Adhesive bonding and miscellaneous chemical manufacture – Methods – Surface bonding and/or assembly therefor
Reexamination Certificate
1995-09-22
2001-11-13
Mayes, Curtis (Department: 1734)
Adhesive bonding and miscellaneous chemical manufacture
Methods
Surface bonding and/or assembly therefor
C156S250000, C156S270000, C156S301000
Reexamination Certificate
active
06315854
ABSTRACT:
The present invention relates to a process for the continuous production of transdermal therapeutic patches having a backing layer, a pressure-sensitive adhesive drug-reservoir-layer, and a removable protective layer, wherein the loss of active substance caused by production is minimized.
A transdermal therapeutic patch (hereinafter abbreviated to TT-patch) is a dosage form which is to be applied to the skin and looks like a traditional plaster, it contains drugs which are to be released via the skin and is known as “Transdermal Therapeutic System”. A therapeutic system may contain one or more drugs which are continuously released at a predetermined rate over a defined period of time to a defined site of application (“Heilmann, Klaus: Therapeutische Systeme—Konzept und Realisation programmierter Arzneiverabreichung”[“Therapeutic Systems—Concept and Realization of Programmed Administration of Drugs”], 4th edition, Ferdinand Enke Verlag Stuttgart, 1984, page 26).
The therapeutic use of such forms of medication is known. In general these forms of administration are composed of several layers and—in the most simple case—consist of a backing layer, a self-adhesive active substance reservoir, and a protective layer which is to be removed prior to application. For obvious reasons, the design of choice for TT-patches is a round or geometric shape having rounded edges. Processes suitable for the series production of TT-patches must ensure a uniform drug content in the individual patches. These processes should be so simple that production can be carried out economically efficient, i.e., above all the loss of active substance must be kept as low as possible.
Such processes are known. A medicinal release system for administering an active substance via the skin is described in German Patent No. 32 22 800; it consists of a support, an adjacent reservoir containing an active substance and a liquid, a Theological agent, such as cellulose, a polysaccharide, or a silicon compound, and a membrane bordering the reservoir for determining the release rate of the active substance from the system. This system exhibits several shortcomings. For example, the individual dosage by spreading a liquid preparation on a defined area and at a defined thickness is very difficult, and a loss of active substances must be expected during production since single pieces have to be eliminated due to diverging drug loads. In addition, if the membrane gets damaged, abrupt drug release must be expected and this might result in fatal consequences to the patient.
German Patent No. 36 29 304 describes a therapeutic system consisting of a drug depot which is covered by a backing layer and contains a liquid active substance or a liquid drug preparation and one or more adjuvants having supporting and distributing functions being completely surrounded by a matrix, a matrix controlling the active substance release, and a pressure-sensitive adhesive fixation facility. The shortcoming of this system is the fact that only liquid drugs or drug preparations may be used and the complicated dosage thereof makes production without drug losses nearly impossible.
In the process for the manufacture of TT-plasters described in German Patent No. 33 15 272 pressure-sensitive adhesive layers containing active substances are applied to a protective layer which is impermeable to the active substance and covered with a likewise impermeable backing layer. Except for the removable protective layer, all layers are cut through when the individual plasters are punched out. The loss of active substance may be considerable due to the refuse remaining between the individual plasters; in this connection it must be considered that the active substances used in transdermal therapy represent hazardous waste.
It is accordingly the object of the present invention to provide a continuous process for manufacturing TT-patches wherein losses of active substance are prevented to a large extent and which does not involve a great deal of technical expenditure. In this process the drug reservoir is produced by known coating techniques, such as coating with drug-containing solutions of pressure-sensitive adhesives, aqueous pressure-sensitive adhesive dispersions, or molten pressure-sensitive adhesive masses.
The drug-containing reservoir consisting of a drug-containing pressure-sensitive adhesive layer and a backing layer is cut into squares or rectangles by cross cutting and slitting the coating material. The quadrangular reservoirs, with the layer formed by the drug-containing pressure-sensitive adhesive, are centrically placed at the desired distances on a removable protective layer projecting in all directions. Subsequently, the protective layer is covered with a backing layer coated with a drug-free pressure-sensitive adhesive. The backing layer is considerably wider than the active substance reservoirs, however, it need not be as wide as the protective layer. Thus the reservoir's backing layer acts as a barrier layer preventing the drug from migrating into the drug-free pressure-sensitive adhesive layer.
After coating, the laminate consisting of a removable film and the drug-containing pressure-sensitive adhesive layer, is covered with a flexible film, which film will serve as a barrier layer in the final product. Then the laminate of removable film, drug-containing pressure-sensitive adhesive layer and flexible film is cut into narrow rolls. By cutting in a transverse direction to the tape and stripping the removable film, quadrangular laminates are obtained consisting of a drug-containing pressure-sensitive adhesive layer (the drug reservoir) and a flexible film. Said quadrangular laminates, with the drug-containing pressure-sensitive adhesive layer, are centrically placed at the desired distances on a removable protective layer projecting at all sides. Subsequently, the protective layer is covered with a backing layer coated with a drug-free pressure-sensitive adhesive, which backing layer is considerably wider than the drug reservoirs, but need not be as wide as the protective layer. Thus the flexible film on the drug reservoir acts as a barrier layer, preventing the drug from migrating into the drug-free pressure-sensitive adhesive layer.
The subsequent punching is carried out along the outlines running at a distance of the drug reservoirs. In this process, the pressure-sensitive adhesive backing layer is cut through whereas the removable protective layer remains intact. The lattice remaining between the individual patches is drug-free waste. The TT-patches according to the present invention are obtained by cutting the protective layer between the reservoirs, the cuts being made vertically with respect to the longitudinal direction.
The TT-patch according to the present invention exhibits a multi-layer structure. The backing layer may consist of flexible or non-flexible material. Polymeric films or metal foils, such as aluminium foils alone or coated with a polymeric substrate, may be used for the production thereof. Textile fabrics may also be used, provided that they are impermeable to the components of the drug-free pressure-sensitive adhesive layer which may optionally consist of a plasticizer or a tackifier. In a preferred embodiment of the present invention, the backing layer is an aluminized foil.
The pressure-sensitive adhesive layer consists of a polymeric matrix with a base polymer and, optionally, common additives. Examples of suitable polymers comprise silicones, rubber, rubber-like synthetic homo-polymers, copolymers or block polymers, polyacrylates and the copolymers thereof, and esters of hydrogenated colophony. In principle all polymers are suitable which are used in the production of pressure-sensitive adhesives and are physiologically acceptable. Particularly preferred are those consisting of acrylate and/or methacrylate when present as block copolymers based on styrene and 1,3-dienes, polyisobutylenes, or polymers and copolymers. Linear styrene styrene-isoprene-styrene block copolymers are preferably used among the bloc
Anhauser Dieter
Deurer Lothar
Hille Thomas
Steinborn Peter
Collard & Roe PC
LTS Lohmann Therapie-Systeme GmbH & Co. KG
Mayes Curtis
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