Oral Dosage Form Containing A Pde 4 Inhibitor As An Active Ingredient And Polyvinylpyrrolidon As Excipient

Abstract

Dosage forms for oral administration of a PDE 4 inhibitor whose solubility is slight are described. They contain PVP binder.

1 - 11 . (canceled) 
     
     
         12 . A solid dosage form in tablet or pellet form for oral administration of a PDE 4 inhibitor, comprising:
 a PDE 4 inhibitor;   a binder in a proportion of 0.5% to 20% by weight; and   one or more suitable pharmaceutical excipients selected from the group consisting of fillers, tablet disintegrants, lubricants, release agents, flavoring substances, buffer substances, preservatives, coloring substances and emulsifiers,   wherein the PDE 4 inhibitor is a compound of the formula I   
       
         
           
           
               
               
           
         
         in which 
         R 1  is difluoromethoxy, 
         R 2  is cyclopropylmethoxy and 
         R 3  is 3,5-dichloropyrid-4-yl, 
         or a salt of this compound, and wherein said dosage form provides immediate release of the PDE 4 inhibitor. 
       
     
     
         13 . The dosage form according to  claim 12 , wherein the PDE 4 inhibitor is N-(3,5 -dichloropyrid-4-yl)-3 -cyclopropylmethoxy-4-difluoromethoxybenzamide (roflumilast). 
     
     
         14 . The dosage form according to  claim 13 , containing from 0.1 mg to 0.5 mg of roflumilast per dosage unit. 
     
     
         15 . The dosage form according to  claim 12 , which is a tablet. 
     
     
         16 . The dosage form according to  claim 12 , wherein the pharmaceutical excipients include at least a filler and wherein the proportion of filler is from 60% to 97% by weight. 
     
     
         17 . The dosage form according to  claim 12 , wherein the pharmaceutical excipients include at least a lubricant or release agent. 
     
     
         18 . The dosage form according to  claim 15 , comprising: roflumilast—0.125 mg; lactose monohydrate—49.660 mg; corn starch—13.390 mg; polyvinylpyrrolidone having a weight average molecular weight of between 1,000,000 and 1,500,000-1.300 mg and magnesium stearate (vegetable)—0.650 mg. 
     
     
         19 . The dosage form according to  claim 15 , comprising: roflumilast—0.250 mg; lactose monohydrate—49.660 mg; corn starch—13.390 mg; polyvinylpyrrolidone having a weight average molecular weight of between 1,000,000 and 1,500,000-1.300 mg; and magnesium stearate (vegetable)—0.650 mg. 
     
     
         20 . The dosage form according to  claim 15 , comprising: roflumilast 0.500 mg; lactose monohydrate 49.660 mg; corn starch 13.390 mg; polyvinylpyrrolidone having a weight average molecular weight of between 1,000,000 and 1,500,000-1.300 mg; and magnesium stearate (vegetable) 0.650 mg. 
     
     
         21 . The dosage form according to  claim 12 , wherein the dosage form provides a mean T max  of less than about 1.5 hr. 
     
     
         22 . A solid oral dosage form in tablet or pellet form for oral administration of a PDE 4 inhibitor, comprising:
 a PDE 4 inhibitor; and   one or more suitable pharmaceutical excipients selected from the group consisting of binders, fillers, tablet disintegrants, lubricants, release agents, flavoring substances, buffer substances, preservatives, coloring substances and emulsifiers,   wherein the PDE 4 inhibitor is a compound of the formula I   
       
         
           
           
               
               
           
         
         in which 
         R 1  is difluoromethoxy, 
         R 2  is cyclopropylmethoxy and 
         R 3  is 3,5-dichloropyrid-4-yl, 
         or a salt of this compound, and wherein said dosage form provides immediate release of the PDE 4 inhibitor and a mean T max  of less than about 1.5 hr. 
       
     
     
         23 . The dosage form according to  claim 22 , wherein the PDE 4 inhibitor is N-(3,5 -dichloropyrid-4-yl)-3 -cyclopropylmethoxy-4-difluoromethoxybenzamide (roflumilast). 
     
     
         24 . The dosage form according to  claim 23 , containing from 0.1 mg to 0.5 mg of roflumilast per dosage unit. 
     
