Claims
- 1. A pharmaceutical carrier or excipient system useful for preparing a pharmaceutical formulation, the carrier or excipient system comprising:
a) a filler and disintegrant component comprising from about 5% to about 82% by weight of the pharmaceutical formulation, of which from about 4% to about 40% by weight of the total formulation comprises one or more pharmaceutically acceptable disintegrants; b) optionally, a wetting agent comprising from about 0.2 to about 5% of the pharmaceutical formulation; c) a lubricant comprising from about 0.2% to about 10% of the pharmaceutical formulation; and d) optionally, a glidant comprising from about 0.1% to about 10% of the pharmaceutical formulation.
- 2. The pharmaceutical carrier or excipient system of claim 1 further comprising from about 0.5% to about 15% by weight of an antioxidant.
- 3. The pharmaceutical carrier or excipient system of claim 2 wherein the antioxidant is selected from ascorbic acid, sodium ascorbate, ascorbyl palmitate, or mixtures thereof.
- 4. A pharmaceutical composition comprising a pharmaceutically effective amount of an active pharmacological agent and carrier or excipient system, the carrier or excipient system comprising:
a) a filler and disintegrant component comprising from about 5% to about 82% by weight of the pharmaceutical formulation, of which from about 4% to about 40% by weight of the total formulation comprises one or more pharmaceutically acceptable disintegrants; b) optionally, a wetting agent comprising from about 0.2 to about 5% of the pharmaceutical formulation; c) a lubricant comprising from about 0.2% to about 10% of the pharmaceutical formulation; and d) optionally, a glidant comprising from about 0.1% to about 10% of the pharmaceutical formulation.
- 5. The pharmaceutical carrier or excipient system of claim 1 further comprising from about 0.5% to about 15% by weight of an antioxidant.
- 6. The pharmaceutical carrier or excipient system of claim 2 wherein the antioxidant is selected from ascorbic acid, sodium ascorbate, ascorbyl palmitate, or mixtures thereof.
- 7. A pharmaceutical composition of claim 4 wherein the pharmacologically active agent is a compound of the formulae I or II:
- 8. The pharmaceutical composition of claim 7 wherein in the compound of the formulae I or II:
R1 is selected from H, OH or the C1-C12 esters or alkyl ethers thereof, benzyloxy, or halogen; R2, R3, R5, and R6 are independently selected from H, OH or the C1-C12 esters or alkyl ethers thereof, halogen, cyano, C1-C6 alkyl, or trihalomethyl; with the proviso that, when R1 is H, R2 is not OH; R4 is selected from H, OH or the C1-C2 esters or alkyl ethers thereof, benzyloxy, halogen, cyano, C1-C6 alkyl, or trihalomethyl; X is selected from H, C1-C6 alkyl, cyano, nitro, trifluoromethyl, halogen; Y is the moiety 25R7 and R8 are selected independently from H, C1-C6 alkyl, or combined by —(CH2)p—, wherein p is an integer of from 2 to 6, so as to form a ring, the ring being optionally substituted by up to three substituents selected from the group of hydrogen, hydroxyl, halo, C1-C4 alkyl, trihalomethyl, C1-C4 alkoxy, trihalomethoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, hydroxy (C1-C4)alkyl, —CO2H, —CN, —CONH(C1-C4), —NH3, C1-C4 alkylamino, C1-C4 dialkylamino, —NHSO2(C1-C4), —NHCO(C1-C4), and —NO3; or a pharmaceutically acceptable salt thereof.
- 9. The pharmaceutical formulation of claim 8 wherein, in the compound of the formulae I or II, the ring formed by a the combination of R7 and R8 by —(CH2)p— is selected from aziridine, azetidine, pyrrolidine, piperidine, hexamethyleneamine or heptamethyleneamine.
