Transdermal delivery system for the administration of rotigotine
An improved Transdermal Delivery System (TDS) comprising a backing layer inert to the components of the matrix, a self-adhesive matrix containing rotigotine and a protective foil or sheet to be removed prior to use, characterized in that the self-adhesive matrix consists of a solid or semi-solid semi-permeable polymer (1) wherein rotigotine in its free base form has been incorporated, (2) which is saturated with rotigotine and contains said rotigotine as a multitude of microreservoirs within the matrix, (3) which is highly permeable for the free base of rotigotine, (4) which is impermeable for the protonated form of rotigotine, (5) wherein the maximum diameter of the microreservoirs is less than the thickness of the matrix. is provided. Said TDS provides for enhanced flux of rotigotine across the TDS/skin interface.
1. A transdermal delivery system (TDS) comprising a self-adhesive matrix of a thickness and a backing layer,
wherein the self-adhesive matrix comprises (1) a solid or semi-solid semi-permeable polymer matrix and (2) microreservoirs comprising rotigotine as free base;
wherein the polymer matrix comprises up to about 10% w/w of protonated rotigotine;
wherein the polymer matrix is permeable to unprotonated rotigotine and substantially impermeable to protonated rotigotine; and
wherein the microreservoirs have a maximum diameter up to 70% of the thickness of the self-adhesive matrix.
2. The TDS of claim 1 , wherein the microreservoirs have a maximum diameter in the range of 5% to 60% of the thickness of the self-adhesive matrix.
3. The TDS of claim 1 , wherein the microreservoirs have a maximum diameter up to 35 μm.
4. The TDS of claim 1 , wherein the polymer matrix comprises greater than 5% to about 10% w/w of protonated rotigotine.
5. The TDS of claim 1 , wherein said free base is produced in situ.
6. The TDS of claim 1 , wherein said free base is isolated prior to its incorporation into the self-adhesive matrix.
7. The TDS of claim 1 , wherein the polymer matrix comprises a silicone-containing pressure sensitive adhesive.
8. The TDS of claim 1 , wherein the polymer matrix comprises two or more silicone-containing pressure sensitive adhesives.
9. The TDS of claim 8 , wherein the two or more silicone-containing pressure sensitive adhesives comprise a blend of a high tack silicone-type pressure sensitive adhesive comprising polysiloxane with a resin and a medium tack silicone-containing pressure sensitive adhesive comprising polysiloxane with a resin.
10. The TDS of claim 1 , wherein the self-adhesive matrix comprises 10 3 to 10 9 microreservoirs per cm 2 of the self-adhesive matrix surface.
11. The TDS of claim 10 , wherein the self-adhesive matrix comprises 10 6 to 10 9 microreservoirs per cm 2 of the self-adhesive matrix surface.
12. The TDS of claim 1 , wherein the self-adhesive matrix is free of particles that can absorb salts of rotigotine at the TDS/skin interface.
13. The TDS of claim 1 , further comprising at least one crystallization inhibitor comprising soluble polyvinylpyrrolidone, a copolymer of polyvinylpyrrolidone and vinyl acetate, polyethylene glycol, polypropylene glycol, glycerol, a fatty acid ester of glycerol and/or a copolymer of ethylene and vinyl acetate.
14. The TDS of claim 13 , wherein the at least one crystallization inhibitor comprises soluble polyvinylpyrrolidone.
15. A transdermal delivery system (TDS) comprising a self-adhesive matrix of a thickness and a backing layer,
wherein the self-adhesive matrix comprises (1) a solid or semi-solid semi-permeable polymer matrix and (2) microreservoirs comprising rotigotine as free base;
wherein the polymer matrix comprises up to about 10% w/w of protonated rotigotine;
wherein the polymer matrix is permeable to unprotonated rotigotine and substantially impermeable to protonated rotigotine; and
wherein the microreservoirs have a mean diameter in the range of 1% to 40% of the thickness of the self-adhesive matrix.
16. The TDS of claim 15 , wherein the microreservoirs have a mean diameter in the range of 1% to 20% of the thickness of the self-adhesive matrix.
17. The TDS of claim 15 , wherein the microreservoirs have a mean diameter from about 0.5 μm to 20 μm.
18. The TDS of claim 15 , wherein the polymer matrix comprises greater than 5% to about 10% w/w of protonated rotigotine.
19. The TDS of claim 15 , wherein said free base is produced in situ.
20. The TDS of claim 15 , wherein said free base is isolated prior to its incorporation into the self-adhesive matrix.
21. The TDS of claim 15 , wherein the polymer matrix comprises a silicone-containing pressure sensitive adhesive.
22. The TDS of claim 15 , wherein the self-adhesive matrix comprises 10 3 to 10 9 microreservoirs per cm 2 of the self-adhesive matrix surface.
23. The TDS of claim 22 , wherein the self-adhesive matrix comprises 10 6 to 10 9 microreservoirs per cm 2 of the self-adhesive matrix surface.
24. The TDS of claim 15 , wherein the self-adhesive matrix is free of particles that can absorb salts of rotigotine at the TDS/skin interface.
25. The TDS of claim 15 , further comprising at least one crystallization inhibitor comprising soluble polyvinylpyrrolidone, a copolymer of polyvinylpyrrolidone and vinyl acetate, polyethylene glycol, polypropylene glycol, glycerol, a fatty acid ester of glycerol and/or a copolymer of ethylene and vinyl acetate.
26. The TDS of claim 25 , wherein the at least one crystallization inhibitor comprises soluble polyvinylpyrrolidone.
27. A method for treatment of a patient suffering from a disease treatable with rotigotine, comprising applying the TDS of claim 1 to the skin of the patient.
28. The method of claim 27 , wherein the disease treatable with rotigotine is Parkinson's Disease.
29. A method for treatment of a patient suffering from a disease treatable with rotigotine, comprising applying the TDS of claim 15 to the skin of the patient.
30. The method of claim 29 , wherein the disease treatable with rotigotine is Parkinson's Disease.