     
         25 . The dosage form according to  claim 22 , wherein the pharmaceutical excipients include at least a binder and wherein the proportion of binder is from 0.5% to 20% by weight. 
     
     
         26 . The dosage form according to  claim 22 , which is a tablet. 
     
     
         27 . The dosage form according to  claim 22 , wherein the pharmaceutical excipients include at least a filler and wherein the proportion of filler is from 60% to 97% by weight. 
     
     
         28 . The dosage form according to  claim 22 , wherein the pharmaceutical excipients include at least a lubricant or release agent. 
     
     
         29 . The dosage form according to  claim 26 , comprising: roflumilast—0.125 mg; lactose monohydrate—49.660 mg; corn starch—13.390 mg; polyvinylpyrrolidone having a weight average molecular weight of between 1,000,000 and 1,500,000-1.300 mg and magnesium stearate (vegetable)—0.650 mg. 
     
     
         30 . The dosage form according to  claim 26 , comprising: roflumilast—0.250 mg; lactose monohydrate—49.660 mg; corn starch—13.390 mg; polyvinylpyrrolidone having a weight average molecular weight of between 1,000,000 and 1,500,000-1.300 mg; and magnesium stearate (vegetable)—0.650 mg. 
     
     
         31 . The dosage form according to  claim 26 , comprising: roflumilast 0.500 mg; lactose monohydrate 49.660 mg; corn starch 13.390 mg; polyvinylpyrrolidone having a weight average molecular weight of between 1,000,000 and 1,500,000-1.300 mg; and magnesium stearate (vegetable) 0.650 mg. 
     
     
         32 . A solid dosage form in tablet or pellet form for oral administration of a PDE4inhibitor, comprising:
 a PDE 4 inhibitor;   a filler in a proportion of 60% to 97% by weight; and one or more suitable pharmaceutical excipients selected from the group consisting of binders, tablet disintegrants, lubricants, release agents, flavoring substances, buffer substances, preservatives, coloring substances and emulsifiers,   wherein the PDE 4 inhibitor is a compound of the formula I   
       
         
           
           
               
               
           
         
         in which 
         R 1  is difluoromethoxy, 
         R 2  is cyclopropylmethoxy and 
         R 3  is 3,5-dichloropyrid-4-yl, 
         or a salt of this compound, and wherein said dosage form provides immediate release of the PDE 4 inhibitor. 
       
     
     
         33 . The dosage form according to  claim 32 , wherein the PDE 4 inhibitor is N-(3,5 -dichloropyrid-4-yl)-3 -cyclopropylmethoxy-4-difluoromethoxybenzamide (roflumilast). 
     
     
         34 . The dosage form according to  claim 33 , containing from 0.1 mg to 0.5 mg of roflumilast per dosage unit. 
     
     
         35 . The dosage form according to  claim 32 , wherein the pharmaceutical excipients include at least a binder and wherein the proportion of binder is from 0.5% to 20% by weight. 
     
     
         36 . The dosage form according to  claim 32 , which is a tablet. 
     
     
         37 . The dosage form according to  claim 32 , wherein the pharmaceutical excipients include at least a lubricant or release agent. 
     
     
         38 . The dosage form according to  claim 36 , comprising: roflumilast—0.125 mg; lactose monohydrate—49.660 mg; corn starch—13.390 mg; polyvinylpyrrolidone having a weight average molecular weight of between 1,000,000 and 1,500,000-1.300 mg and magnesium stearate (vegetable)—0.650 mg. 
     
     
         39 . The dosage form according to  claim 36 , comprising: roflumilast—0.250 mg; lactose monohydrate—49.660 mg; corn starch—13.390 mg; polyvinylpyrrolidone having a weight average molecular weight of between 1,000,000 and 1,500,000-1.300 mg; and magnesium stearate (vegetable)—0.650 mg. 
     
     
         40 . The dosage form according to  claim 36 , comprising: roflumilast 0.500 mg; lactose monohydrate 49.660 mg; corn starch 13.390 mg; polyvinylpyrrolidone having a weight average molecular weight of between 1,000,000 and 1,500,000-1.300 mg; and magnesium stearate (vegetable) 0.650 mg. 
     
     
         41 . The dosage form according to  claim 32 , wherein the dosage form provides a mean T max  of less than about 1.5 hr.