Fentanyl Transdermal Delivery System
Described is a transdermal device comprising a backing layer; an adhesive matrix comprising fentanyl as an active agent suspended on a plurality of pressure sensitive adhesives along with a cross-linked moisture absorbent comprising cross-linked polyvinylpyrrolidone; and a release layer. Also described is a method of relieving pain, which comprising applying said transdermal device to the skin of a patient in need thereof.
1 . A transdermal delivery system comprising:
a backing layer;
an adhesive matrix comprising fentanyl, an analgetically effective relative of fentanyl, or mixtures thereof, a plurality of pressure sensitive adhesives selected from a silicone adhesive, a polyacrylate adhesive, and combinations thereof, and a cross-linked moisture absorbent comprising cross-linked polyvinylpyrrolidone; and
a release liner.
2 . The transdermal delivery system of claim 1 , wherein the fentanyl comprises crystals having a particle size (d 50 ) in a range of about 5 to 20 microns as measured by laser diffraction.
3 . The transdermal delivery system of claim 2 , wherein the particle size (d 50 ) is in the range of about 10 to about 15 microns.
4 . The transdermal delivery system of claim 1 , wherein the polyacrylate adhesive is present in the adhesive matrix in an amount in a range of about 1.0 to about 4.0% w/w.
5 . The transdermal delivery system of claim 1 , wherein the silicone adhesive is present in the adhesive matrix in an amount in a range of about 80 to about 90% w/w.
6 . The transdermal delivery system of claim 1 , wherein the fentanyl is present in the adhesive matrix in an amount in a range of about 3 to about 5% w/w.
7 . The transdermal delivery system of claim 1 , wherein the cross-linked polyvinylpyrrolidone is present in the adhesive matrix in an amount in a range of about 2 to about 6% w/w.
8 . The transdermal delivery system of claim 1 , wherein the silicone adhesive further comprises a silicone medical fluid.
9 . The transdermal delivery system of claim 8 , wherein the silicone medical fluid comprises dimethicone.
10 . The transdermal delivery system of claim 9 , wherein the dimethicone is present in the adhesive matrix in an amount in a range of about 2 to about 7% w/w.
11 . The transdermal delivery system of claim 1 , wherein the release liner comprises one or more of paper, coated paper, plastic films, polyolefins made of high density polyethylene (HDPE), low density polyethylene (LDPE), polypropylene (PP) plastic resin, fluoropolymer-coated films.
12 . The transdermal delivery system of claim 11 , wherein the release liner comprises LDPE.
13 . The transdermal delivery system of claim 11 , wherein the release liner comprises a fluoropolymer-coated polyethylene terephthalate (PET) film.
14 . The transdermal delivery system of claim 1 , wherein the backing layer comprises films of polyethylene, polyethylene terephthalate (PET), polypropylene, polyurethane, ethylene vinyl acetate (EVA) of polyamide, metal foils, or paper, alone or coated with a polymeric material, or mixtures thereof.
15 . The transdermal delivery system of claim 14 , wherein the backing layer comprises a PET-EVA laminate.
16 . The transdermal delivery system of claim 1 , wherein the backing layer has a thickness of less than about 2.5 mil.
17 . The transdermal delivery system of claim 1 , wherein the transdermal delivery system has reduced cold flow when compared to transdermal delivery systems that do not contain cross-linked polyvinylpyrrolidone.
18 . The transdermal delivery system of claim 1 , wherein the transdermal delivery system has skin flux in a range of about 2 to about 6 mcg/cm 2 /h.
19 . A transdermal delivery system comprising:
a backing layer;
an adhesive matrix comprising:
3.5 to 4.5% w/w fentanyl,
80 to 90% w/w silicone adhesive,
1 to 4% w/w polyacrylate adhesive, and
2 to 6% w/w cross-linked polyvinylpyrrolidone; and
a release liner.
20 . The transdermal delivery system of claim 19 , the adhesive matrix further comprising 2 to 7% w/w silicone medical fluid.
21 . A method of relieving pain comprising: applying to skin of a patient in need thereof the transdermal delivery system of claim 1 .
22 . A method of relieving pain comprising: applying to skin of a patient in need thereof the transdermal delivery system of claim 19 .