Pharmaceutical composition including pimobendan

Abstract

A solid formulation includes pimobendan or a pharmaceutically acceptable salt thereof, which is homogenously dispersed with a polyvalent acid and a flavor suitable to animals.

1 . A solid formulation comprising a homogenous dispersion of:
 pimobendan or a pharmaceutically acceptable salt thereof;   a polyvalent acid selected from the group consisting of citric acid, acetic acid, maleic acid, tartaric acid or their anhydrides; and   a flavor acceptable to small animals;   wherein the flavor is homogenously dispersed within such solid formulation.   
     
     
         2 . The solid formulation according to  claim 1 , further comprising one or more pharmaceutically acceptable carriers and/or excipients. 
     
     
         3 . The solid formulation according to  claim 1 , wherein the one or several excipients are selected from the group consisting of diluents, disintegrants, carriers, binders, flow regulators, lubricants and solvents. 
     
     
         4 . The solid formulation according to  claim 2 , wherein the binder is selected from the group consisting of polyvidone/povidone, methylcellulose, hydroxypropylmethylcellulose (HPMC), hydroxymethylcellulose, starch and gelatine. 
     
     
         5 . The solid formulation according to  claim 2 , wherein the disintegrant/carrier is selected from the group consisting of lactose, starch, cellulose, microcrystalline cellulose and methylcellulose. 
     
     
         6 . The solid formulation according to  claim 5 , wherein the lactose consists of coarse particles greater than 200 μm in size. 
     
     
         7 . The solid formulation according to  claim 2 , wherein the starch or various starches are selected from the group consisting of native starch, gelatinized starch, partly gelatinized starch, starch powder, starch granules, chemically modified starch and swellable physically modified starch. 
     
     
         8 . The solid formulation according to  claim 2 , wherein the disintegrant is selected from the group consisting of croscarmellose sodium, sodium starch glycolate, pregelatinised starch and cross-linked polyvinylpyrrolidone. 
     
     
         9 . The solid formulation according to  claim 2 , wherein the flow regulator is selected from the group consisting of silica, preferably colloidal anhydrous silica, calcium silicate, magnesium silicate and talc. 
     
     
         10 . The solid formulation according to  claim 2 , wherein the lubricant is selected from the group consisting of magnesium stearate, calcium stearate, glyceryl behenate, polyethylene glycol, stearic acid and talc. 
     
     
         11 . The solid formulation according to  claim 2 , wherein the flavor is selected from the group consisting of artificial beef flavors, artificial chicken flavors, pork liver extract, artificial meat flavor and honey flavor. 
     
     
         12 . The solid formulation according to  claim 1 , further comprising 0.5 to 20 mg of pimobendan. 
     
     
         13 . The solid formulation according to  claim 1 , wherein the content of pimobendan in relation to citric acid anhydrous is 1:10 to 1:40. 
     
     
         14 . The solid formulation according to  claim 1 , wherein the weight of the whole solid formulation is in the range of 250 mg to 3000 mg. 
     
     
         15 . The solid formulation according to  claim 1 , wherein the solid formulation is a tablet or a granule. 
     
     
         16 . The solid formulation according to  claim 1 , wherein the solid formulation is a tablet and consists of 1.25 mg, 2.5 mg, 5 mg or 10 mg pimobendan, and further consists of lactose, corn starch, croscarmellose-sodium, citric acid, artificial beef flavor, polyvidone, colloidal anhydrous silica and magnesium stearate. 
     
     
         17 . The solid formulation according to  claim 1 , wherein the solid formulation is a tablet and consists of 1.25 mg, 2.5 mg, 5 mg or 10 mg pimobendan, and further consists of 35 to 50% (w/w) lactose, 25 to 50% (w/w) corn starch, 1 to 5% (w/w) croscarmellose-sodium, 2.5 to 10% (w/w) citric acid, 5 to 30% (w/w) artificial beef flavor, 1 to 5% (w/w) polyvidone, 0.1 to 1% (w/w) colloidal anhydrous silica and 0.25 to 1.5% (w/w) magnesium stearate. 
     
     
         18 . A method of prevention and/or treatment of congestive heart failure in a mammal, the method comprising administering the solid formulation of  claim 1  to the mammal. 
     
     
         19 . A fluid-bed granulation process comprising:
 a) spraying an aqueous dispersion of pimobendan and an aqueous solution of a binder onto a solid support comprising one or several carriers and/or excipients, flavor and citric acid anhydrous;   b) drying the mixture of a);   c) sieving and de-agglomerating the mixture of b);   d) adding a flow regulator to the mixture of c);   e) adding a lubricant to the mixture of d);   f) blending the mixture of e) for uniformity of granules to obtain final granules; and   g) compressing the final granules off) to tablets.   
     
     
         20 . The fluid-bed granulation process according to  claim 19 , wherein the binder of step a) is povidone, and the solid support of step a) comprises lactose, starch, flavor and citric acid anhydrous.