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1. WO2007103867 - PRÉPARATIONS SOUS FORME DE COMPRIMÉ ET PROCÉDÉS ASSOCIÉS

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

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What is claimed is:

1. A pharmaceutical formulation comprising:
(a) a pharmaceutically effective amount of an active pharmacological agent having Formula I:



I
wherein:
Ri is hydrogen, hydroxyl, halogen, Ci_6 alkyl, C1-6 trifluoroalkyl, C3.8 cycloalkyl, Ci_6 alkoxy, C1-6 trifluoroalkoxy, C1-6 thioalkyl, C1-6 sulfoxoalkyl, C^ sulfonoalkyl, C6-i0 aryl, -NO2, -NR5R6, -N(R5)COR6, -CN, -CHFCN, -CF2CN, C2_7 alkynyl, C2_7 alkenyl, or a 5- or 6-membered heterocyclic ring having 1 to 4 heteroatoms selected from O, N and S; wherein said alkyl or alkenyl moieties are optionally substituted with hydroxyl, -CN, halogen, trifluoroalkyl, trifluoroalkoxy, -COR5, -CO2R5, -NO2, CONR5R6, NR5R6 or N(R5)COR6;
R2 and R2a are each, independently, hydrogen, hydroxyl, halogen, C1-6 alkyl, C1^ aIkOXy, C2.7 alkenyl, C2.7 alkynyl, C1-6 trifluoroalkyl, or C1-6 trifluoroalkoxy; wherein said alkyl or alkenyl moieties are optionally substituted with hydroxyl, -CN, halogen, trifluoroalkyl, trifluoroalkoxy, -COR5, -CO2R5, -NO2, CONR5R6, NR5R6 or N(R5)COR6;

R3, R3a, and R4 are each, independently, hydrogen, Ci-6 alkyl, alkenyl of 2-7 carbon atoms, C2.7 alkynyl, halogen, C1^ alkoxy, C1-6 trifluoroalkyl, or C1-6 trifluoroalkoxy; wherein said alkyl or alkenyl moieties are optionally substituted with hydroxyl, -CN, halogen, trifluoroalkyl, trifluoroalkoxy, -COR5, -CO2R5, -NO2, CONR5R6, NR5R6 or N(R5)COR6;
R5, R6 are each, independently hydrogen, C^6 alkyl, or C6.10 aryl;
X is O, S, or NR7; and
R7 is hydrogen, C1-6 alkyl, or C6.10 aryl, -COR5, -CO2R5 Or -SO2R5;
or pharmaceutically acceptable salt thereof; and
(b) a carrier or exicipient system comprising: (i) a first diluent/filler component comprising from about 30% to about 95% by weight of said formulation;
(ii) an optional second diluent/filler component comprising, when present, up to about 40% by weight of said pharmaceutical formulation;
(iii) a disintegrant component comprising from about 0.5% to about 20% by weight of said pharmaceutical formulation;
(iv) a binder component comprising from about 0.5% to about 10% by weight of said pharmaceutical formulation;
(v) a wetting agent component comprising from about 0.5% to about 8% by weight of said pharmaceutical formulation; and
(vi) an optional lubricant component comprising, when present, from about 0.01 % to about 5% by weight of said pharmaceutical formulation;
with the proviso that when said pharmaceutical formulation comprises one or more ingredients selected from metallic lauryl sulfate, sodium lauryl sulfate, metal alkyl sulfate, polyethylene glycol, glyceride of fatty ester, Poloxamer 188, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene castor oil derivative, sugar ester of fatty acid, polyglycolized glyceride, quaternary ammonium amine compound, and docusate sodium, then the sum of the amounts of said ingredients does not exceed about 8% by weight of said pharmaceutical formulation.

2. The pharmaceutical formulation of claim 1 wherein said active pharmacological agent comprises from about 0.01 % to about 80% of said pharmaceutical formulation.

3. The pharmaceutical formulation of claim 1 or claim 2 wherein:
(a) said first diluent/filler component comprises from about 40% to about 80% by weight of said pharmaceutical formulation;
(b) said optional second diluent/filler component, when present, comprises up to about 20% by weight of said pharmaceutical formulation;
(c) said disintegrant component comprises from about 1 % to about 10% by weight of said pharmaceutical formulation;
(d) said binder component comprises from about 1 % to about 8% by weight of said pharmaceutical formulation;

(e) said wetting agent component comprises from about 1 % to about 7% by weight of said pharmaceutical formulation;
(f) said optional lubricant component, when present, comprises from about 0.1 % to about 5% by weight of said pharmaceutical formulation; and
(g) said active pharmacological agent comprises from about 0.1 % to about 50% by weight of said pharmaceutical formulation.

