Soft tablet containing high molecular weight cellulosics

Abstract

The invention relates to an immediate release tablet capable of being chewed or disintegrated in the oral cavity, which comprises a pharmaceutically active ingredient having an optional tastemasking coating, and a matrix comprising hydroxyalkylcellulose having a weight average molecular weight of from about 60,000 to about 5,000,000. The tablet possesses exceptionally good mouthfeel and stability.

We claim:  
     
         1 . An immediate release dosage form capable of being chewed or disintegrated in the oral cavity prior to swallowing, comprised of: 
 a. a plurality of particles comprising a pharmaceutically active ingredient; and    b. a matrix comprising, based upon the total weight of the dosage form, from about 0.1 percent to about 25 percent of a hydroxyalkylcellulose having a weight average molecular weight of from about 60,000 to about 5,000,000 and/or a viscosity of from about 3,000 mPa.S to about 150,000 mPa.s in a 2% aqueous solution,    wherein the pharmaceutically active ingredient is coated with a taste masking coating.    
     
     
         2 . The dosage form of  claim 1 , wherein the hydroxyalkylcellulose is a hydroxypropylcellulose having a weight average molecular weight of from about 140,000 to about 1,150,000.  
     
     
         3 . The dosage form of  claim 1 , wherein the hydroxyalkylcellulose is a hydroxypropylmethylcellulose having a viscosity of from about 3,000 mPa.S to about 150,000 mPa.s in a 2% aqueous solution.  
     
     
         4 . The dosage form of  claim 1 , wherein the matrix further comprises a water-disintegratable, compressible carbohydrate selected from the group consisting of dextrose monohydrate, mannitol, sorbitol, xylitol, and mixtures thereof.  
     
     
         5 . The dosage form of  claim 1 , wherein the pharmaceutically active ingredient is selected from the group consisting of acetaminophen, acetyl salicylic acid, ibuprofen, naproxen, ketoprofen, flurbiprofen, diclofenac, cyclobenzaprine, meloxicam, rofecoxib, celecoxib, and pharmaceutically acceptable salts, esters, isomers, and mixtures thereof.  
     
     
         6 . The dosage form of  claim 1 , wherein the pharmaceutically active ingredient is selected from the group consisting of pseudoephedrine, phenylpropanolamine, chlorpheniramine, dextromethorphan, diphenhydramine, astemizole, terfenadine, fexofenadine, loratadine, cetirizine, mixtures thereof and pharmaceutically acceptable salts, esters, isomers, and mixtures thereof.  
     
     
         7 . The dosage form of  claim 1 , wherein the dosage form is a tablet.  
     
     
         8 . The dosage form of  claim 1 , wherein the dosage form is comprised of, based upon the total weight of the dosage form, 
 a. from greater than about 0.25 percent and less than about 70 percent of the coated particles comprising the pharmaceutically active ingredient, said coated particles comprising, based upon the total weight of the coated particles, from greater than about 1 percent and less than about 50 percent of the taste masking coating; and    b. from greater than about 0.5 percent and less than about 10 percent of the hydroxyalkylcellulose in the matrix.    
     
     
         9 . The dosage form of  claim 8 , wherein the taste masking coating is comprised of: 
 a) at least one solubilizable polymer; and    b) at least one insoluble film forming polymer.    
     
     
         10 . The dosage form of  claim 9 , wherein the solubilizable polymer is selected from the group consisting of enteric polymers, reverse enteric polymers, water soluble polymers, and mixtures and copolymers thereof.  
     
     
         11 . The dosage form of  claim 10 , wherein the enteric polymers are selected from the group consisting of shellac, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, cellulose acetate phthalate, polyvinylacetate phthalate, polymethacrylate-based polymers and mixtures and copolymers thereof.  
     
     
         12 . The dosage form of  claim 10 , wherein the enteric polymers are selected from the group consisting of hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, cellulose acetate phthalate, polyvinylacetate phthalate, and mixtures thereof.  
     
     
         13 . The dosage form of  claim 10 , wherein the reverse enteric polymers are methylaminoethyl-methacrylate and/or neutral methacrylic acid esters.  
     
     
         14 . The dosage form of  claim 10 , wherein the water soluble polymers are selected from the group consisting of hydroxypropylmethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, methylcellulose, polyvinyl pyrrolidone, polyethylene glycol, polyvinyl alcohols, sodium carboxymethylcellulose, and mixtures thereof.  
     
     
         15 . The dosage form of  claim 10  wherein the insoluble polymers are selected from the group consisting of cellulose acetate, cellulose acetate butyrate, cellulose triacetate, ethylcellulose, neutral ester co-polymer of ethyl acylate and methyl methacrylate, poly(ethyl acrylate, methyl methacrylate, trimethylammonioethyl methacrylate chloride) in a ratio of 1:2:0.1, and mixtures and copolymers thereof.  
     
     
         16 . The dosage form of  claim 9 , wherein the taste masking coating is comprised of: 
 a. a first polymer selected from the group consisting of cellulose acetate and/or cellulose acetate butyrate; and    b. a second polymer selected from the group consisting of enteric polymers, reverse enteric polymers, water soluble polymers, and mixtures and copolymers thereof,    wherein the weight ratio of the second polymer to the first polymer is within the range of about 5:95 to about 80:20.    
     
     
         17 . The dosage form of  claim 9 , wherein the hydroxyalkylcellulose is selected from the group consisting of hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxyethylmethylcellulose, hydroxypropylmethylcellulose, and mixtures thereof.  
     
     
         18 . The dosage form of  claim 9 , wherein the hydroxyalkylcellulose is hydroxypropylcellulose and/or hydroxypropylmethylcellulose.  
     
     
         19 . The dosage form of  claim 9 , wherein the dosage form is a tablet of manufactured by a direct compression or dry granulation process.  
     
     
         20 . The dosage form of  claim 9 , wherein said dosage form meets USP dissolution requirements for immediate release forms of said pharmaceutically active ingredient.  
     
     
         21 . The dosage form of  claim 9 , which has a moisture content of not more than about 5 percent as measured by weight loss on drying at 105 degrees Celsius.  
     
     
         22 . An immediate release dosage form capable of being chewed or disintegrated in the oral cavity prior to swallowing, comprised of: 
 a. a plurality of coated particles comprising, based upon the total weight of the dosage form, from greater than about 12 percent and less than about 40 percent of a pharmaceutically active ingredient selected from the group consisting of acetaminophen, acetyl salicylic acid, ibuprofen, naproxen, ketoprofen, flurbiprofen, diclofenac, cyclobenzaprine, meloxicam, rofecoxib, celecoxib, and pharmaceutically acceptable salts, esters, isomers, and mixtures thereof, said coated particles further comprising, based upon the total weight of the coated particles, from greater than about 5 percent and less than about 30 percent of a taste masking coating comprised of cellulose acetate, hydroxymethylcellulose phthalate, and polysorbate-80 at a ratio of 43:53:4, wherein the taste masking coating substantially covers the active ingredient; and    b. a matrix comprising, based upon the total weight of the dosage form, from about 0.5 percent to about 10.0 percent of hydroxypropylmethylcellulose and/or hydroxypropylcellulose having a weight average molecular weight of from about 60,000 to about 5,000,000 and/or a viscosity of from about 3,000 mPa.S to about 150,000 mPa.s in a 2% aqueous solution.    
     
     
         23 . The immediate release dosage form of  claim 22 , wherein the matrix further comprises a water-disintegratable, compressible carbohydrate selected from the group consisting of dextrose monohydrate, mannitol, sorbitol, xylitol, and mixtures thereof.