Transdermal analgesic systems with reduced abuse potential
A transdermal analgesic system having reduced potential for abuse, wherein the system provides for the controlled release of the antagonist at a rate sufficient to provide an abuse limiting release rate ratio of the antagonist to the analgesic when the dosage form is subject to abuse is disclosed.
1. A transdermal patch system for administering an analgesic through the skin, the system having a reduced potential for abuse, comprising:
(a) an analgesic reservoir layer comprising an analgesic, the analgesic being selected from the group consisting of fentanyl and analogs thereof;
(b) an antagonist reservoir layer comprising an antagonist for the analgesic that is dispersed within a polymer, wherein the antagonist is insoluble in the antagonist reservoir polymer, the antagonist reservoir layer comprising an external edge of the system;
(c) a barrier layer, the barrier layer separating the antagonist reservoir layer from the analgesic reservoir layer, the barrier layer being impermeable to the analgesic and to the antagonist; wherein the system (i) prevents release of the antagonist from the system upon securing the system to a human patient for a period of up to 7 days; and (ii) provides release of the antagonist at a rate sufficient to provide an abuse limiting release rate ratio of the antagonist to the analgesic upon ingestion or immersion of the system in a solvent.
2. The system of claim 1 , wherein the analgesic is selected from fentanyl, alfentanil, lofentanil, remifentanil, sufentanil and trefentanil.
3. The system of claim 1 , wherein the analgesic is fentanyl.
4. The system of claim 1 , wherein the analgesic is sufentanil.
5. The system of claim 1 , wherein the system further comprises:
(d) an antagonist release rate controlling means, wherein the antagonist release rate controlling means includes a rate control membrane, a porous or a microporous membrane, or an impermeable film wherein the release is controlled through the external edge of the system.
6. The system of claim 5 , wherein the antagonist release rate controlling means is disposed on the skin distal surface of the antagonist reservoir layer.
7. The system of claim 1 , wherein the analgesic reservoir layer comprises an amount of analgesic sufficient to induce and maintain analgesia in a human patient for a period of at least three days.
8. The system of claim 4 suitable for administration of the analgesic for at least 3 days and up to 7 days.
9. The system of claim 1 , wherein the analgesic reservoir layer comprises a single phase formulation free of undissolved components.
10. The system of claim 1 , wherein the analgesic reservoir layer comprises a polymer.
11. The system of claim 10 , wherein the polymer is an adhesive polymer.
12. The system of claim 10 , wherein the material forming the analgesic reservoir layer has a solubility for the analgesic of 1 wt % to 25 wt % of the total polymer composition.
13. The system of claim 12 , wherein the analgesic is fentanyl.
14. The system of claim 1 , wherein the analgesic reservoir layer comprises 0.05 to 1.75 mg/cm 2 of the analgesic.
15. The system of claim 1 , wherein the analgesic reservoir layer comprises a polymeric matrix comprising 1 wt % to 20 wt % of the analgesic, and a permeation enhancer.
16. The system of claim 15 , further comprising an analgesic release rate controlling means disposed between the analgesic reservoir layer and the skin, wherein the release rate controlling means is less permeable to the analgesic than to the permeation enhancer.
17. The system of claim 1 , wherein the antagonist reservoir layer is disposed on the skin distal surface of the barrier layer, and the analgesic reservoir layer is disposed on the skin proximal surface of the barrier layer.
18. The system of claim 1 , wherein the polymer of the antagonist reservoir layer is selected from polyolefin, polyethylene, polyoctene, polyvinyl acetate, polymethyl acrylate, polyethyl acrylate, polystyrene, polyethyleneoctene copolymers, ethylene-vinyl acetate copolymer (EVA), ethylenemethyl acrylate copolymers (EMA), ethylene-acrylic acid copolymer, and ethylene-ethylacrylate copolymer.
19. The system of claim 1 , wherein the system exhibits a standardized C max of 0.01 to 0.2 ng/ml-cm 2 .
20. The system of claim 1 , wherein the system exhibits a normalized C max of 3.3 to 82.5 ng/ml-(mg/h).
21. The system of claim 1 , wherein on administration over skin the transdermal analgesic system exhibits a steady state analgesic flux of 0.1 to 10 μg/h-cm 2 .