4. The pharmaceutical formulation of claim 1 wherein:
(a) said first diluent/filler component comprises from about 40% to about 80% by weight of said pharmaceutical formulation;
(b) said optional second diluent/filler component, when present, comprises from about 10% to about 20% by weight of said pharmaceutical formulation;
(c) said disintegrant component comprises from about 1 % to about 7% by weight of said pharmaceutical formulation;
(d) said binder component comprises from about 1 % to about 5% by weight of said pharmaceutical formulation;
(e) said wetting agent component comprises from 1.3% to about 5% by weight of said pharmaceutical formulation;
(f) said optional lubricant component, when present, comprises from about 0.1 % to about 2% by weight of said pharmaceutical formulation; and
(g) said active pharmacological agent comprises from about 0.1 % to about 50% by weight of said pharmaceutical formulation.

5. The pharmaceutical formulation of claim 1 wherein:
(a) said first diluent/filler component comprises from about 40% to about 80% by weight of said pharmaceutical formulation;
(b) said optional second diluent/filler component, when present, comprises from about 10% to about 20% by weight of said pharmaceutical formulation;
(c) said disintegrant component comprises from about 3% to about 5% by weight of said pharmaceutical formulation;

(d) said binder component comprises from about 1 % to about 3% by weight of said pharmaceutical formulation;
(e) said wetting agent component comprises from 1.5% to about 4% by weight of said pharmaceutical formulation;
(f) said optional lubricant component, when present, comprises from about 0.1 % to about 1 % by weight of said pharmaceutical formulation; and
(g) said active pharmacological agent comprises from about 0.1 % to about 40% by weight of said pharmaceutical formulation.

6. The pharmaceutical formulation of claim 1 wherein:
(a) said first diluent/filler component comprises from about 60% to about 80% by weight of said pharmaceutical formulation;
(b) said optional second diluent/filler component, when present, comprises from about 10% to about 20% by weight of said pharmaceutical formulation;
(c) said disintegrant component comprises about 4% by weight of said pharmaceutical formulation;
(d) said binder component comprises about 2% by weight of said pharmaceutical formulation;
(e) said wetting agent component comprises about 2% by weight of said pharmaceutical formulation;
(f) said optional lubricant component, when present, comprises from about 0.1 % to about 1 % by weight of said pharmaceutical formulation; and
(g) said active pharmacological agent comprises from about 1 % to about 10% by weight of said pharmaceutical formulation.

7. The pharmaceutical formulation of claim 1 wherein:
(a) said first diluent/filler component comprises from about 40% to about 60% by weight of said pharmaceutical formulation;
(b) said optional second diluent/filler component, when present, comprises from about 10% to about 20% by weight of said pharmaceutical formulation;

(c) said disintegrant component comprises about 4% by weight of said pharmaceutical formulation;
(d) said binder component comprises about 2% by weight of said pharmaceutical formulation;
(e) said wetting agent component comprises about 2% by weight of said pharmaceutical formulation;
(f) said optional lubricant component, when present, comprises from about 0.1 % to about 1 % by weight of said pharmaceutical formulation; and
(g) said active pharmacological agent comprises from about 10% to about 30% by weight of said pharmaceutical formulation.

