Water soluble polymer-based rapidly dissolving tablets and production processes thereof

Abstract

The invention provides for novel compressed tablets capable of rapidly disintegrating in aqueous solutions, comprising at least one non-saccharide water soluble polymer, which are free of organic solvent residues, and methods of making such pharmaceuticals.

What is claimed is:  
     
         1 . A physiologically acceptable tablet comprising: 
 a compressed tablet formulation free of organic solvent residue that rapidly disintegrates when placed in a body cavity, that comprises at least one water soluble non-saccharide polymer, and that has a hardness factor of between about 0.5 kilopounds to about 12.0 kilopounds.    
     
     
         2 . The tablet of  claim 1 , wherein the compressed tablet has a hardness factor of over 6 kilopounds.  
     
     
         3 . The tablet of  claim 1 , wherein the water soluble polymer is selected from the group consisting of polyvinylpyrrolidone, polyethylene glycol, sodium alginate, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, and hydroxyethyl cellulose.  
     
     
         4 . The tablet of  claim 1 , wherein the water soluble polymer comprises a polyvinylpyrrolidone.  
     
     
         5 . The tablet of  claim 4 , wherein the polyvinylpyrrolidone is selected from the group consisting of N-vinyl pyrrolidone, 3-methyl N-vinylpyrrolidone, N-vinyl amide pyrrolidone, N-vinyl acetate pyrrolidone, vinylpyrrolidone-vinyl acetate copolymer, and acrylamide-vinylpyrrolidone co-polymer.  
     
     
         6 . The tablet of  claim 4 , wherein the polyvinylpyrrolidone has a molecular weight of less than about three million daltons.  
     
     
         7 . The tablet of  claim 6 , wherein the polyvinylpyrrolidone has a molecular weight of less than about fifty thousand daltons.  
     
     
         8 . The tablet of  claim 7 , wherein the polyvinylpyrrolidone has a molecular weight of about thirty thousand daltons.  
     
     
         9 . The tablet of  claim 1 , wherein the formulation further comprises a saccharide of low moldability.  
     
     
         10 . The tablet of  claim 9 , wherein the saccharide of low moldability is mannitol, lactose, glucose, sucrose, lactitol, or a mixture thereof.  
     
     
         11 . The tablet of  claim 9 , wherein the saccharide of low moldability is about 25% to about 99% of the weight of the tablet.  
     
     
         12 . The tablet of  claim 1 , wherein the formulation further comprises a saccharide of high moldability, with the proviso that the formulation does not contain starch.  
     
     
         13 . The tablet of  claim 12 , wherein the saccharide of high moldability is maltose, maltitol, sorbitol, or a mixture thereof.  
     
     
         14 . The tablet of  claim 12 , wherein the saccharide of high moldability is about 0.5% to about 20% of the tablet.  
     
     
         15 . The tablet of  claim 1 , wherein the water soluble polymer comprises about 0.5% to about 20% of the dry weight of the tablet.  
     
     
         16 . The tablet of  claim 15 , wherein the water soluble polymer is polyvinylpyrrolidone and comprises about 5% of the dry weight of the tablet.  
     
     
         17 . The tablet of  claim 1 , wherein the tablet further comprises a pharmaceutically active ingredient.  
     
     
         18 . The tablet of  claim 1 , wherein the tablet dissolves in about 1 to about 40 seconds in an aqueous solution.  
     
     
         19 . The tablet of  claim 18 , wherein the tablet dissolves in the oral cavity and the aqueous solution is saliva.  
     
     
         20 . The tablet of  claim 1 , wherein the formulation further comprising at least one additive agent selected from the group consisting of a disintegrant, a flavorant, an artificial sweetener, a perfume, and a colorant.  
     
     
         21 . The pharmaceutical tablet of  claim 1 , wherein the tablet is suitable for delivery to a body cavity of the group consisting of the oral, buccal, sublingual, vaginal, nasal, rectal, and urethral cavity.  
     
     
         22 . The process for producing a pharmaceutical tablet, comprising the following steps: 
 (a) granulating a formulation comprising at least one non-saccharide, water soluble polymer and at least one active ingredient together, wherein no organic solvents are included in the formulation;    (b) compressing the product of the granulation into a tablet form;    (c) humidifying the tablet by exposing the product of step (b) to an aerated environment at least about 50% to 100% relative humidity; and    (d) drying the tablet, wherein the hardness of the tablet is at least about 6 kilopounds.    
     
     
         23 . The process of  claim 22 , wherein the non-saccharide, water soluble polymer comprises a polyvinylpyrrolidone.  
     
     
         24 . The process of  claim 23 , wherein the polyvinylpyrrolidone has a molecular weight of about thirty thousand daltons.  
     
     
         25 . The process of  claim 23 , wherein the polyvinylpyrrolidone is at about 5% of the dry weight of the formulation.  
     
