Directly compressible acetaminophen compositions

• US 20010044472A1
• Filed: 03/14/2001
• Published: 11/22/2001
• Est. Priority Date: 09/16/1999
• Status: Active Grant

• Current Assignee: Rhodia Incorporated
• Original Assignee: Rhodia Incorporated
• Inventors: Camarco, Wayne, Upadhyay, Ajay Hasmukhlal
• Granted Patent: US 6,607,750 B2
• Time in Patent Office: Days
• US Class Current: 514/629
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00

Abstract

Acetaminophen compositions are disclosed which are capable of being directly compressed, without addition of other components, into an tablet dosage form, and which include, based on the total weight of the dry components of the composition, from about 80 percent by weight to about 98 percent by weight acetaminophen, a fluidizing agent, a binder compound, a starch, a disintegrant and a lubricant.

Claims

1. A particulate acetaminophen composition capable of being directly compressed, without addition of other components, into a compressed dosage form, said composition comprising, based on the total weight of the dry components of the composition, from 91 to 98 percent by weight acetaminophen and further comprising a fluidizing agent, a binder compound, a disintegrant and a lubricant, said composition comprising free flowing granules, at least a portion of said granules each comprising at least one acetaminophen-rich core, said acetaminophen-rich core comprising acetaminophen and fluidizing agent and having an outer surface, and a binder-rich region supported on at least a portion of the outer surface of the acetaminophen-rich core, said binder-rich region comprising binder compound, wherein, based on the dry weight of the components of the respective acetaminophen-rich core and binder-rich region, the acetaminophen-rich core comprises a relatively higher amount of acetaminophen than the binder-rich region and the binder-rich region comprises a relatively higher amount of binder than the acetaminophen-rich core.

2. The composition of

claim 1

, wherein the composition comprises, based on the total weight of the dry components of the composition, from 91 to 98 percent by weight acetaminophen, from 0.1 to 3.5 percent by weight disintegrant, from 0.5 to 3.25 percent by weight binder compound, from 0 to 4 percent by weight pregelatinized starch, from 0.1 to 1.25 percent by weight fluidizing agent and from 0.1 to 2 percent by weight lubricant.

3. The composition of

claim 1

, wherein at least a portion of the free flowing granules each comprise of agglomerates of two or more acetaminophen cores and associated binder rich regions.

4. The composition of

claim 1

, wherein the binder-rich regions are formed by atomizing a binder solution onto fluidized particles of acetaminophen and fluidizing agent in a fluidized bed process.

5. A particulate acetaminophen composition capable of being directly compressed, without addition of other components, into a compressed dosage form, said composition comprising, based on the total weight of the dry components of the composition, from 80 percent by weight to 98 percent by weight acetaminophen and further comprising a fluidizing agent, a binder compound, a disintegrant and a lubricant, said composition comprising free flowing granules, said granules exhibiting a surface area of greater than 0.8 square meters per gram.

6. The composition of

claim 5

, wherein the composition comprises, based on the total weight of the dry components of the composition, from 91 to 98 percent by weight acetaminophen, from 0.1 to 3.5 percent by weight disintegrant, from 0.5 to 3.25 percent by weight binder compound, from 0 to 4 percent by weight pregelatinized starch, from 0.1 to 1.25 percent by weight fluidizing agent and from 0.1 to 2 percent by weight lubricant.

7. The composition of

claim 5

, wherein the composition exhibits a particle size distribution such that such that a maximum of 30 percent by weight is retained on a 60 US mesh screen, a maximum of 75 percent by weight is retained on a 100 US mesh screen, a maximum of 95 percent by weight is retained on a 200 US mesh screen, and a minimum of 80 percent by weight is retained on a 325 US mesh screen.

8. The composition of

claim 5

, wherein the granules are formed by atomizing a binder solution onto fluidized particles comprising acetaminophen particles and fluidizing agent in a fluidized bed process.

9. The composition of

claim 5

, further comprising a co-active ingredient selected from decongestant, antihistamine, cough suppressant and narcotics and mixtures thereof.

10. The composition of

claim 9

, wherein the co-active ingredient is selected from pseudoephedrine hydrochloride, dextromethorphan hydrobromide, phenylpropanolamine hydrochloride, chlorpheniramine maleate, propoxyphen napsylate, hydrocodone, codeine phosphate and mixtures thereof.

12. The composition of

claim 9

, wherein the composition comprises, based on the total weight of the dry components of the composition, from 91 to 98 percent by weight acetaminophen, from 0.1 to 3.5 percent by weight disintegrant, from 0.5 to 3.25 percent by weight binder compound, from 0 to 4 percent by weight pregelatinized starch, from 0.1 to 1.25 percent by weight fluidizing agent and from 0.1 to 2 percent by weight lubricant.

11. A particulate acetaminophen composition capable of being directly compressed, without addition of other components, into a compressed dosage form, said composition comprising from 91 to 98 percent by weight acetaminophen and further comprising a fluidizing agent, a binder compound, a disintegrant and a lubricant, said composition comprising free flowing granules wherein at least a portion of said granules are made by atomizing a binder solution onto a fluidized bed of particles of the acetaminophen and fluidizing agent in a fluidized bed process.

13. An acetaminophen composition capable of being directly compressed, without addition of other components, into a compressed dosage form, said composition comprising, based on the total weight of the dry components of the composition, from greater than 95 to 98 percent by weight acetaminophen and further comprising, a combined amount of from about 2 to less than 5 percent by weight, a binder compound, a disintegrant and a lubricant.

14. The composition of

claim 13

, wherein the composition comprises, based on the total weight of the dry components of the composition, from greater than 95 to 98 percent by weight acetaminophen, from 0.05 to less than 4.9 percent by weight disintegrant, from 0.05 to less than 4.9 percent by weight binder compound and from 0.05 to 3 percent by weight lubricant.

15. The composition of

claim 13

, wherein the binder-rich regions are formed by atomizing a binder solution onto fluidized particles of acetaminophen and fluidizing agent in a fluidized bed process.

16. An acetaminophen-containing compressed dosage form, comprising from 91 percent by weight to 98 percent by weight acetaminophen and exhibiting an initial dissolution of greater than 80% according to US Pharmacopeia test method number 711, as applied to acetaminophen.

17. The compressed dosage form of

claim 16

, wherein the composition comprises from greater than 95 percent by weight to 98 percent by weight acetaminophen.

18. The compressed dosage form of

claim 16

, wherein the composition comprises, based on the total weight of the dry components of the composition, from 91 to 98 percent by weight acetaminophen, from 0.1 to 3.5 percent by weight disintegrant, from 0.5 to 3.25 percent by weight binder compound and from 0.1 to 2 percent by weight lubricant.

19. The compressed dosage form of

claim 16

, wherein the composition comprises from greater than 95 to 98 percent by weight acetaminophen, from 0.05 to 4.9 percent by weight disintegrant, from 0.05 to 4.9 percent by weight binder compound and from 0.05 to 3 percent by weight lubricant.

20. An acetaminophen composition capable of being directly compressed into an acetaminophen tablet, said composition comprising from about 80 to about 95 wt % acetaminophen, from about I to about 4 wt % essentially water-insoluble tablet/capsule disintegrant, from about 0.5 to about 5.0 wt % polyvinylpyrrolidone, from about 0.5 to about 5.0 wt % totally pregelatinized starch, about 0.25 to about 3.0 wt % of a fluidizing agent, from about 0.25 to about 3.0 wt % of a lubricant, and optionally up to about 10 wt % of a co-active ingredient, the weight percents being based on the total weight of the dry components of the composition, the composition also comprising a moisture content of up to about 1.5 wt % based on the total weight of the dry components of granulation composition, wherein the composition comprises free flowing granules, said granules comprising an acetaminophen blend and a binder coating the blend, said acetaminophen blend comprising the acetaminophen, the disintegrant, a minor portion of the starch, at least a portion of the fluidizing agent and, optionally, a portion of the lubricant, and said binder comprising polyvinylpyrolidone, the remaining starch and the remaining lubricant.

21. A directly compressible acetaminophen granulation composition of

claim 20

wherein the fluidizing agent is silicon dioxide, the lubricant is stearic acid, and the tablet/capsule disintegrant is selected from crosslinked sodium carboxymethyl-cellulose and crosslinked polyvinylpyrrolidone.

22. A directly compressible acetaminophen granulation composition of

claim 20

wherein the acetaminophen comprises at least about 90% by weight.

23. A directly compressible acetaminophen granulation composition of

claim 20

wherein the acetaminophen comprises greater than 90% by weight.

24. A directly compressible acetaminophen granulation composition of

claim 20

wherein the acetaminophen is finely divided particles of acetaminophen such that a maximum of 30 wt % is retained on a 60 US mesh screen, a maximum of 75 wt % is retained on a 100 US mesh screen, a maximum of 95 wt % is retained on a 200 US mesh screen, and a minimum of 80 wt % is retained on a 325 US mesh screen.

25. A directly compressible acetaminophen granulation composition of

claim 20

, wherein the acetaminophen comprises about 87.5 to about 92.5 wt %, the crosslinked sodium carboxymethylcellulose or crosslinked polyvinylpyrrolidone comprises from about 1.5 to about 3.5 wt %, the polyvinylpyrrolidone comprises from about 2.75 to about 3.25 wt %, the totally pregelatinized starch comprises from about 2.0 to about 4.0 wt %, the silicon dioxide comprises from about 0.25 to about 1.25 wt %, and the stearic acid comprises from about 0.25 to about 1.25 wt %.

26. A directly compressible acetaminophen granulation composition of

claim 20

having a surface area of from about 0.8 to about 1.0 m²/g.

27. A tablet comprising the granulation composition of

claim 20

.