8. The pharmaceutical formulation of any one of claims 1 to 7 wherein:
(a) said first diluent/filler component comprises one or more of mannitol, lactose, sucrose, maltodextrin, sorbitol, xylitol, powdered cellulose, microcrystalline cellulose, carboxymethylcellulose, carboxyethylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, methylhydroxyethylcellulose, starch, sodium starch glycolate, pregelatinized starch, a calcium phosphate, a metal carbonate, a metal oxide, or a metal aluminosilicate;
(b) said second optional diluent/filler component, when present, comprises one or more of mannitol, lactose, sucrose, maltodextrin, sorbitol, xylitol, powdered cellulose, microcrystalline cellulose, carboxymethylcellulose, carboxyethylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, methylhydroxyethylcellulose, starch, pregelatinized starch, sodium starch glycolate, a calcium phosphate, a metal carbonate, a metal oxide, or a metal aluminosilicate;
(c) said disintegrant component comprises one or more of croscarmellose sodium, carmellose calcium, crospovidone, alginic acid, sodium alginate, potassium alginate, calcium alginate, an ion exchange resin, an effervescent system based on food acids and an alkaline carbonate component, clay, talc, starch, pregelatinized starch, sodium starch glycolate, cellulose floe, carboxymethylcellulose, hydroxypropylcellulose, calcium silicate, a metal carbonate, sodium bicarbonate, calcium citrate, or calcium phosphate;
(d) said binder component comprises one or more of polyvinylpyrrolidone, copovidone, hydroxypropylcellulose, hydroxypropylmethylcellulose, crosslinked poly(acrylic acid), gum arabic, gum acacia, gum tragacanath, lecithin, casein, polyvinyl alcohol, gelatin, or kaolin;
(e) said wetting agent component comprises one or more of metallic lauryl sulfate, polyethylene glycol, glycerides of fatty ester, polyoxyethylene-polyoxypropylene copolymer, polyoxyethylene-alkyl ether, metal alkyl sulfate, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene castor oil derivative, sugar ester of fatty acid, polyglycolized glyceride, quaternary ammonium amine compound, lauroyl macrogol glycerides, caprylocaproyl macrogolglycerides, stearoyl macrogol glycerides, linoleoyl macrogol glycerides, oleoyl macrogol glycerides, polyethoxylated vegetable oil, polyethoxylated sterol, polyethoxylated cholesterol, polyethoxylated glycerol fatty acid ester, polyethoxylated fatty acid ester, sulfosuccinate, taurate, or docusate sodium; and
(f) said optional lubricant component, when present, comprises one or more of stearic acid, metallic stearate, sodium stearyl fumarate, fatty acid, fatty alcohol, fatty acid ester, glyceryl behenate, mineral oil, vegetable oil, paraffin, leucine, silica, silicic acid, talc, propylene glycol fatty acid ester, polyethylene glycol, polypropylene glycol, polyalkylene glycol or sodium chloride.

9. The pharmaceutical formulation of any one of claims 1 to 8 wherein:
(d) said binder component comprises one or more of polyvinylpyrrolidone, copovidone, crosslinked poly(acrylic acid), lecithin, casein, polyvinyl alcohol, or gelatin; and
(e) said wetting agent component comprises one or more of polyoxyethylene-polyoxypropylene copolymer, polyoxyethylene-alkyl ether, metal alkyl sulfate, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene castor oil derivative, sugar ester of fatty acid, polyglycolized glyceride, quaternary ammonium amine compound, lauroyl macrogol glycerides, caprylocaproyl macrogolglycerides, stearoyl macrogol glycerides, linoleoyl macrogol glycerides, oleoyl macrogol glycerides, polyethoxylated vegetable oil, polyethoxylated glycerol fatty acid ester, polyethoxylated fatty acid ester, or docusate sodium.

10. The pharmaceutical formulation of any one of claims 1 to 9 wherein:
(a) said first diluent/filler component comprises mannitol;

(b) said second optional diluent/filler component, when present, comprises microcrystalline cellulose;
(c) said disintegrant component comprises croscarmellose sodium;
(d) said binder component comprises polyvinylpyrrolidone;
(e) said wetting agent component comprises sodium lauryl sulfate; and
(f) said optional lubricant component, when present, comprises magnesium stearate.

1 1. A pharmaceutical formulation comprising:
(a) a pharmaceutically effective amount of an active pharmacological agent having Formula I as defined in claim 1 or pharmaceutically acceptable salt thereof; and
(b) a carrier or exicipient system comprising:
(i) a first diluent/filler component comprising from about 38% to about 95% by weight of said formulation;
(ii) an optional second diluent/filler component comprising, when present, from about 5% to about 25% by weight of said pharmaceutical formulation;
(iii) a disintegrant component comprising from about 0.5% to about 20% by weight of said pharmaceutical formulation;
(iv) a binder component comprising from about 0.5% to about 5% by weight of said pharmaceutical formulation;
(v) a wetting agent component comprising from 1.3% to about 5% by weight of said pharmaceutical formulation; and
(vi) an optional lubricant component comprising, when present, from about 0.01 % to about 5% by weight of said pharmaceutical formulation;
with the proviso that when said pharmaceutical formulation comprises one or more ingredients selected from metallic lauryl sulfate, sodium lauryl sulfate, metal alkyl sulfate, polyethylene glycol, glyceride of fatty ester, Poloxamer 188, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene castor oil derivative, sugar ester of fatty acid, polyglycolized glyceride, quaternary ammonium amine compound, and docusate sodium, then the sum of the amounts of said ingredients does not exceed about 5% by weight of said pharmaceutical formulation.

