Soluble estradiol capsule for vaginal insertion

Abstract

According to various embodiments of this disclosure, pharmaceutical formulations comprising solubilized estradiol are provided. In various embodiments, such formulations are encapsulated in soft capsules which may be vaginally inserted for the treatment of vulvovaginal atrophy

1 . A method of treating a symptom of vulvovaginal atrophy in a female human patient in need thereof, the method comprising administering to the female human a soft gelatin capsule intravaginally once daily for 14 days and one capsule twice weekly thereafter, the soft gelatin capsule comprising 1 to 10 mcg estradiol and a solubilizing means for solubilizing the estradiol, wherein
 administering the soft gelatin capsule intravaginally to the female human in need thereof provides an estradiol AUC and estradiol C max  that are each 80% to 125% of the estradiol AUC and estradiol Cmax obtained upon intravaginal administration of a reference soft gelatin capsule in a reference human female patient, the reference soft gelatin capsule consisting of a soft gelatin shell and a reference fill material within the soft gelatin shell, wherein the reference fill material consists of
 approximately 270 mg of a C8 to C10 triglyceride composition containing at least about 80 percent by weight of a mixture of caprylic acid and capric acids; 
 approximately 30 mg of a surfactant containing a mixture of PEG-6 stearate, PEG-32 stearate, and ethylene glycol palmitostearate; and 
 1 to 10 mcg of estradiol 
 further wherein the reference fill material has a viscosity of between 50 to 1000 cP as measured at 25° C. 
   
     
     
         2 . The method of  claim 1 , wherein the symptom of vulvovaginal atrophy is dyspareunia. 
     
     
         3 . The method of  claim 1 , wherein the soft gelatin capsule disintegrates in the patient's vagina leaving minimal to no capsule residue. 
     
     
         4 . The method of  claim 1 , wherein the soft gelatin capsule and the reference soft gelatin capsule have substantially similar shapes and sizes. 
     
     
         5 . The method of  claim 4 , wherein the soft gelatin capsule and the reference soft gelatin capsule have identical shapes and sizes. 
     
     
         6 . The method of  claim 1 , wherein administering the soft gelatin capsule does not substantially raise circulating estradiol blood levels of the patient following administration.