Steroid hormone pharmaceutical formulations

Abstract

This disclosure provides pharmaceutical compositions for delivering estradiol to a subject in need thereof, as well as methods of administering the compositions, and methods of using them.

1 . A vaginal insert comprising a therapeutically effective amount of estradiol; and a solubilizing agent, wherein the solubilizing agent comprises at least one C 2 -C 5  fatty acid or a glycol ester, monoglyceride, diglyceride, or triglyceride thereof. 
     
     
         2 . The vaginal insert of  claim 1 , wherein the therapeutically effective amount of estradiol is from about 1 microgram to about 25 micrograms. 
     
     
         3 .- 6 . (canceled) 
     
     
         7 . The vaginal insert of  claim 1 , further comprising a second solubilizing agent selected from the group consisting of a mixture of PEG-6 stearate, ethylene glycol palmitostearate, and PEG-32 stearate; a mixture of hard fat, glyceryl ricinoleate, ceteth-20, and steareth-20; polyoxyl 40 hydrogenated castor oil USP; hard fat polyoxyl 20 cetostearyl ether; and combinations thereof. 
     
     
         8 . The vaginal insert of  claim 7 , wherein the second solubilizing agent is a mixture of PEG-6 stearate, ethylene glycol palmitostearate, and PEG-32 stearate. 
     
     
         9 . The vaginal insert of  claim 1 , wherein the viscosity of the composition is about 5 cP to about 3000 cP at room temperature. 
     
     
         10 . (canceled) 
     
     
         11 . The vaginal insert of  claim 1 , wherein the insert further comprises a capsule encapsulating the therapeutically effective amount of estradiol and the solubilizing agent. 
     
     
         12 . (canceled) 
     
     
         13 . The vaginal insert of  claim 1 , wherein the solubilizing agent comprises at least one C 3  fatty acid or a glycol mono- or di-ester thereof, a monoglyceride, diglyceride, or triglyceride thereof, or a combination of any of the foregoing. 
     
     
         14 . A vaginal insert comprising:
 (a) a therapeutically effective amount of estradiol;   (b) a first solubilizing agent comprising one or more polyethylene glycol mono- or di-esters of a hydroxy C 16 -C 26  fatty acid; and   (c) a second solubilizing agent comprising a mixture of PEG-6 stearate, ethylene glycol palmitostearate, and PEG-32 stearate.   
     
     
         15 . The vaginal insert of  claim 14 , wherein the therapeutically effective amount of estradiol is from about 1 microgram to about 25 micrograms. 
     
     
         16 .- 20 . (canceled) 
     
     
         21 . The vaginal insert of  claim 14 , wherein the insert further comprises a capsule encapsulating the estradiol, the first solubilizing agent, and the second solubilizing agent. 
     
     
         22 . (canceled) 
     
     
         23 . A vaginal insert comprising:
 (d) a therapeutically effective amount of estradiol;   (e) a first solubilizing agent comprising propylene glycol monolaurate; and   (f) a second solubilizing agent comprising polyoxyl 40 hydrogenated castor oil USP.   
     
     
         24 . The vaginal insert of  claim 23 , wherein the therapeutically effective amount of estradiol is from about 1 microgram to about 25 micrograms. 
     
     
         25 .- 28 . (canceled) 
     
     
         29 . The vaginal insert of  claim 23 , wherein the viscosity of the composition is about 5 cP to about 3000 cP at room temperature. 
     
     
         30 . (canceled) 
     
     
         31 . The vaginal insert of  claim 23 , wherein the insert further comprises a capsule encapsulating the estradiol, the first solubilizing agent, and the second solubilizing agent. 
     
     
         32 . (canceled) 
     
     
         33 . A method of treating an estrogen-deficient state, comprising administering to a female in need thereof, the vaginal insert of  claim 1 . 
     
     
         34 . (canceled) 
     
     
         35 . The method of  claim 33 , wherein the estrogen-deficient state is selected from the group consisting of vulvovaginal atrophy, dysuria, dyspareunia, estrogen-deficient urinary state, and vaginal bleeding associated with sexual activity. 
     
     
         36 . (canceled) 
     
     
         37 . A method of treating an estrogen-deficient state, comprising administering to a female in need thereof, the vaginal insert of  claim 14 . 
     
     
         38 . (canceled) 
     
     
         39 . The method of  claim 37 , wherein the estrogen-deficient state is selected from the group consisting of vulvovaginal atrophy, dysuria, dyspareunia, estrogen-deficient urinary state, and vaginal bleeding associated with sexual activity. 
     
     
         40 . (canceled) 
     
     
         41 . A method of treating an estrogen-deficient state, comprising administering to a female in need thereof, the vaginal insert of  claim 23 . 
     
     
         42 . (canceled) 
     
     
         43 . The method of  claim 41 , wherein the estrogen-deficient state is selected from the group consisting of vulvovaginal atrophy, dysuria, dyspareunia, estrogen-deficient urinary state, and vaginal bleeding associated with sexual activity. 
     
     
         44 . (canceled)