, propoxyphene, flunitrazepam, barbiturates, amytal, nembutal, seconal, phenobarbital; benzodiazepines, zolpidem, zaleplon, eszopiclone, amphetamines, methylphenidate, or a combination thereof.

33 . The composition of claim 1 , wherein the active pharmaceutical ingredient comprises hydrocodone or oxycodone.

34 - 41 . (canceled)

42 . The composition of claim 1 , wherein the tamper resistant controlled release matrix comprises:
(a) soybean oil; (b) ethyl cellulose; (e) hydroxypropylmethyl cellulose; (f) polyethylene glycol; (g) hydrocodone or oxycodone; and optionally (h) BHT; and (i) BHA.

43 . The composition of claim 42 , wherein the tamper resistant controlled release matrix comprises:
(a) about 30% to about 70% soybean oil; (b) about 1% to about 7% Ethocel™ 20 cP; (c) about 1% to about 30% Methocel™ K100M; (d) about 2% to about 40% polyethylene glycol 400; (e) about 10.5% of hydrocodone or oxycodone; and optionally (f) about 0.25% BHT; and (g) about 0.1% BHA.

44 - 47 . (canceled)

48 . The composition of claim 1 , wherein the soft capsule shell comprises:
(a) about 25% to about 50% of at least one film-forming polymer; (b) about 15% to about 25% of at least one plasticizer; and (c) about 20% to about 40% of a solvent,
wherein the at least one film-forming polymer comprises gelatin, the at least one plasticizer comprises glycerol, and the solvent comprises water.

49 . The composition of claim 47 , wherein the soft capsule shell comprises:
(a) about 42% of at least one film-forming polymer; (b) about 20% of at least one plasticizer; and (c) about 38% of a solvent.

50 . (canceled)

51 . A method for making a tamper resistant controlled release matrix dosage form comprising:
(i) heating one or more liquid lipophilic vehicles to about 60° C. and adding one or more organogelators until completely dissolved to form a first clear gel mixture; (ii) hydrating one or more hydrophilic polymers with one or more hydrophilic vehicles; (iii) mixing one or more active pharmaceutical ingredients with the mixture of step (b) to form a second uniform mixture; and (iv) adding the second uniform mixture of step (c) to the first clear gel mixture of (i) to form a final uniform matrix composition, wherein the tamper resistant controlled release matrix dosage form comprises
(a) soybean oil;
(b) ethyl cellulose;
(e) hydroxypropylmethyl cellulose;
(f) polyethylene glycol; and
(g) hydrocodone or oxycodone.

52 - 57 . (canceled)

58 . A tamper resistant oral pharmaceutical composition comprising a tamper resistant controlled release matrix comprising:
(a) about 30% to about 70% soybean oil; (b) about 1% to about 7% Ethocel™ 20 cP; (c) about 1% to about 30% Methocel™ K100M; (d) about 2% to about 40% polyethylene glycol 400; (e) about 10.5% of hydrocodone or oxycodone; and optionally (f) about 0.25% BHT; and (g) about 0.1% BHA.
wherein the matrix is resistant to tampering and has controlled release properties;
the matrix being encapsulated in a soft capsule shell comprising:
(h) about 25% to about 50% gelatin;
(i) about 15% to about 25% glycerol; and
(j) about 20% to about 40% water.

59 - 63 . (canceled)

64 . A method for treating, reducing the symptoms or onset of, or prophylaxis of pain stemming from diabetic neuropathy, chronic arthritis, osteoarthritis, rheumatoid arthritis, acute tendonitis, bursitis, headaches, migraines, chronic neuropathies, shingles, premenstrual symptoms, sports injuries, malignancy, radiculopathy, sciatica/sciatic pain, sarcoidosis, necrobiosis, lipoidica or granuloma annulare comprising administering to a subject in need thereof the pharmaceutical composition of claim 1 .

65 - 79 . (canceled)

Assignees

• Banner Life Sciences Llc

Inventors

• Gosangari Saujanya
• Hughey Justin
• Dyakonov Tatyana
• Vamvakas George
• Fatmi Aqeel A

Classifications

• A61K31/485 Primary

  Morphinan derivatives, e.g. morphine, codeine · CPC title

• A61K9/4866 Primary

  Organic macromolecular compounds · CPC title

• A61K9/4858

  Organic compounds · CPC title

• A61K9/4875

  Compounds of unknown constitution, e.g. material from plants or animals (oils, fats, waxes, shellac A61K9/4858) · CPC title

• A61K31/437

  the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline · CPC title