12. The pharmaceutical formulation of claim 1 1 wherein:
(a) said first diluent/filler component comprises one or more of mannitol, lactose, sucrose, maltodextrin, sorbitol, xylitol, powdered cellulose, microcrystalline cellulose, carboxymethylcellulose, carboxyethylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, methylhydroxyethylcellulose, starch, sodium starch glycolate, pregelatinized starch, a calcium phosphate, a metal carbonate, a metal oxide, or a metal aluminosilicate;
(b) said second optional diluent/filler component, when present, comprises one or more of mannitol, lactose, sucrose, maltodextrin, sorbitol, xylitol, powdered cellulose, microcrystalline cellulose, carboxymethylcellulose, carboxyethylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, methylhydroxyethylcellulose, starch, pregelatinized starch, sodium starch glycolate, a calcium phosphate, a metal carbonate, a metal oxide, or a metal aluminosilicate;
(c) said disintegrant component comprises one or more of croscarmellose sodium, carmellose calcium, crospovidone, alginic acid, sodium alginate, potassium alginate, calcium alginate, an ion exchange resin, an effervescent system based on food acids and an alkaline carbonate component, clay, talc, starch, pregelatinized starch, sodium starch glycolate, cellulose floe, carboxymethylcellulose, hydroxypropylcellulose, calcium silicate, a metal carbonate, sodium bicarbonate, calcium citrate, or calcium phosphate;
(d) said binder component comprises one or more of polyvinylpyrrolidone, copovidone, hydroxypropylcellulose, hydroxypropylmethylcellulose, crosslinked poly(acrylic acid), gum arabic, gum acacia, gum tragacanath, lecithin, casein, polyvinyl alcohol, gelatin, or kaolin;
(e) said wetting agent component comprises one or more of metallic lauryl sulfate, polyethylene glycol, glycerides of fatty ester, polyoxyethylene-polyoxypropylene copolymer, polyoxyethylene-alkyl ether, metal alkyl sulfate, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene castor oil derivative, sugar ester of fatty acid, polyglycolized glyceride, quaternary ammonium amine compound, lauroyl macrogol glycerides, caprylocaproyl macrogolglycerides, stearoyl macrogol glycerides, linoleoyl macrogol glycerides, oleoyl macrogol glycerides, polyethoxylated vegetable oil, polyethoxylated sterol, polyethoxylated cholesterol, polyethoxylated glycerol fatty acid ester, polyethoxylated fatty acid ester, sulfosuccinate, taurate, or docusate sodium; and
(f) said optional lubricant component, when present, comprises one or more of stearic acid, metallic stearate, sodium stearyl fumarate, fatty acid, fatty alcohol, fatty acid ester, glyceryl behenate, mineral oil, vegetable oil, paraffin, leucine, silica, silicic acid, talc, propylene glycol fatty acid ester, polyethylene glycol, polypropylene glycol, polyalkylene glycol, or sodium chloride.

13. The pharmaceutical formulation of claim 1 1 or claim 12 wherein:
(d) said binder component comprises one or more of polyvinylpyrrolidone, copovidone, crosslinked poly(acrylic acid), lecithin, casein, polyvinyl alcohol, or gelatin; and
(e) said wetting agent component comprises one or more of polyoxyethylene-polyoxypropylene copolymer, polyoxyethylene-alkyl ether, metal alkyl sulfate, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene castor oil derivative, sugar ester of fatty acid, polyglycolized glyceride, quaternary ammonium amine compound, lauroyl macrogol glycerides, caprylocaproyl macrogolglycerides, stearoyl macrogol glycerides, linoleoyl macrogol glycerides, oleoyl macrogol glycerides, polyethoxylated vegetable oil, polyethoxylated glycerol fatty acid ester, polyethoxylated fatty acid ester, or docusate sodium.

14. The pharmaceutical formulation of claim 1 1 wherein:
(a) said first diluent/filler component comprises mannitol;
(b) said second optional diluent/filler component, when present, comprises microcrystalline cellulose;
(c) said disintegrant component comprises croscarmellose sodium;
(d) said binder component comprises polyvinylpyrrolidone;
(e) said wetting agent component comprises sodium lauryl sulfate; and
(f) said optional lubricant component, when present, comprises magnesium stearate.

15. The pharmaceutical formulation of any one of claims 1 1 to 14 wherein said active pharmacological agent comprises from about 0.01 % to about 80% of said pharmaceutical formulation.

