Title of Invention

AN ASSEMBLY FOR ADHESIVE ATTACHMENT TO THE SKIN OR MUCOSA A STACKED PLURALITY OF COMPONENTS FOR THE MANUFACTURE THEREOF, AND A SYSTEM FOR HANDLING OF

Abstract The invention relates to an assembly for adhesive attachment to the skin or mucosa of a host. Said assembly includes an outer backing layer (112) including an inner surface and an outer surface, a first layer of adhesive (110) disposed on said inner surface of said outer backing layer (112), an inner backing layer (124) including an inner surface and an outer surface, a second layer of adhesive (122) disposed on said inner surface of said inner backing layer (124) for adhesive attachment of said assembly to said skin or mucosa of said host. An intermediate release liner (104) disposed between said first layer of adhesive (110) and said outer surface of said inner backing layer (124), said intermediate release liner (104) including an inner surface and an outer surface is also disclosed. Both said inner surface and said outer surface of said intermediate release liner (104) includes a releasable surface. Said intermediate release liner (104) further includes at least one open area (114), and wherein said first adhesive layer includes a portion adhesively bonded to and in direct contact with said outer surface of said liner backing layer at said at least one open area and the remaining portion of said first adhesive layer temporarily covered by said intermediate release liner (104). The invention provides transdermal patch systems for use in the application of active agents to a patient or host.
Full Text The present invention relates to an assembly for adhesive
attachment to the skin or mucosa, a stacked plurality of components
for the manufacture thereof, and a system for handling of a plurality
of adhesive coated elements
[0001] The present application claims the benefit of Application
Serial No. 11/296,604, filed December 7, 2005, entitled TWO-SIDED NON-
STICK RELEASE FILM, the disclosure of which is hereby incorporated
herein by reference.
BACKGROUND OF THE INVENTION
[0002] The present invention relates in general to an assembly for
adhesive attachment to the skin or mucosa of a host. More
particularly, the present invention relates to transdermal patches and
wound dressings, and to methods for their manufacture. Still more
particularly, the present invention relates to improvements in the
manufacture of adhesive patches.
[0003] The use of various systems for adhesive attachment to the
skin or mucosa of a patient or host has become increasingly
significant. These assemblies can be in the form of wound dressings
for direct adhesive application to the skin, without any active agent
therein, or transdermal patches for the transdermal delivery of
various active agent or drug systems in connection with such
attachment. In connection with the general means for preparing such
assemblies, there has been an increase in the need to facilitate the
handling of adhesive containing assemblies or patches, and for then
maintaining them as separable units. In connection with transdermal
patch systems, there have been problems engendered by the use of
various drugs in which the drug is employed in admixture with an
adhesive-based system for application to the skin, or with a non-
adhesive-based system with an outer drug permeable adhesive layer.
[0004] Simple monolithic transdermal systems incorporate their active
agents, i.e., drugs, directly into a single pressure-sensitive
adhesive layer. These systems have the advantage of being thin,
elegant, and relatively easy to manufacture, but must compromise
between optimizing the adhesive matrix for drug delivery versus its
ability to adhere to the skin. In addition, these systems still
present challenges in connection with their large volume handling and
manufacture.

[0005] The known "double-disk" transdermal patch uses a larger
auxiliary patch over a smaller active agent delivery patch to
improve or ensure adhesion to the skin. The adhesive matrixes of
the inner and outer patches can be independently optimized for
active agent delivery and adhesion, respectively. When the inner
and outer patches are laminated together to form the completed
system, their adhesive matrixes come into direct contact and
begin to equilibrate. As the systems equilibrate, time-dependent
changes occur such as the loss of active agents from the inner
patch and the simultaneous accumulation of active agents in the
outer patch. This phenomena can alter the performance of the
transdermal patch if any of the components in the inner patch,
especially those that are needed to achieve or sustain active
agent delivery, have appreciable affinity for the outer patch
adhesive matrix. Moreover, this effect will become more profound
with time until equilibrium is achieved.
[0006] One solution, in preventing the equilibrium of the two
adhesive matrixes is to maintain their physical separation, and
not to allow the adhesivea to come into direct contact with each
other during storage. Following application to the skin, these
adhesive matrixes will be in direct contact, but the equilibrium
process, typically two-three years, is slow compared to the
transdermal delivery process, generally less than or equal to
seven days. However, in the double-disk transdermal patch, the
circumferential edge of the inner patch containing the active
agent is exposed to the overlying outer patch and its adhesive
matrix. This structure of the double-disk transdermal patch
allows for the circumferential migration of active agent from the
inner patch into the adhesive matrix of the outer patch.
[0007] A solution to some of these problems is set forth in
U.S. Patent Publication No. 2005/0037059, which is owned by the
assignee of the present application. This application discloses
the use of a physical barrier between the patches during storage
so that the migration of active agents is inhibited between the
inner and outer patches. In accordance with this disclosure, the
inner and outer patches are adhered together in a manner creating
an annular flap circumferentially about the outer portion of the
inner patch and a disposable release liner is interposed between
the annular flap and the adhesive material of the outer patch.
The outer flap, which contains the active agent, is thus said to
be isolated from the underlying portion of the outer portion by
the release liner which is releasably attached to the adhesive on
the outer patch. This product has proven to be quite successful,
but a desire still exists for a more efficient product for
completely segregating the annular flap containing the active
agent from the underlying portion of the outer patch.
SUMMARY OF THE INVENTION
[0008] In accordance with the present invention, these and
other objects have now been realized by the discovery of an
assembly for adhesive attachment to the skin or mucosa of a host,
the assembly comprising an outer backing layer including an inner
surface and an outer surface, a first layer of adhesive disposed
on the inner surface of the outer backing layer, an inner backing
layer, and an intermediate release liner disposed between the
first layer of adhesive and the inner backing layer, the
intermediate release liner including an inner surface and an
outer surface, both the inner surface and the outer surface of
the intermediate release liner including a releasable surface.
Preferably, the intermediate release liner includes at least one
open area and the first adhesive layer includes a portion adhered
to the inner backing layer at the at least one open area.
[0009] In accordance with one embodiment of the assembly of
the present invention, the intermediate release liner comprises a
single sheet having the releasable surfaces disposed on both
sides of the single sheet.
[0010] In accordance with another embodiment of the assembly
of the present invention, the intermediate release liner
comprises a laminate including at least a pair of sheets affixed
to each other, each of the pair of sheets including an inner
surface and an outer surface, each inner surface of the pair of
sheets being juxtaposed with each other and each of the outer
surfaces of the pair of sheets including the releasable surface.
[0011] In accordance with another embodiment of the assembly
of the present invention, the intermediate release liner
comprises an active agent impermeable material. Preferably, the
intermediate release layer is releasably adhered to both the
first layer of adhesive and the inner backing layer.
[0012] In accordance with another embodiment of the assembly
of the present invention, the first adhesive layer comprises
pressure-sensitive adhesive material for adhering the assembly to
the skin or mucosa of the host.
[0013] In accordance with another embodiment of the assembly
of the present invention, at least one of the pair of sheets
comprises a transparent sheet. Preferably, the other of the pair
of sheets comprises an opaque sheet. In a preferred embodiment,
the assembly includes printed material on the inner surface of
the other of the pair of sheets.
[0014] In accordance with the present invention, a system has
been discovered for the handling of a plurality of adhesive-
coated elements, the system comprising a first adhesive-coated
material including an outer backing layer having an inner surface
and an outer surface and a first layer of adhesive disposed on
the inner surface of the outer backing layer, a second adhesive-
coated element including an inner surface and an outer surface,
the inner surface of the second adhesive-coated element including
an inner backing layer, and an intermediate release liner
disposed between the first layer of adhesive and the inner
backing layer of the second adhesive-coated element, the
intermediate release liner including an inner surface and an
outer surface, both the inner surface and the outer surface of
the intermediate release liner including a releasable surface.
In a preferred embodiment, the intermediate release liner
comprises a single sheet having the releasable surface disposed
on both sides of the single sheet.
[0015] In accordance with one embodiment of the system of the
present invention, the intermediate release liner comprises a
laminate including at least a pair of sheets affixed to each
other, each of the pair of sheets including an inner surface and
an outer surface, the inner surfaces of the pair of sheets being
juxtaposed with each other and each of the outer surfaces of the
pair of sheets including the releasable surface.

