.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Claims for Patent: 7,887,845

« Back to Dashboard

Claims for Patent: 7,887,845

Title:Antiviral compositions
Abstract:The present invention is concerned with pharmaceutical compositions of antiviral compounds which can be administered to a mammal, in particular a human, suffering from a viral infection. These compositions comprise particles obtainable by melt-extruding a mixture comprising one or more antiviral compounds and one or more appropriate water-soluble polymers and subsequently milling said melt-extruded mixture.
Inventor(s): Verreck; Geert (Malle, BE), Baert; Lieven (Brugge 2, BE)
Assignee: Janssen Pharmaceutica NV (BE)
Application Number:11/347,071
Patent Claims: 1. A particle comprising a solid dispersion comprising (a) 4-[[4-amino-5-bromo-6-(4-cyano-2,6-dimethylphenyloxy)-2-pyrimidinyl]amino- ]benzonitrile, a N-oxide, a pharmaceutically acceptable addition salt, or a quaternary amine thereof and (b) one or more pharmaceutically acceptable water-soluble polymers.

2. The particle according to claim 1 wherein the water-soluble polymer is a polymer that has an apparent viscosity of 1 to 5000 mPas when dissolved at 20.degree. C. in an aqueous solution at 2% (w/v).

3. The particle according to claim 1 wherein the water-soluble polymer is selected from the group consisting of: alkylcelluloses, hydroxyalkylcelluloses, hydroxyalkyl alkylcelluloses, carboxyalkylcelluloses, alkali metal salts of carboxyalkylcelluloses, carboxyalkylalkylcelluloses, carboxyalkylcellulose esters, starches, pectines, chitin derivates, di-, oligo- or polysaccharides, polyacrylic acids and the salts thereof, polymethacrylic acids, the salts and esters thereof, methacrylate copolymers, polyvinylalcohol, polyalkylene oxides and -copolymers of ethylene oxide and propylene oxide.

4. The particle according to claim 3 wherein the water-soluble polymer is selected from the group consisting of methylcellulose; hydroxymethylcellulose; hydroxyethylcellulose; hydroxypropylcellulose; hydroxybutylcellulose; hydroxyethyl methylcellulose; hydroxypropyl methylcellulose; carboxymethylcellulose; sodium carboxymethylcellulose; carboxymethylethylcellulose; sodium carboxymethylamylopectine; chitosan; trehalose; cyclodextrins; alginic acid, alkali metal and ammonium salts thereof; carrageenans; galactomannans; tragacanth; agar-agar; gummi arabicum; guar gummi; xanthan gummi; polyethylene oxide; polypropylene oxide; and copolymers of ethylene oxide and propylene oxide.

5. The particle according to claim 3 wherein the water-soluble polymer is selected from poly(butyl methacrylate, (2-dimethylaminoethyl)methacrylate, methyl methacrylate) (1:2:1) and hydroxypropyl methylcellulose.

6. The particle according to claim 3 wherein the water-soluble polymer is poly(butyl methacrylate, (2-dimethylaminoethyl)methacrylate, methyl methacrylate) (1:2:1).

7. The particle according to claim 3 wherein the water-soluble polymer is hydroxypropyl methylcellulose.

8. The particle according to claim 7 wherein the hydroxypropyl methylcellulose has an apparent viscosity from about 1 to about 100 mPas when dissolved at 20.degree. C. in an aqueous solution at 2% (w/v).

9. The particle according to claim 8 wherein the hydroxypropyl methylcellulose has an apparent viscosity from about 3 to about 15 mPas when dissolved at 20.degree. C. in an aqueous solution at 2% (w/v).

10. The particle according to claim 9 wherein the hydroxypropyl methylcellulose has an apparent viscosity of about 5 mPas when dissolved at 20.degree. C. in an aqueous solution at 2% (w/v).

11. The particle according to claim 10 wherein the hydroxypropyl methylcellulose is hydroxypropyl methylcellulose HPMC 2910 5 mPas.

12. The particle according to claim 1 wherein the weight-by-weight ratio of (a):(b) is in the range of 1:1 to 1:899.

13. The particle according to claim 1 wherein the weight-by-weight ratio of (a):(b) is in the range of 1:1 to 1:100.

14. The particle according to claim 1 wherein the weight-by-weight ratio of (a):(b) is in the range of 1:1 to 1:5.

15. The particle according to claim 1 wherein the weight-by-weight ratio of (a):(b) is in the range of from about 1:1 to about 1:3.

16. The particle according to claim 1 wherein the weight-by-weight ratio of (a):(b) is in the range of about 1:3 to about 1:5.

17. The particle according to claim 1 wherein the weight-by-weight ratio of (a):(b) is in the range of about 1:1 to about 1:1.5.

18. The particle according to claim 1 wherein the weight-by-weight ratio of (a):(b) is in the range of about 1:1.5 to about 1:3.

