Fentanyl suspension-based silicone adhesive formulations and devices for transdermal delivery of fentanyl
Silicone adhesive formulations are provided, in which fentanyl particles are suspended one or more a solvated silicone adhesives. The formulations can be used for manufacturing improved, matrix-type transdermal devices for administering fentanyl.
1 . A monolithic patch for administering fentanyl transdermally to an individual, comprising:
(a) a backing layer substantially impervious to the fentanyl to be administered transdermally;
(b) a fentanyl-containing adhesive layer in contact with at least a portion of the backing layer, the adhesive layer being cast from a formulation comprising a blend of fentanyl particles suspended in one or more solvated silicone adhesives; and
(c) a removable release liner in contact with the adhesive layer.
2 . The patch of claim 1 , wherein the one or more solvated silicone adhesives is a heptane-solvated silicone adhesive.
3 . The patch of claim 2 , wherein the adhesive layer comprises about 1% to about 10% w/w fentanyl.
4 . The patch of claim 3 , wherein the adhesive layer comprises about 3% to about 7% w/w fentanyl.
5 . The patch of claim 4 , wherein the adhesive layer comprises about 4% w/w fentanyl.
6 . The patch of claim 2 , wherein the adhesive layer comprises about 5% to about 15% w/w fentanyl.
7 . The patch of claim 6 , wherein the adhesive layer comprises about 8% to about 12% w/w fentanyl.
8 . The patch of claim 7 , wherein the adhesive layer comprises about 9.5% w/w fentanyl.
9 . The patch of claim 8 , wherein the adhesive layer comprises about 9.1% w/w fentanyl.
10 . The patch of claim 1 , wherein the fentanyl is the fentanyl free base.
11 . The patch of claim 1 , wherein the backing layer is a polyolefin.
12 . The patch of claim 1 , wherein the fentanyl is suspended uniformly in the solvated silicone adhesives as small particles.
13 . The patch of claim 1 , wherein the fentanyl-containing adhesive layer is cast from a formulation comprising a blend of a slurry of fentanyl in a silicone fluid blended with one or more solvated silicone adhesives.
14 . The patch of claim 13 , wherein the fentanyl-containing layer comprises up to about 25% w/w silicone fluid.
15 . The patch of claim 14 , wherein the fentanyl-containing layer comprises about 2% to about 10% w/w silicone fluid.
16 . The patch of claim 15 , wherein the fentanyl-containing layer comprises about 6.5% w/w silicone fluid.
17 . The patch of claim 13 , wherein the silicone fluid comprises polydimethylsiloxane.
18 . The patch of claim 1 , which further comprises a fentanyl-free adhesive layer between and in contact with said backing layer and said fentanyl-containing adhesive layer which extends at least partially beyond said fentanyl-containing adhesive layer.
19 . The patch of claim 18 , wherein the fentanyl-containing adhesive layer is cast from a formulation comprising a blend of a slurry of fentanyl in a silicone fluid blended with one or more solvated silicone adhesives.
20 . The patch of claim 19 , wherein the fentanyl-containing layer comprises up to about 25% w/w silicone fluid.
21 . A method for making a laminate, which is useful for making a monolithic patch for transdermal administration of fentanyl, comprising:
a) selecting a solvent that can substantially or fully solvate a silicone adhesive while keeping fentanyl, when blended with the solvated adhesive, suspended in the solvated adhesive;
b) blending fentanyl particles with one or more silicone adhesives which are solvated with the above solvent, to form a blend formulation in which fentanyl particles are suspended in the solvated adhesives;
c) casting the blend formulation onto a support material; and
d) removing the solvent, to produce a laminate containing the support material and a fentanyl suspension-containing adhesive layer.
22 . The method of claim 21 , wherein the support material is a backing layer or release liner.
23 . The method of claim 21 , wherein the blend formulation is treated prior to the casting step to disperse the fentanyl throughout the formulation and particle size is maintained by passing the formulation through a mixing device.
24 . The method of claim 21 , wherein the solvent is heptane.
25 . The method of claim 24 , wherein the silicone adhesive is solvated in about 20% to about 50% heptane.
26 . The method of claim 25 , wherein the silicone adhesive is solvated in about 30% heptane.
