Ibuprofen and acetaminophen tablet

11918,693

16/910485

June 24, 2020

The present invention provides novel compositions, methods of treatment and methods of manufacture of large scale, commercially viable ibuprofen and acetaminophen tablets. The unique characteristics and synergistic effects resulting from the disclosed compositions, methods of treatment and methods of manufacture demonstrate a product with optimal analgesia, anti-pyresis, safety profiles and large-scale manufacturability. The inventions described herein surprisingly show the unique composition and method of manufacturing for a large-scale commercial batch of a novel ibuprofen and acetaminophen tablet.

GlaxoSmithKline Consumer Healthcare Holdings (US) LLC (Wilmington, DE, US)

HALEON US HOLDINGS LLC (Wilmington, DE, US)

1. An oral tablet comprising: active pharmaceutical ingredients ibuprofen and acetaminophen, wherein the ibuprofen is present in an amount of 100 to 300 mg and acetaminophen is present in an amount of 150 to 600 mg, wherein the ratio of ibuprofen to acetaminophen is 1:3 to 1:1 by weight; and wherein the tablet further comprises intragranular and extragranular components, wherein the intragranular component comprises the active ingredients, a binding agent, a disintegrating agent and a glidant; and the extragranular components comprise a disintegrating agent, a glidant and a lubricant, said tablet being essentially free of unmodified starch, and wherein pregelatinized starch and hypromellose are the sole intragranular binding agents.

2. The oral tablet according to claim 1 comprising: (i) the active ingredients present intragranularly; (ii) 5% to 20% by weight pregelatinized starch present intragranularly; (iii) 0.5% to 2.5% by weight Hypromellose present intragranularly; (iv) 0.5% to 3% by weight of glyceryl dibehenate present extragranularly; (v) 1% to 10% by weight croscarmellose present intragranularly and extragranularly; and (vi) 1% to 5% by weight colloidal silicon dioxide present intragranularly and extragranularly.

3. The oral tablet according to claim 1 comprising: (i) the active ingredients present intragranularly; (ii) 8% to 15% by weight pregelatinized starch, present intragranularly; (iii) 1% to 2% by weight Hypromellose, present intragranularly; (iv) 1% to 2% by weight of glyceryl dibehenate, present extragranularly; (v) 5% to 8% by weight croscarmellose, present intragranularly and extragranularly; and (vi) 2% to 4% by weight colloidal silicon dioxide, present intragranularly and extragranularly.

4. The oral tablet according to claim 2 or 3 wherein the ibuprofen is present in an amount of 125 mg and acetaminophen in an amount of 250 mg; or the ibuprofen is present in an amount of 250 mg and acetaminophen in an amount of 500 mg.

5. The oral tablet according to claim 1 wherein the pregelatinized starch is present in an amount from 4% to 25% by weight.

6. The oral tablet according to claim 1 wherein the Hypromellose is present in an amount from 1% to 2% by weight.

7. The oral tablet according to claim 1 wherein pregelatinized starch is present as a first binding agent in an amount ranging from 8 to 15% by weight and Hypromellose is present as a second binding agent in an amount from 1% to 2% by weight.

8. The oral tablet according to claim 1 wherein the weight ratio of pregelatinized starch to Hypromellose is about 7:1 to about 12:1.

9. The oral tablet according to claim 1 wherein the disintegrant comprises a super disintegrant present intragranularly, extragranularly or both intragranularly and extragranularly.

10. The oral tablet according to claim 1 wherein the super disintegrant is present both intragranularly and extragranularly.

11. The oral tablet according to claim 9 or 10 wherein the super disintegrant is a cross-linked carboxymethyl cellulose.

12. The oral tablet according to claim 10 wherein the super disintegrant is present intragranularly in an amount from 0.5% to 5% by weight, and present extragranularly in an amount from 0.5% to 5% by weight.

13. The oral tablet according to claim 1 wherein the glidant comprises colloidal silicon dioxide.

14. The oral tablet according to claim 13 wherein the colloidal silicon dioxide is present intragranularly in an amount from 0.5% to 2% by weight and present extragranularly in an amount from 0.5% to 2% by weight.

15. The oral tablet according to claim 1 wherein the lubricant comprises glyceryl behenate.

16. The oral tablet according to claim 15 wherein the glyceryl behenate is present extragranularly in an amount from 0.5% to 2% by weight.

17. The oral tablet according to claim 1 where the intragranular component is present as a population of granules having a d50 of about 100 to about 200.

18. The oral tablet according to claim 1 wherein ibuprofen is present in an amount of 110 mg to 140 mg, and acetaminophen, in an amount of 230 mg to 270 mg.

19. The oral tablet according to claim 18 wherein ibuprofen is present in an amount of 125 mg and acetaminophen, in an amount of 250 mg.

20. The oral tablet according to claim 1 wherein ibuprofen is present in an amount of 250 mg and acetaminophen, in an amount of 500 mg.

21. A method for treating a mammalian subject in need thereof to relieve pain and/or inflammation, comprising orally administering to the subject the oral tablet of claim 1 , said administration being optionally repeated at intervals of 8 hours until the subject attains relief from pain and/or inflammation.

22. A method for treating fever in a mammalian subject in need thereof, comprising orally administering to the subject an anti-pyretic composition comprising the oral tablet of claim 1 , said administration being optionally repeated until the subject attains relief from fever.

23. The method according to claim 22 wherein the method provides a statistically significant faster onset of action over 0-2 hours relative to placebo.

24. A process for the preparing of an oral tablet according to claim 1 comprising the steps of preparing a granulate, admixing the granulate with any desired extragranular component to form a master blend, and compressing the master blend into the oral tablet.

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