Bazedoxifene ascorbate

Abstract

The present invention is directed to bazedoxifene ascorbate, compositions containing the same, dispersions thereof, preparations thereof, and uses thereof.

1 . An ascorbic acid salt of bazedoxifene. 
   
   
       2 . A composition comprising the salt of  claim 1  and a pharmaceutically acceptable carrier. 
   
   
       3 . A method of preparing the salt of  claim 1  comprising combining bazedoxifene free base and ascorbic acid. 
   
   
       4 . The method of  claim 3  wherein about equimolar amounts of bazedoxifene free base and ascorbic acid are combined. 
   
   
       5 . The method of  claim 3  wherein said combining is carried out in a solvent. 
   
   
       6 . The method of  claim 5  wherein said solvent comprises an alcohol. 
   
   
       7 . The method of  claim 6  wherein said alcohol comprises ethanol. 
   
   
       8 . A salt prepared by the method of  claim 3 . 
   
   
       9 . A solid dispersion comprising the salt of  claim 1  and a dispersing agent. 
   
   
       10 . The solid dispersion of  claim 9  wherein said dispersing agent comprises a cellulose, hyaluronate, alginate, polysaccharide, heteropolysaccharide, poloxamers, poloxamines, ethylene vinyl acetate, polyethylene glycol, dextran, polyvinylpyrrolidone, chitosan, polyvinylalcohol, propylene glycol, polyvinylacetate, phosphatidylcholines, miglyol, polylactic acid, polyhydroxybutyric acid, mixture of two or more thereof or copolymer thereof. 
   
   
       11 . The solid dispersion of  claim 9  wherein said dispersing agent comprises polyvinylpyrrolidone. 
   
   
       12 . The solid dispersion of  claim 9  wherein the weight ratio of said salt to said dispersing agent is about 1:99 to about 99:1. 
   
   
       13 . The solid dispersion of  claim 9  wherein the weight ratio of said salt to said dispersing agent is about 1:99 to about 60:40. 
   
   
       14 . The solid dispersion of  claim 9  wherein the weight ratio of said salt to said dispersing agent is about 1:99 to about 10:90. 
   
   
       15 . The solid dispersion of  claim 9  wherein the weight ratio of said salt to said dispersing agent is about 5:95. 
   
   
       16 . The solid dispersion of  claim 9  wherein the weight ratio of said salt to said dispersing agent is about 40:60 to about 60:40. 
   
   
       17 . The solid dispersion of  claim 9  wherein the weight ratio of said salt to said dispersing agent is about 1:1. 
   
   
       18 . A method of preparing the solid dispersion of  claim 9  comprising:
 a) combining said salt and said dispersing agent in solution, wherein said solution comprises a solvent; and   b) removing said solvent to yield said solid dispersion.   
   
   
       19 . The method of  claim 18  wherein said solvent is an organic solvent. 
   
   
       20 . The method of  claim 19  wherein said organic solvent comprises an alcohol. 
   
   
       21 . The method of  claim 20  wherein said alcohol comprises ethanol. 
   
   
       22 . A solid dispersion prepared by the method of  claim 18 . 
   
   
       23 . A method of preparing the solid dispersion of  claim 9  comprising:
 a) combining said salt with melted dispersing agent to form a liquid mixture; and   b) solidifying said liquid mixture to form said solid dispersion.   
   
   
       24 . The method of  claim 23  wherein said melted dispersing agent is prepared by heating said dispersing agent to a temperature above about 30° C. 
   
   
       25 . The method of  claim 23  wherein said solidifying comprises cooling said liquid mixture to a temperature at or below about 25° C. 
   
   
       26 . A solid dispersion prepared by the method of  claim 23 . 
   
   
       27 . A composition comprising the solid dispersion of  claim 9  and a pharmaceutically acceptable carrier. 
   
   
       28 . A method of treating a mammal having a disease or syndrome associated with estrogen deficiency or excess of estrogen comprising administering to said mammal a therapeutically effective amount of the salt of  claim 1 . 
   
   
       29 . A method of treating a mammal having a disease or disorder associated with proliferation or abnormal development of endometrial tissues comprising administering to said mammal a therapeutically effective amount of the salt of  claim 1 . 
   
   
       30 . A method of lowering cholesterol in a mammal comprising administering to said mammal a therapeutically effective amount of the salt of  claim 1 . 
   
   
       31 . A method of inhibiting bone loss in a mammal comprising administering to said mammal a therapeutically effective amount of the salt of  claim 1 . 
   
   
       32 . A method of treating breast cancer in a mammal comprising administering to said mammal a therapeutically effective amount of the salt of  claim 1 . 
   
   
       33 . A method of treating postmenopausal woman for one or more vasomotor disturbances comprising administering to said postmenopausal woman a therapeutically effective amount of the salt of  claim 1 . 
   
   
       34 . The method of  claim 33  wherein said vasomotor disturbance is hot flush.