PHARMACEUTICAL COMPOSITION INCLUDING PIMOBENDAN

• US 20140363510A1
• Filed: 08/21/2014
• Published: 12/11/2014
• Est. Priority Date: 03/08/2004
• Status: Abandoned Application

• Current Assignee: Boehringer Ingelheim Vetmedica GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim Vetmedica GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Folger, Martin A., Hassel, Bernhard, Henke, Stefan, Lehmann, Jens
• Application Number:
  US14/465,273
• Publication Number:
  US 20140363510A1
• Time in Patent Office: Days
• US Class Current: 424/489
• CPC Class Codes: A61K 31/501 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 47/46 Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure

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.

Claims

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 μ

m 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.