[0016] In accordance with another embodiment of the system or
the present invention, the first and second adhesive-coated
elements are adapted to include an active agent for release to
the skin or mucosa of a host.
[0017] In accordance with another embodiment of the system of
the present invention, the intermediate release liner comprises
an active agent impermeable material.
[0018] In accordance with another embodiment of the system of
the present invention, the intermediate release liner is
releasably adhered to both the first layer of adhesive and the
inner backing layer of the second adhesive-coated element.
[0019] In accordance with another embodiment of the system of
the present invention, the first adhesive layer comprises
pressure-sensitive adhesive material.
[0020] In accordance with another embodiment of the system of
the present invention, the releasable surface of the inner
surface of the intermediate release liner has a first release
force, and the releasable surface of the outer surface of the
intermediate release liner has a second release force, and the
first and second release forces are different from each other.
[0021] The assembly of the present invention thus not only
permits the handling of multiple layered systems, but also
inhibits migration of active agents between inner and outer
patches by maintaining a physical barrier between the patches
during storage. Indeed, it prevent adhesive exposed at the edge
of the smaller adhesive system from adhering to the release film
of the larger system, and thus accomplishes this result in a more
efficient manner than has been known in the past. In applying
the assembly or device of the present invention to the handling
of stacked adhesive units, it is clear that the assemblies are
not limited to transdermal patches or indeed to any systems in
which active agents are being employed to the skin or mucosa of a
host. Thus, the present system is able to broadly inhibit
migration of any component of the assembly, including both active
and non-active agents and other ingredients but also including
non-active excipients, penetration enhancers, plasticizers, and

the like, between the inner and outer layers of adhesive-
containing assemblies such as patches.
[0022] More specifically, in one embodiment, the assembly or
device of the present invention is in the nature of a double-disk
system which includes an active agent containing inner patch
permanently attached to an adhesive outer patch through an
opening provided in a release liner for the outer patch. The
inner patch includes an active agent impermeable backing layer,
active agent layer containing the active agent to be delivered to
the skin or mucosa of a host, which may also be an adhesive
matrix layer and a disposable release liner. The outer patch
includes a backing layer, adhesive matrix layer which may contain
additional active agents, and a disposable release liner
preferably of active agent impermeable material, and which
includes a releasable surface on both its inner and outer
surfaces. The opening in the release liner of the outer patch
exposes a portion of the outer patch adhesive matrix. The
opening is smaller in size than the active agent inner patch, and
provides an anchor point for the inner patch while preventing
contact between the inner and outer patches prior to use.
[0023] In one embodiment of the present invention there is
described a assembly for the release of an active agent to the
skin or mucosa of a host, the assembly comprising an outer layer
having adhesive properties; an inner layer having an active agent
impermeable layer, the inner layer having a portion thereof
adhered to the outer layer; and a release liner interposed
between a portion of the impermeable layer and a portion of the
outer layer, whereupon removal of the release liner exposes the
outer layer for adhering the assembly to the skin or mucosa of a
host.
[0024] In accordance with the present invention, a stacked
plurality of components has been devised for the manufacture of
an assembly for adhesive attachment to the skin or mucosa of a
host, comprising a first plurality of outer backing layers
including an inner surface and an outer surface, and a first
layer of adhesive disposed on the inner surface of the plurality
of outer backing layers, and a second plurality of intermediate
release liners including an inner surface and an outer surface,
both the inner and outer surfaces of the plurality of
intermediate release liners including a releasable surface,
whereby the first plurality of outer backing layers and the
second plurality of intermediate release liners can be stacked
together without adhering to each other. In a preferred
embodiment, the intermediate release liner comprises a single
sheet having the releasable surfaces disposed on both sides of
the single sheet.
[0025] In accordance with one embodiment of the stacked
plurality of components of the present invention, the
intermediate release liner comprises a laminate including at
least a pair of sheets affixed to each other, each of the pair of
sheets including an inner surface and an outer surface, the inner
surfaces of the pair of sheets being juxtaposed with each other
and each of the outer surfaces of the pair of sheets including
the releasable surface.
[0026] In accordance with another embodiment of the stacked
plurality of components of the present invention, the first
adhesive layer comprises pressure-sensitive adhesive material for
adhering the assembly to the skin or mucosa of the host. In a
preferred embodiment, at least one of the pair of sheets
comprises a transparent sheet. Preferably, the other of the pair
of sheets comprises an opaque sheet. In a preferred embodiment,
the assembly includes printed material on the inner surface of
the other of the pair of sheets.
[0027] In accordance with the present invention, a method has
also been discovered for producing an adhesive layer for use in
the manufacture of an assembly for attachment to the skin or
mucosa of a host, the method comprising coating an adhesive layer
onto a release liner having a first surface and a second surface,
both of the first and second surfaces including a releasable
surface, laminating a backing layer onto the first surface of the
release liner, temporarily removing the release liner from the
adhesive layer, die cutting the release liner, and rejoining the
release liner to the adhesive layer. Preferably, the die cutting
step comprises slitting the release liner into a plurality of
release liner portions. In a preferred embodiment, the die
cutting includes punching an opening in the release liner.
[0028] In accordance with one embodiment of the method of the
present invention, the method includes drying the coated release
liner.
[0029] In accordance with another embodiment of the method of
the present invention, the method includes removing waste from
the adhesive layer.
[0030] In accordance with another embodiment of the method of
the present invention, the method includes winding the rejoined
release liner and the backing layer onto a roll.
BRIEF DESCRIPTION OF THE DRAWINGS
[0031] The subject matter regarded as the invention is
particularly pointed out and distinctly claimed in the concluding
portion of the specification. The invention, however, both as to
organization and method of operation, together with features,
objects, and advantages thereof may best be understood by
reference to the following detailed description when read with
the accompanying drawings in which:
[0032] FIG. 1 is a perspective unassembled exploded view of
the components of an assembly for the release of an active agent
for application to the skin or mucosa of a host in accordance
with one embodiment of the present invention; •
[0033] FIG. 2 is an assembled cross-sectional view of the
assembly shown in Fig. 1;
[0034] FIG. 3 is a top plan view of the assembly shown in FIG.
1;
[0035] FIG. 3A is a top plan view of another embodiment of a
portion of the assembly shown in FIG. 1;
[0036] FIG. 4 is a cross-sectional view of the application of
the assembly shown in FIG. 2 adhered to the skin or mucosa of a
host;
[0037] FIG. 5 is a perspective unassembled exploded view of
the components of an assembly for the release of an active agent
for application to the skin or mucosa of a host in accordance
with another embodiment of the present invention;
[00381 FIG. 6 is an assembled cross-sectional view of the
assembly shown in FIG. 5;
[00331 FIG. 7 is a top plan view of the assembly shown in FIG.
6;
[0040] FIGS. 8-10 are diagrammatic illustrations of one
embodiment a method of forming assemblies in accordance with the
present invention; and
[0041] FIG. 11 is a perspective unassembled exploded view of
the components for a system to manufacture a multiplicity of
adhesive-containing assemblies.
DETAILED DESCRIPTION
[0042] In describing the preferred embodiments of the
invention illustrated in the drawings, specific terminology will
be used for the sake of clarity. However, the invention is not
intended to be limited to the specific terms so selected, and it
is to be understood that each specific term includes all
technical equivalents that operate in a similar manner to
accomplish a similar purpose.
[0043] Referring now to the drawings, wherein like reference
numerals represent like elements, there is shown in FIG. 1 the
unassembled components of an assembly for the administration of
one or more active agents to the skin or mucosa of a host in
accordance with one embodiment of the present invention. The
assembly 100 generally includes an outer patch 102, an outer
patch release layer 104, an inner patch 106 and an inner patch
release layer 108. The outer and inner patches 102, 106 and
release layers 104, 108, which are typically planar layers, are
assembled to one another to form a laminate composite structure
in the nature of a double disk assembly as to be described
hereinafter.
[0044] The outer patch 102 includes a flexible adhesive layer
110 and a co-extensive protective backing layer 112 adhered
thereto. The adhesive layer 110 provides the primary adhesion of
the assembly 100 to the skin or mucosa of a host. Preferably,
the adhesive layer 110 is a pressure-sensitive adhesive suitable
for contact with the skin or mucosa of a host, e.g.,
dermatologically acceptable. Optionally, the adhesive layer may
be admixed with an active agent or other drug to be administered
to a host. In that case, the adhesive layer 110 will be formed
from active agent permeable material to allow administration of
the active agent.
[0045] The backing layer 112 is preferably a thin sheet which
is co-extensive with the bottom surface of the adhesive layer
110. Because of the area of skin to which the assembly 100 is to
be attached, the backing layer 112 may be flesh-colored for
cosmetic reasons and/or bear identifying marks. The backing
layer 112 normally provides support and a protective covering for
the assembly 100. The backing layer 112 may be formed from a
sheet of active agent impermeable or permeable material.
Preferably, the backing layer 112 will be formed from active
agent impermeable material when an active agent is present in the
adhesive layer 110.
[0046] The outer patch release layer 104 covers the top
surface of the adhesive layer 110 prior to use of the assembly
100 to both protect the adhesive layer from inactivation by
ambient dust or other contaminants and to provide an active agent
migration barrier as to be described, both with respect to the
adhesive layer 110 and with respect to the flexible active agent
layer 122 and/or the adhesive layer 126 of the inner patch 106.
The release layer 104 has a sufficient surface area and shape to
extend at least to the peripheral edges of the adhesive layer
110. An opening 114 within the release layer 104 exposes a
portion of the top surface of the adhesive layer 110 of the
underlying outer patch 102. The release layer 104 may be formed
as a single sheet of material, or multiple sections 116, 118
which are separated by one or more slits 120. Preferably, the
release layer 104 is formed from a sheet of active agent
impermeable material thereby providing a migration barrier with
respect to the active agents in both the inner patch 106 and the
outer patch 102.
[0047] The inner patch 106 includes a flexible active agent
layer 122 and a co-extensive active agent impermeable backing
layer 124 adhered to the bottom surface thereof. The active
agent layer 122 may be formed from a thermoplastic polymeric
matrix which is admixed with the active agent or drug components,
and optionally, an active agent enhancer. The polymeric matrix
for the active agent layer 122 preferably has pressure-sensitive
adhesive properties, or in the alternative, the active agent
layer may be coated with an active agent permeable adhesive layer
126 as shown in phantom.
[0048] The inner patch release layer 108 may be formed as a
similar sheet as release layer 104 from one or more sections 128,
130 separated by a slit 132. The release layer 108 has a surface
area and shape to at least extend to the perimeter of the top
surface of the active agent layer 122. The release layer 108
covers the top surface of the active agent layer 122 prior to use
of the assembly 100 to prevent the release of the active agent.
When the active agent layer 122 has pressure-sensitive adhesive
properties, or is covered with an active agent permeable adhesive
layer, the release layer 108 provides protection from
inactivation by ambient dust or other contaminants.
[0049] The assembly 100 is shown in assembled relationship in
FIGS. 2 and 3 in the nature of a laminate composite assembly of
generally planar layers. The release liner 104 includes
releasable surfaces 115 and 117, respectively, and is thus
releasably adhered in co-extensive contact with the top surface
of adhesive layer 110 of the outer patch 102, and to the outer
surface of active agent permeable backing layer 124, and thus
also with respect to any active agent and/or adhesive, and/or any
other ingredient of the active agent layer 122 and/or adhesive
layer 126.
[0050] In the case where the release liner 104 includes a
single sheet of material, release coatings must be applied to
both sides of the release liner 104. The release coatings
generally employed comprise coatings of silicon, teflon, or other
suitable such coatings which are conventional in the preparation
of release layers. These can include, for example, fluorocarbon
and fluorosilicone coatings which are compatible with silicone-
based adhesives.
[0051] The opening 114 in release layer 104 exposes a portion
of the top surface of the underlying adhesive layer 110. The

