RELATED APPLICATION

This application claims priority from U.S. Provisional Patent Application No.

61/672,083, filed on July 16, 2012 and incorporated by reference herein in its entirety.

FIELD

The field of the present disclosure includes transdermal drug delivery, and more particularly in the field of packaging of transdermal delivery systems.

BACKGROUND

Transdermal drug delivery is, in most cases, packaged as one patch per pouch. The unit dosage pouching generally is intended to maintain the stability of the product. This is an important consideration for patches containing drugs that are unstable in the presence of air or water vapor (such as drugs that are subject to oxidation or subject to forming hydrates), drugs that are light sensitive (such as clonidine), drugs that are subject to loss through vaporization (such as nicotine) and for patches containing permeation enhancers (such as ethanol) with corresponding stability issues.

There are a number of drugs useful for transdermal administration that are not characterized by these stability limitations. These transdermal systems lend themselves to unique multi-unit pouching.

SUMMARY

A pouching system for transdermal delivery systems in which multiple transdermal systems are located on a common release liner and placed in a single, resealable pouch. The number of patches on the liner sheet and the number of sheets in the single pouch can be fixed to facilitate dosing compliance by corresponding to easily remembered recurring calendar events (e.g. one week or one month). The invention is equally applicable to matrix and liquid and solid reservoir multilaminate transdermal systems assuming the patch components and patch functionality demonstrate sufficient stability

The disclosure provides a packaging of transdermal delivery systems in multi-patch format where several patches are located on a common release liner and the liner containing the patches is sealed into a pouch. In one embodiment, the pouch is resealable following the initial opening. In other embodiments, the patches are located on the common liner with abutting edges or with spacing between the patch edges.

In another embodiment, more than one common liner, each with more than one transdermal patch, is placed in the pouch. The number of patches on the common liner and their spatial arrangement can be established to improve dosing compliance by corresponding to recurring calendar events. The number of patches on the common liners and their spatial arrangement can also be established to improve dosing compliance by corresponding to recurring calendar events.

In other embodiments, the patches on the common liner are of multiple sizes to allow dose titration by the patient. In other embodiments, the patches on the common liners are of multiple sizes to allow dose titration by the patient. In other embodiments, the patches on the common liner are sequentially numbered to facilitate dosing compliance by the patient. In other embodiments, the patches on the common liners are sequentially numbered to facilitate dosing compliance by the patient.

The disclosure also provides a dosage regimen to a subject comprising providing the packaging arrangement described above.

BRIEF DESCRIPTION OF FIGURES

Figure 1 is a cross-sectional view of a matrix transdermal patch system.

· Layer 1 is the system backing film.

• Layer 2 is the adhesive drug matrix.

• Layer 3 is the removable release liner.

Figure 2 is a cross-sectional view of a multilaminate, solid reservoir transdermal system.

Layer 1 is the system backing film.

Layer 4 is the solid drug reservoir.

Layer 5 is the rate controlling membrane.

Layer 6 is the contact adhesive.

Layer 3 is the removable release liner.

Figure 3 is a cross-sectional view of a multilaminate, liquid reservoir transdermal system Layer 1 is the system backing film.

Layer 7 is the liquid drug reservoir sealed between the backing and membrane.

Layer 5 is the rate controlling membrane.

Layer 6 is the contact adhesive.

Layer 3 is the removable release liner.

Figure 4 is a view of transdermal patches with abutting edges on a single release liner. This embodiment represents a four week supply of transdermal patches.

• Item 8 is one of several transdermal patches on a common release liner.

• Item 9 shows the kiss cut through the patch down to the liner upper surface to allow removal of individual patches from the common liner.

Figure 5 is a view of transdermal patches with spacing between edges on a single release liner. This embodiment represents a thirty day supply of transdermal patches.

• Item 10 is one of several patches on a common release liner.

• Item 11 is the common release liner.

Figure 6 is a view of a resealable pouch containing a 30 day duration of patches on a single release liner with spacing between edges.

• Item 12 is the pouch for containing the transdermal patches.

• Item 13 is the heat seal closing the pouch for storage before initial use.

• Item 14 denotes the cut line for initial pouch opening.

• Item 15 is the interlocking manual resealing strip.

• Item 16 is the transdermal patches on a common release liner (as shown in Figure 5) inside the pouch. DETAILED DESCRIPTION

Transdermal drug delivery systems are available in three primary types. These are the drug in adhesive matrix design (Figure 1), the solid reservoir multilaminate design (Figure 2), and the Liquid reservoir multilaminate design (Figure 3). All three designs have the common components of a system backing layer, an adhesive layer for adhering the patch to the skin, and a release liner layer. The purpose of the release liner is to protect the adhesive layer until patch use when it is removed and discarded. All transdermal patches have cut edges at least for the contact adhesive layer. The cut edges potentially allow loss of drug to the surrounding environment and ingress of potentially reactive oxygen and water vapor into the patch. For some patches, additional components, such as permeation enhancers, may similarly experience loss or reaction. To prevent loss or reaction of drug and other components, transdermal patches are generally placed individually in impermeable pouches and the pouches heat sealed to establish a barrier. Many transdermal product formulations contain drugs or other components that require this maximization of protection from loss or reaction. For these products, the costs associated with individual pouching of patches must be borne, eventually by the consumer, to achieve acceptable product stability.

