Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Web – sheet or filament bases; compositions of bandages; or...
Reexamination Certificate
1995-12-26
2001-11-13
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...
C424S078020, C424S449000, C424S486000, C424S487000
Reexamination Certificate
active
06316022
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention is directed to a transdermal drug delivery system containing low molecular weight drugs which are liquid at or about room temperatures, its method of making and method of use. In particular, the present invention is directed to a transdermal drug delivery system for the transdermal application of one or more drugs, which during processing is substantially free of water and liquids which have a normal boiling point (a) optionally below processing temperatures and (b) greater than or equal to the normal boiling point of the low molecular weight drugs, and to a transdermal drug delivery system which comprises a polymer matrix including high shear resistance polymers.
2. Description of Related Art
The use of a transdermal drug delivery system, for example a pressure-sensitive adhesive containing a medicament, namely, a drug, as a means for administering therapeutically effective amounts of the medicament is well known. Such known delivery systems involve incorporation of a medicament into a carrier such as a polymeric and/or a pressure-sensitive adhesive formulation. The pressure-sensitive adhesive must adhere effectively to the skin and permit migration of the medicament from the carrier through the skin and into the bloodstream of the patient.
The use of low molecular weight drugs, which are generally liquid at or about room temperatures, such as deprenyl [phenyl isopropylmethylpropynylamine, N, ∝-dimethyl-N-2-propynyl-benzeneethanamine]: and more particularly the levorotatory form of the compound, also known as L-deprenyl, L-deprenil, L-deprenaline and selegiline and hereinafter referred to broadly as selegiline), in treating human beings or other animals is well known in the art. For example, WO 91/185592 describes the use of selegiline for treating Parkinson's disease and increasing the life-expectancy of human beings. U.S. Pat. No. 5,192,808 describes the use of selegiline in the treatment of Cushing's disease in humans and animals.
The use of low molecular weight drugs such as selegiline, in transdermal compositions is also generally known in the art. For example, European patent application 509,761 and PCT WO 89/09051 describe the use of transdermal compositions containing selegiline for the treatment of Parkinson's disease. WO 92/21333 describes the use of a transdermal composition containing selegiline for treating withdrawal symptoms and reducing the craving of addictive psychostimulants, addictive opiates, alcohol, or nicotine. The compositions described in WO 89/09051 include a transdermal preparation of a mixture of L-deprenyl in the hydrophilic polymer Eudragit E 100 and a non-swellable acrylate polymer Durotack 28-2416 and a plasticizer such as Brij 97. European patent application no. 473,252 and Canadian patent application no. 2,022,552 describe the use of selegiline in transdermal compositions for the treatment of Parkinson's disease. U.S. Pat. No. 5,242,950 describes the use of a transdermal patch containing selegiline for macular degeneration. U.S. Pat. No. 4,868,218 describes the transdermal application of selegiline in the treatment of depression. Nicotine and nitroglycerine are drugs, normally liquid at or about room temperatures, for which there is considerable art on transdermal use.
However, most reported transdermal systems, such as those described above, use drugs having the salt form of a base drug which is less volatile and has a much higher boiling point than the free-base form of the drug. Transdermal drug delivery systems which use the free-base form of the drug, all suffer from the loss of the drug during manufacture of the transdermal system. This loss is due to the volatile nature of the drug during the drying stage in the production of cast systems. European patent application 593,807 describes a transdermal system that attempts to solve the problem of liquid drug loss. However, this transdermal system requires the use of multilayers of polymeric adhesive which contributes toward increased cost and complexity.
Another related problem with liquid, low molecular weight drugs, is the plasticizing effect that the drug has on the polymer matrix in the transdermal drug delivery system. Namely, the low molecular weight base form of the drug has an excessive plasticizing effect on the polymer, resulting in a composition that is “leggy or gummy.” This renders the composition unsuitable for adhesion to the epidermis.
SUMMARY OF THE INVENTION
One object of the present invention is to provide a transdermal drug delivery system which does not suffer from the substantial loss of low molecular weight drugs which are liquid at or about room temperatures, during production of the transdermal system. Another object of the present invention is to produce a low molecular weight drug containing transdermal drug delivery system which is simpler in composition and design than the transdermal systems known in the art.
Still another object of the present invention is to provide a high loadable transdermal drug delivery system which contains a therapeutically effective amount of one or more drugs at least one of which is of low molecular weight and liquid at or about room temperatures, but does not excessively plasticize the polymer or polymers of the transdermal drug delivery system.
In accomplishing the foregoing objects, there has been provided according to one aspect of the present invention a pressure sensitive transdermal drug delivery system comprising: a blend of (a) one or more polymers; and (b) a therapeutically effective amount of one or more drugs, at least one of which is of low molecular weight and liquid at or about room temperatures. The system is substantially free of water and liquids having a normal boiling point (a) optionally below processing temperatures and (b) equal to or greater than (≧) the normal boiling points of the low molecular weight drugs.
In another preferred embodiment, the low molecular weight and liquid drug comprises selegiline, especially the free base form. In still another preferred embodiment, the acrylic-based polymer is present in an amount of about 10 to about 90 weight per cent (%) based on the dry weight of the total transdermal system. In still another preferred embodiment, the polymer is a pressure-sensitive adhesive, which includes a blend of an acrylic-based polymer and a silicone-based polymer. In yet another preferred embodiment, the drug is present in an amount from about 1-40 weight %, preferably from about 5-25 weight % and more preferably from about 8-16 weight %, based on the dry weight of the total transdermal system.
According to another aspect of the present invention, there has been provided a method of producing a transdermal drug delivery system. The method comprises the steps of producing a blend of: (a) one or more polymers in a volatile solvent(s); and (b) a therapeutically effective amount of one or more drugs, at least one of which is of low molecular weight and liquid at or about room temperatures. The blend is substantially free of water and liquids having a normal boiling point which is ≧ the normal boiling points of the one or more low molecular weight drugs other than the volatile solvents. The blend is then formed into a polymer matrix and the polymer matrix is dried to remove the volatile solvents. The resulting system is substantially free of water and liquids having a normal boiling point (a) optionally below processing temperatures and (b) ≧ the normal boiling points of the one or more low molecular weight drugs.
According to still another aspect of the present invention, there has been provided a method of treating a human with a therapeutically effective amount of one or more low molecular weight drugs which are liquid at or about room temperatures. The method comprises the steps of: (1) applying to the skin of a human, a transdermal drug delivery system which comprises a blend of: (a) one or more polymers; and (b) a therapeutically effective amount of one or more drugs,
Houze David
Mantelle Juan
Dodson Shelley A.
Foley & Lardner
Noven Pharmaceuticals Inc.,
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