Ibuprofen and narcotic analgesic compositions

• US 6,348,216 B1
• Filed: 06/10/1997
• Issued: 02/19/2002
• Est. Priority Date: 06/10/1996
• Status: Expired due to Term

• Current Assignee: Abbvie Deutschland GmbH & Company KG (Abbvie Incorporated)
• Original Assignee: Knoll Pharmaceutical Company (Abbvie Incorporated)
• Inventors: Lai, Jin-Wang, Kushla, Gregory P., Polli, Gerald P.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Seidleck, Brian K.
• Application Number:
  US08/872,216
• Time in Patent Office: 1,715 Days
• Field of Search: 424/464, 424/465, 424/468, 424/470, 424/469, 424/489, 424/494, 424/493, 514/960, 514/282
• US Class Current: 424/465
• 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 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 33/00 Medicinal preparations containing inorganic active ingredients
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

Provided herein are compositions and methods of making compositions of ibuprofen in combination with a narcotic analgesic. Specifically provided is a pharmaceutical tablet composition comprising ibuprofen; a narcotic analgesic; colloidal silicon dioxide; a filler selected from the group consisting of microcrystalline cellulose and powdered cellulose; a disintegrant selected from the group consisting of croscarmellose sodium, crospovidone, and sodium starch glycolate; a binder consisting of an akylhydroxy methylcellulose; a starch; and a lubricant. Also provided herein is a method of preparing a pharmaceutical tablet composition comprising: (a) Granulating ibuprofen, a narcotic analgesic, a first glidant, a first disintegrant, a binder, and starch to form granules wherein said granulating step comprises a wet granulation process; (b) blending the granules with extra-granular material comprised of a second glidant, a second disintegrant, a filler and starch to form a blend of granules and extra-granular material; and (c) compressing the blend into a tablet.

Claims

1. A pharmaceutical tablet comprising a compressed composition substantially free of lactose and polyvinylpyrrolidone, said compressed composition comprising a granule comprised of:

a) ibuprofen;

b) hydrocodone bitartrate;

c) colloidal silicon dioxide;

d) a filler selected from the group consisting of microcrystalline cellulose and powdered cellulose;

e) a disintegrant; and

a

f) starch;

wherein the granule is formed by a wet granulation process and said granule comprises the ibuprofen and the hydrocodone bitartrate in a single phase; and

wherein the composition further comprises an extra granule material comprising a lubricant; and

wherein the composition flows well, has good compression performance and can be compressed over a wider range of compression forces with no substantial change in the disintegration time of the tablet; and

wherein said ibuprofen, said hydrocodone bitartrate, and said lubricant are present in said tablet in a single phase.

2. A pharmaceutical tablet composition comprising a tablet material comprised of:

a) about 25% to about 63%, by total weight of the tablet, of ibuprofen;

b) about 0.6% to about 3.8%, by weight, of hydrocodone bitartrate;

c) colloidal silicon dioxide wherein the weight of the colloidal silicon dioxide is provided in a range, of the total weight of the tablet, of about 0.5% to about 3%;

d) a filler selected from the group consisting of microcrystalline cellulose and powdered cellulose, wherein the weight of the filler is provided in a range, of the total weight of the tablet, of about 10% to about 42%;

e) a disintegrant selected from the group consisting of croscarmellose sodium, crospovidone, and sodium starch glycolate wherein the weight of the disintegrant is provided in a range, of the total weight of the tablet, of about 4% to about 10%;

f) a binder comprising an alkylhydroxy methylcellulose wherein the weight of the binder is provided in a range, of the total weight of the tablet composition, of about 2% to less than 6%;

g) a starch provided in a weight range, of the total weight of the tablet composition, of about 11% to about 20%; and

h) a lubricant wherein the lubricant is provided in an amount less than 1% by weight of the total weight of the tablet;

and wherein the tablet comprises a compressed blend of a granule and extra granule material and wherein the granule comprises granulate material comprised of;

1) the ibuprofen;

2) the hydrocodone bitartrate;

3) about 0.5% to about 2.0%, of the total weight of the tablet composition, of colloidal silicon dioxide;

4) about 9.5% to about 22%, of the total weight of the tablet composition, of filler;

5) about 4%, of the total weight of the tablet composition, of disintegrant;

6) about 6% to about 12%, of the total weight of the tablet composition of starch;

wherein the extra granule material comprises the remaining amount of the tablet material;

the composition is substantially free of lactose and polyvinylpyrrolidone and wherein the composition flows well, has good compression performance and can be compressed over a wide range of compression forces with no substantial change in the disintegration time of the tablet.

3. The composition as recited in claim 2 wherein the weight of the filler is provided in range, of the total weight of the tablet composition, of about 15% to about 25%.

4. The composition as recited in claim 2 wherein the weight of the disintegrant is provided in a range of about 6% to about 8%.

5. The composition as recited in claim 3 wherein the weight of the disintegrant is provided in a range of about 6% to about 8%.