- 10. The method of claim 7 utilizing a compound of the formulae I or II, wherein R1 is OH; R2-R6 are as defined in claim 1; X is selected from the group of Cl, NO2, CN, CF3, or CH3; and Y is the moiety
- 11. A pharmaceutical composition of claim 4 wherein the active pharmacological agent is a compound of the formulae (III) or (IV):
- 12. A pharmaceutical composition of claim 11 wherein:
R1 is selected from H, OH or the C1-C12 esters or alkyl ethers thereof, benzyloxy, or halogen; R2, R3, R5, and R6 are independently selected from H, OH or the C1-C12 esters or alkyl ethers thereof, halogen, cyano, C1-C6 alkyl, or trihalomethyl, preferably trifluoromethyl, with the proviso that, when R1 is H, R2 is not OH; R4 is selected from H, OH or the C1-C12 esters or alkyl ethers thereof, benzyloxy, halogen, cyano, C1-C6 alkyl, or trihalomethyl; X is selected from H, C1-C6 alkyl, cyano, nitro, trifluoromethyl, halogen; Y is the moiety 28R7 and R8 are selected independently from H, C1-C6 alkyl, or combined by —(CH2)p—, wherein p is an integer of from 2 to 6, so as to form a ring, the ring being optionally substituted by up to three substituents selected from the group of hydrogen, hydroxyl, halo, C1-C4 alkyl, trihalomethyl, C1-C4 alkoxy, trihalomethoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, hydroxy (C1-C4)alkyl, —CO2H, —CN, —CONH(C1-C4), —NH3, C1-C4 alkylamino, C1-C4 dialkylamino, —NHSO2(C1-C4), —NHCO(C1-C4), and —NO3; or a pharmaceutically acceptable salt thereof.
- 13. A pharmaceutical composition of claim 11 wherein R1 is OH; R2-R6 are as defined above; X is selected from the group of Cl, NO2, CN, CF3, or CH3; and Y is the moiety
- 14. A pharmaceutical composition of claim 11 wherein R7 and R8 are concatenated together as —(CH2)p—, wherein p is an integer of from 2 to 6, preferably 4 to 6, the ring so formed is optionally substituted with 1-3 substituents selected from a group containing C1-C3 alkyl, trifluoromethyl, halogen, hydrogen, phenyl, nitro, —CN.
- 15. A pharmaceutical composition of claim 4 wherein the active pharmacological agent is a compound of the formulae (V) or (VI):
- 16. A pharmaceutical composition of claim 15 wherein:
R1 is selected from H, OH or the C1-C12 esters or alkyl ethers thereof, benzyloxy, or halogen; R2, R3, R5, and R6 are independently selected from H, OH or the C1-C12 esters or alkyl ethers thereof, halogen, cyano, C1-C6 alkyl, or trihalomethyl, preferably trifluoromethyl, with the proviso that, when R1 is H, R2 is not OH; R4 is selected from H, OH or the C1-C12 esters or alkyl ethers thereof, benzyloxy, halogen, cyano, C1-C6 alkyl, or trihalomethyl; X is selected from H, C1-C6 alkyl, cyano, nitro, trifluoromethyl, halogen; Y is the moiety 31R7 and R8 are selected independently from H, C1-C6 alkyl, or combined by —(CH2)p—, wherein p is an integer of from 2 to 6, so as to form a ring, the ring being optionally substituted by up to three substituents selected from the group of hydrogen, hydroxyl, halo, C1-C4 alkyl, trihalomethyl, C1-C4 alkoxy, trihalomethoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, hydroxy (C1-C4)alkyl, —CO2H, —CN, —CONH(C1-C4), —NH3, C1-C4 alkylamino, C1-C4 dialkylamino, —NHSO2(C1-C4), —NHCO(C1-C4), and —NO3; or a pharmaceutically acceptable salt thereof.
- 17. A pharmaceutical composition of claim 15 wherein R1 is OH; R2-R6 are as defined above; X is selected from the group of Cl, NO2, CN, CF3, or CH3; and Y is the moiety
- 18. A pharmaceutical composition of claim 15 wherein R7 and R8 are concatenated together as —(CH2)p—, wherein p is an integer of from 2 to 6, preferably 4 to 6, the ring so formed is optionally substituted with 1-3 substituents selected from a group containing C1-C3 alkyl, trifluoromethyl, halogen, hydrogen, phenyl, nitro, —CN.
