Modified release formulations of memantine oral dosage forms

• US 20060051416A1
• Filed: 06/16/2005
• Published: 03/09/2006
• Est. Priority Date: 06/17/2004
• Status: Active Grant

• Current Assignee: Allergan Pharmaceuticals International Ltd. (Abbvie Incorporated)
• Original Assignee: Forest Laboratories Incorporated (Abbvie Incorporated)
• Inventors: Mahashabde, Shashank, Dedhiya, Mahendra G., Periclou, Antonia, Rao, Niranjan, Abramowitz, Wattanaporn, Rastogi, Suneel K.
• Granted Patent: US 8,039,009 B2
• Time in Patent Office: Days
• US Class Current: 424/468
• CPC Class Codes: A61K 31/13 Amines A61K31/04 takes precedence
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives 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 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention provides pharmaceutical compositions given once daily containing at least one therapeutically active ingredient selected from the group consisting of memantine and a pharmaceutically acceptable salt of memantine, and a pharmaceutically acceptable polymeric matrix carrier. The dosage forms of the invention sustain the release of the therapeutically active agent from about 4 to about 24 hours when said dosage form is exposed to aqueous solutions. following entry of said form into a use environment, wherein said dosage form has a dissolution rate of more than about 80% after passage of about 6 hours to about 12 hours following said entry into said use environment.

Claims

1. A modified release solid oral dosage form comprising:

(a) at least one therapeutically active ingredient selected from the group consisting of memantine and a pharmaceutically acceptable salt of memantine, and

(b) a pharmaceutically acceptable polymeric carrier substantially contributing to the modification of the release of said active ingredient,

said dosage form sustaining release of said therapeutically active agent from about 4 hours to about 24 hours following entry of said form into a use environment, wherein said dosage form has a dissolution rate of more than about 80% after passage of about 6 hours to about 12 hours following said entry into said use environment.

2. The modified release solid oral dosage form according to claim 1, wherein said active ingredient is memantine hydrochloride.

3. The modified release solid oral dosage form according to claim 1, wherein the dissolution rate of more than about 80% is achieved after about 12 hours.

4. The modified release solid oral dosage form of claim 3, comprising the active ingredient in an amount within the range of from about 1.0% w/w to about 20% w/w.

5. The modified release solid oral dosage form according to claim 1, wherein the dissolution rate of more than about 80% is achieved after about 6 hours.

6. The modified release solid oral dosage form of claim 5, wherein the active ingredient is present in amounts ranging from about 1.0% w/w to about 35% w/w.

7. The modified release solid oral dosage form of claim 1, wherein the polymeric carrier is a polymeric matrix.

8. The modified release solid oral dosage form of claim 7, wherein the polymeric matrix is a swellable matrix and comprises hydroxypropyl methylcellulose.

9. The modified release solid oral dosage form of claim 8, wherein the dissolution rate of more than about 80% is achieved after about 12 hours, and wherein the hydroxypropyl methylcellulose is present in amounts from about 50% w/w to about 80% w/w.

10. The modified release solid oral dosage form of claim 8, wherein the dissolution rate of more than about 80% is achieved after about 6 hours, and wherein the hydroxypropyl methylcellulose is present in amounts from about 20% w/w to about 70% w/w.

11. The modified release solid oral dosage form of claim 1, further comprising a filler.

12. The modified release solid oral dosage form of claim 11, wherein the filler is lactose monohydrate.

13. The modified release solid oral dosage form of claim 12, wherein the dissolution rate of more than about 80% is achieved after about 12 hours, and the lactose monohydrate is present in an amount from about 5% w/w to about 50% w/w.

14. The modified release solid oral dosage form of claim 12, wherein the dissolution rate of more than about 80% is achieved after about 6 hours, and the lactose monohydrate is present in amounts from about 5% w/w to about 75% w/w.

17. The modified release solid oral dosage form of claim 11, wherein the filler is dicalcium phosphate.

18. The modified release solid oral dosage form of claim 17, wherein the dicalcium phosphate is present in an amount from about 7% w/w to about 40% w/w.