inner patch 106 is adhered to the outer patch 102 by bonding the
impermeable backing layer 124 to the adhesive layer 110 exposed
within the opening 114. The surface area of the opening 114 is
smaller than the surface area of inner patch 106. This results
in the inner patch 106 having an annular portion in the nature of
a flap surrounding opening 114, which is not bonded to the
adhesive layer 110 as a result of an interposed portion of the
release liner 104. Likewise, the peripheral edges of the active
agent layer 122 and/or the adhesive layer 126 are separated from
the adhesive layer 110 by a portion of the release liner 104.
The presence of releasable surface 115 thereon thus also prevents
this active agent, adhesive or other material from adhering to
the surface of release layer 104. The impermeable backing layer
124 and impermeable release layer 104 therefore not only isolate
the active agent layer 122 to inhibit migration of an active
agent from the active agent layer to the adhesive layer 110
during storage of the assembly 100 prior to use, but also prevent
any adhesive from adhesive layer 126 from migrating from the edge
of inner patch 106 to adhere to the prior non-release-coated
surface of release liner 104 so as to interfere with removal of
the release liner prior to use.
[0052] The assembly 10 0 is prepared for application to the
skin or mucosa of a host by removing release layers 104, 108. To
facilitate removal of release layer 104, it is preferable that at
least a portion of the release layer extend beyond the periphery
of the underlying adhesive layer 110. The extended portion may
be in the nature of a tab or annular portion circumscribing the
entire perimeter or portion of the adhesive layer 110 as shown in
FIG. 3. In this manner, each section 116, 118 of the release
layer 104 may be removed to expose the top surface of the
adhesive layer 110 surrounding the inner patch 106 containing the
active agent. The exposed surface portion of the adhesive layer
110 will have sufficient surface area to provide adhesion of the
assembly 100 to the skin or mucosa of a host during use. Removal
of the sections 116, 118 are undertaken individually as a result
of their separation by slit 120. This enables removal of the
sections 116, 118 notwithstanding a portion of the sections
"surrounding the opening 114 being interposed between the adhesive
layer 110 and impermeable backing layer 124 of the inner patch
106. Most significantly, the presence of releasable surfaces 115
and 117 on both sides of release liner 104 permits this operation
to proceed seamlessly, and without adherence to either side
thereof or contact of the user's fingers with either adhesive.
[0053] In a like manner, the release layer 108, which in this
case requires a releasable surface on only one side thereof,
i.e., the side facing adhesive layer 126 and/or active agent
layer 122, is removed from the top surface of the active agent
layer 122 by grasping an extended portion of sections 128, 130.
It is therefore possible, and in some cases desirable, for the
individual sections 128 and 130 of release layer 108 to have
extended portions which extend beyond the perimeter of the inner
patch 106. For example, reference is made to PIG. 3A hereof in
which the sections 128 and 13 0 of the inner patch release layer
108 include an outer circumference which is larger than the
circumference of the inner patch 106 and furthermore includes
extended tab-like sections 130a and 128a, preferably at both ends
of the release layer 108. In this manner, preferably after the
outer patch release layer 104 has been removed, the inner patch
release layer 108 can be removed by grasping tabs 130a and 128a,
to thus remove the portions 128 and 130 thereof. The assembly
100 is adhered to the skin or mucosa of a host 134 as shown in
FIG. 4 with the active agent layer 122 in contact with the host.
The host to which an active agent is administered by means of the
inventive assembly may be any host on which a drug or other
active agent has the desired effect. The host may be, for
example, a mammal such as a human being, or, for that matter, any
warm-blooded or cold-blooded animal. The advantage of
administering the active agent may be therapeutic or
experimental. The assembly 100 of this invention may also be
used for any other advantageous purpose.
[0054] The extended sections of the release layer 108 may be
as described above with respect to FIG. 3A or as described with
respect to release layer 104. However, it is to be understood
that it is not required that the release layers 104, 108 extend

