Drug delivery system based on polyethylene vinylacetate copolymers

1. A drug delivery system consisting of one or more compartments, said compartments comprise a progestogenic compound dissolved in a thermoplastic polyethylene vinylacetate copolymer whereby,

if the delivery system consists of one compartment, the compartment comprises

(i) a core of a thermoplastic polyethylene vinylacetate copolymer containing 30 to 50 wt % vinylacetate comprising the progestogenic compound, the progestogenic compound being dissolved in the polyethylene vinylacetate copolymer at a concentration below the saturation level at 25° C. between 0.1 and 1.0 wt %, based on the weight of the core, and an estrogenic compound; and

(ii) a skin of a thermoplastic polyethylene vinylacetate copolymer covering the core, the copolymer containing 1 to 15 wt % vinylacetate, the skin being permeable for both compounds, and the skin having a thickness in the range of 10 to 110 μm;

if the delivery system consists of more than one compartment, only one compartment comprises

(iii) the progestogenic compound, the progestogenic compound being dissolved in a core of a thermoplastic polyethylene vinylacetate copolymer containing 30 to 50 wt % vinylacetate at a concentration below the saturation level at 25° C. between 0.1 and 1.0 wt %, based on the weight of the core, and an estrogenic compound; and

(iv) a skin of a thermoplastic polyethylene vinylacetate copolymer covering the core, the copolymer containing 1 to 15 wt % vinylacetate, the skin being permeable for both compounds, and the skin having a thickness in the range of 10 to 110 μm,

wherein the drug delivery system is physically stable when stored at or above room temperature.

2. A drug delivery system according to claim 1 , wherein the progestogenic compound is a steroidal progestogenic compound and/or the estrogenic compound is a steroidal estrogenic compound.

3. A drug delivery system according to claim 1 , wherein the polyethylene vinylacetate copolymer of the core is a copolymer containing 30 to 50 wt % vinylacetate.

4. A drug delivery system according to claim 1 , wherein the progestogenic compound is etonogestrel.

5. A drug delivery system according to claim 4 wherein the release on day 21 of etonogestrel of the drug delivery system is 80 μg/day or more.

6. A drug delivery system according to claim 1 , wherein the estrogenic compound is ethinyl estradiol.

7. A drug delivery system according to claim 1 , wherein the system is ring-shaped.

8. A drug delivery system according to claim 1 , wherein the drug delivery system consists of one compartment.

9. A drug delivery system according to claim 1 , wherein the drug delivery system is a drug delivery system for intravaginal use.

10. A contraceptive kit or kit for hormone-replacement therapy comprising the drug delivery system according to claim 1 .

11. A combination preparation to provide contraception whilst simultaneously to treat a sexually transmitted disease comprising the drug delivery system according to claim 1 .

12. A drug delivery system according to claim 3 , wherein the skin has a thickness in the range of 20 to 100 μm.

13. A drug delivery system according to claim 3 wherein the skin has a thickness in the range of 30 to 70 μm.

14. A drug delivery system according to claim 3 , wherein the polyethylene vinylacetate copolymer of the skin is a copolymer containing 1 to 14 wt % vinylacetate.

15. A drug delivery system according to claim 3 , wherein the polyethylene vinylacetate copolymer of the skin is a copolymer containing 1 to 12 wt % vinylacetate.

16. A drug delivery system consisting of one or more compartments, said compartments comprise a progestogenic compound dissolved in a thermoplastic polyethylene vinylacetate copolymer whereby,

if the delivery system consists of one compartment, the compartment comprises

(i) a core of a thermoplastic polyethylene vinylacetate copolymer, the copolymer containing 32 to 50 wt % vinylacetate, and the core comprising a progestogenic compound, the progestogenic compound being dissolved in the polyethylene vinylacetate copolymer at a concentration below the saturation level at 25° C. between 0.1 and 1.0 wt %, based on the weight of the core, and an estrogenic compound; and

(ii) a skin of a thermoplastic polyethylene vinylacetate copolymer covering the core, the copolymer containing 14 to 28 wt % vinylacetate, the skin being permeable for both compounds, and the skin having a thickness of 70 to 250 μm;

if the delivery system consists of more than one compartment, only one compartment comprises

(iii) the progestogenic compound, the progestogenic compound being dissolved in a core of a thermoplastic polyethylene vinylacetate copolymer at a concentration below the saturation level at 25° C. between 0.1 and 1.0 wt %, based on the weight of the core, the copolymer containing 32 to 50 wt % vinylacetate, and an estrogenic compound; and

(iv) a skin of a thermoplastic polyethylene vinylacetate copolymer covering the core, the copolymer containing 14 to 28 wt % vinylacetate, the skin being permeable for both compounds, and the skin having a thickness of 70 to 250 μm

wherein the drug delivery system is physically stable when stored at or above room temperature.

17. A drug delivery system according to claim 16 , wherein the skin has a thickness in the range of 110 to 250 μm.

18. A drug delivery system according to claim 16 , wherein the polyethylene vinylacetate copolymer of the skin is a copolymer containing 16 to 25 wt % vinylacetate.

19. A method of manufacturing a drug delivery system according to claim 7 comprising the steps of:

(i) producing a medicated homogenous polyethylene vinylacetate copolymer core granulate, comprising a progestogenic and an estrogenic compound;

(ii) co-extruding the core granulate with a polyethylene vinylacetate copolymer skin granulate, resulting in a copolymer fiber comprising a core covered by a skin; and

(iii) assembling the fibre into a ring.

20. A method according to claim 19 , wherein the core granulate in step (i) is lubricated with a lubricant.

21. A method of contraception in a female patient, the method comprising:

(a) positioning a drug delivery system of claim 1 within the vaginal tract of the patient; and

(b) retaining the system within the vaginal tract for approximately 21 days.