16. A pharmaceutical formulation comprising:
(a) a pharmaceutically effective amount of an active pharmacological agent having Formula I as defined in claim 1or pharmaceutically acceptable salt thereof; and
(b) a carrier or exicipient system comprising:
(i) a first diluent/filler component comprising from about 38% to about 95% by weight of said formulation;
(ii) an optional second diluent/filler component comprising, when present, from about 5% to about 25% by weight of said pharmaceutical formulation;
(iii) a disintegrant component comprising from about 0.5% to 20% by weight of said pharmaceutical formulation;
(iv) a binder component comprising from about 1 % to about 3% by weight of said pharmaceutical formulation;
(v) a wetting agent component comprising from about 1.3% to about 4% by weight of said pharmaceutical formulation; and
(vi) an optional lubricant component comprising, when present, from about 0.01 % to about 5% by weight of said pharmaceutical formulation;
with the proviso that when said pharmaceutical formulation comprises one or more ingredients selected from metallic lauryl sulfate, sodium lauryl sulfate, metal alkyl sulfate, polyethylene glycol, glyceride of fatty ester, Poloxamer 188, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene castor oil derivative, sugar ester of fatty acid, polyglycolized glyceride, quaternary ammonium amine compound, and docusate sodium, then the sum of the amounts of said ingredients does not exceed about 4% by weight of said pharmaceutical formulation.

17. The pharmaceutical formulation of claim 16 wherein:
(a) said first diluent/filler component comprises one or more of mannitol, lactose, sucrose, maltodextrin, sorbitol, xylitol, powdered cellulose, microcrystalline cellulose, carboxymethylcellulose, carboxyethylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, methylhydroxyethylcellulose, starch, sodium starch glycolate, pregelatinized starch, a calcium phosphate, a metal carbonate, a metal oxide, or a metal aluminosilicate;
(b) said second optional diluent/filler component, when present, comprises one or more of mannitol, lactose, sucrose, maltodextrin, sorbitol, xylitol, powdered cellulose, microcrystalline cellulose, carboxymethylcellulose, carboxyethylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, methylhydroxyethylcellulose, starch, pregelatinized starch, sodium starch glycolate, a calcium phosphate, a metal carbonate, a metal oxide, or a metal aluminosilicate;
(c) said disintegrant component comprises one or more of croscarmellose sodium, carmellose calcium, crospovidone, alginic acid, sodium alginate, potassium alginate, calcium alginate, an ion exchange resin, an effervescent system based on food acids and an alkaline carbonate component, clay, talc, starch, pregelatinized starch, sodium starch glycolate, cellulose floe, carboxymethylcellulose, hydroxypropylcellulose, calcium silicate, a metal carbonate, sodium bicarbonate, calcium citrate, or calcium phosphate;
(d) said binder component comprises one or more of polyvinylpyrrolidone, copovidone, hydroxypropylcellulose, hydroxypropylmethylcellulose, crosslinked poly(acrylic acid), gum arabic, gum acacia, gum tragacanath, lecithin, casein, polyvinyl alcohol, gelatin, or kaolin;
(e) said wetting agent component comprises one or more of metallic lauryl sulfate, polyethylene glycol, glycerides of fatty ester, polyoxyethylene-polyoxypropylene copolymer, polyoxyethylene-alkyl ether, metal alkyl sulfate, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene castor oil derivative, sugar ester of fatty acid, polyglycolized glyceride, quaternary ammonium amine compound, lauroyl macrogol glycerides, caprylocaproyl macrogolglycerides, stearoyl macrogol glycerides, linoleoyl macrogol glycerides, oleoyl macrogol glycerides, polyethoxylated vegetable oil, polyethoxylated sterol, polyethoxylated cholesterol, polyethoxylated glycerol fatty acid ester, polyethoxylated fatty acid ester, sulfosuccinate, taurate, or docusate sodium; and
(f) said optional lubricant component, when present, comprises one or more of stearic acid, metallic stearate, sodium stearyl fumarate, fatty acid, fatty alcohol, fatty acid ester, glyceryl behenate, mineral oil, vegetable oil, paraffin, leucine, silica, silicic acid, talc, propylene glycol fatty acid ester, polyethylene glycol, polypropylene glycol, polyalkylene glycol, or sodium chloride.

