TRANSDERMAL PHARMACEUTICAL COMPOSITIONS COMPRISING A SERM
The present invention relates to transdermal pharmaceutical compositions such as gels containing a SERM selected from the group consisting of endoxifen, droloxifene, clomifene, raloxifene, tamoxifen, 4-OH tamoxifen, toremifene, danazol and the pharmaceutically acceptable salts thereof, and to methods of making and using the same.
1 . A pharmaceutical composition for topical administration to a skin surface wherein said composition comprises:
(i) 0.01 to 10% (w/w) of endoxifen or a pharmaceutically acceptable salt thereof,
(ii) 60 to 80% (w/w) of at least one monoalcohol
(iii) 0 to 10% (w/w) of at least one penetration enhancer,
(iv) 0 to 5% (w/w) of at least one gelling agent,
(v) 0.01 to 30% (w/w) of at least one moisturizer, and
(vi) q.s. 100% (w/w) water.
2 . A pharmaceutical composition for topical administration to a skin surface wherein said composition comprises:
(i) 1 to 8% (w/w) of droloxifene or a pharmaceutically acceptable salt thereof,
(ii) 60 to 80% (w/w) of at least one monoalcohol
(iii) 0 to 10% (w/w) of at least one penetration enhancer
(iv) 0 to 5% (w/w) of at least one gelling agent,
(v) 0 to 30% (w/w) of at least one moisturizer and
(vi) q.s. 100% (w/w) water.
3 . A pharmaceutical composition for topical administration to a skin surface wherein said composition comprises:
(i) 3 to 7% (w/w) of clomifene or a pharmaceutically acceptable salt thereof,
(ii) 60 to 80% (w/w) of at least one monoalcohol,
(iii) 0 to 10% (w/w) of at least one penetration enhancer,
(iv) 0 to 5% (w/w) of at least one gelling agent,
(v) 0 to 30% (w/w) of at least one moisturizer, and
(vi) q.s. 100% (w/w) water.
4 . A pharmaceutical composition for topical administration to a skin surface wherein said composition comprises:
(i) 0.01 to 10% (w/w) of raloxifene or a pharmaceutically acceptable salt thereof,
(ii) 60 to 80% (w/w) of at least one monoalcohol,
(iii) 0 to 10% (w/w) of at least one penetration enhancer,
(iv) 0 to 5 (w/w) of at least one gelling agent,
(v) 0.01 to 30% (w/w) of at least one moisturizer, and
(vi) q.s. 100% (w/w) water.
5 . A pharmaceutical composition for topical administration to a skin surface wherein said composition comprises:
(i) 0.01 to 1% (w/w) of toremifene or a pharmaceutically acceptable salt thereof,
(ii) 60 to 80% (w/w) of at least one monoalcohol,
(iii) 0 to 10% (w/w) of at least one penetration enhancer,
(iv) 0 to 5 (w/w) of at least one gelling agent,
(v) 0.01 to 30% (w/w) of at least one moisturizer, and
(vi) q.s. 100% (w/w) water.
6 . A pharmaceutical composition according to claim 1 , wherein the composition comprises a penetration enhancer selected from the group consisting of oleic acid, propylene glycol and/or a mixture thereof.
7 .- 10 . (canceled)
11 . A dose packet, unit dose packet or multiple dose packet containing a pharmaceutical composition according to claim 1 .
12 . A dispenser, optionally with hand pump, containing a pharmaceutical composition according to claim 1 .
13 . A process for preparing a pharmaceutical composition according to claim 1 comprising preparing a mixture comprising:
(i) at least one monoalcohol,
(ii) endoxifen or a pharmaceutically acceptable salt thereof,
(iii) an aqueous vehicle,
(iv) optionally, at least one penetration enhancer,
(v) optionally, at least one gelling agent, and
(vi) optionally, at least one moisturizer.
14 . A method of administering a therapeutically effective amount of endoxifen or a pharmaceutically acceptable salt thereof, to a patient in need thereof, comprising topically administering to a surface of skin of said patient a pharmaceutical composition according to claim 1 .
15 . A method for treating a patient suffering from or at risk of developing a breast disorder comprising topically administering to a surface of skin of a patient in need thereof a therapeutically effective amount of a pharmaceutical composition according to claim 1 .
16 . A method according to claim 15 , wherein the breast disorder is selected from benign breast diseases, gynecomastia, breast cancer, mastalgia and conditions involving dense breast tissue.
17 . A method for treating a patient suffering from or at risk of estrogen imbalance, comprising topically administering to a surface of skin of said patient a pharmaceutical composition according to claim 1 .
18 . A pharmaceutical composition according to claim 1 , comprising 2 to 5% (w/w) of endoxifen or a pharmaceutically acceptable salt thereof.
19 . A pharmaceutical composition according to claim 1 , wherein the monoalcohol is selected from ethanol and isopropanol.
20 . A pharmaceutical composition according to claim 1 , wherein the gelling agent is selected from polyacrylic acids, cellulosics, and mixtures thereof.
21 . A pharmaceutical composition according to claim 1 , wherein the moisturizer is glycerine.