Abuse Deterrent Immediate Release Formulation

• US 20160106680A1
• Filed: 05/30/2014
• Published: 04/21/2016
• Est. Priority Date: 05/31/2013
• Status: Abandoned Application

• Current Assignee: Pharmascience Incorporated (Joddes Limitã©E)
• Original Assignee: Pharmascience Incorporated (Joddes Limitã©E)
• Inventors: Talwar, Naresh, Bhandari, Krishna Hari
• Application Number:
  US14/894,213
• Publication Number:
  US 20160106680A1
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/4458 only substituted in position 2, e.g. methylphenidate
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/4985 Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/5513 1,4-Benzodiazepines, e.g. diazepam or clozapine
• CPC Class Codes: A61K 31/5517 condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/205 Polysaccharides, e.g. alginate, gums; Cyclodextrin
• 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

Abstract

The present invention relates to an immediate release orally administrable abuse-deterrent pharmaceutical formulation comprising: at least one pharmaceutically active ingredient susceptible to abuse; at least one gelling polymeric compound selected from the group consisting of: polysaccharides, sugars, sugar derived alcohols, starches, starch derivatives, cellulose derivatives, Carrageenan, pectin, sodium alginate, gellan gum, xanthan gum, poloxamer, Carbopol®, PolyOx®, povidone, hydroxypropyl methylcellulose (HPMC), hypermellose, and combinations thereof; at least one disintegrant and optionally at least one surfactant, wherein said formulation exhibit properties related to deterring the abuse, via injection or nasal inhalation when being tampered and exposed to aqueous, alcoholic, acidic and basic media.

Claims

1. An immediate release orally administrable abuse-deterrent pharmaceutical formulation comprising:

a) at least one pharmaceutically active ingredient susceptible to abuse within a matrix;

b) at least one gelling polymeric compound, selected from a group consisting of;

a natural resin, a natural gum, a polymer and a combination thereof;

c) at least one disintegrant; and

d) optionally a surfactant.

4. The immediate release orally administrable abuse-deterrent pharmaceutical formulation of claim 1 further comprising at least one other pharmaceutically acceptable excipient,

wherein said formulation provides release of the active pharmaceutical ingredient and has an in vitro dissolution profile that is equal to or greater than 80 percent of the drug dissolved in 30 minutes after administration as measured by USP type I or II dissolution apparatus as described in USP XXVI (2003).

5. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 1, wherein the active pharmaceutical ingredient susceptible to abuse is selected from the group consisting of:

opioids and morphine derivatives;

antidepressants;

stimulants;

hallucinogenics;

hypnotics; and

tranquilizers.

6. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 1, wherein the active pharmaceutical ingredient susceptible to abuse is selected from the group consisting of:

amphetamine, alprazolam, codeine, diazepam, fentanyl and analogs thereof, hydrocodone, hydromorphone HCl, lorazepam, meperidine, morphine, methylphenidate, methadone, nitrazepam, oxycodone HCL, oxymorphone, propoxyphene, temazepam, tramadol, zolpidem, and zopiclone.

7. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 1, wherein the active pharmaceutical ingredient susceptible to abuse is present in an amount ranging from about 0.05% w/w to about 10% w/w based on the total weight of said formulation.

8. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 1, wherein the active pharmaceutical ingredient susceptible to abuse is present in an amount ranging from about 0.05% w/w to about 5.0% w/w based on the total weight of said formulation.

9. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 1, wherein the active pharmaceutical ingredient susceptible to abuse is present in an amount ranging from about 0.05% w/w to about 3.0% w/w based on the total weight of said formulation.

10. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 1, wherein said formulation provides an in vitro dissolution profile which is equal to or greater than 75% of the active pharmaceutical ingredient susceptible to abuse dissolved in 20 minutes after administration.

11. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 1, wherein said formulation provides an in vitro dissolution profile which is equal to or greater than 75% of the active pharmaceutical ingredient susceptible to abuse dissolved in 10 minutes after administration.

12. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 1, wherein said formulation provides an in vitro dissolution profile which is equal to or greater than 75% of the active pharmaceutical ingredient susceptible to abuse dissolved in 30 minutes after administration.

13. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 1, wherein the gelling polymeric compound is selected from the group comprising consisting of:

polysaccharides, sugars, sugar derived alcohols, starches, starch derivatives, cellulose derivatives, carrageenan, pectin, sodium alginate, gellan gum, xanthan gum, poloxamer, carbopol, polyox, konjac glucomannan, povidone, hydroxypropyl methylcellulose (HPMC), hypermellose, and combinations thereof.

14. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 1, wherein the gelling polymeric compound is present in an amount ranging from 1% w/w to 30% w/w.

16. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 1, wherein the gelling polymeric compound is a combination of konjac glucomannan and at least one additional gelling polymeric compound and is present in an amount ranging from about 1% w/w to about 20% w/w.

17. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 16, wherein the gelling polymeric compound is a combination of konjac glucomannan and an additional gelling polymeric compound selected from the group consisting of polysaccharides, sugars, sugar derived alcohols, starches, starch derivatives, cellulose derivatives, Carrageenan, pectin, sodium alginate, gellan gum, xanthan gum, poloxamer, Carbopol®

, PolyOx®

, povidone, hydroxypropyl methylcellulose (HPMC), hypermellose, and combinations thereof.

18. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 17, wherein the ratio of konjac glucomannan to the additional gelling polymeric compound is between about 3:

1 to about 9;

1.

19. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 1, wherein the formulation comprises a surfactant is selected from the group consisting of:

sodium lauryl sulfate, poloxamer, sorbitan monoesters and glyceryl monooleates and combinations thereof.

20. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 19, wherein the surfactant is sodium lauryl sulfate and is present in an amount ranging from about 1% w/w to about 10% w/w.

21. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 1, wherein said formulation further comprises a nasal irritant selected from the group consisting of capsaicin, piperine, allyl isothiocyanante, sodium lauryl sulfate and combinations thereof.

23. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 1, wherein said formulation comprises a therapeutically effective amount of pharmaceutically active ingredient susceptible to abuse, at least one gelling polymeric compound, at least one surfactant, along with at least one pharmaceutically acceptable excipient selected from the group consisting of:

fillers, diluents, lubricants, and combinations thereof.

24. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 23, wherein the filler is selected from the group consisting of:

cellulose, dibasic calcium phosphate, calcium carbonate, sucrose, lactose, glucose, microcrystalline cellulose, mannitol, sorbitol, maltol, pregelatinized starch, corn starch, and combinations thereof.

25. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 24, wherein the filler is microcrystalline cellulose and is present in an amount ranging from about 30% w/w to about 80% w/w based on the total weight of said formulation.

26. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 1, wherein the disintegrant is selected from the group consisting of:

crospovidone, sodium starch glycolate, sodium pregelatinized starch, modified corn starch and combinations thereof.

27. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 26, wherein the disintegrant is crospovidone and is present in an amount ranging from about 2% w/w to about 20% w/w based on the total weight of said formulation.

28. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 26, wherein the disintegrant is crospovidone and is present in an amount ranging from about 2% w/w to about 15% w/w based on the total weight of said formulation.

30. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 1, wherein said formulation provides an immediate release of the active pharmaceutical ingredient susceptible to abuse when the tablet is taken orally and, upon tampering and exposure to an aqueous, alcoholic, acidic and/or basic media, said formulation becomes an uninjectable and unsyringeable gel.

31. The abuse-deterrent immediate release orally administrable pharmaceutical formulation of claim 6, wherein the formulation comprises 1% w/w to 30% w/w of the gelling polymeric compound, which comprises konjac glukomannan and at least one other gelling polymer compound selected from a natural gum, a polymer, and a combination thereof.

32. The immediate release orally administrable abuse-deterrent pharmaceutical formulation of claim 1, wherein upon exposing the formulation to aqueous, alcoholic, acidic or basic media the formulation forms a non-injectable, non-syringeable and non-filtrable gel within 5 min.

33. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 16, wherein the ratio of konjac glucomannan to the additional gelling polymeric compound or combinations thereof, is between about 1:

2 to about 9;

2.

42. A method of treating a disease or disorder in a patient comprising administering to the patient an immediate release orally administrable abuse-deterrent pharmaceutical formulation of claim 1, wherein the disease or disorder is attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), narcolepsy, anxiety, generalized anxiety disorder (GAD), panic disorder, obsessive-compulsive disorder (OCD), insomnia, or pain.

2. (canceled)

3. An immediate release orally administrable abuse deterrent pharmaceutical formulation comprising:

at least one pharmaceutically active ingredient susceptible to abuse;

konjac glucomanan;

at least one other gelling polymeric compound selected from the group consisting of;

polysaccharides, sugars, sugar derived alcohols, starches, starch derivatives, cellulose derivatives, Carrageenan, pectin, sodium alginate, gellan gum, xanthan gum, poloxamer, Carbopol®

, PolyOx®

, povidone, hydroxypropyl methylcellulose (HPMC), hypermellose, and combinations thereof, and at least one disintegrant, wherein said formulation provides an immediate release of the pharmacologically active ingredient when the tablet is taken orally and, upon tampering, becomes an uninjectable and unsyringeable gel when exposed to aqueous, alcoholic, acidic or basic media.

34. The immediate release orally administrable abuse-deterrent pharmaceutical formulation of claim 3 further comprising at least one other pharmaceutically acceptable excipient, wherein said formulation provides release of the active pharmaceutical ingredient and has an in vitro dissolution profile that is equal to or greater than 75 percent of the drug dissolved in less than 30 minutes after administration as measured by USP type I or II dissolution apparatus as described in USP XXVI (2003).

35. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 34, wherein the active pharmaceutical ingredient susceptible to abuse is selected from the group consisting of:

amphetamine, alprazolam, codeine, diazepam, fentanyl and analogs thereof, hydrocodone, hydromorphone HCl, lorazepam, meperidine, morphine, methylphenidate, methadone, nitrazepam, oxycodone HCL, oxymorphone, propoxyphene, temazepam, tramadol, zolpidem, and zopiclone, and is present in an amount ranging from about 0.05% w/w to about 10.0% w/w based on the total weight of said formulation.

36. The abuse-deterrent immediate release orally administrable pharmaceutical formulation according to claim 34, wherein the formulation comprises 1% w/w to 30% w/w of the gelling polymeric compound, which comprises konjac glukomannan and at least one other gelling polymer compound selected from a natural gum, a polymer, and a combination thereof.

37. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 34, wherein the ratio of konjac glucomannan to the additional gelling polymeric compound or combinations thereof is between about 1:

1 to about 9;

1.

38. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 34, wherein the ratio of konjac glucomannan to the additional gelling polymeric compound or combinations thereof is between about 1:

2.

39. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 34, wherein the ratio of konjac glucomannan to the additional gelling polymeric compound or combinations thereof is between about 3:

1

40. The abuse-deterrent immediate release orally administrable pharmaceutical formulation of claim 3, wherein the konjac glucomannan and at least one other gelling polymer are present in an amount ranging from about 1% w/w to about 30% w/w based on the total weight of said formulation.

41. The immediate release orally administrable abuse-deterrent pharmaceutical formulation according to claim 3, wherein the ratio of konjac glucomannan to the additional gelling polymeric compound is between about 3:

1 to about 9;

1.

15. (canceled)

22. (canceled)

29. (canceled)