Salts of Zuclomiphene
The present invention provides salts of zuclomiphene and crystalline forms thereof. Specific salts of zuclomiphene provided by the present invention include sulphate, phosphate, succinate, L-tartrate, tosylate, L-malate, maleate, malonate, fumarate, glycolate, and hemi-citrate. Also provided are pharmaceutical compositions including the zuclomiphene salts and crystalline forms thereof and the use of these salts in the treatment of a disorder selected from the group including osteoporosis, bone fractures, loss of bone mineral density (BMD) and hot flashes in a subject suffering therefrom.
1 . A salt of zuclomiphene selected from the group consisting of zuclomiphene sulphate, zuclomiphene phosphate, zuclomiphene succinate, zuclomiphene L-tartrate, zuclomiphene tosylate, zuclomiphene L-malate, zuclomiphene maleate, zuclomiphene malonate, zuclomiphene fumarate, zuclomiphene glycolate, and zuclomiphene hemi-citrate.
2 . The sulphate salt of claim 1 , characterized by a PXRD diffractogram comprising peaks, expressed in degrees 2θ (±0.2°), at 5.2°, 14.6° and 20.6°.
3 . The sulphate salt of claim 2 , further comprising at least three peaks in the PXRD diffractogram, expressed in degrees 2θ (±0.2°), selected from the group consisting of: 10.0°, 10.3°, 12.2°, 12.4°, 12.9°, 15.1°, 16.0°, 17.4°, 22.2° and 22.9°.
4 . The sulphate salt of claim 2 , characterized by a DSC thermogram comprising an endothermic peak with a peak onset at approximately 152° C. and a peak maximum at approximately 155° C.
5 . The phosphate salt of claim 1 , characterized by a PXRD diffractogram comprising peaks, expressed in degrees 2θ (±0.2°), at 4.5°, 9.0° and 19.3°.
6 . The succinate salt of claim 1 , characterized by a PXRD diffractogram comprising peaks, expressed in degrees 2θ (±0.2°), at 5.5°, 10.1° and 17.3°.
7 . The L-tartrate salt of claim 1 , characterized by a PXRD diffractogram comprising peaks, expressed in degrees 2θ (±0.2°), at 6.0°, 9.0° and 12.0°.
8 . The tosylate salt of claim 1 , characterized by a PXRD diffractogram comprising peaks, expressed in degrees 2θ (±0.2°), at 5.6°, 11.1° and 18.1°.
9 . The L-malate salt of claim 1 , characterized by a PXRD diffractogram comprising peaks, expressed in degrees 2θ (±0.2°), at 6.4°, 12.8° and 22.5°.
10 . The maleate salt of claim 1 , characterized by a PXRD diffractogram comprising peaks, expressed in degrees 2θ (±0.2°), at 6.6°, 13.2° and 20.5°.
11 . The malonate salt of claim 1 , characterized by a PXRD diffractogram comprising peaks, expressed in degrees 2θ (±0.2°), at 6.8°, 13.6° and 18.2°.
12 . The fumarate salt of claim 1 , characterized by a PXRD diffractogram comprising peaks, expressed in degrees 2θ (±0.2°), at 6.9°, 13.9° and 17.9°.
13 . The glycolate salt of claim 1 , characterized by a PXRD diffractogram comprising peaks, expressed in degrees 2θ (±0.2°), at 6.0°, 9.0° and 18.2°.
14 . The hemi-citrate salt of claim 1 , characterized by a PXRD diffractogram comprising peaks, expressed in degrees 2θ (±0.2°), at 5.0°, 13.3° and 16.8°.
15 . The hemi-citrate salt of claim 14 , further comprising at least three peaks in the PXRD diffractogram, expressed in degrees 2θ (±0.2°), selected from the group consisting of: 9.5°, 10.9°, 14.6°, 15.7°, 18.2°, 20.2°, 20.9°, 21.6° and 24.0.
16 . The hemi-citrate salt of claim 14 , characterized by a DSC thermogram comprising an endothermic peak with a peak onset at approximately 82° C. and a peak maximum at approximately 86° C.
17 . A pharmaceutical composition comprising a salt of zuclomiphene according to claim 1 , and one or more pharmaceutically acceptable excipients.
18 . The pharmaceutical composition of claim 17 , wherein the pharmaceutical composition is a capsule or a tablet.
19 . A method for treating a disorder selected from the group consisting of osteoporosis, bone fractures, loss of bone mineral density (BMD) and hot flashes comprising administering an effective amount of a salt of claim 1 .
20 . The method of claim 19 , wherein the treatment comprises suppressing or inhibiting hot flashes in a male patient undergoing androgen deprivation therapy for the treatment of prostate cancer.