6. The composition as recited in claim 2 wherein the weight of the colloidal silicon dioxide is in a range of the total weight of the tablet, of about 1.5% to about 2%.

7. The composition as recited in claim 3 wherein the weight of the colloidal silicon dioxide is in a range, of the total weight of the tablet, of about 1.5% to about 2%.

8. The composition as recited in claim 4 wherein the weight of the colloidal silicon dioxide is in a range, of the total weight of the tablet, of about 1.5% to about 2%.

9. The composition as recited in claim 5 wherein the weight of the colloidal silicon dioxide is in a range, of the total weight of the tablet, of about 1.5% to about 2%.

10. The composition as recited in claim 2 wherein the weight of the binder is in a range, of the total weight of the tablet, of about 3% to about 4%.

11. The composition as recited in claim 3 wherein the weight of the binder is in a range, of the total weight of the tablet, of about 3% to about 4%.

12. The composition as recited in claim 4 wherein the weight of the binder is in a range, of the total weight of the tablet, of about 3% to about 4%.

13. The composition as recited in claim 5 wherein the weight of the binder is in a range, of the total weight of the tablet, of about 3% to about 4%.

14. The composition as recited in claim 6 wherein the weight of the binder is in a range, of the total weight of the tablet, of about 3% to about 4%.

15. The composition as recited in claim 7 wherein the weight of the binder is in a range, of the total weight of the tablet, of about 3% to about 4%.

16. The composition as recited in claim 8 wherein the weight of the binder is in a range, of the total weight of the tablet, of about 3% to about 4%.

17. The composition as recited in claim 9 wherein the weight of the binder is in a range, of the total weight of the tablet, of about 3% to about 4%.

18. The composition as recited in claim 2 wherein the weight of the starch is in a range, of the total weight of the tablet, of about 6% to about 8%.

19. The composition as recited in claim 3 wherein the weight of the starch is in a range, of the total weight of the tablet, of about 6% to about 8%.

20. The composition as recited in claim 4 wherein the weight of the starch is in a range, of the total weight of the tablet, of about 6% to about 8%.

21. The composition as recited in claim 5 wherein the weight of the starch is in a range, of the total weight of the tablet, of about 6% to about 8%.

22. The composition as recited in claim 6 wherein the weight of the starch is in a range, of the total weight of the tablet, of about 6% to about 8%.

23. The composition as recited in claim 7 wherein the weight of the starch is in a range, of the total weight of the tablet, of about 6% to about 8%.

24. The composition as recited in claim 8 wherein the weight of the starch is in a range, of the total weight of the tablet, of about 6% to about 8%.

25. The composition as recited in claim 9 wherein the weight of the starch is in a range, of the total weight of the tablet, of about 6% to about 8%.

26. The composition as recited in claim 10 wherein the weight of the starch is in a range, of the total weight of the tablet, of about 6% to about 8%.

27. The composition as recited in claim 11 wherein the weight of the starch is in a range, of the total weight of the tablet, of about 6% to about 8%.

28. The composition as recited in claim 12 wherein the weight of the starch is in a range, of the total weight of the tablet, of about 6% to about 8%.

29. The composition as recited in claim 13 wherein the weight of the starch is in a range, of the total weight of the tablet, of about 6% to about 8%.

30. The composition as recited in claim 14 wherein the weight of the starch is in a range, of the total weight of the tablet, of about 6% to about 8%.

31. The composition as recited in claim 15 wherein the weight of the starch is in a range, of the total weight of the tablet, of about 6% to about 8%.

32. The composition as recited in claim 16 wherein the weight of the starch is in a range, of the total weight of the tablet, of about 6% to about 8%.

33. The composition as recited in claim 17 wherein the weight of the starch is in a range, of the total weight of the tablet, of about 6% to about 8%.

34. A pharmaceutical composition comprising tablet material comprised of:

a) about 50% ibuprofen;

b) about 1.88% hydrocodone bitartrate;

c) about 1.5% colloidal silicon dioxide;

d) about 19.3% microcrystalline cellulose as the filler;

e) about 8% sodium croscarmellose as the disintegrant;

f) about 3.25% hydroxypropyl methylcellulose as the binder;

g) about 15.6% corn starch as the starch;

h) about 0.5% magnesium stearate, wherein the total percent of the tablet material is equal to about 100% of the weight of the tablet;

wherein the tablet comprises a compressed blend of a granule and extra granulate material wherein the granule comprises as a portion of the tablet material that comprises the total weight of the tablet as follows;

a) about 50% ibuprofen;

b) about 1.9% hydrocodone bitartrate;

c) about 0.75% colloidal silicon dioxide;

d) about 9.5% microcrystalline cellulose;

e) about 4.0% croscarmellose sodium;

f) about 10.6% corn starch; and

g) about 3.3% hydroxypropyl methylcellulose; and

the extra granule material comprises the remaining amount of tablet material and the composition is substantially free of lactose and polyvinylpyrrolidone.