Other transdermal products are not characterized by the above discussed instabilities. For these products, pouching of the patches provides the simpler protection against contamination or adulteration during shipping and storage prior to distribution to the consumer. Once in the consumer's hand, the high barrier properties of the individual pouches are no longer required and represent wasted cost. For these patches, the individual pouch can be replaced by a single resealable pouch containing multiple patches on a common release liner. For shipping and distribution, the pouch containing multiple patches would be heat sealed exactly as a single patch pouch. The consumer would remove this heat seal upon the initial opening of the pouch, remove the sheet of patches on the common release liner, remove one patch from the liner, leaving the liner intact, apply the patch to their skin, replace the liner with the remaining patches in the pouch, and manually reseal the pouch using the provided interlocking seal.

Patches can be arranged on the common liner with abutting edges to minimize the liner size and manufacturing waste. In this arrangement, the patches are kiss cut at the edges through all layers of the patch down to the common release liner. In an alternative arrangement, the patches are cut in a corresponding manner, but with removal of a web of waste between the patches, leaving patches with spacing between the edges on the common release liner. This arrangement may facilitate patch removal from the liner for some patches. The patches can be arranged on the liner in such a manner as to facilitate dosing compliance by presenting the product such that it corresponds to recurring calendar events. In one example, the common liner might contain four rows of seven patches with each row corresponding to a week of dosing of a 24 hour duration patch. Many such arrangements are possible depending on the size and dosing duration of the patch. In some instances, it may be desirable for the pouch to contain more than one common liner as long as each common liner contains multiple patches.

Other arrangements are also possible. The patches can be arranged to correspond with any week or month on a calendar. In this way, the dosing schedule of the patches is shown and compliance can be monitored as patches are removed from the backing. In other embodiments, the specific arrangement of the weeks of the month is not specified, but dates that could match with any month are displayed on each patch on a multi-patch backing. In certain embodiments, the backing contains 28, 29, 30 or 31 patches. In certain embodiments, the multi-patch backing includes 31 patches.

In some embodiments, each day represented on a common liner corresponds with more than one patch. In these embodiments, In some specific embodiments, each day includes 2, 3, 4, 5, 6, 7, 8, 9, 10 or more patches they correspond with each day on a common liner. In certain embodiments, each patch is meant to be administered at a specific time of day. In some of these embodiments, the time each patch is meant to be administered is printed on the backing of the patch or around where the patch is located on the common liner. In other embodiments, either the morning (AM) or afternoon/evening (PM) is indicated for each patch for each day.

In certain embodiments, each patch includes a symbol on the removable release liner or the system backing film or both. In some embodiments, the symbol on the removable release liner is visible when the patch is removed from the common liner. In other embodiments, the symbol is visible on the system backing film both when the patch is still on the common liner and when the patch is applied to a subject. The symbol can be a date, time, drug type or any other symbol that helps to identify the patch and when it should be administered. In certain embodiments, the symbol on the removable release liner indicates that the patch has been used. This symbol could be an "X".

In certain embodiments, the patches on a common liner each have varying doses of active agent. In some of these embodiments, a symbol associated with each patch indicates the dose associated with the patch. The disclosure also provides kits with multiple sheets of common liners each with multiple transdermal patches. Each of these common liners can be associated with the dosing schedule of patches for any given period of time. These periods of time can be days, weeks months or years, For example, each sheet can be associated with the dosing of patches for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23 or 24 hours. In other embodiments, each sheet is associated with dosing of patches for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or 31 days. In other embodiments, each sheet is associated with dosing of patches for 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months. In other embodiments, each sheet is associated with dosing of patches for 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 years.

EXAMPLE

A transdermal nitroglycerin product according to Figures 1, 4, and 6 where:

The system backing layer is a bilaminate film of PET and EVA (3M

Scotchpak® 9730)

The release liner is a fluoropolymer coated PET film (3M Scotchpak®

1022)

The drug containing matrix layer is 6 weight percent nitroglycerin in an acrylic adhesive such as Duro Tak® 87-2510. The adhesive layer is approximately 4 mils thick. The adhesive layer is cast from solvent onto the release liner, the backing is laminated to the adhesive. The finished trilaminate is kiss cut to create removable individual patches on the release liner, and the section of liner containing the desired number of individual patches is cut. The dosage strength of the patch is determined by its area. The common liner containing the individual patches is placed in the resealable pouch and a permanent heat seal is made outside of the resealable seal area.