CO-CRYSTALS AND PHARMACEUTICAL FORMULATIONS COMPRISING THE SAME

• US 20110236478A1
• Filed: 02/24/2011
• Published: 09/29/2011
• Est. Priority Date: 09/03/2008
• Status: Active Grant

• Current Assignee: Vertex Pharmaceuticals Incorporated
• Original Assignee: Vertex Pharmaceuticals Incorporated
• Inventors: Kline, Billie J., Knezic, Dragutin, Dokou, Eleni, Gasparac, Rahela, Jurkauskas, Valdas
• Granted Patent: US 8,541,025 B2
• Time in Patent Office: Days
• 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 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/497 containing further heterocyclic rings
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

An immediate release formulation of an active ingredient.

Claims

1. A pharmaceutical composition comprising:

an active ingredient, and

one or more excipients present in an amount about at least 1% of the total weight of the formulation,

wherein;

the active ingredient comprises a co-crystal, the co-crystal comprising VX-950 and a co-former of 4-hydroxybenzoic acid.

2. The formulation of claim 1, wherein the co-crystal is present in amount about at 1 to 99% of the total weight of the formulation.

3. The formulation of claim 1, wherein the co-crystal is present in amount about at least 50% of the total weight of the formulation.

4. The formulation of claim 1, wherein the co-crystal is present in amount about at least 68% of the total weight of the formulation.

5. The formulation of claim 1, wherein the molar ratio of the active ingredient with respect to the co-former ranges from about 5:

1 to about 1;

5.

6. The formulation of claim 1, wherein the molar ratio of VX-950 with respect to the co-former is about 1:

1.

7. The formulation of claim 1 wherein the one or more excipients is selected from the group consisting of a filler, a surfactant, a glidant, a lubricant and a disintegrant.

8. The formulation of claim 1 wherein the one or more excipients includes one or more fillers.

9. The formulation of claim 8 wherein the one or more fillers is selected from one or more from the group consisting of the following:

mannitol, lactose, sucrose, dextrose, maltodextrin, sorbitol, xylitol, powdered cellulose, microcrystalline cellulose, silicified microcrystalline cellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, methylhydroxyethylcellulose, talc, starch, pregelatinized starch, dibasic calcium phosphate, calcium sulfate and calcium carbonate.

10. The formulation of claim 9 wherein the one or more fillers is microcrystalline cellulose, lactose or a combination thereof

11. The formulation of claim 9 wherein the one or more fillers are microcrystalline cellulose, and lactose.

12. The formulation of claim 1 wherein the one or more excipients includes one or more disintegrants.

15. The formulation of claim 1 wherein the one or more excipients includes one or more surfactants.

18. The formulation of claim 1 wherein the one or more excipients includes one or more glidants.

20. The formulation of claim 18, wherein the one or more glidants is colloidal silica.

21. The formulation of claim 1 wherein the one or more excipients includes one or more lubricants.

22. The formulation of claim 21, wherein the one or more lubricants is selected from one or more from the group consisting of the following:

talc, fatty acid, stearic acid, magnesium stearate, calcium stearate, sodium stearate, glyceryl monostearate, sodium lauryl sulfate, sodium stearyl fumarate, hydrogenated oils, fatty alcohol, fatty acid ester, glyceryl behenate, mineral oil, vegetable oil, leucine, sodium benzoate, or a combination thereof

23. The formulation of claim 21, wherein the one or more lubricants is sodium stearyl fumarate.

24. The formulation of claim 1 comprising:

about 5 wt. % to 99 wt. % of the co-crystal;

about 5 wt. % to 60 wt. % of a first filler;

about 5 wt. % to 60 wt. % of a second filler;

about 1 wt. % to 30 wt. % of a disintegrant;

about 0.1 wt. % to 30 wt. % of a surfactant;

about 0.1 wt. % to 20 wt. % of a glidant; and

about 0.1 wt. % to 30 wt. % of a lubricant.

25. The formulation of claim 1 comprising:

about 50 wt. % to 75 wt. % of the co-crystal;

about 5 wt. % to 15 wt. % of a first filler;

about 5 wt. % to 15 wt. % of a second filler;

about 1 wt. % to 10 wt. % of a disintegrant;

about 1 wt. % to 10 wt. % of a surfactant;

about 0.1 wt. % to 10 wt. % of a glidant; and

about 1 wt. % to 10 wt. % of a lubricant.

