US2002031548A1PendingUtilityA1
Pharmaceutical compositions of estrogenic agents
Est. expiryJul 6, 2020(expired)· nominal 20-yr term from priority
A61P 5/30A61K 9/2013A61K 9/2018A61K 47/12A61K 9/2054A61K 31/404A61K 9/2059A61K 47/00
40
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Claims
Abstract
This invention comprises novel pharmaceutical carrier or excipient systems and oral pharmaceutical formulations comprising as an active ingredient raloxifene, amoxifen, droloxifene, arzoxifene, or CP 336156, or analogs thereof, or a compound of the formulae I or wherein Z is a moiety selected from the group of: wherein: R 1 is selected from H, OH or the C 1 -C 12 esters alkyl ethers thereof, benzyloxy, or halogen; or C 1 -C 4 halogenated ethers; R 2 , R 3 , R 4 , R 5 , and R 6 are H, OH or C 1 -C 12 esters or alkyl ethers thereof, halogens, or C 1 -C 4 halogenated ethers, cyano, C 1 -C 6 alkyl, or CF 3 , with the proviso that, when R 1 is H, R 2 is not OH; Y is the moiety: R 7 and R 8 are alkyl or concatenated together to form an optionally substituted, nitrogen-containing ring; or a pharmaceutically acceptable salt thereof; and excipients chosen from pharmaceutical fillers, glidants, lubricants, wetting agents and antioxidants.
Claims
exact text as granted — not AI-modifiedWhat is claimed:
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:
wherein Z is a moiety selected from the group of:
wherein:
R 1 is selected from H, OH or the C 1 -C 12 esters or C 1 -C 12 alkyl ethers thereof, benzyloxy, or halogen; or C 1 -C 4 halogenated ethers;
R 2 , R 3 , R 5 and R 6 are independently selected from H, OH or the C 1 -C 12 esters or C 1 -C 12 alkyl ethers thereof, halogens, or C 1 -C 4 halogenated ethers, cyano, C 1 -C 6 alkyl, or trifluoromethyl, with the proviso that, when R 1 is H, R 2 is not OH;
R 4 is selected from H, OH or the C 1 -C 12 esters or C 1 -C 12 alkyl ethers thereof, halogens, or C 1 -C 4 halogenated ethers, benzyloxy, cyano, C 1 -C 6 alkyl, or trifluoromethyl;
X is selected from H, C 1 -C 6 alkyl, cyano, nitro, trifluoromethyl, halogen;
n is 1, 2 or 3;
Y is selected from:
a) the moiety:
wherein R 7 and R 8 are independently selected from the group of H, C 1 -C 6 alkyl, or phenyl optionally substituted by CN, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, —OH, —CF 3 , or —OCF 3 ;
b) a five-membered saturated, unsaturated or partially unsaturated heterocycle containing up to two heteroatoms selected from the group consisting of —O—, —NH—, —N(C 1 C 4 alkyl)-, —N═, and —S(O) m —, wherein m is an integer of from 0-2, optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C 1 -C 4 alkyl, trihalomethyl, C 1 -C 4 alkoxy, trihalomethoxy, C 1 -C 4 acyloxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, hydroxy (C 1 -C 4 )alkyl, —CO 2 H—, —CN—, —CONHR 1 —, —NH 2 —, C 1 -C 4 alkylamino, di(C 1 -C 4 )alkylamino, —NHSO 2 R 1 —, —NHCOR 1 —, —NO 2 , and phenyl optionally substituted with from one to three (C 1 -C 4 )alkyl groups;
c) a six-membered saturated, unsaturated or partially unsaturated heterocycle containing up to two heteroatoms selected from the group consisting of —O—, —NH—, —N(C 1 C 4 alkyl)-, —N═, and —S(O) m —, wherein m is an integer of from 0-2, optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C 1 -C 4 alkyl, trihalomethyl, C 1 -C 4 alkoxy, trihalomethoxy, C 1 -C 4 acyloxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, hydroxy (C 1 -C 4 )alkyl, —CO 2 H—, —CN—, —CONHR 1 —, —NH 2 —, C 1 -C 4 alkylamino, di(C 1 -C 4 )alkylamino, —NHSO 2 R 1 —, —NHCOR 1 —, —NO 2 , and phenyl optionally substituted with from one to three (C 1 -C 4 )alkyl groups;
