Transdermal delivery patch

Abstract

A composition suitable for use in a transdermal delivery patch for administration of a biologically active compound, the composition comprising a phosphate compound of tocopherol and a polymer carrier.

1 . A matrix layer suitable for use in a transdermal delivery patch for administration of a biologically active compound, the matrix layer comprising a mixture of a mono-tocopheryl phosphate compound and a di-tocopheryl phosphate compound and a polymer carrier wherein the polymer carrier is present in an amount within the range of about 30% w/w to about 95% w/w of the total concentration of the matrix layer. 
     
     
         2 . The matrix layer of  claim 1 , wherein the mono-tocopheryl phosphate compound is selected from the group consisting of mono-(tocopheryl)phosphate, mono-(tocopheryl)phosphate monosodium salt, mono-(tocopheryl)phosphate disodium salt, mono-(tocopheryl)phosphate monopotassium salt and mono-(tocopheryl)phosphate dipotassium salt, and the di-tocopheryl phosphate compound is selected from the group consisting of di-(tocopheryl)phosphate, di-(tocopheryl)phosphate monosodium salt and di-(tocopheryl)phosphate monopotassium salt. 
     
     
         3 . The matrix layer of  claim 1 , wherein the ratio (% w/w) of the mixture of the mono-tocopheryl phosphate compound and the di-tocopheryl phosphate compound is at least 2:1, within a range of about 4:1 to about 1:4, within a range of about 6:4 to about 8:2, about 2:1, about 6:4, or about 8:2. 
     
     
         4 . The matrix layer of  claim 1 , wherein the mixture of the mono-tocopheryl phosphate compound and the di-tocopheryl phosphate compound is present in an amount within a range of about 0.01% w/w to about 10% w/w, within the range of about 0.1% w/w to about 5% w/w, within the range of about 0.1% w/w to about 3% w/w, within the range of about 0.1% w/w to about 2% w/w, within the range of about 0.1% w/w to about 1%/w/w or within the range of about 0.1% w/w to about 0.5% w/w, of the total concentration of the matrix layer. 
     
     
         5 . (canceled) 
     
     
         6 . The matrix layer of  claim 1 , wherein the polymer carrier comprises a natural or synthetic polymer, co-polymer, terpolymer, or combination thereof. 
     
     
         7 . The matrix layer of  claim 6 , wherein the natural polymers are selected from the group consisting of rubbers, elastomers, polysaccharides including cellulose, natural resins including shellac and amber; and, the synthetic polymers are selected from the group consisting of acrylates, polyacrylates, polyalkyl acrylates, polyamides, polyesters, polycarbonates, polyimides, polystyrenes, acrylonitrile butadiene styrene, polyacrylonitrile, polybutadiene, poly(butylene terephthalate), poly(ether sulphone), poly(ether)ketones, polyethylene, poly(ethylene glycol), poly(ethylene terphthalate), polypropylene, polytetratfluoroethylene, styrene-acrylonitrile resin, poly(trimethylene terephthalate), polyurethanes, polyvinyl butyral, polyvinylchlorides, polyvinylidenedifluoride, povidones, poly(vinyl pyrrolidone), polychloroprene, fluoroelastomers, chloro-sulphonated rubbers, hypromellose, polyolefine elastomer, polyacrylamide, chlorinated polyethylene, polyethersulphone, nylon, liquid crystal polymers, polyethylene terephthalate (PET), polyphenylsulphone, polypthalaminepolyvinyl alcohol derivatives, poly ethylene glycols, ethylene vinyl acetate, polymethyl methacrylate, cellulose derivatives such as ethyl cellulose, hydroxylpropyl methyl cellulose, sugar derivatives (gums) including derivatives of sorbitol and mannitol, silicone oil and silicone oil derivatives, polysiloxanes including amine-resistant polysiloxanes, and siloxanes. 
     
     
         8 . The matrix layer of  claim 6 , wherein the polymer carrier is selected from acrylates, povidones, siloxanes, polyvinyl pyrrolidone, polysiloxanes, amine-resistant polysiloxanes, polyalkyl acrylates, and polymethyl methacrylates. 
     
     
         9 . The matrix layer of  claim 1 , wherein the polymer carrier is present in an amount within the range of about 30% w/w to about 80% w/w, or within the range of about 55% w/w to about 65% w/w, of the total weight of the matrix layer. 
     
     
         10 . The matrix layer of  claim 1 , wherein the polymer carrier is present in an amount within the range of about 85% w/w to about 95% w/w, or within the range of about 90% w/w to about 95% w/w, of the total weight of the matrix layer. 
     