- 19. A pharmaceutical composition of claim 4 wherein the active pharmacological agent is a compound of the formulae (VII) or (VIII):
- 20. A pharmaceutical composition of claim 19 wherein:
R1 is selected from H, OH or the C1-C12 esters or alkyl ethers thereof, benzyloxy, or halogen; R2, R3, R5, and R6 are independently selected from H, OH or the C1-C12 esters or alkyl ethers thereof, halogen, cyano, C1-C6 alkyl, or trihalomethyl, preferably trifluoromethyl, with the proviso that, when R1 is H, R2 is not OH; R4 is selected from H, OH or the C1-C12 esters or alkyl ethers thereof, benzyloxy, halogen, cyano, C1-C6 alkyl, or trihalomethyl; X is selected from H, C1-C6 alkyl, cyano, nitro, trifluoromethyl, halogen; Y is the moiety 34R7 and R8 are selected independently from H, C1-C6 alkyl, or combined by —(CH2)p—, wherein p is an integer of from 2 to 6, so as to form a ring, the ring being optionally substituted by up to three substituents selected from the group of hydrogen, hydroxyl, halo, C1-C4 alkyl, trihalomethyl, C1-C4 alkoxy, trihalomethoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, hydroxy (C1-C4)alkyl, —CO2H, —CN, —CONH(C1-C4), —NH3, C1-C4 alkylamino, C1-C4 dialkylamino, —NHSO2(C1-C4), —NHCO(C1-C4), and —NO3; or a pharmaceutically acceptable salt thereof.
- 21. A pharmaceutical composition of claim 19 wherein R1 is OH; R2-R6 are as defined above; X is selected from the group of Cl, NO2, CN, CF3, or CH3; and Y is the moiety
- 22. A pharmaceutical composition of claim 19 wherein R7 and R8 are concatenated together as —(CH2)p—, wherein p is an integer of from 2 to 6, preferably 4 to 6, the ring so formed is optionally substituted with 1-3 substituents selected from a group containing C1-C3 alkyl, trifluoromethyl, halogen, hydrogen, phenyl, nitro, —CN.
- 23. A pharmaceutical composition of claim 4 wherein the active pharmacological agent is 1-[4-(2-Azepan-1yl-ethoxy)-benzyl]-2-(4-hydroxy-phenyl)-3-methyl-1H-indol-5-ol or a pharmaceutically acceptable salt thereof.
- 24. A pharmaceutical composition of claim 4 wherein the active pharmacological agent is 2-(4-Hydroxy-phenyl)-3-methyl-1-(4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol or a pharmaceutically acceptable salt thereof.
- 25. A pharmaceutical composition of claim 4 wherein the active pharmacological agent is selected from the group of raloxifene, tamoxifen, droloxifene, arzoxifene or CP 336156, or a pharmaceutically acceptable salt thereof.
- 26. A pharmaceutical composition comprising:
a) a pharmaceutically effective amount of 1-[4-(2-Azepan-1yl-ethoxy)-benzyl]-2-(4-hydroxy-phenyl)-3-methyl-1H-indol-5-ol or 2-(4-Hydroxy-phenyl)-3-methyl-1-(4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol, or a pharmaceutically acceptable salt thereof; b) a filler and disintegrant component comprising between about 50% and about 80% of the formulation, with from about 4% to about 40% of the formulation comprising one or more disintegrant agents; c) a wetting agent comprising between about 0.5% and about 2.5% of the formulation; d) a lubricant comprising between about 0.2% and about 5% of the formulation; and e) a glidant comprising between about 0.1% and about 5% of the formulation.
- 27. The pharmaceutical composition of claim 26 further comprising an antioxidant at a concentration of from about 0.5% to about 5% by weight of the composition, the antioxidant being selected from the group of ascorbic acid, sodium ascorbate, ascorbyl palmitate, or mixtures thereof.