beyond the periphery of their underlying adhesive layer 110 and
active agent layer 122, respectively. The extension of the
release layers 104, 108 merely facilitates removal of the release
layers by the user prior to application of the assembly 100.
[0055] The individual components of the assembly 100 have been
illustrated as being rectangular in shape for illustrative
purposes only. It is to be understood that the assembly 100 and
its components may have any other shape, such as square, round,
oval and the like. For example, the outer patch 102 may have a
square shape, while the inner patch 106 may be circular. In
addition, it is not a requirement of the present invention that
opening 114 be rectangular, and may be in the form of a polygon,
such as a hexagonal shape for example, or may be formed as a
plurality of non-contiguous openings within the release layer
104. The opening 114 serves one function of enabling bonding of
the inner patch 105 to the outer patch 102 in assembling the
assembly 100. In addition, the surface area of opening 114 in
relationship to the surface area of the inner patch 108 defines
the extent of the circumferential portion of the inner patch
which is separated from the adhesive layer 110 by the interposed
release layer 104. Accordingly, the size, shape and location of
the opening 114 can be tailored to accommodate the migration of
an active agent based upon, for example, the migration rate of
the active agent within the active agent layer 122. In addition,
the size of the opening 114 can also be employed to effect
migration of an active agent between adhesive layers,- namely,
from adhesive layer 110 through the opening 114 into the active
agent layer 122 and/or the adhesive layer 126.
[0056] Referring to PIGS. 5-7, there is disclosed another
embodiment of an assembly 136 adapted for the administration of
an active agent to the skin or mucosa of a host. The assembly
136 differs in one aspect from the assembly 100 in the shape of
its component parts. In this regard, the assembly 106 includes a
circular outer patch 138, a square or rectangular outer patch
release layer 140, a circular inner patch 142 and a circular
inner patch release layer 144.
[0057] The outer patch 138 includes an adhesive layer 14S and
a co-extensive outer backing layer 148. The adhesive layer 146
may be in the nature of a pressure-sensitive adhesive, and
optionally, admixed with an active agent or other drug to be
administered to a host. In this event, the backing layer 148
will be in the nature of a sheet of active agent impermeable
material.
[0058] The release layer 140, like release layer 104, is
preferably formed from a sheet of active agent impermeable
material which is releasably adhered to both the top surface of
the adhesive layer 146 of the outer patch 138 and to the exposed
edge of the active agent layer 154 (or, alternately the adhesive
layer 126) of the inner patch 142, by means of having releasable
surfaces 153 and 155, respectively, on both sides of the release
layer 140. The release layer 140 includes an opening 150 which
exposes a portion of the top surface of the adhesive layer 146
through which the inner patch 142 is adhered. Removal of the
release layer 140 is facilitated by a slit 152 extending from an
outer edge of the release layer to the opening 150.
[0059] The inner patch 142 includes an active agent layer 154
which may be a mixture of polymeric materials along with the
active agent or other ingredients so as to posses pressure-
sensitive adhesive properties for adhering (at least in part) the
assembly 136 to the skin or mucosa of a host. That is, the
overall ability of the assembly 136 to adhere reliably to the
skin or mucosa of the host can depend on both the inner patch 142
and the outer patch 13 8 and the adhesives thereof. The top
surface of the active agent layer 154 can be coated with an
active agent permeable adhesive layer 126, but as is the case
with the adhesive layer 126 shown and discussed with respect to
FIG. 2, the layer can be eliminated, and is optional therein. It
is also contemplated, although not shown, that the inner patch
142 may include a rate-controlling polymer layer to provide a
means for controlling the rate at which the active agent is
released from the surface of the inner patch 142 to the skin or
mucosa of the host. The rate-controlling polymer layer may be
adhered to the surface of the active agent layer 154 using any

suitable active agent permeable adhesive such as that used for
active agent layer 154 or adhesive layer 12 5.
[0060] The inner patch 142 further includes an active agent
impermeable backing layer 156 adhered to the bottom surface of
the active agent layer 154. The impermeable backing layer 156
may be adhered using the pressure-sensitive adhesive properties
of the active agent layer 154, or by a layer, not shown, of
preferably an active agent impermeable adhesive. The release
layer 144, similar to release layer 108, is releasably adhered to
the active agent layer 154 or, alternately, the adhesive layer
126 of the inner patch 142 for preventing release of the active
agent and for protecting and preventing contamination to the
adhesive properties of the inner patch prior to application to
the host and initiation of therapy. It can thus be seen that
release layer 144 requires only a single releasable surface
corresponding to releasable surface 153 or releasable surface 155
on both sides of release layer 140. The opposite side of release
layer 144 from that which is in contact with either the active
agent layer 154 or the adhesive layer 126 of the inner patch 142
thus does not require a releasable surface since it will not be
in contact with any surface from which it needs to be released.
[0061] A portion of the release layer 140 is interposed
between a portion of the bottom surface of the inner patch 142
and the top surface of the adhesive layer 146 of the outer patch
138. The inner patch 142, release layer 140, and outer patch 138
are aligned and stacked one upon the other so as to form an
assembly in which an annular portion of the release layer 140 is
interposed between the outer edge of inner patch 142 and the
inner edge of release layer opening 150. This annular region
separating the outer edge of inner patch 142 and the inner edge
of opening 150 isolates active agent layer 154 from adhesive
layer 146 to prevent migration of any active agent (s)
therebetween. Similarly, the presence of releasable surface 153
in the upper surface of release liner 140 prevents any adhesive
from adhesive layer 126, and most particularly from the exposed
edges of the adhesive layer 126, for adhesively attaching the
inner patch 142 to the surface 153 of the release layer 140.