     
         11 . The matrix layer of  claim 1 , wherein the polymer carrier further comprises inert carrier components selected from the group consisting of anti-tacking agents, tackifiers, and plasticizers. 
     
     
         12 . The matrix layer of  claim 11 , wherein the anti-tacking agent is succinic acid. 
     
     
         13 . The matrix layer of  claim 11 , wherein the anti-tacking agent is present in an amount of less than about 1%/w/w, up to about 1%/w/w, or up to about 5% w/w, of the total weight of the matrix layer. 
     
     
         14 . (canceled) 
     
     
         15 . The matrix layer of  claim 11 , wherein the tackifier is selected from the group consisting of acrylic, N-butyl-methacrylic copolymer, acrylic methyl, acrylic 2-ethylhexyl copolymer, polyacrylic acid, methacrylic copolymer L, aminoalkylmethacrylate copolymer E, rosin esters, hydrogenated rosins, dipropylene glycol dibenzoate, mixed hydrocarbons, and acrylic copolymers. 
     
     
         16 . The matrix layer of  claim 11 , wherein the plasticizer is selected from the group consisting of phthalates, esters of polycarboxylic acids with linear or branched aliphatic alcohols of moderate chain length, acetylated monoglycerides, alkyl citrates, triethyl citrate (TEC), acetyl triethyl citrate (ATEC), tributyl citrate (TBC), acetyl tributyl citrate (ATBC), trioctyl citrate (TOC), acetyl trioctyl citrate (ATOC), trihexyl citrate (THC), acetyl trihexyl citrate (ATHC), butyryl trihexyl citrate (BTHC, trihexyl o-butyryl citrate), trimethyl citrate (TMC), methyl laurate, lauric acid, lauryl lactate, lauryl alcohol, alkyl sulphonic acid phenyl ester, diethylene glycol monoethyl ether, bis(2-ethylhexyl)phthalate (DEHP), diisooctyl phthalate (DIOP), bis(n-butyl)phthalate (DnBP, DBP), diisobutyl phthalate (DIBP), bis(2-ethylhexyl)adipate (DEHA), dimethyl adipate (DMAD), monomethyl adipate (MMAD), dioctyl adipate (DOA), ethyl oleate, sorbitan monooleate, glycerol monooleate, dibutyl sebacate (DBS), dibutyl maleate (DBM), diisobutyl maleate (DIBM), benzoates, epoxidized vegetable oils, tris(tromethamine), N-ethyl toluene sulfonamide (o/p ETSA), N-(2-hydroxypropyl)benzene sulfonamide (HP BSA), N-(n-butyl)benzene sulfonamide (BBSA-NBBS), tricresyl phosphate (TCP), tributyl phosphate (TBP), triethylene glycol dihexanoate (3G6, 3 GH), tetraethylene glycol diheptanoate (4G7), 1,3-butyleneglycol, dipropylene glycol, PEG400, Span 80, and polyvinylpyrrolidone. 
     
     
         17 . The matrix layer of  claim 11 , wherein the inert carrier components are present in an amount within the range of 0.001% w/w to about 50% w/w, within the range of 0.001% w/w to about 40% w/w, or within the range of 0.001% w/w to about 30% w/w, of the total weight of the matrix layer. 
     
     
         18 . The matrix layer of  claim 1 , wherein the matrix layer comprises an anti-tacking agent and a plasticizer in a total amount of about 35% w/w of the total weight of the matrix layer. 
     
     
         19 . The matrix layer of  claim 18 , wherein the anti-tacking agent is succinic acid and the plasticizer is dibutyl sebacate. 
     
     
         20 . The matrix layer of  claim 1 , wherein the polymer carrier and optional inert carrier components is present in an amount within the range of about 50% w/w to about 99% w/w, within the range of about 80% w/w to about 98% w/w, within the range of about 90% w/w to about 98% w/w, or in an amount of about 95% w/w, of the total weight of the matrix layer. 
     
     
         21 - 22 . (canceled) 
     
     
         23 . A transdermal delivery patch for administration of a biologically active compound comprising a matrix layer as defined in  claim 1 . 
     
     
         24 - 40 . (canceled) 
     
     
         41 . A method for preparing a transdermal delivery patch for administration of a bioloigically active compound comprising the steps of:
 (i) combining a polymer carrier and optional inert carrier components with a suitable solvent;   (ii) combining (i) with a dispersion comprising a biologically active compound and a mixture of a mono-tocopheryl phosphate compound and a di-tocopheryl phosphate compound;   (iii) stirring (ii) until complete homogenisation is achieved;   (iv) placing the composition of (iii) in a suitable mould or casting the composition of (iii) on a surface;   (v) drying the composition under heat.   
     
     
         42 - 43 . (canceled)