26. The formulation of claim 1 comprising:

about 67 wt. % of the co-crystal,

about 12 wt. % of a first filler;

about 12 wt. % of a second filler;

about 3 wt. % of a disintegrant;

about 2 wt. % of a surfactant;

about 1 wt. % of a glidant; and

about 3 wt. % of a lubricant.

27. The formulation of claim 1, wherein the one or more excipients comprises microcrystalline cellulose, lactose, croscarmellose sodium, sodium lauryl sulfate, colloidal silica and sodium stearyl fumarate.

28. The formulation of claim 1 comprising:

about 10 wt. % to 99 wt. % of the co-crystal;

about 5 wt. % to 60 wt. % of microcrystalline cellulose;

about 5 wt. % to 60 wt. % of lactose;

about 1 wt. % to 30 wt. % of croscarmellose sodium;

about 1 wt. % to 30 wt. % of sodium lauryl sulfate;

about 0.1 wt. % to 20 wt. % of colloidal silica; and

about 1 wt. % to 30 wt. % of sodium stearyl fumarate.

29. The formulation of claim 1 comprising:

about 50 wt. % to 75 wt. % of the co-crystal;

about 5 wt. % to 15 wt. % of microcrystalline cellulose;

about 5 wt. % to 15 wt. % of lactose;

about 1 wt. % to 10 wt. % of croscarmellose sodium;

about 1 wt. % to 10 wt. % of sodium lauryl sulfate;

about 0.1 wt. % to 10 wt. % of colloidal silica and

about 1 wt. % to 10 wt. % of sodium stearyl fumarate.

30. The formulation of claim 1 comprising:

about 67 wt. % of the co-crystal,

about 12 wt. % of microcrystalline sodium;

about 12 wt. % lactose;

about 3 wt. % of croscarmellose sodium;

about 2 wt. % of sodium lauryl sulfate;

about 1 wt. % of colloidal silica; and

about 3 wt. % of sodium stearyl fumarate.

31. The formulation of claim 1, wherein the formulation is in a form of a capsule, tablet, pill, powder, granule, aqueous suspension or solution.

32. The formulation of claim 1, wherein the formulation is in a form of a capsule.

33. The formulation of claim 1, wherein the formulation is in a form of a tablet.

34. The formulation of claim 33, wherein the tablet is coated.

35. The formulation of claim 1, wherein the formulation is an immediate release formulation.

13. The formulation of claim 13, wherein the one or more disintegrants is selected from one or more from the group consisting of the following:

croscarmellose sodium, sodium alginate, calcium alginate, alginic acid, starch, pregelatinized starch, sodium starch glycolate, crospovidone, cellulose and its derivatives, carboxymethylcellulose calcium, carboxymethylcellulose sodium, soy polysaccharide, guar gum, an ion exchange resin, an effervescent system based on food acids and an alkaline carbonate component, and sodium bicarbonate.

14. The formulation of claim 13, wherein the one or more disintegrants is croscarmellose sodium.

16. The formulation of claim 16, wherein the one or more surfactants is selected from one or more from the group consisting of the following:

sodium lauryl sulfate, docusate sodium, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene 20 stearyl ethers, polyoxyethylene alkyl ethers, polyoxyethylene castor oil derivatives, pegylated hydrogenated castor oils, sorbitan esters of fatty acids, Vitamin E or tocol derivatives, vitamin E TPGS, tocopheryl esters, lecithin, phospholipids and their derivatives, poloxamers, stearic acid, oleic acid, oleic alcohol, cetyl alcohol, mono and diglycerides, propylene glycol esters of fatty acids, glycerol esters of fatty acids, ethylene glycol palmitostearate, polyoxylglycerides, propylene glycol monocaprylate, propylene glycol monolaurate and polyglyceryl oleate.

17. The formulation of claim 16, wherein the one or more surfactants is sodium lauryl sulfate.

19. The formulation of claim 19, wherein the one or more glidants is selected from one or more from the group consisting of the following:

talc, colloidal silica, magnesium oxide, magnesium silicate, leucine and starch.

36-63. -63. (canceled)