Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Web – sheet or filament bases; compositions of bandages; or...
Reexamination Certificate
1999-02-06
2002-01-08
Dodson, Shelley A. (Department: 1616)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Web, sheet or filament bases; compositions of bandages; or...
C424S448000
Reexamination Certificate
active
06337086
ABSTRACT:
BACKGROUND OF THE INVENTION
This invention relates to a transdermal drug delivery device for the controlled release of a pharmaceutical agent which contains a silicone skin contact pressure-sensitive adhesive made from an adhesive composition which contains a well defined concentration of silanol such that it remains adherent to the skin.
Pressure sensitive adhesive (PSA) compositions are well known in the art and many are commercially available. Generally, silicone PSA's are produced by either blending or condensing a silicone resin and a polydiorganosiloxane. These types of silicone pressure sensitive adhesives have been disclosed for example in U.S. Pat. Nos. 2,736,721, 2,814,601, 2,857,356, and 3,528,940. The adhesion of such materials can be varied by altering the ratio of units in the resinous material or the ratio of resin to polydiorganosiloxane.
The use of silicone based PSAs in transdermal drug delivery devices is also known in the art. Examples of such devices can be found in U.S. Pat. Nos. 3,731,683 (Zaffaroni); U.S. Pat. No. 3,797,494 (Zaffaroni); U.S. Pat. No. 4,031,894 (Uhrquhart, et al.) and U.S. Pat. No. 4,336,243 (Sanvordeker, et al.). Such devices are held in contact with the skin by means of a pressure-sensitive adhesive and the devices are typically intended to be left in contact with the skin for a period of 24 hours or more. In view of the extended period of contact with the skin, the adhesive should be capable of adhering to the skin for at least that length of time and should also be reasonably non-irritating and non-sensitizing to the skin.
Silicone pressure-sensitive adhesives are known to be non-irritating and non-sensitizing to the skin and have been used as adhesives for certain devices such as those for the controlled release of nitroglycerine. Silicone PSAs are known in the art and are commercially available.
U.S. Pat. No. RE 35,474 teaches a transdermal drug delivery device for the controlled delivery of amino-functional drugs. This patent teaches that aminofunctional drugs interfere with the properties of PSAs by catalyzing the reaction of silicon bonded hydroxyl (silanol) groups and, thereby, cause increased increase shear of the PSA material and, thus, loss of tack during storage. The reference teaches that this effect can be inhibited by chemically treating the PSAs with an agent which reduces their silanol content. This patent, however, teaches that the amount of agent used to treat the PSA must be an amount of at least 0.8 moles triorganosilyl units for every mole of silanol. This amount of treating agent generally reduces the silanol concentration of the PSA to levels below about 7700. The present inventors, however, have now discovered that when the silanol content is too low, further crosslinking of the adhesive network is sufficiently reduced and this loosely crosslinked network becomes plasticized and oozy, thus resulting in poor PSA quality.
Accordingly, one of the objects of the present invention is to provide silicone PSAs having a low, but well defined concentrations of silanol are useful in transdermaldrug delivery device applications.
SUMMARY OF THE INVENTION
The present invention relates to a transdermal drug delivery device for the controlled transdermal delivery of an active pharmaceutical agent. The device comprises (A) a drug delivery device comprising an active pharmaceutical agent and a means for its controlled delivery through the skin; and (B) a silicone pressure sensitive adhesive for maintaining contact between the device and the skin of a wearer. The silicone pressure sensitive adhesive comprises (i) between about 40 and about 70 parts by weight of at least one resin copolymer comprising triorganosiloxy units of the formula R
3
SiO
1/2
and tetrafunctional siloxy units of the formula SiO
4/2
in a ratio of about 0.6 to 0.9 triorganosiloxy units for each tetrafunctional siloxy unit and (ii) between about 30 and about 60 parts by weight of at least one polydiorganosiloxane comprising ARSiO units terminated with endblocking TRASiO
1/2
units, wherein the polydiorganosiloxane has a viscosity of from about 100 centipoise to about 30,000,000 centipoise at 25° C. and each R is as above, each A radical is independently selected from R or halohydro-carbon radicals having from 1 to 6 inclusive carbon atoms, each T radical is independently selected from the group consisting of R, OH, H or OR′, and each R′ is independently an alkyl radical of from 1 to 4 inclusive carbon atoms. The silanol content of the silicone pressure sensitive adhesive composition is reduced by chemically treating at least a portion of (i), (ii) or the mixture of (i) and (ii) with at least one chemical treating agent (iii) that reacts with silicon-bonded hydroxyl groups to reduce the silicon-bonded hydroxyl content of the composition to a range of between about 8000 and about 13,000.
The present invention also relates to methods for producing the above silicone pressure sensitive adhesive compositions.
DETAILED DESCRIPTION OF THE INVENTION
The present invention is based on the unexpected discovery that silicone pressure sensitive adhesive (PSA) compositions must contain a certain concentration of silicon bonded hydroxyl groups (silanol) to be useful for certain applications. Specifically, when silicone PSAs are used in transdermal drug delivery devices, the silanol content of the PSA must be adjusted based on the active pharmaceutical agent to ensure that the adhesive strength remains acceptable over time. When the silanol content of the adhesive is too high, the drug can cause the silanols to condense, resulting in increased shear of the adhesive and, thus, decreased adhesive strength. When the silanol content of the adhesive is too low, on the other hand, there is little crosslinking of the adhesive network and the materials is plasticized (softened) to too high a degree, thus resulting in unwanted flow (cold flow).
The transdermal drug delivery devices used in the present invention are not critical and many such devices are known in the art and are available commercially. Generally, they comprise an active pharmaceutical agent (drug) and a means for its controlled delivery through the skin. In one generic embodiment, the device can comprise a suitable reservoir for holding the drug and the means for controllably releasing the drug. In another embodiment, the device can comprise a matrix, such as, for example, the drug and the PSA or a layered matrix such as, for example, a matrix with a layer of the PSA. Similarly, the device could be an elastomeric body (which could be adhesive in nature) impregnated with a drug, wherein the elastomer matrix controls the release of the drug.
Generally, one surface of the transdermal drug delivery device is coated with a silicone pressure-sensitive adhesive to maintain the device in contact with the skin of the wearer. If desired, a backing material comprising a conventional drug impermeable film coated with a conventional release coating for silicone PSAs can be applied over the silicone PSA during storage.
When the device coated with the silicone PSA comes in contact with the skin, the drug diffuses from the device, including the PSA, at a controlled rate and permeates through the epidermis into the dermis. This diffusion-permeation process allows the drug device to maintain a therapeutic concentration for 24 hours or more. As such, it can be seen that the drug will come into contact with the silicone PSA and, thus, may cause untoward reactions.
As is well known to those skilled in the art, other types of transdermal drug delivery devices are available and, with the exception of a drug in combination with silicone PSAs as will be described in more detail below, the form of the transdermal drug delivery device and means by which the delivery of such drugs are controlled are not critical. For example, the elastomeric body could be replaced by a solution of the drug to be delivered contained within a container comprising a semipermeable membrane which controls the release rate of the drug to the skin. T
Kanios David Paul
Mantelle Juan
Nartker Linda Sue
Raul Victor Albert
Ulman Katherine Lynn
Dodson Shelley A.
Dow Corning Corporation
Gobrogge Roger E.
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