Upon removal of the release layer 140, an annular portion of the
top surface of the adhesive layer 146 is exposed surrounding the
perimeter of the inner patch 142. The adhesive layer 146
provides sufficient adhesion to adhere the assembly 136 to the
skin or mucosa of a host. The adhesion of the assembly 136 may
optionally be enhanced by the inner patch 142 having either
pressure-sensitive adhesion properties or the incorporation of an
active agent permeable adhesive layer 126.
[0062] As previously described, the active agent or drug is
contained within the active agent layer 122, 154, and optionally
in the adhesive layer 110, 145. The active agent may be, for
example, systemic or topical drugs. Individual active agents or
mixtures thereof, if desired, can be employed. Any drug which
passes through the skin or mucosa of a host can be employed for
internal administration in the assembly of the invention so long
as the drug will pass through the permeable adhesive layer or
layers present. The active agent and thermoplastic matrix
polymer can be melt-blended in an extruder and then formed into
the active agent layer 122, 154 or adhesive layer 110, 146 by
extrusion. Other known processes for incorporation of the active
agent such as solvent blending are contemplated.
[0063] Suitable systemic drugs for administration by the
assemblies of the present invention include psychoactive agents
such as nicotine, caffeine, mesocarb, mefexamide, cannabinols
such as THC, and the like, sedatives such as diazepam,
mepiridine, uldazepam, tybamate, metaclazepam, tetrabarbitol and
the like, antidepressants such as amitryptyline, imipramine
desipramine, nialamide, melitracen, isocarboxazid, and the like,
anticonvulsants such as phenobarbitol, carbamazepine,
methsuximide, 2-ethyl-2-phenylmalonamide (PEMA), phenytoin and
the like, steroids such as progesterone, testosterone,
pregnanediol, progestin, estradiol, anabolic steroids and the
like, analgesics, including narcotic analgesics such as codeine,
morphine, fentanyl, analorphine, demeral and the like, and
analgesics such as acetaminophen, aspirin, and the like,
antimicrobial agents such as sulconazole, siccanin, silver
sulfadiazine, bentiacide, and the like, tranquilizers such as
alprazolam, meprobamate and the like, antineoplastic agents such
as sulfosfamide, rufocromomycin and the like, and antibiotic
agents such as tetracycline, penicillin, streptozcin and the
like.
[0064] The quantity of active agent present is that quantity
sufficient to provide a pharmaceutically or physiologically
effective dosage rate of the active agent to a host in need
thereof. This quantity can be readily determined by those of
ordinary skill in the art without undue experimentation as shown
in the examples set forth below.
[0065] The assembly 10 0, 136 of the present invention
optionally include a rate-controlling polymer layer. The
polymers suitable for use as the rate-controlling polymer layer
are conventional in the art and need not be discussed in detail
here. Some preferred materials include, for example,
polyethylene, polypropylene, ethylene vinyl acetate copolymer
(EVA), copolyesters (e.g., HYTREL) and polyurethanes.
[0066] The rate of permeation of the active agent through the
rate-controlling polymer layer depends on factors such as the
affinity of the active agent for the polymer layer, molecular
size of the active agent, polymeric structure of the carrier
layer and the thickness of the layer. Therefore, the appropriate
rate-controlling polymeric material and its thickness depend on
the active agent used and the desired rate of permeation. The
selection of a polymer layer and its thickness provides a means,
if desired, for controlling the dosage rate to the skin or
mucosa.
[00673 Further, an enhancer to promote the penetration of the
active agent through the skin may be included in either the
active agent layers 122, 154, rate-controlling polymer layers or
the active agent permeable adhesive layers, if present. The
enhancer may be incorporated into these layers by solvent
blending or, more preferably, by melt-blending by the same
process utilized to incorporate the active agent into either the
active agent layers 122, 154 or the adhesive layers 110, 146,
which adhesive layers may also include an enhancer.
[0068] Suitable enhancers include those described in United
States Patent No. 4,573,996, such as the following enhancers:
monovalent, saturated and unsaturated aliphatic and
cycloaliphatic alcohols having 6 to 12 carbon atoms such as
cyclohexanol, lauryl alcohol and the like; aliphatic and
cycloaliphatic hydrocarbons such as mineral oils; cycloaliphatic
and aromatic aldehydes and ketones such as cyclohexanone; N,N-di
(lower alkyl) acetamides such as N,N-diethyl acetamide, N,N-
dimethyl acetamide, N-(2-hydroxyethyl) acetamide, and the like;
aliphatic and cycloaliphatic esters such as isopropyl myristate
and lauricidin; N,N-di (lower alkyl) sulfoxides such as
decylmethyl sulfoxide; essential oils; nitrated aliphatic and
cycloaliphatic hydrocarbons such as N-methyl-2-Pyrrolidone,
Azone; salicylates, polyalkylene glycol silicates; aliphatic
acids such as oleic acid and lauric acid, terpenes such as
cineole, surfactants such as sodium lauryl sulfate, siloxanes
such as hexamethyl siloxane; mixtures of the above materials; and
the like.
[0069] The backing layer 124, 156 is preferably made of a
material or combination of materials that is substantially
impermeable to the layer or layers with which it can be in
contact, e.g., to the active agent layers 122, 154, the adhesive
layer 110, 146 and the active agents or ingredients contained
therein, the adhesives, etc. In this regard, a primary objective
is to prevent migration or seepage of the active agents or
ingredients through the backing layer 124, 156 of the inner patch
106, 142 into the underlying adhesive layer 110, 146. The
backing layer 112, 148 may also be made from a similar material
being impermeable to the active agents, particularly when the
active agents are present also within the adhesive layer 110,
146. The backing layer 112, 148 is not required to be
impermeable to the active agents, particularly when there are no
active agents in the adhesive layer 110, 146. Thus, it is not
necessary in all instances that the backing layer 112, 148 be
impermeable to the active agents.
[0070] By impermeable, it is meant that the other components
in contact with the backing layer or component under
consideration will not appreciably permeate through such layer or
component for the normal period of use and storage of the
assembly. Some suitable materials for the backing layer include,
for example, cellophane, cellulose acetate, ethyl cellulose,
plasticized vinyl acetate-vinyl chloride copolymers,
ethylene-vinyl acetate copolymer, polyethylene terephthalate,
polyvinyl chloride, nylon, polyethylene, polypropylene and
polyvinylidene chloride (e.g., SARAN), or combinations/laminates
thereof.
[0071] The assembly 100, 136 includes a release liner attached
to the assembly such as at the surfaces to be adhered to the skin
or mucosa of a host. The release liner may be made of the same
materials suitable for use in the backing layer provided they are
active agent impermeable. Most significantly, the release liner
104, 140' must include releasable surfaces on both faces thereof.
These release liners are thus made removable or releasable from
the adhesive layers or active agent layers by, for example,
conventional treatment with silicon. Teflon or other suitable
coating on the surface thereof. The application of such, coatings
on both surfaces of these release liners 104, 140 thus not only
accomplishes the purpose of ready release from the surface of the
adhesive layers 110, 146 on the outer patches, but they also
permit release from any adhesive or other such materials present
on the inner patches 106, 142, such as will be present along the
outer edges or surfaces thereof. The removal of the assembly
100, 136 from the release liner may also be provided by
mechanical treatment of the protective layer, e.gr., by embossing
the protective liner.
[0072] While the release liners between the inner and outer
patches used in the present invention must include releasable
surfaces on both faces thereof, this can be accomplished in a
number of ways. As is discussed above, in the embodiment in
which a single sheet of material is employed, a release coating
is applied to. both surfaces of that sheet. The release coating
can be applied to a single sheet, or a conventional release liner
having releasable surfaces on one surface thereof can be modified
to include a second release surface on the opposite side thereof.
In the alternative, however, the release liners 104, 140 of the
present invention can be produced from a laminate of two or more
sheets. In the embodiment in which, for example, two sheets are
used, two separate conventional one-sided release liner films can
be attached together, thus producing a laminated sheet with
release coatings on either surface. In addition two uncoated
sheets can be attached together and then releasable surfaces
produced on both outer surfaces thereof after such attachment.
All of the above provides additional flexibility to the
manufacturer which can apply various commercially available
release films or custom manufactured release films to one or both
of the surfaces simultaneously, in separate operations, or the
like.
[0073] In the case of either a single or multiple sheet
release liner 104, 140, in one preferred embodiment of this
invention it is possible to have either the same or dissimilar
release coatings applied to the two sides of the liner itself.
It is thus possible to selectively alter the release
characteristics of one or both sides of the release liner for
particular purposes. For example, when laminating a coated
adhesive to itself, it would be possible to predict which bond
has a lighter or heavier release force for removal therefrom. In
this manner, one could, for example, isolate a dried film or
apply a dried film to a new substrate when constructing a
multilayer laminate from dissimilar materials or building up
multiple layers of a common adhesive. Therefore, in quantifying
particular release forces or differentiating between the release
forces on the two sides of release liner 104, 140, one could
conventionally utilize a standard adhesive tape and devise a
standard measurement based on the force required to peel that
tape from the release liner. On the other hand, the required
peel force to separate the layers of the finished product could
be directly quantified and tabulated if that were desirable.
[0074] In one particular embodiment of the present invention,
in which a laminated construction is employed, one layer in the
laminate could be a commercially available single-sided release
film, which has a clear configuration. This is, in turn,
attached to a second laminate which is also possibly a
commercially available film (with or without a release coating),
but in which case it is a colored or opaque release film. In one
particular embodiment, for example, the second or opaque release
film may be printed on the non-release surface thereof [before or
after the application of a release agent if necessary). In this
manner, the resultant product is a printed two-sided release film
in which the printing is visible through the release coating on
the first clear single-sided release film discussed above.
[0075] Examples of suitable pressure-sensitive-adhesive
materials for use in the present invention as an active agent
impermeable adhesive include some natural rubber and synthetic
rubber adhesives and cross-linkable laminating adhesives.
Examples of suitable natural rubber adhesives include R-1072 from
B.F. Goodrich Co., No. 735 from C.L. Hathaway, and No. 5702 from
Evans St. Clair. Examples of synthetic rubber adhesives include
Jowatherem 270-00 and Jowatherem S-3202 from Jowat Corp. and 70-
9416 from National Starch. Other suitable laminating adhesives
include the Dow Coming laminating silicone adhesives and the
Lord Corporation Tycel 7900 series laminating adliesives. Also
contemplated are acrylic copolymers such as those available from
National Starch and Chemical Co. of Bridgewater, New Jersey under
the marks DURO-TAK 87-2515 and DURO-TAK 87-2287. The adhesives
most impermeable to most active ingredients are cross-linkable
laminating adhesives, which are well-known to those of ordinary
skill in the art.
[0076] The active agent permeable adhesive layers are
preferably a pressure-sensitive adhesive. Any of the well-known,
dermatologically acceptable, pressure-sensitive adhesives which
permit drug migration therethrough can be used in the present
invention. Some suitable permeable adhesives include acrylic or
methacrylic resins such as polymers of alcohol esters of acrylic
or methacrylic acids and alcohols such as n-butanol, isopentanol,
2-methylbutanol, 1-methyl-butanol, 1-methyl-pentanol, 2-
methylpentanol, 3-methylpentanol, 2-ethyl-butanol, isooctanol, n-
decanol, or n-dodecanol, alone or copolymerized with
ethylenically unsaturated monomers such as acrylic acid,