- 28. The pharmaceutical composition of claim 26 further being coated with a film coating comprising from about 0.3% to about 8% by weight of the composition.
- 29. A pharmaceutical composition comprising:
a) a pharmaceutically effective amount of 1-[4-(2-Azepan-1yl-ethoxy)-benzyl]-2-(4-hydroxy-phenyl)-3-methyl-1H-indol-5-ol or 2-(4-Hydroxy-phenyl)-3-methyl-1-(4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol, or a pharmaceutically acceptable salt thereof; b) a filler and disintegrant component of one or more pharmaceutically acceptable fillers and disintegrants comprising between about 54% and about 87% of the formulation, the disintegrants therein comprising from about 25% to about 35% of the formulation, by weight; c) a wetting agent comprising between about 0.55% and about 2.7% of the formulation; d) a lubricant comprising between about 0.2% and about 5.5% of the formulation; and e) a glidant comprising between about 0.1% and about 5.5% of the formulation.
- 30. The pharmaceutical composition of claim 29 further comprising an antioxidant at a concentration of from about 0.5% to about 5% by weight of the composition, the antioxidant being selected from the group of ascorbic acid, sodium ascorbate, ascorbyl palmitate, or a mixture thereof.
- 31. The pharmaceutical composition of claim 29 further being coated with a film coating comprising from about 0.3% to about 8% by weight of the composition.
- 32. A pharmaceutical composition comprising, by weight:
a) from about 2% to about 8% 1-[4-(2-Azepan-1yl-ethoxy)-benzyl]-2-(4-hydroxy-phenyl)-3-methyl-1H-indol-5-ol or 2-(4-Hydroxy-phenyl)-3-methyl-1-(4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol, or a pharmaceutically acceptable salt thereof; b) lactose from about 32% to about 38%; c) microcrystalline cellulose from about 32% to about 38%; d) pregelatinized starch from about 12% to about 16%; e) ascorbic acid from about 1% to about 2%; f) sodium lauryl sulfate from about 1% to about 2%; g) sodium starch glycolate from about 4% to about 8%; h) silicon dioxide from about 0.1% to about 0.2%; and i) magnesium stearate from about 0.3% to about 0.7%.
- 33. A pharmaceutical composition comprising, by weight:
a) from about 0.1% to about 25% 1-[4-(2-Azepan-1yl-ethoxy)-benzyl]-2-(4-hydroxy-phenyl)-3-methyl-1H-indol-5-ol or 2-(4-Hydroxy-phenyl)-3-methyl-1-(4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol, or a pharmaceutically acceptable salt thereof; b) from about 20% to about 80% lactose; c) from about 4% to about 40% pregelatinized starch; d) from about 0.2% to about 5% sodium lauryl sulfate; e) from about 0.5% to about 15% ascorbic acid; f) from about 0.1% to about 10% silicon dioxide; and g) from about 0.2% to about 10% magnesium stearate.
- 34. A pharmaceutical composition of claim 33 comprising, by weight:
a) from about 5% to about 18% 1-[4-(2-Azepan-1yl-ethoxy)-benzyl]-2-(4-hydroxy-phenyl)-3-methyl-1H-indol-5-ol or 2-(4-Hydroxy-phenyl)-3-methyl-1-(4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol, or a pharmaceutically acceptable salt thereof; b) from about 47% to about 77% lactose; c) from about 25% to about 35% pregelatinized starch; d) from about 1% to about 2% sodium lauryl sulfate; e) from about 1% to about 3% ascorbic acid; f) from about 0.1% to about 0.5% silicon dioxide; and g) from about 0.2% to about 0.5% magnesium stearate.
Parent Case Info
[0001] This application claims the benefit of U.S. Provisional Application No. 60/216,192, filed Jul. 6, 2000.
Provisional Applications (1)
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Number |
Date |
Country |
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60216192 |
Jul 2000 |
US |