Pharmaceutical compositions for piperidinoalkanol compounds

Abstract

The invention provides a pharmaceutical composition in solid unit dosage form, comprising, a) a therapeutically effective amount of a piperidinoalkanol compound or a pharmaceutically acceptable salt thereof; and, b) at least one inert ingredient.

What is claimed is:  
     
         1 . A pharmaceutical composition comprising, 
 a) a therapeutically effective amount of a piperidinoalkanol compound or a pharmaceutically acceptable salt thereof wherein said piperidinoalkanol compound has a particle surface area of greater than about 1.0 m 2 /g; and    b) at least one inert ingredient.    
     
     
         2 . The pharmaceutical composition according to  claim 1  wherein the inert ingredient is a disintegrant.  
     
     
         3 . A pharmaceutical composition in solid unit dosage form, comprising; 
 a) a therapeutically effective amount of a piperidinoalkanol compound or a pharmaceutically acceptable salt thereof; and    b) at least one inert ingredient.    
     
     
         4 . The pharmaceutical composition in solid unit dosage form according to  claim 3  wherein the inert ingredient is a disintegrant.  
     
     
         5 . The pharmaceutical composition in solid unit dosage form according to  claim 3 , wherein said piperidinoalkanol compound is of the formula  
       
         
           
           
               
               
           
         
       
       wherein X is a number ranging from about zero to 5, and the individual optical isomers thereof.  
     
     
         6 . The pharmaceutical composition in solid unit dosage form according to  claim 5 , wherein X is zero.  
     
     
         7 . The pharmaceutical composition in solid unit dosage form according to  claim 5 , wherein at least one inert ingredient is selected from the group consisting of croscarmellose sodium, lactose, microcrystalline cellulose, pregelatinized starch, gelatin, calcium carbonate, magnesium stearate and sodium starch glycolate.  
     
     
         8 . The pharmaceutical composition in solid unit dosage form according to  claim 7  wherein said inert ingredients comprise croscarmellose sodium, lactose, microcrystalline cellulose, pregelatinized starch and gelatin.  
     
     
         9 . The pharmaceutical composition in solid unit dosage form according to  claim 8  wherein croscarmellose sodium, microcrystalline cellulose, lactose, pregelatinized starch and gelatin are present in amounts of about 1% to about 10%, 20% to about 85%, 20% to about 85%, 1% to about 30% and 1% to about 15%, respectively, by weight of the composition.  
     
     
         10 . The pharmaceutical composition in solid unit dosage form according to  claim 8  wherein croscarmellose sodium, microcrystalline cellulose, lactose, pregelatinized starch and gelatin are present in amounts of about 4.8%, 33.8%, 33.8%, 9.6% and 3.5%, respectively, by weight of the composition.  
     
     
         11 . The pharmaceutical composition in solid unit dosage form according to  claim 7  wherein said inert ingredients comprise microcrystalline cellulose, pregelatinized starch, gelatin, magnesium stearate, calcium carbonate and sodium starch glycolate.  
     
     
         12 . The pharmaceutical composition in solid unit dosage form according to  claim 11  wherein microcrystalline cellulose, pregelatinized starch, gelatin, magnesium stearate, calcium carbonate and sodium starch glycolate are present in amounts of about 20% to about 85%, 5% to about 50%, 1% to about 15%, 0.05% to about 3%, 5% to about 50% and 1% to about 15%, respectively, by weight of the composition.  
     
     
         13 . The pharmaceutical composition in solid unit dosage form according to  claim 11  wherein microcrystalline cellulose, pregelatinized starch, gelatin, magnesium stearate, calcium carbonate and sodium starch glycolate are present in amounts of about 34.9%, 29.4%, 3.3%, 0.5%, 15.6%, 5.6%, respectively, by weight of the composition.  
     
     
         14 . The pharmaceutical composition in solid unit dosage form according to  claim 7  wherein said inert ingredients comprise croscarmellose sodium, microcrystalline cellulose, lactose, pregelatinized starch, gelatin and magnesium stearate.  
     
     
         15 . The pharmaceutical composition in solid unit dosage form according to  claim 14  wherein croscarmellose sodium, microcrystalline cellulose, lactose, pregelatinized starch, gelatin and magnesium stearate are present in amounts of about 1% to about 10%, 20% to about 85%, 20% to about 85%, 1% to about 30%, 1% to about 15% and 0.05% to about 3.0%, respectively, by weight of the composition.  
     