     
         26 . The process of  claim 23 , wherein the polyvinylpyrrolidone is selected from the group consisting of N-vinyl pyrrolidone, 3-methyl N-vinylpyrrolidone, N-vinyl amide pyrrolidone, N-vinyl acetate pyrrolidone, vinylpyrrolidone-vinyl acetate copolymer, and acrylamide-vinylpyrrolidone co-polymer.  
     
     
         27 . The process of  claim 22 , wherein in step (a) the formulation further comprises at least one lubricant and at least one filler.  
     
     
         28 . The process of  claim 27 , wherein the lubricant is in the range of about 0.5% to about 1.0% of the dry weight of the formulation.  
     
     
         29 . The process of  claim 27 , wherein the lubricant in the formulation is magnesium stearate or calcium stearate.  
     
     
         30 . The process of  claim 27 , wherein the filler in the formulation is in the range of about 80% to about 98% of the dry weight of the formulation.  
     
     
         31 . The process of  claim 30 , wherein the filler in the formulation is in the range of about 95% of the dry weight of the formulation.  
     
     
         32 . The process of  claim 27 , wherein the filler in the formulation is mannitol.  
     
     
         33 . The process of  claim 22 , wherein in step (a) the temperature during granulation ranges from about 10° C. to 70° C.  
     
     
         34 . The process of  claim 22 , wherein in step (b) the compression is by press molding.  
     
     
         35 . The process of  claim 22 , wherein in step (b) the compression produces a tablet with a hardness of about 0.3 to about 6.0 kilopounds.  
     
     
         36 . The process of  claim 22 , wherein in step (c) the humidification is between about 50% and about 100% relative humidity.  
     
     
         37 . The process of  claim 36 , wherein in step (c) the humidification is at about 85% relative humidity.  
     
     
         38 . The process of  claim 22 , wherein in step (c) the temperature is at about 25° C.  
     
     
         39 . The process of  claim 22 , wherein in step (c) the humidification step lasts for about 30 minutes.  
     
     
         40 . The process of  claim 22 , wherein in step (c) the humidification step lasts for about 60 minutes.  
     
     
         41 . The process of  claim 40 , wherein the hardness of the dried tablet is about 4 kilopounds to about 5 kilopounds.  
     
     
         42 . The process of  claim 22 , wherein in step (c) the humidification step lasts for about 120 minutes.  
     
     
         43 . The process of  claim 42 , wherein the hardness of the dried tablet is about 5 kilopounds to about 12 kilopounds.  
     
     
         44 . The process of  claim 43 , wherein the hardness of the dried tablet is about 7 kilopounds.  
     
     
         45 . The process of  claim 22 , wherein step (d) occurs at a higher temperature and lower relative humidity than that of step (c).  
     
     
         46 . The process of  claim 22 , wherein step (d) occurs at a temperature of about 40° C.  
     
     
         47 . The process of  claim 22 , wherein step (d) occurs at a relative humidity of about 30%.  
     
     
         48 . A tablet made by a process comprising the following steps: 
 (a) granulating a formulation comprising at least one water soluble, non-saccharide polymer and at least one active ingredient together, wherein no organic solvents are included in the formulation;    (b) compressing the product of the granulation into a tablet form;    (c) humidifying the tablet by exposing the product of step (b) to an aerated environment at least about 50% to 100% relative humidity; and    (d) drying the tablet, wherein the hardness of the dried tablet is about 0.5 kilopounds to about 12 kilopounds.    
     
     
         49 . The tablet of  claim 48 , wherein water soluble, non-saccharide polymer is a polyvinylpyrrolidone.  
     
     
         50 . The tablet of  claim 49 , wherein the polyvinylpyrrolidone is selected from the group consisting of N-vinyl pyrrolidone, 3-methyl N-vinylpyrrolidone, N-vinyl amide pyrrolidone, N-vinyl acetate pyrrolidone, vinylpyrrolidone-vinyl acetate copolymer, and acrylamide-vinylpyrrolidone co-polymer.  
     
     
         51 . The tablet of  claim 49 , wherein the polyvinylpyrrolidone is at about 5% of the dry weight of the formulation and the humidification step is about 60 minutes.  
     
     
         52 . The tablet of  claim 51 , wherein the hardness of the dried tablet is about 4 kilopounds to about 5 kilopounds.  
     
     
         53 . The tablet of  claim 48 , wherein the polyvinylpyrrolidone is at about 5% of the dry weight of the formulation and the humidification step is about 120 minutes.  
     
     
         54 . The tablet of  claim 53 , wherein the hardness of the dried tablet is about 5 kilopounds to about 12 kilopounds.  
     
     
         55 . The tablet of  claim 54 , wherein the hardness of the dried tablet is about 7 kilopounds.