Oral transmucosal delivery of drugs or any other ingredients via the inner buccal cavity

Abstract

A device and method for the oral transmucosal delivery of active substances to the oral cavity utilizing an unplasticized polyvinyl pyrrolidone polymer (PVP) as the primary mucoadhesive. The device is applied and adheres to the mucosa of the oral cavity without causing side effects or leaving an unpleasant taste. Preferably the device is a bilayer tablet having a mucoadhesive layer and an overlying active substance containing layer. The mucoadhesive layer may contain PVP as the only adhesive or may be combined with other hydrophilic polymeric substances. The active layer also contains a hydrophilic polymer carrier. The layers in the device dissolve and release the active substance to the oral cavity and is particularly adapted for the delivery of substances active in the oral cavity such as breath fresheners and substances to combat dry mouth. It is also useful for the delivery of ionic drugs such as peptides.

What is claimed is:  
     
         1 . A device for the oral transmucosal delivery of active substances to the oral cavity comprising a mucoadhesive layer and at least one overlying active substance layer said mucoadhesive layer having one surface adapted to contact the mucosal surface of the oral cavity for adhering thereto and an opposing surface in contact with and adhering to an overlying active substance containing layer characterized in that the mucoadhesive layer contains a mucoadhesive composition comprising at least 50% by weight of a non-plasticized polyvinyl pyrrolidone polymer having a weight average molecular weight of between about 10,000 and 700,000.  
     
     
         2 . A device according to    claim 1    wherein said mucoadhesive layer contains from 20 to 99% by weight of said mucoadhesive composition.  
     
     
         3 . A device according to    claim 2    wherein said mucoadhesive composition consists of non-plasticized polyvinyl pyrrolidone polymer.  
     
     
         4 . A device according to    claim 2    wherein said mucoadhesive composition comprises about 50 to 95% by weight of non-plasticized polyvinyl pyrrolidone polymer and 5 to 50% by weight of an additional functionally suitable hydrophilic polymer or copolymer.  
     
     
         5 . A device according to    claim 4    wherein said additional hydrophilic polymer or copolymer is a member selected from the group consisting of acrylic acid polymers, hydroxypropyl cellulose, methylcellulose, polyethylene oxide, polyvinyl pyrrolidone, gaur-gum, pectins, starches, gelatin and casein.  
     
     
         6 . A device according to    claim 3    or    4    wherein the overlying active substance layer contains from about 3 to 60% by weight of a hydrophilic polymer in which the active substance is intimately contained.  
     
     
         7 . A device according to    claim 6    wherein the active substance is a breath freshener and is present in the active substance layer in amounts of between about 10 to 60% by weight.  
     
     
         8 . A device according to    claim 7    wherein the mucoadhesive layer also contains an active substance in amounts of between about 5 to 40% by weight.  
     
     
         9 . A device according to    claim 8    wherein the mucoadhesive composition content of the mucoadhesive layer is present in amounts of between about 20 to 60% by weight.  
     
     
         10 . A device according to    claim 9    wherein the breath freshener is an odorant member selected from the group consisting of peppermint, spearmint, menthol, grape, cherry, lemon, strawberry, orange, licorice, lime and any mixtures thereof.  
     
     
         11 . A device according to    claim 8    wherein the surface area of said mucoadhesive layer adapted for contact with the mucosal surface is between about 0.5 and 10 cm 2 .  
     
     
         12 . A device according to    claim 11    wherein said device is a tablet.  
     
     
         13 . A device according to    claim 12    wherein the thickness of the mucoadhesive layer is between about 0.1 and 3 mm.  
     
     
         14 . A device according to    claim 6    wherein the active substance is a drug and is present in the active substance layer in amounts of between about 0.1 to 10% by weight.  
     
     
         15 . A device according to    claim 14    wherein the drug is an ionic drug.  
     
     
         16 . A device according to    claim 15    wherein said ionic drug is a peptide.  
     
     
         17 . A device according to    claim 14    wherein the mucoadhesive layer also contains a chemical permeation enhancer in amounts of between about 2 to 20% by weight.  
     
     
         18 . A device according to    claim 17    wherein the chemical permeation enhancer is a bile acid or a salt thereof.  
     
     
         19 . A device according to    claim 18    wherein said drug is an ionic drug.  
     
     
         20 . A device according to    claim 19    wherein said ionic drug is a peptide.  
     