     
         16 . The pharmaceutical composition in solid unit dosage form according to  claim 14  wherein croscarmellose sodium, microcrystalline cellulose, lactose, pregelatinized starch, gelatin and magnesium stearate are present in amounts of about 4.8%, 33.7%, 33.7%, 9.6%, 3.5% and 0.5%, respectively, by weight of the composition.  
     
     
         17 . The pharmaceutical composition in solid unit dosage form according to  claim 14  wherein croscarmellose sodium, microcrystalline cellulose, lactose, pregelatinized starch, gelatin and magnesium stearate are present in amounts of about 4.8%, 25.7%, 25.7%, 9.6%, 3.5% and 0.75%, respectively, by weight of the composition.  
     
     
         18 . The pharmaceutical composition in solid unit dosage form according to  claim 7  wherein said inert ingredients comprise microcrystalline cellulose, pregelatinized starch, magnesium stearate, calcium carbonate and sodium starch glycolate.  
     
     
         19 . The pharmaceutical composition in solid unit dosage form according to  claim 18  wherein microcrystalline cellulose, pregelatinized starch, magnesium stearate, calcium carbonate and sodium starch glycolate are present in amounts of about 20% to about 85%, 5% to about 50%, 0.05% to about 3%, 5% to about 50% and 1% to about 15%, respectively, by weight of the composition.  
     
     
         20 . The pharmaceutical composition in solid unit dosage form according to  claim 18  wherein microcrystalline cellulose, pregelatinized starch, magnesium stearate, calcium carbonate and sodium starch glycolate are present in amounts of about 36.5%, 31.0%, 0.5%, 15.6%, and 5.6%, respectively, by weight of the composition.  
     
     
         21 . The pharmaceutical composition in solid unit dosage form according to  claim 18  wherein microcrystalline cellulose, pregelatinized starch, magnesium stearate, calcium carbonate and sodium starch glycolate are present in amounts of about 21.1%, 30.0%, 0.75%, 15.6%, and 10.0%, respectively, by weight of the composition.  
     
     
         22 . The pharmaceutical composition in solid unit dosage form according to  claim 7  wherein said inert ingredients comprise croscarmellose sodium, microcrystalline cellulose, pregelatinized starch, and magnesium stearate.  
     
     
         23 . The pharmaceutical composition in solid unit dosage form according to  claim 22  wherein croscarmellose sodium, microcrystalline cellulose, pregelatinized starch, and magnesium stearate are present in amounts of about 1% to about 10%, 20% to about 85%, 5% to about 50% and 0.05% to about 3%, respectively, by weight of the composition.  
     
     
         24 . The pharmaceutical composition in solid unit dosage form according to  claim 22  wherein croscarmellose sodium, microcrystalline cellulose, pregelatinized starch, and magnesium stearate are present in amounts of about 6%, 33.3%, 30% and 0.75%, respectively, by weight of the composition.  
     
     
         25 . The pharmaceutical composition in solid unit dosage form as in either claims  10 ,  13 ,  16 ,  17 ,  20 ,  21  or  24  wherein said piperidinoalkanol compound is 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylbenzeneacetic acid hydrochloride.  
     
     
         26 . The pharmaceutical composition in solid unit dosage form according to  claim 25  wherein 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylbenzeneacetic acid hydrochloride is present in an amount of about 5 mg to about 180 mg.  
     
     
         27 . A pharmaceutical composition prepared by a wet granulation process comprising, preparing the wet granulation wherein a compound of formula;  
       
         
           
           
               
               
           
         
       
       wherein X is a number ranging from about zero to 5, and the individual optical isomers thereof, 
 a diluent and a disintegrant are mixed with a solution of a binding agent; the wet granulation is screened, the wet granulation is dried, and the dry granulation is screened.  
 
     
     
         28 . A pharmaceutical composition prepared by a wet granulation process comprising, preparing the wet granulation wherein a compound of formula;  
       
         
           
           
               
               
           
         
       
       wherein X is a number ranging from about zero to 5, and the individual optical isomers thereof, 
 a diluent and a disintegrant are mixed with a solution of a binding agent; the wet granulation is screened, the wet granulation is dried and the dry granulation is combined with a lubricant.  
 
     
     
         29 . A pharmaceutical composition in solid unit dosage form prepared by a process comprising, blending together a compound of the formula;  
       
         
           
           
               
               
           
         
       
       wherein X is a number ranging from about zero to 5, and the individual optical isomers thereof, with microcrystalline cellulose, lactose and pregelatinized starch; adding a solution of gelatin in water with mixing; drying and, milling the mixture; and adding croscarmellose sodium with mixing.  
     
     
         30 . A pharmaceutical composition in solid unit dosage form according to  claim 29  wherein the resulting mixture is filled into capsules.  
     
