Monolithic intravaginal rings comprising progesterone and methods of making and uses thereof

1. A method of manufacturing a monolithic intravaginal progesterone ring, comprising:

(a) mixing progesterone, a polysiloxane elastomer composition, and a pharmaceutically acceptable hydrocarbon or glycerol esters of a fatty acid or pharmaceutically acceptable oil, to form a homogeneous mixture;

(b) placing the homogeneous mixture into a mold; and

(c) curing the homogeneous mixture in the mold to form a monolithic intravaginal progesterone ring comprising about 10% to about 30% by weight of the progesterone, about 60% to about 80% by weight of polysiloxane elastomer, and about 1% to about 8% by weight of the pharmaceutically acceptable hydrocarbon or glycerol esters of fatty acid or pharmaceutically acceptable oil, wherein the progesterone is homogeneously dispersed in the elastomer.

2. The method of claim 1 , wherein the polysiloxane elastomer is a diorganopolysiloxane elastomer.

3. The method of claim 2 , wherein the diorganopolysiloxane elastomer is a dimethylpolysiloxane elastomer.

4. The method of claim 3 , wherein the dimethylpolysiloxane elastomer is vinyl end blocked.

5. The method of claim 3 , wherein the dimethylpolysiloxane elastomer further comprises a dimethylmethylhydrogen polysiloxane crosslink.

6. The method of claim 1 , wherein the polysiloxane elastomer composition comprises, as separate components, (i) dimethylpolysiloxane vinyl end-blocked polymer, non-crystalline trimethylsilyl treated fumed silica, and a platinum silicone complex and (ii) dimethylpolysiloxane vinyl end-blocked polymer, non-crystalline trimethylsilyl treated fumed silica, dimethylmethylhydrogen polysiloxane, and 2-methyl-3-butyn-2-ol.

7. The method of claim 6 , wherein step (a) comprises:

(a1) mixing a first portion of the progesterone, the polysiloxane elastomer composition component (i), and a first portion of the pharmaceutically acceptable hydrocarbon or glycerol esters of fatty acid or pharmaceutically acceptable oil, to form a first homogenous mixture;

(a2) mixing a second portion of the progesterone, the polysiloxane elastomer composition component (ii), and a second portion of the pharmaceutically acceptable hydrocarbon or glycerol esters of fatty acid or pharmaceutically acceptable oil, to form a second homogenous mixture; and

(a3) mixing the first homogenous mixture with the second homogenous mixture.

8. The method of claim 1 , wherein the pharmaceutically acceptable hydrocarbon or glycerol esters of fatty acid or pharmaceutically acceptable oil is selected from mineral oil, silicone oil, and combinations thereof.

9. The method of claim 1 , wherein the pharmaceutically acceptable hydrocarbon or glycerol esters of fatty acid or pharmaceutically acceptable oil is mineral oil.

10. The method of claim 1 , wherein the polysiloxane elastomer is a dimethylpolysiloxane elastomer, and wherein the ratio of progesterone to dimethylpolysiloxane elastomer to pharmaceutically acceptable hydrocarbon or glycerol esters of fatty acid in the ring is about 4:15:1.

11. The method of claim 1 , wherein step (b) comprises injecting the homogeneous mixture into the mold.

12. The method of claim 1 , wherein step (c) comprises curing at a temperature of from about 60° C. to about 180° C.

13. The method of claim 1 , wherein step (c) comprises curing at a temperature of from about 70° C. to about 150° C.

14. The method of claim 1 , wherein step (c) comprises curing at a temperature of from about 80° C. to about 120° C.

15. The method of claim 1 , wherein the intravaginal ring comprises:

(a) from about 15% to about 25% by weight of the progesterone;

(b) from about 70% to about 80% by weight of a dimethylpolysiloxane elastomer; and

(c) from about 1% to about 8% by weight of the pharmaceutically acceptable hydrocarbon or glycerol esters of a fatty acid or pharmaceutically acceptable oil.