18. The pharmaceutical formulation of claim 16 or claim 17 wherein:
(d) said binder component comprises one or more of polyvinylpyrrolidone, copovidone, crosslinked poly(acrylic acid), lecithin, casein, polyvinyl alcohol, or gelatin; and
(e) said wetting agent component comprises one or more of polyoxyethylene-polyoxypropylene copolymer, polyoxyethylene-alkyl ether, metal alkyl sulfate, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene castor oil derivative, sugar ester of fatty acid, polyglycolized glyceride, quaternary ammonium amine compound, lauroyl macrogol glycerides, caprylocaproyl macrogolglycerides, stearoyl macrogol glycerides, linoleoyl macrogol glycerides, oleoyl macrogol glycerides, polyethoxylated vegetable oil, polyethoxylated glycerol fatty acid ester, polyethoxylated fatty acid ester, or docusate sodium.

19. The pharmaceutical formulation of claim 16 wherein:
(a) said first diluent/filler component comprises mannitol;
(b) said second optional diluent/filler component, when present, comprises microcrystalline cellulose;
(c) said disintegrant component comprises croscarmellose sodium;
(d) said binder component comprises polyvinylpyrrolidone;
(e) said wetting agent component comprises sodium lauryl sulfate; and
(f) said optional lubricant component, when present, comprises magnesium stearate.

20. The pharmaceutical formulation of any one of claims 16 to 19 wherein said active pharmacological agent comprises from about 0.01 % to about 80% of said pharmaceutical formulation.

21. The pharmaceutical formulation of any one of claims 1 to 20 wherein said active pharmacological agent is 2-(3-fluoro-4-hydroxyphenyl)-7-vinyl-1 ,3-benzoxazol-5-ol, or a pharmaceutically acceptable salt thereof.

22. A tablet comprising the pharmaceutical formulation of any one of claims 1 to 21.

23. A process for preparing the pharmaceutical formulation of any one of claims 1 to 21 comprising:
(a) mixing the active pharmacological agent with the first diluent/filler component, the disintegrant component, and the optional second filler/diluent component, if present, to form an initial mixture; and
(b) granulating said initial mixture with an aqueous solution comprising the wetting agent component to form a granulated mixture.

24. The process of claim 23 wherein (a) comprises:
(i) mixing said active pharmacological agent with at least a portion of said first diluent/filler component to form a first mixture; and
(ii) mixing said first mixture with the remainder of said first diluent/filler component, if any, said disintegrant component, and said optional second filler/diluent component, if present, to form said initial mixture.

25. The process of claim 23 or claim 24 wherein said aqueous solution further comprises the binder component.

26. The process of any one of claims 23 to 25 further comprising:
(i) drying said granulated mixture to form a dried granulated mixture; and (ii) mixing the optional lubricant component, if present, with said dried granulated mixture to form a final mixture.

27. The process of claim 26 wherein (ii) comprises:
(a) mixing said optional lubricant component, if present, with a portion of said dried granulated mixture; and
(b) mixing the mixture from (i) with the remainder of said dried granulated mixture.

28. The process of claim 27 wherein (b) is carried out in a blender.

29. The process of claim 23 comprising:
(i) mixing said active pharmacological agent with at least a portion of said first diluent/filler component to form a first mixture;
(ii) mixing said first mixture with the remainder of said first diluent/filler component, if any, said disintegrant component, and said optional second filler/diluent component, if present, to form said initial mixture;
(iii) granulating said initial mixture with an aqueous solution comprising the wetting agent component to form a granulated mixture
(iv) drying said granulated mixture to form a dried granulated mixture;
(v) mixing the optional lubricant component, if present, with said at least a portion of said dried granulated mixture; and
(vi) mixing the mixture from (v) with the remainder of said dried granulated mixture, if any.

30. The process of claim 29 wherein said aqueous solution further comprises the binder component.

31. A process for producing the pharmaceutical formulation of any one of claims 1 to 21 comprising:
(i) mixing said first diluent/filler component, said optional second diluent/filler component, if present, said disintegrant component, said binder component, said wetting agent component, and said active pharmacological agent to form a first mixture; and
ii) optionally granulating said first mixture.

32. The process of claim 31 wherein said first mixture further comprises the optional lubricant component.

33. A product of the process of any one of claims 23 to 32.

34. A process for producing a tablet comprising compressing the pharmaceutical formulation of any one of claims 1 to 21.

35. The process of claim 34 further comprising milling said pharmaceutical formulation prior to said compressing of the pharmaceutical formulation.

36. The process of claim 34 or claim 35 wherein said compression is direct compression.