d) a seven-membered saturated, unsaturated or partially unsaturated heterocycle containing up to two heteroatoms selected from the group consisting of —O—, —NH—, —N(C 1 C 4 alkyl)-, —N═, and —S(O) m —, wherein m is an integer of from 0-2, optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C 1 -C 4 alkyl, trihalomethyl, C 1 -C 4 alkoxy, trihalomethoxy, C 1 -C 4 acyloxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, hydroxy (C 1 -C 4 )alkyl, —CO 2 H—, —CN—, —CONHR 1 —, —NH 2 —, C 1 -C 4 alkylamino, di(C 1 -C 4 )alkylamino, —NHSO 2 R 1 —, —NHCOR 1 —, —NO 2 , and phenyl optionally substituted with from one to three (C 1 -C 4 )alkyl groups; or
e) a bicyclic heterocycle containing from 6-12 carbon atoms either bridged or fused and containing up to two heteroatoms selected from the group consisting of —O—, —NH—, —N(C 1 C 4 alkyl)-, and —S(O) m —, wherein m is an integer of from 0-2, optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C 1 -C 4 alkyl, trihalomethyl, C 1 -C 4 alkoxy, trihalomethoxy, C 1 -C 4 acyloxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, hydroxy (C 1 -C 4 )alkyl, —CO 2 H—, —CN—, —CONHR 1 —, —NH 2 —, C 1 -C 4 alkylamino, di(C 1 -C 4 )alkylamino, —NHSO 2 R 1 —, —NHCOR 1 —, —NO 2 , and phenyl optionally substituted with from one to three (C 1 -C 4 )alkyl groups;
or a pharmaceutically acceptable salt thereof.
8 . The pharmaceutical composition of claim 7 wherein in the compound of the formulae I or II:
R 1 is selected from H, OH or the C 1 -C 12 esters or alkyl ethers thereof, benzyloxy, or halogen;
R 2 , R 3 , R 5 , and R 6 are independently selected from H, OH or the C 1 -C 12 esters or alkyl ethers thereof, halogen, cyano, C 1 -C 6 alkyl, or trihalomethyl; with the proviso that, when R 1 is H, R 2 is not OH;
R 4 is selected from H, OH or the C 1 -C 2 esters or alkyl ethers thereof, benzyloxy, halogen, cyano, C 1 -C 6 alkyl, or trihalomethyl;
X is selected from H, C 1 -C 6 alkyl, cyano, nitro, trifluoromethyl, halogen;
Y is the moiety
R 7 and R 8 are selected independently from H, C 1 -C 6 alkyl, or combined by —(CH 2 )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, C 1 -C 4 alkyl, trihalomethyl, C 1 -C 4 alkoxy, trihalomethoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, hydroxy (C 1 -C 4 )alkyl, —CO 2 H, —CN, —CONH(C 1 -C 4 ), —NH 3 , C 1 -C 4 alkylamino, C 1 -C 4 dialkylamino, —NHSO 2 (C 1 -C 4 ), —NHCO(C 1 -C 4 ), and —NO 3 ;
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 R 7 and R 8 by —(CH 2 )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 R 1 is OH; R 2 -R 6 are as defined in claim 1; X is selected from the group of Cl, NO 2 , CN, CF 3 , or CH 3 ; and Y is the moiety
and R 7 and R 8 are concatenated together as —(CH 2 ) r —, wherein r is an integer of from 4 to 6, to form a ring optionally substituted by up to three substituents selected from the group of hydrogen, hydroxyl, halo, C 1 -C 4 alkyl, trihalomethyl, C 1 -C 4 alkoxy, trihalomethoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, hydroxy (C 1 -C 4 )alkyl, —CO 2 H, —CN, —CONH(C 1 -C 4 )alkyl, —NH 2 , C 1 -C 4 alkylamino, di(C 1 -C 4 )alkylamino, —NHSO 2 (C 1 -C 4 )alkyl, —NHCO(C 1 -C 4 )alkyl, and —NO 2 ;
or a pharmaceutically acceptable salt thereof.