     
         31 . A pharmaceutical composition in solid unit dosage form according to  claim 29  wherein the microcrystalline cellulose, lactose, pregelatinized starch, gelatin and croscarmellose sodium are combined in amounts of about 33.8%, 33.8%, 9.6%, 3.5% and 4.8%, respectively, by weight of the composition.  
     
     
         32 . A pharmaceutical composition in solid unit dosage form according to  claim 29  wherein the microcrystalline cellulose, lactose, pregelatinized starch, gelatin, croscarmellose sodium and magnesium stearate are combined in amounts of about 33.7%, 33.7%, 9.6%, 3.5%, 4.8% and 0.5%, respectively, by weight of the composition.  
     
     
         33 . A pharmaceutical composition in solid unit dosage form prepared by a process comprising blending together a compound of the formula;  
       
         
           
           
               
               
           
         
       
       wherein X is a number ranging from about zero to 5, and the individual optical isomers thereof, with microcrystalline cellulose, lactose and pregelatinized starch; adding a solution of gelatin in water with mixing; drying and milling the granulated mixture; adding croscarmellose sodium with mixing; and adding magnesium stearate with mixing.  
     
     
         34 . A pharmaceutical composition in solid unit dosage form according to  claim 33  wherein the final mixture is pressed into tablets.  
     
     
         35 . A pharmaceutical composition in solid unit dosage form according to  claim 33  wherein the microcrystalline cellulose, lactose, pregelatinized starch, gelatin, croscarmellose sodium and magnesium stearate are combined in amounts of about 33.7%, 33.7%, 9.6%, 3.5%, 4.8% and 0.5%, respectively, by weight of the composition.  
     
     
         36 . A pharmaceutical composition in solid unit dosage form prepared by a process comprising blending together a compound of the formula;  
       
         
           
           
               
               
           
         
       
       wherein X is a number ranging from about zero to 5, and the individual optical isomers thereof, with microcrystalline cellulose, calcium carbonate and pregelatinized starch; adding a solution of gelatin in water with mixing; drying the granulated mixture; adding additional microcrystalline cellulose and sodium starch glycolate with blending; and adding magnesium stearate with blending.  
     
     
         37 . A pharmaceutical composition in solid unit dosage form according to  claim 36  wherein the final mixture is pressed into tablets.  
     
     
         38 . A pharmaceutical composition in solid unit dosage form according to  claim 36  wherein the microcrystalline cellulose, calcium carbonate, pregelatinized starch, gelatin, sodium starch glycolate and magnesium stearate are combined in total amounts of about 34.9%, 15.6%, 29.4%, 3.3%, 5.6% and 0.5%, respectively, by weight of the composition.  
     
     
         39 . A pharmaceutical composition in solid unit dosage form prepared by a process comprising blending together a compound of the formula;  
       
         
           
           
               
               
           
         
       
       wherein X is a number ranging from about zero to 5, and the individual optical isomers thereof, with microcrystalline cellulose, calcium carbonate and pregelatinized starch; adding water with mixing; drying the granulated mixture; adding additional microcrystalline cellulose and sodium starch glycolate, with blending; and adding magnesium stearate with blending.  
     
     
         40 . A pharmaceutical composition in solid unit dosage form according to  claim 39  wherein the final mixture is pressed into tablets.  
     
     
         41 . A pharmaceutical composition in solid unit dosage form according to  claim 39  wherein the microcrystalline cellulose, calcium carbonate, pregelatinized starch, sodium starch glycolate and magnesium stearate are combined in total amounts of about 336.5%, 15.6%, 31.0%, 5.6% and 0.5%, respectively, by weight of the composition.  
     
     
         42 . A pharmaceutical composition in solid form according to  claim 16  wherein the final mixture is pressed into a tablet from which the quantity of compound of the formula;  
       
         
           
           
               
               
           
         
       
       wherein X is a number ranging from about zero to 5, and the individual optical isomers thereof, dissolved in 45 minutes, is not less than 75% of label in water at about 37° C. and about 50 rpm when measured using USP Apparatus 2.  
     
     
         43 . A pharmaceutical composition in solid form according to claims  17 ,  21  or  24  wherein the final mixture is pressed into a tablet from which the quantity of compound of the formula;  
       
         
           
           
               
               
           
         
       
       wherein X is a number ranging from about zero to 5, and the individual optical isomers thereof, dissolved in 45 minutes, is not less than 75% of label in 0.001 N aqueous hydrochloric acid at about 37° C. and about 50 rpm when measured using USP Apparatus 2.