methacryiic acid, acrylamide, methacrylamides, N-alkoxymethyl
acrylamides, N-alkoxymethyl methacrylamides, N-t-butyl-
acrylamide, itaconic acid, vinyl acetate, N-branched alkyl
maleamic acids wherein the alkyl group has 10-24 carbon atoms,
glycol diacrylates, or mixtures of these monomers; polyurethane
elastomers; vinyl polymers such as polyvinyl alcohol, polyvinyl
ethers, polyvinyl pyrrolidone, and polyvinyl acetate; urea
formaldehyde resins; phenol formaldehyde resins, resorcinol
formaldehyde resins; cellulose derivatives such as
ethylcellulose, methylcellulose, nitrocellulose, cellulose
acetate butyrate and carboxymethylcellulose; and natural gums
such as guar, acacia, pectina, starch, destria, gelatin, casein,
etc.
[0077] Other suitable pressure-sensitive adhesives include
polyisobutylene pressure-sensitive adhesives, rubber
pressure-sensitive adhesives and silicone pressure-sensitive
adhesives. The adhesives may also be compounded with tackifiers
and stabilizers as is well-known in the art.
[0078] Adhesives that are preferred for their active agent
permeability include acrylic copolymer adhesives such as Avery
Chemical Company's AS-351 HSX, preferably at a coating weight of
between 75 and 125 g/m2. This pressure-sensitive adhesive is a
cross-linkable polymer which provides a permanently tacky film.
[0079] Other such adhesives that can also be used for these
purposes include an acrylic pressure-sensitive adhesive sold by
National Starch and Chemical Co. under the designation DURO-
TAK 80-1054. This adhesive has a solids content of 47.5%, a
viscosity of 3,000 cps., and plasticity (Williams) of 2.9 mm. It
is generally used with a solvent system including ethyl acetate,
heptane, isopropyl alcohol and toluene. Another such adhesive is
sold by the UCB Group under the designation GELVA Multipolymer
Emulsion 2484, and comprises a stable aqueous acrylic emulsion
pressure-sensitive adhesive having a solids content of 59% and a
viscosity of 1,500 to 2,300 cps. Examples of other acrylic
adhesives include Gelva 788 and 733 from UCB, PS-41 from C.L.-
Hathaway, Vr-0833 from H.B. Fuller, Adcot 73A207A from Morton
Chemical, Nos. 80-2404, 80-1054, 72-9056 and 72-9399 from
National Starch, Nos. E-2015, E-2067 and E-1960 from Rohm & Haas,
M-6112 from Uniroyal, Inc. and Daratak 74 L from W.R. Grace.
Suitable rubber adhesives include Duro-Tak 36-6172 from National
Starch and Morstik 11B from Morton Chemical. An example of a
suitable silicone adhesive is 7-4502 from Dow corning.
[0080] The width (i.e., surface area) and thickness of the
permeable adhesive layer for contact with the skin or mucosa is
that width and thickness which provides sufficient permeability
to the active agent or active agent enhancer, adequately adhere
to the skin or mucosa, and provide a suitable surface area to
allow the dosage rate desired to the skin or mucosa. These
widths and thicknesses are conventional in the art and therefore
need not be discussed in detail here.
[0081] The active agent layers 122, 154 are preferably
monolithic polymeric active agent carrier layers. Thus, in
essence, these monolithic active agent carrier layers are admixed
by means of melt-blending with the active agent or drug component
or active agent enhancer, or both, and basically comprise a
thermoplastic polymeric matrix. However, monolithic polymer
matrix carrier layers which blend the active agent with a matrix
polymer in a common solvent and then evaporate the solvent to
form a plastic film are contemplated. As is readily understood
by those of ordinary skill in the art, the step of melt-blending
requires the use of a thermoplastic polymer, that is, one that
softens and melts when exposed to heat and then returns to its
original condition when cooled. Suitable thermoplastic matrix
polymers are the thermoplastic polyurethanes, including the
polyether polyurethanes. These include such commercial
polyurethane compositions such as Dow Chemical Company's
PELLETHANE, including its 2363-80 AE grade thereof; K.J. Quin's
Q-THANE; B.F. Goodrich's ESTANE; Mobay Chemical Company's TXIN;
and others.
[0082] Suitable thermoplastic matrix polymers also include
various polyesters, such as the copolymers of various cyclic
polyesters including DuPont's HYTREL, including its 4056 grade
thereof, and General Electric's LOMOD both of which are
copolymers of polyether prepolymers and polybutylene
terephthalate and polyisobutylene terephthalate, respectively, as
well as Eastman Chemical's PCCE. Other suitable polymers include
ethylene methacrylic and acrylic acid copolymers. For example,
ethylene methacrylic acid having the commercial designation
NUCREL 699 is particularly suitable as a thermoplastic matrix
polymer.
[0083] The various layers of the assembly 100, 136 of the
present invention may he combined to form a laminate by methods
conventional in the art. one such process includes combining the
active agent and a thermoplastic matrix polymer by melt-blending
the two components forming the polymer layers by extrusion.
Another known process is referred to as a solvent-blend process
using solvated components which form an admixture that is coated
onto a substrate such as a release liner and subsequently dried.
The melt-blending process is described in further detail in
United States Patent No. 6,010,715, the disclosure of which is
incorporated herein by reference.
[0084] There are also known various materials for use in the
construction of the assembly 100, 136 of the present invention
for the backing layers, release layers, adhesive layers, active
agent layers, pressure-sensitive adhesive layers, active agent
permeable adhesive layers, active agent impermeable adhesive
layers, active agent impermeable layers, active agent permeable
adhesive layers, etc. Suitable materials are disclosed in United
States Patent Nos. 5,064,422, 5,123,900, 5,503,844 and 5,948,433,
the disclosures of which are incorporated herein by reference.
[0085] Referring to FIGS. 8-10, there is illustrated one
example of a method of manufacturing the assembly 100, 136 via a
solvent-blending process. With reference to the assembly 100,
the active agent layer 122 is formed by admixing solvated polymer
materials such as those having pressure-sensitive adhesive
properties in conjunction with the active agent to be
administered to the skin or mucosa of a host. The active agent
polymeric admixture is coated onto a release liner, dried,
laminated with an active agent impermeable backing layer, and
wound into a continuous supply roll 150. The release liner is
separated from the active agent layer and back slit to form slit
132 while the active agent layer is die cut to the desired size
and shape of the inner patch 106. The release liner and active
agent layer are re-joined, followed by removal of the extraneous
active agent layer.
[0086] In a similar solvent-blending process as shown in
FIG. 9, the pressure-sensitive adhesive matrix materials forming
the adhesive layer 110 are coated onto a release liner which has
release characteristics on both sides thereof, dried, laminated
with a backing layer, and wound to form a supply roll 162. The
release liner is removed from the adhesive layer, die cut to form
opening 114 and back slit to form slit 120. The release liner is
re-joined with the adhesive layer, followed by the removal of the
waste adhesive layer.
[0087] Referring to FIG. 10, the supported active agent layer
122 is aligned overlying and in registration with the supported
adhesive layer 110, and adhered thereto through the opening in
the release liner in a continuous process. The release liner for
the active agent layer is cut to appropriate size and shape,
followed by a guillotine process for severing the outer patch
release layer to form the completed assembly 100.
[0088] It is to be understood that the above description of a
method of making the assembly 100, 136, as described with
reference to FIGS. 8-10, is by way of one illustrative example
only. In this regard, it is contemplated that other methods for
manufacturing the assembly 100, 13 6 are contemplated, and
accordingly, the described method is not to be interpreted as any
limitation upon the scope of the present invention.
[0089] The present invention also finds significant utility in
connection with more general application to the handling of
stacked adhesive units. Reference is made, for example, to
FIG. 11 which shows two of a potential multiplicity of adhesive
units, each of which comprises an adhesive-containing patch or
strip 162, which is made up of a backing layer 172 upon which is
deposited an adhesive layer 170. Onto the adhesive surface of
each of these layers is then applied a release layer 164. Each
of these release layers 164 thus includes a single sheet of
material, a laminate of material, or multiple sections 166, 168,