11 . A pharmaceutical composition of claim 4 wherein the active pharmacological agent is a compound of the formulae (III) or (IV):
wherein the substituents R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , n, X, and Y are as defined in claim 7 , or a pharmaceutically acceptable salt thereof.
12 . A pharmaceutical composition of claim 11 wherein:
R 1 is selected from H, OH or the C 1 -C 12 esters or alkyl ethers thereof, benzyloxy, or halogen;
R 2 , R 3 , R 5 , and R 6 are independently selected from H, OH or the C 1 -C 12 esters or alkyl ethers thereof, halogen, cyano, C 1 -C 6 alkyl, or trihalomethyl, preferably trifluoromethyl, with the proviso that, when R 1 is H, R 2 is not OH;
R 4 is selected from H, OH or the C 1 -C 12 esters or alkyl ethers thereof, benzyloxy, halogen, cyano, C 1 -C 6 alkyl, or trihalomethyl;
X is selected from H, C 1 -C 6 alkyl, cyano, nitro, trifluoromethyl, halogen;
Y is the moiety
R 7 and R 8 are selected independently from H, C 1 -C 6 alkyl, or combined by —(CH 2 )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, C 1 -C 4 alkyl, trihalomethyl, C 1 -C 4 alkoxy, trihalomethoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, hydroxy (C 1 -C 4 )alkyl, —CO 2 H, —CN, —CONH(C 1 -C 4 ), —NH 3 , C 1 -C 4 alkylamino, C 1 -C 4 dialkylamino, —NHSO 2 (C 1 -C 4 ), —NHCO(C 1 -C 4 ), and —NO 3 ;
or a pharmaceutically acceptable salt thereof.
13 . A pharmaceutical composition of claim 11 wherein R 1 is OH; R 2 -R 6 are as defined above; X is selected from the group of Cl, NO 2 , CN, CF 3 , or CH 3 ; and Y is the moiety
and R 7 and R 8 are concatenated together as —(CH 2 ) r —, wherein r is an integer of from 4 to 6, to form a ring optionally substituted by up to three substituents selected from the group of hydrogen, hydroxyl, halo, C 1 -C 4 alkyl, trihalomethyl, C 1 -C 4 alkoxy, trihalomethoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, hydroxy (C 1 -C 4 )alkyl, —CO 2 H, —CN, —CONH(C 1 -C 4 )alkyl, —NH 2 , C 1 -C 4 alkylamino, di(C 1 -C 4 )alkylamino, —NHSO 2 (C 1 -C 4 )alkyl, —NHCO(C 1 -C 4 )alkyl, and —NO 2 ; or a pharmaceutically acceptable salt thereof.
14 . A pharmaceutical composition of claim 11 wherein R 7 and R 8 are concatenated together as —(CH 2 )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 C 1 -C 3 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):
wherein the variable substituents including R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , n, X, and Y are as defined in claim 7 , or a pharmaceutically acceptable salt thereof.
16 . A pharmaceutical composition of claim 15 wherein:
R 1 is selected from H, OH or the C 1 -C 12 esters or alkyl ethers thereof, benzyloxy, or halogen;
R 2 , R 3 , R 5 , and R 6 are independently selected from H, OH or the C 1 -C 12 esters or alkyl ethers thereof, halogen, cyano, C 1 -C 6 alkyl, or trihalomethyl, preferably trifluoromethyl, with the proviso that, when R 1 is H, R 2 is not OH;
R 4 is selected from H, OH or the C 1 -C 12 esters or alkyl ethers thereof, benzyloxy, halogen, cyano, C 1 -C 6 alkyl, or trihalomethyl;
X is selected from H, C 1 -C 6 alkyl, cyano, nitro, trifluoromethyl, halogen;
Y is the moiety
R 7 and R 8 are selected independently from H, C 1 -C 6 alkyl, or combined by —(CH 2 )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, C 1 -C 4 alkyl, trihalomethyl, C 1 -C 4 alkoxy, trihalomethoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, hydroxy (C 1 -C 4 )alkyl, —CO 2 H, —CN, —CONH(C 1 -C 4 ), —NH 3 , C 1 -C 4 alkylamino, C 1 -C 4 dialkylamino, —NHSO 2 (C 1 -C 4 ), —NHCO(C 1 -C 4 ), and —NO 3 ;
or a pharmaceutically acceptable salt thereof.