19. The modified release solid oral dosage form of claim 1, further comprising a lubricant.

20. The modified release solid oral dosage form of claim 19, wherein the lubricant is magnesium stearate.

21. The modified release solid oral dosage form of claim 20, wherein the dissolution rate of more than about 80% is achieved after about 12 hours, and wherein the magnesium stearate is present in an amount within the range from about 0.8% w/w to about 1.2% w/w.

22. The modified release solid oral dosage form of claim 20, wherein the dissolution rate of more than about 80% is achieved after about 6 hours, and wherein the magnesium stearate is present in an amount within the range from about 0.4% w/w to about 0.6% w/w.

23. The modified release solid oral dosage form of claim 1, further comprising one or more components selected from the group consisting of carriers, excipients, anti-adherants, fillers, stabilizing agents, binders, colorants, glidants, and lubricants.

29. The modified release solid oral dosage form of claim 1, wherein the dissolution rate exhibited by said modified release solid oral dosage form after about 1 hour is at least about 10% and up to about 35%.

30. The modified release solid oral dosage form of claim 1, wherein the dissolution rate exhibited by said modified release solid oral dosage form after about 2 to about 6 hours is at least about 30% and up to about 60%.

31. The modified release solid oral dosage form of claim 1, wherein said modified release solid oral dosage form is administered once-a-day.

32. A method for treating a disorder selected from the group consisting of mild, moderate and severe Alzheimer'"'"'s dementia, and neuropathic pain, wherein the method comprises administering a modified release solid oral dosage form of claim 1.

15. The modified release solid oral dosage form of claim I 1, wherein the filler is microcrystalline cellulose.

16. The modified release solid oral dosage form of claim 15, wherein the microcrystalline cellulose is present in an amount from about 5% w/w to about 80% w/w.

24. A modified release solid oral dosage form, comprising

(a) between about 2.5% w/w and about 20.0% w/w of memantine hydrochloride;

(b) between about 68% w/w and about 77% w/w of hydroxypropyl methyl cellulose;

(c) between about 6.9% w/w and about 15% w/w of lactose monohydrate;

(d) between about 0.8% w/w and about 1.3% w/w of fumed silica;

(e) between about 3.0% w/w and about 5.0% w/w of talc; and

(f) between about 0.9% w/w and about 1.1% w/w of magnesium stearate;

wherein the dissolution rate of memantine hydrochloride of more than about 80% is achieved after about 12 hours.

28. The modified release solid oral dosage form of one of claims 24-27 wherein said modified release solid oral dosage form is a tablet.

25. A modified release solid oral dosage form, comprising:

(a) between about 5% w/w and about 35% w/w of memantine hydrochloride;

(b) between about 54% w/w and about 65% w/w of hydroxypropyl methyl cellulose;

(c) between about 7% w/w and about 24% w/w of lactose monohydrate;

(d) between about 0.8% w/w and about 1.3% w/w of fumed silica;

(e) between about 3.0% w/w and about 5.0% w/w of talc; and

(f) between about 0.4% w/w and about 0.6% w/w of magnesium stearate;

wherein the dissolution rate of memantine hydrochloride of more than about 80% is achieved after about 6 hours.

26. A modified release solid oral dosage form, comprising:

(a) between about 5% w/w and about 35% w/w of memantine hydrochloride;

(b) between about 54% w/w and about 65% w/w of hydroxypropyl methyl cellulose;

(c) between about 7% w/w and 40% w/w of microcrystalline cellulose;

(d) between about 0.8% w/w and about 1.3% w/w of fumed silica;

(e) between about 3.0% w/w and about 5.0% w/w of talc; and

(f) between about 0.4% w/w and about 0.6% w/w of magnesium stearate;

wherein the dissolution rate of memantine hydrochloride of more than about 80% is achieved after about 6 hours.

27. A modified release solid oral dosage form, comprising:

(a) between about 5% w/w and about 35% w/w of memantine hydrochloride;

(b) between about 54% w/w and about 65% w/w of hydroxypropyl methyl cellulose;

(c) between about 7% w/w and 40% w/w of dicalcium phosphate;

(d) between about 0.8% w/w and about 1.3% w/w of fumed silica;

(e) between about 3.0% w/w and about 5.0% w/w of talc; and

(f) between about 0.4% w/w and about 0.6% w/w of magnesium stearate;

wherein the dissolution rate of memantine hydrochloride of more than about 80% is achieved after about 6 hours.