which can be separated by one or more slits 180. When these
units are in a stacked configuration, such as during their
manufacture, the lower surface 1S7 of each of the release layers
164 is in contact with the upper surface of the adhesive layer
170 on each of the adhesive-coated layers 162. The upper surface
of each of these release layers 1S4, however, in accordance with
the present invention, also includes release coatings on both
portions 166 and 168 thereof. This layer will be in contact with
the backing layer 172 on the adhesive-containing patch, but any
of the adhesive 170 which passes around the edge of the unit and
comes in contact with the upper surfaces 166 and 168 of the
release layer 164 will not now adhere to that surface, which
would interrupt the manufacturing process if it were permitted to
occur. In this manner, it is possible to prevent any undue
sticking of the individual units to any surface of the release
liner. In addition, by carefully selecting the degree of release
on the upper and lower surfaces 167 and 166, 168, of release
layers 164, it can be clearly controlled as to how the units
separate from each other, how much force is required, etc.
[0090] Another example of the utility of the present invention
can be illustrated by considering the intermediate transdermal
system manufacturing step of die cutting prior to packaging.
When it is desirable to die cut individual systems, but one
wishes to package those systems in a separate operation, the die
cut systems may be rewound on the continuous release liner after
removing the waste adhesive layer. When there is a tendency for
the adhesive to contact the back of the continuous release liner
of the adjacent leaf in a roll, the systems may be distorted or
damaged when the roll is unwound during subsequent processing
steps. A release layer as described with releasing agent on both
sides will prevent adjacent leaves of the roll from adhering to
one another.
[0091] Although the invention herein has been described with
reference to particular embodiments, it is to be understood that
these embodiments are merely illustrative of the principles and
applications of the present invention. It is therefore to be
understood that numerous modifications may be made to the
illustrative embodiments and that other arrangements may be
devised without departing from the spirit and scope of the
present invention as defined by the appended claims.
INDUSTRIAL APPLICABILITY
[0092] The present invention provides transdermal patch
systems for use in the application of active agents to a patient
or host in which inner and outer patches are provided with the
active agent in the outer patch and in which the annular flap
containing the active agent is completely segregated from the
underlying portion of the patch. A far more efficient system for
applying all of the active agent is thereby produced.
We claim:
1. An assembly for adhesive attachment to the skin or
mucosa of a host, with an inner surface disposed for attachment
to said skin or mucosa and an outer surface distal from said
skin or mucosa, said assembly including an outer backing layer
(112) including an inner surface and an outer surface, a first
layer of adhesive (110) disposed on said inner surface of said
outer backing layer (112), an inner backing layer (124)
including an inner surface and an outer surface, a second layer
of adhesive (122) disposed on said inner surface of said inner
backing layer (124) for adhesive attachment of said assembly to
said skin or mucosa of said host, an intermediate release liner
(104) disposed between said first layer of adhesive (110) and
said outer surface of said inner backing layer (124), said
intermediate release liner (104) including an inner surface and
an outer surface, both said inner surface and said outer surface
of said intermediate release liner (104) including a releasable
surface, said intermediate release liner (104) further including
at least one open area (114), and wherein said first adhesive
layer includes a portion adhesively bonded to and in direct
contact with said outer surface of said inner backing layer at
said at least one open area and the remaining portion of said
first adhesive layer temporarily covered by said intermediate
release liner (104), and an inner release liner (108) covering
said second layer of adhesive and comprising the innermost layer
of said assembly, whereby both said intermediate release liner
(104) and said inner release liner can be adhesively released
from said assembly, prior to such release can inhibit migration
of components of said first and second adhesive layers, and upon
removal of said inner release liner said second layer of