17 . A pharmaceutical composition of claim 15 wherein R 1 is OH; R 2 -R 6 are as defined above; X is selected from the group of Cl, NO 2 , CN, CF 3 , or CH 3 ; and Y is the moiety
and R 7 and R 8 are concatenated together as —(CH 2 ) r —, wherein r is an integer of from 4 to 6, to form a ring optionally substituted by up to three substituents selected from the group of hydrogen, hydroxyl, halo, C 1 -C 4 alkyl, trihalomethyl, C 1 -C 4 alkoxy, trihalomethoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, hydroxy (C 1 -C 4 )alkyl, —CO 2 H, —CN, —CONH(C 1 -C 4 )alkyl, —NH 2 , C 1 -C 4 alkylamino, di(C 1 -C 4 )alkylamino, —NHSO 2 (C 1 -C 4 )alkyl, —NHCO(C 1 -C 4 )alkyl, and —NO 2 ; or a pharmaceutically acceptable salt thereof.
18 . A pharmaceutical composition of claim 15 wherein R 7 and R 8 are concatenated together as —(CH 2 )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 C 1 -C 3 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):
wherein the variable substituents including R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , n, X, and Y are as defined in claim 7 , or a pharmaceutically acceptable salt thereof.
20 . A pharmaceutical composition of claim 19 wherein:
R 1 is selected from H, OH or the C 1 -C 12 esters or alkyl ethers thereof, benzyloxy, or halogen;
R 2 , R 3 , R 5 , and R 6 are independently selected from H, OH or the C 1 -C 12 esters or alkyl ethers thereof, halogen, cyano, C 1 -C 6 alkyl, or trihalomethyl, preferably trifluoromethyl, with the proviso that, when R 1 is H, R 2 is not OH;
R 4 is selected from H, OH or the C 1 -C 12 esters or alkyl ethers thereof, benzyloxy, halogen, cyano, C 1 -C 6 alkyl, or trihalomethyl;
X is selected from H, C 1 -C 6 alkyl, cyano, nitro, trifluoromethyl, halogen;
Y is the moiety
R 7 and R 8 are selected independently from H, C 1 -C 6 alkyl, or combined by —(CH 2 )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, C 1 -C 4 alkyl, trihalomethyl, C 1 -C 4 alkoxy, trihalomethoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, hydroxy (C 1 -C 4 )alkyl, —CO 2 H, —CN, —CONH(C 1 -C 4 ), —NH 3 , C 1 -C 4 alkylamino, C 1 -C 4 dialkylamino, —NHSO 2 (C 1 -C 4 ), —NHCO(C 1 -C 4 ), and —NO 3 ;
or a pharmaceutically acceptable salt thereof.
21 . A pharmaceutical composition of claim 19 wherein R 1 is OH; R 2 -R 6 are as defined above; X is selected from the group of Cl, NO 2 , CN, CF 3 , or CH 3 ; and Y is the moiety
and R 7 and R 8 are concatenated together as —(CH 2 ) r —, wherein r is an integer of from 4 to 6, to form a ring optionally substituted by up to three substituents selected from the group of hydrogen, hydroxyl, halo, C 1 -C 4 alkyl, trihalomethyl, C 1 -C 4 alkoxy, trihalomethoxy, C 1 -C 4 alkylthio, C 1 -C v4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, hydroxy (C 1 -C 4 )alkyl, —CO 2 H, —CN, —CONH(C 1 -C 4 )alkyl, —NH 2 , C 1 -C 4 alkylamino, di(C 1 -C 4 )alkylamino, —NHSO 2 (C 1 -C 4 )alkyl, —NHCO(C 1 -C 4 )alkyl, and —NO 2 ; or a pharmaceutically acceptable salt thereof.
22 . A pharmaceutical composition of claim 19 wherein R 7 and R 8 are concatenated together as —(CH 2 )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 C 1 -C 3 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.Join the waitlist — get patent alerts
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