     
         21 . A device according to    claim 14    wherein the surface area of said mucoadhesive layer adapted for contact with the mucosal surface is between about 0.5 and 10 cm 2 .  
     
     
         22 . A device according to    claim 21    wherein said device is a tablet.  
     
     
         23 . A device according to    claim 22    wherein the thickness of the mucoadhesive layer is between about 0.1 and 3 mm.  
     
     
         24 . A method for the oral transmucosal delivery of active substances to the oral cavity comprising applying to the mucosa of said oral cavity a device comprising a mucoadhesive layer and at least one overlying active substance layer said mucoadhesive layer having one surface which is in contact with the mucosal surface of the oral cavity and adhering thereto and having an opposing surface in contact with and adhering to an overlying active substance containing layer characterized in that the mucoadhesive layer contains a mucoadhesive composition comprising at least 50% by weight of a non-plasticized polyvinyl pyrrolidone polymer having a weight average molecular weight of between about 10,000 and 700,000; retaining said device adhering to said mucosa until said active substance in said active substance layer has been released and said active substance layer and said mucoadhesive layer have dissolved in said oral cavity.  
     
     
         25 . A method according to    claim 24    wherein said mucoadhesive layer contains from 20 to 99% by weight of said mucoadhesive composition.  
     
     
         26 . A method according to    claim 25    wherein said mucoadhesive composition consists of non-plasticized polyvinyl pyrrolidone polymer.  
     
     
         27 . A method according to    claim 25    whrein said mucoadhesive composition comprises about 50 to 95% by weight of non-plasticized polyvinyl pyrrolidone polymer and 5 to 50% by weight of an additional functionally suitable hydrophilic polymer or copolymer.  
     
     
         28 . A method according to    claim 27    wherein said additional hydrophilic polymer or copolymer is a member selected from the group consisting of acrylic acid polymers, hydroxypropyl cellulose, methylcellulose, polyethylene oxide, polyvinyl pyrrolidone, gaur-gum, pectins, starches, gelatin and casein.  
     
     
         29 . A method according to    claim 26    or    27    wherein the overlying active substance layer contains from about 3 to 60% by weight of a hydrophilic polymer in which the active substance is intimately contained.  
     
     
         30 . A method according to    claim 29    wherein the active substance is a breath freshener and is present in the active substance layer in amounts of between about 10 to 60% by weight.  
     
     
         31 . A method according to    claim 30    wherein the mucoadhesive layer also contains an active substance in amounts of between about 5 to 40% by weight.  
     
     
         32 . A method according to    claim 31    wherein the mucoadhesive composition content of the mucoadhesive layer is present in amounts of between about 20 to 60% by weight.  
     
     
         33 . A method according to    claim 32    wherein the device is adhered to the hard palate.  
     
     
         34 . A method according to    claim 33    wherein the breath freshener is an odorant member selected from the group consisting of peppermint, spearmint, menthol, grape, cherry, lemon, strawberry, orange, licorice, lime and any mixtures thereof.  
     
     
         35 . A method according to    claim 33    wherein the surface area of said mucoadhesive layer adapted for contact with the mucosal surface is between about 0.5 and 10 cm 2 .  
     
     
         36 . A method according to    claim 35    wherein said device is a tablet.  
     
     
         37 . A method according to    claim 36    wherein the thickness of the mucoadhesive layer is between about 0.1 and 3 mm.  
     
     
         38 . A method according to    claim 30    wherein the active substance is a drug and is present in the active substance layer in amounts of between about 0.1 to 10% by weight.  
     
     
         39 . A method according to    claim 38    wherein the drug is an ionic drug.  
     
     
         40 . A method according to    claim 39    wherein said ionic drug is a peptide.  
     
     
         41 . A method according to    claim 38    wherein the mucoadhesive layer also contains a chemical permeation enhancer in amounts of between about 2 to 20% by weight.  
     
     
         42 . A method according to    claim 41    wherein the chemical permeation enhancer is a bile acid or a salt thereof.  
     
     
         43 . A method according to    claim 42    wherein said drug is an ionic drug.  
     
     
         44 . A method according to    claim 43    wherein said ionic drug is a peptide.  
     
     
         45 . A method according to    claim 38    wherein the surface area of said mucoadhesive layer adapted for contact with the mucosal surface is between about 0.5 and 10 cm 2 .  
     
     
         46 . A method according to    claim 45    wherein said device is a tablet.  
     
     
         47 . A method according to    claim 46    wherein the thickness of the mucoadhesive layer is between about 0.1 and 3 mm.