adhesive comprises said innermost layer of said assembly for
attachment to said skin or mucosa of said host.
2. The assembly as claimed in claim 1 wherein said
intermediate release liner (104) comprises a laminate including
at least a pair of sheets affixed to each other, each of said
pair of sheets including an inner surface and an outer surface,
said inner surfaces of said pair of sheets being juxtaposed with
each other and each of said outer surfaces of said pair of
sheets including said releasable surface.
3. The assembly as claimed in claim 1 wherein said
intermediate release liner (104) comprises an active agent
impermeable material.
4. The assembly as claimed in claim 3 wherein said
intermediate release liner (104) is releasably adhered to both
said first layer of adhesive (110) and said inner backing layer
(124) .
5. The assembly as claimed in claim 1 wherein said first
adhesive layer comprises pressure-sensitive adhesive material
for adhering said assembly to the skin or mucosa of said host.
6. A system for the handling of a plurality of adhesive-
coated elements, said system comprising a first adhesive-coated
element (102) including an outer backing layer (112) having an
inner surface and an outer surface, and a first layer of
adhesive (110) disposed on said inner surface of said outer
backing layer (112), a second adhesive-coated element including
an inner surface and an outer surface, said outer surface of
said second adhesive-coated element including an inner backing
layer (124), and a second layer of adhesive disposed on said
inner surface of said second adhesive-coated element, and an
intermediate release liner (104) disposed between and in direct
contact with said first layer of adhesive (110) and said inner
backing layer (124) of said second adhesive-coated element, and
an inner release liner (108) covering said inner surface of said
second adhesive-coated element, said intermediate release liner
(104) including an inner surface and an outer surface, both said
inner surface and said outer surface of said intermediate
release liner (104) including a releasable surface whereby both
said intermediate release liner (104) and said inner release
liner can be adhesively released from said system and can
inhibit migration of components of said first and second layers
of adhesive.
7. The system as claimed in claim 6 wherein said
intermediate release liner (104) comprises a laminate including
at least a pair of sheets affixed to each other, each of said
pair of sheets including an inner surface and an outer surface,
said inner surfaces of said pair of sheets being juxtaposed with
each other, and each of said outer surfaces of said pair of
sheets including said releasable surface.
8. The system as claimed in claim 6 wherein at least one
of said first and second adhesive-coated elements are adapted to
include an active agent for release to the skin or mucosa of a
host.
9. The system as claimed in claim 6 wherein said
releasable surface on said inner surface of said intermediate
release liner (104) has a first release force, and said
releasable surface on said outer surface of said intermediate
release liner (104) has a second release force, and said first
and second release forces being different from each other.
10. A stacked plurality of components for the manufacture
of an assembly for adhesive attachment to the skin or mucosa of
a host, comprising a first plurality of outer backing layers
including an inner surface and an outer surface, and a first
layer of adhesive (110) disposed on said inner surface of said
plurality of outer backing layers, and a second plurality of
intermediate release liners including an inner surface and an
outer surface, both said inner and outer surfaces of said
plurality of intermediate release liners including a releasable
surface, whereby said first plurality of outer backing layers
and said second plurality of intermediate release liners can be
stacked together without adhering to each other.
11. The stacked plurality of components as claimed in
claim 10 wherein said intermediate release liner (104) comprises
a single sheet having said releasable surfaces disposed on both
sides of said single sheet.
12. The stacked plurality of components as claimed in
claim 10 wherein said intermediate release liner (104)comprises
a laminate including at least a pair of sheets affixed to each
other, each of said pair of sheets including an inner surface
and an outer surface, said inner surfaces of said pair of sheets
being juxtaposed with each other and each of said outer surfaces
of said pair of sheets including said releasable surface.
13. The stacked plurality of components as claimed in
claim 10 wherein said first layer of adhesive (110) comprises
pressure-sensitive adhesive material for adhering said assembly
to the skin or mucosa of said host.

The invention relates to an assembly for adhesive attachment to the skin or mucosa of a host.
Said assembly includes an outer backing layer (112) including an inner surface and an outer
surface, a first layer of adhesive (110) disposed on said inner surface of said outer backing layer
(112), an inner backing layer (124) including an inner surface and an outer surface, a second
layer of adhesive (122) disposed on said inner surface of said inner backing layer (124) for
adhesive attachment of said assembly to said skin or mucosa of said host. An intermediate
release liner (104) disposed between said first layer of adhesive (110) and said outer surface of
said inner backing layer (124), said intermediate release liner (104) including an inner surface
and an outer surface is also disclosed. Both said inner surface and said outer surface of said
intermediate release liner (104) includes a releasable surface. Said intermediate release liner
(104) further includes at least one open area (114), and wherein said first adhesive layer includes
a portion adhesively bonded to and in direct contact with said outer surface of said liner backing
layer at said at least one open area and the remaining portion of said first adhesive layer
temporarily covered by said intermediate release liner (104). The invention provides transdermal
patch systems for use in the application of active agents to a patient or host.

Documents:

02359-kolnp-2008-abstract.pdf

02359-kolnp-2008-claims.pdf

02359-kolnp-2008-correspondence others.pdf

02359-kolnp-2008-description complete.pdf

02359-kolnp-2008-drawings.pdf

02359-kolnp-2008-form 1.pdf

02359-kolnp-2008-form 2.pdf

02359-kolnp-2008-form 3.pdf

02359-kolnp-2008-form 5.pdf

02359-kolnp-2008-gpa.pdf

02359-kolnp-2008-international publication.pdf

02359-kolnp-2008-international search report.pdf

2359 -KOLNP-2008-CORRESPONDENCE OTHERS-1.1.pdf

2359 -kolnp-2008-form 13.pdf

2359-KOLNP-2008-(30-03-2012)-PETITION UNDER RULE 137.pdf

2359-KOLNP-2008-(30-04-2012)-CORRESPONDENCE.pdf

2359-KOLNP-2008-(30-04-2012)-FORM-27.pdf

2359-KOLNP-2008-ABSTRACT-1.1.pdf

2359-KOLNP-2008-ABSTRACT.pdf

2359-KOLNP-2008-AMANDED CLAIMS-1.1.pdf

2359-KOLNP-2008-AMANDED CLAIMS.pdf

2359-kolnp-2008-assignment.pdf

2359-KOLNP-2008-CANCELLED PAGES.pdf

2359-KOLNP-2008-CLAIMS-1.1.pdf

2359-KOLNP-2008-CORRESPONDENCE OTHERS 1.2.pdf

2359-KOLNP-2008-CORRESPONDENCE-1.3.pdf

2359-KOLNP-2008-CORRESPONDENCE-1.4.pdf

2359-KOLNP-2008-DESCRIPTION (COMPLETE)-1.1.pdf

2359-KOLNP-2008-DESCRIPTION (COMPLETE).pdf

2359-KOLNP-2008-DRAWINGS.pdf

2359-KOLNP-2008-FORM 1-1.1.pdf

2359-KOLNP-2008-FORM 1.pdf

2359-KOLNP-2008-FORM 13-1.1.pdf

2359-KOLNP-2008-FORM 13-1.2.pdf

2359-kolnp-2008-form 18.pdf

2359-KOLNP-2008-FORM 2-1.1.pdf

2359-KOLNP-2008-FORM 2.pdf

2359-KOLNP-2008-FORM 3-1.1.pdf

2359-KOLNP-2008-FORM 3.pdf

2359-KOLNP-2008-OTHERS PCT FORM.pdf

2359-KOLNP-2008-OTHERS-1.1.pdf

2359-KOLNP-2008-OTHERS-1.2.pdf

2359-KOLNP-2008-PETITION UNDER RULE 137.pdf

2359-KOLNP-2008-REPLY TO EXAMINATION REPORT.pdf

abstract-2359-kolnp-2008.jpg


Patent Number 248838
Indian Patent Application Number 2359/KOLNP/2008
PG Journal Number 35/2011
Publication Date 02-Sep-2011
Grant Date 29-Aug-2011
Date of Filing 12-Jun-2008
Name of Patentee MYLAN TECHNOLOGIES, INC.
Applicant Address 110 LAKE STREET ST. ALBANS VT
Inventors:
# Inventor's Name Inventor's Address
1 BARNETT, BRAD, L. 24 JONES COURT SWANTON VT 05488
2 MILLER, KENNETH, J. 17 QUARRY COURT ST. ALBANS VT 05478
3 FLETCHER, MERTIN 9 HODGES COURT ST. ALBANS VT 05478
PCT International Classification Number A61F 13/15
PCT International Application Number PCT/US2006/045255
PCT International Filing date 2006-11-22
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 11/296,604 2005-12-07 U.S.A.