27 . The method of claim 21 , wherein the fentanyl is the fentanyl free base.
28 . The method of claim 21 , wherein fentanyl particles are suspended uniformly in the solvated silicone adhesives as small particles.
29 . A method for making a laminate, which is useful for making a monolithic patch for transdermal administration of fentanyl, comprising:
a) selecting a solvent that can substantially or fully solvate a silicone adhesive while keeping fentanyl particles, when blended with the solvated adhesive, suspended in the solvated adhesive;
b) solvating said silicone adhesive in said solvent;
c) forming a slurry of fentanyl particles in a silicone fluid;
d) blending the slurry from step c) with the solvated silicone adhesive of step b) so as to form a blend formulation in which fentanyl particles are suspended in the solvated adhesive;
e) casting the blend formulation onto a support material; and
f) removing the solvent to produce a laminate containing the support material and a fentanyl suspension-containing adhesive layer.
30 . The method of claim 29 , wherein the support material is a backing layer or release liner.
31 . The method of claim 29 , wherein the solvated silicone adhesive is divided into a first portion and a second portion, the slurry of fentanyl particles is blended with a first portion of the solvated silicone adhesive, the resulting blend is passed through a mixing device to form a suspension, and the resulting suspension is blended with the second portion of the solvated silicone adhesive.
32 . The method of claim 29 , wherein the solvent is heptane.
33 . The method of claim 32 , wherein the silicone adhesive is solvated in about 20% to about 50% heptane.
34 . The method of claim 29 , wherein the fentanyl is fentanyl free base.
35 . The method of claim 29 , wherein fentanyl particles are suspended uniformly in the solvated silicone adhesive as small particles.
36 . A method for administering fentanyl transdermally to an individual in need of such administration, comprising applying to the skin of the individual a monolithic patch comprising:
(a) a backing layer substantially impervious to the fentanyl to be administered transdermally; and
(b) a fentanyl-containing adhesive layer in contact with the backing layer, the adhesive layer being cast from a formulation comprising a blend of fentanyl suspended in one or more solvated silicone adhesives.
37 . The method of claim 36 , wherein the solvated silicone adhesives are heptane-solvated silicone adhesives.
38 . The method of claim 37 , wherein the adhesive layer comprises about 1% to about 10% w/w fentanyl.
39 . The method of claim 38 , wherein the adhesive layer comprises about 3% to about 7% w/w fentanyl.
40 . The method of claim 39 , wherein the adhesive layer comprises about 4% w/w fentanyl.
41 . The method of claim 40 , wherein the fentanyl is administered transdermally for a period of about 3 days.
42 . The method of claim 37 , wherein the adhesive layer comprises about 5% to about 15% w/w fentanyl.
43 . The method of claim 42 , wherein the adhesive layer comprises about 8% to about 12% fentanyl.
44 . The method of claim 43 , wherein the adhesive layer comprises about 9.5% w/w fentanyl.
45 . The method of claim 37 , wherein the adhesive layer comprises about 9.1% w/w fentanyl.
46 . The method of claims 44 , wherein the fentanyl is administered transdermally for a period of about 7 days.
47 . The method of claims 45 , wherein the fentanyl is administered transdermally for a period of about 7 days.
48 . The method of claim 36 , wherein the fentanyl is the fentanyl free base.
49 . The method of claim 36 , wherein the fentanyl-containing adhesive layer is cast from a formulation comprising a blend of a slurry of fentanyl in silicone fluid blended with one or more solvated silicone adhesives.
50 . The method of claim 49 , wherein the fentanyl-containing adhesive layer comprises up to about 25% w/w silicone fluid.
51 . The method of claim 50 , wherein the fentanyl-containing adhesive layer comprises about 2% to about 10% w/w silicone fluid.
52 . The method of claim 51 , wherein the fentanyl-containing adhesive layer comprises about 6.5% w/w silicone fluid.
53 . The method of claim 48 , wherein fentanyl particles are suspended uniformly in the solvated silicone adhesives as small particles.
54 . The method of claim 36 , wherein the backing layer is a polyolefin.
55 . The method of claim 23 , wherein said mixing device comprises a high shear colloid mill or homogenizer.