19. The particle according to claim 1 wherein 4-[[4-amino-5-bromo-6-(4-cyano-2,6-dimethylphenyloxy)-2-pyrimidinyl]amino- ]benzonitrile; a N-oxide, a pharmaceutically acceptable addition salt, or a quaternary amine thereof, is in a non-crystalline phase.

20. The particle as claimed in claim 1 wherein the solid dispersion is in the form of a solid solution comprising (a) and (b), or in the form of a dispersion wherein amorphous or microcrystalline (a) or amorphous or microcrystalline (b) is dispersed more or less evenly in a solid solution comprising (a) and (b).

21. The particle as claimed in claim 1 having a particle size of less than 1500 .mu.m.

22. The particle as claimed in claim 1 having a particle size of less than 250 .mu.m.

23. The particle as claimed in claim 1 having a particle size of less than 125 .mu.m.

24. The particle as claimed in claim 1 further comprising one or more pharmaceutically acceptable excipients.

25. A solid dispersion comprising (a) 4-[[4-amino-5-bromo-6-(4-cyano-2,6-dimethylphenyloxy)-2-pyrimidinyl]amino- ]benzonitrile; a N-oxide, a pharmaceutically acceptable addition salt, or a quaternary amine thereof; and (b) one or more pharmaceutically acceptable water-soluble polymers.

26. The solid dispersion according to claim 25 wherein the water soluble polymer is selected from the group consisting of: alkylcelluloses, hydroxyalkylcelluloses, hydroxyalkyl alkylcelluloses, carboxyalkylcelluloses, alkali metal salts of carboxyalkylcelluloses, carboxyalkylalkylcelluloses, carboxyalkylcellulose esters, starches, pectines, chitin derivates, di-, oligo- or polysaccharides, polyacrylic acids and the salts thereof, polymethacrylic acids, the salts and esters thereof, methacrylate copolymers, polyvinylalcohol, polyalkylene oxides and -copolymers of ethylene oxide and propylene oxide.

27. The solid dispersion according to claim 25 wherein the weight-by-weight ratio of components (a):(b) in the range of 1:1 to 1:899.

28. The solid dispersion according to claim 25 which is in the form of a solid solution comprising (a) and (b).

29. The solid dispersion according to claim 25 wherein the solid dispersion is in the form of a solid solution comprising (a) and (b), or in the form of a dispersion wherein amorphous or microcrystalline (a) or amorphous or microcrystalline (b) is dispersed more or less evenly in a solid solution comprising (a) and (b).

30. A pharmaceutical dosage form comprising a therapeutically effective amount of particles as claimed in claim 1.

31. The dosage form according to claim 30 which is a tablet.

32. The dosage form according to claim 31 for immediate release of 4-[[4-amino-5-bromo-6-(4-cyano-2,6-dimethylphenyloxy)-2-pyrimidinyl]amino- ]-benzonitrile; a N-oxide, a pharmaceutically acceptable addition salt, or a quaternary amine thereof; upon oral ingestion wherein said particles are homogeneously distributed throughout a mixture of a diluent and a disintegrant.

33. A dosage form according to claim 30 surrounded by a film-coat comprising a film-forming polymer, a plasticizer and optionally a pigment.

34. The dosage form according to claim 32 wherein the diluent is a spray-dried mixture of lactose monohydrate and microcrystalline cellulose (75:25), and the disintegrant is crospovidone or croscarmellose.

35. The dosage form according to claim 30 wherein the weight of said particles is at least 40% of the total weight of the dosage form.

36. The dosage form according to claim 30 containing from 200 to 400 mg of 4-[[4-amino-5-bromo-6-(4-cyano-2,6-dimethylphenyloxy)-2-pyrimidinyl]am- ino]-benzonitrile; a N-oxide, a pharmaceutically acceptable addition salt, or a quaternary amine thereof; per unit dosage form.

37. The dosage form according to claim 30 containing from 5 to 200 mg of 4-[[4-amino-5-bromo-6-(4-cyano-2,6-dimethylphenyloxy)-2-pyrimidinyl]amino- ]-benzonitrile; a N-oxide, a pharmaceutically acceptable addition salt, or a quaternary amine thereof; per unit dosage form.

38. A process of preparing a particle according to claim 1 characterized by spray-drying of a solution of the components (a) and (b).

39. A particle according to claim 1 consisting of a solid solution comprising two parts by weight of 4-[[4-amino-5-bromo-6-(4-cyano-2,6-dimethylphenyloxy)-2-pyrimidinyl]amino- ]benzonitrile; a N-oxide, a pharmaceutically acceptable addition salt, or a quaternary amine thereof; and three parts by weight of hydroxypropyl methylcellulose HPMC 2910 5 mPas, obtainable by blending said components, extruding the blend at a temperature in the range of 20.degree. C.-300.degree. C., grinding the extrudate, and optionally sieving the thus obtained particles.

