METHOD OF OBTAINING COMPOSITION OF ESTRADIOL WITH SLOW-BREAKDOWN (OPTIONS), ESTRADIOL AND CHOLESTEROL MICROSPHERE AND METHOD FOR SIMULTANEOUS CONTRACEPTION AND HORSE SUBSTITUTION

摘要

The present invention relates to a method for producing a slow-release estradiol composition, comprising: (a) creating particles consisting mainly of estradiol and cholesterol, where either or both of them are in amorphous or polymorphic form; (b) conducting atmospheric exposure to said particles at a relative humidity of about 25% or less for at least about 12 hours; (c) conducting exposure to an atmosphere saturated with acetone and water on said particles for at least about 48 hours at from about 50 to about 65 ° C; (d) drying the particles at from about 35 to about 50 ° C for about 24 hours or more; and (e) recovering said particles; where the dissolution rate of estradiol (SRE) of the reduced particles is less than about 15%. The invention also relates to microspheres of estradiol and cholesterol in a molar ratio of about 1: 1, having an EED of about 6% or less, and also to a method for simultaneous contraception and hormone replacement therapy. The slow release compositions of the present invention provide the dual benefits of a low dose estradiol composition with a low frequency administration regimen. The compositions may be administered parenterally once a month or less frequently.