40. A process of preparing a solid dispersion according to claim 25 characterized by (a) spray-drying of a solution of the components (a) and (b); (b) preparing a solution of the components (a) and (b), pouring said solution onto a large surface so as to form a thin film, and evaporating the solvent therefrom; or (c) melt-extruding the components (a) and (b).

41. A pharmaceutical package suitable for commercial sale comprising a container, an oral dosage form of 4-[[4-amino-5-bromo-6-(4-cyano-2,6-dimethylphenyloxy)-2-pyrimidinyl]amino- ]benzonitrile; a N-oxide, a pharmaceutically acceptable addition salt, or a quaternary amine thereof; as claimed in claim 30, and associated with said package written matter.

42. The particle according to claim 7 wherein the weight-by-weight ratio of (a):(b) is in the range of about 1:1 to about 1:3.

43. The particle according to claim 11 wherein the weight-by-weight ratio of (a):(b) is in the range of about 1:1 to about 1:3.

44. The particle according to claim 7 wherein the weight-by-weight ratio of (a):(b) is about 1:3.

45. The particle according to claim 11 wherein the weight-by-weight ratio of (a):(b) is about 1:3.

46. A solid dispersion according to claim 25 wherein the water-soluble polymer is hydroxypropyl methylcellulose.

47. A solid dispersion according to claim 25 wherein the water-soluble polymer is HPMC 2910 mPas.

48. A solid dispersion according to claim 46 wherein the weight-by-weight ratio of (a):(b) is in the range of about 1:1 to about 1:3.

49. A solid dispersion according to claim 47 wherein the weight-by-weight ratio of (a):(b) is in the range of about 1:1 to about 1:3.

50. A solid dispersion according to claim 46 wherein the weight-by-weight ratio of (a):(b) is about 1:3.

51. A solid dispersion according to claim 47 wherein the weight-by-weight ratio of (a):(b) is about 1:3.

52. The dosage form according to claim 30 containing 200 mg of 4-[[4-amino-5-bromo-6-(4-cyano-2,6-dimethylphenyloxy)-2-pyrimidinyl]amino- ]benzonitrile; a N-oxide, a pharmaceutically acceptable addition salt, or a quaternary amine thereof; per unit dosage form.

53. The particle according to claim 7 wherein (a) is 4-[[4-amino-5-bromo-6-(4-cyano-2,6-dimethylphenyloxy)-2-pyrimidinyl]amino- ]benzonitrile.

54. The particle according to claim 11 wherein (a) is 4-[[4-amino-5-bromo-6-(4-cyano-2,6-dimethylphenyloxy)-2-pyrimidinyl]amino- ]benzonitrile.

55. The particle according to claim 44 wherein (a) is 4-[[4-amino-5-bromo-6-(4-cyano-2,6-dimethylphenyloxy)-2-pyrimidinyl]amino- ]benzonitrile.

56. The particle according to claim 45 wherein (a) is 4-[[4-amino-5-bromo-6-(4-cyano-2,6-dimethylphenyloxy)-2-pyrimidinyl]amino- ]benzonitrile.

57. The solid dispersion according to claim 46 wherein (a) is 4-[[4-amino-5-bromo-6-(4-cyano-2,6-dimethylphenyloxy)-2-pyrimidinyl]amino- ]benzonitrile.

58. The solid dispersion according to claim 47 wherein (a) is 4-[[4-amino-5-bromo-6-(4-cyano-2,6-dimethylphenyloxy)-2-pyrimidinyl]amino- ]benzonitrile.

59. The solid dispersion according to claim 50 wherein (a) is 4-[[4-amino-5-bromo-6-(4-cyano-2,6-dimethylphenyloxy)-2-pyrimidinyl]amino- ]benzonitrile.

60. The solid dispersion according to claim 51 wherein (a) is 4-[[4-amino-5-bromo-6-(4-cyano-2,6-dimethylphenyloxy)-2-pyrimidinyl]amino- ]benzonitrile.

61. The dosage form according to claim 52 containing 200 mg of 4-[[4-amino-5-bromo-6-(4-cyano-2,6-dimethylphenyloxy)-2-pyrimidinyl]amino- ]benzonitrile per unit dosage form.

62. The particle according to claim 1 wherein (a) is 4-[[4-amino-5-bromo-6-(4-cyano-2,6-dimethylphenyloxy)-2-pyrimidinyl]amino- ]benzonitrile.

63. The particle according to claim 24 wherein (a) is 4-[[4-amino-5-bromo-6-(4-cyano-2,6-dimethylphenyloxy)-2-pyrimidinyl]amino- ]benzonitrile.

64. The particle according to claim 63 wherein the water-soluble polymer is hydroxypropyl methylcellulose.

65. The particle according to claim 64 wherein the water-soluble polymer is HPMC 2910 mPas.

66. The particle according to claim 65 wherein the weight-by-weight ratio of (a):(b) is about 1:3.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc