Pharmaceutical Composition Comprising Pimobendan

• US 20120148640A1
• Filed: 02/22/2012
• Published: 06/14/2012
• Est. Priority Date: 03/08/2004
• Status: Active Grant

• 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, Schmalz, Jens
• Granted Patent: US 8,846,680 B2
• Time in Patent Office: Days
• US Class Current: 424/400
• 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

The invention relates to novel solid formulations comprising as pharmaceutically active compound pimobendan and to processes for producing such solid formulations. The invention furthermore relates to a method for manufacturing a medicament for the prevention and/or treatment of congestive heart failure, wherein the solid formulations according to the invention are used.

Claims

1-12. -12. (canceled)

13. A fluid-bed granulation process, comprising the steps of:

a) spraying an aqueous solution of pimobendan and a binder onto a solid support comprising one or several carriers or excipients, flavor and citric acid anhydride and

b) drying the sprayed mixture;

c) sieving and de-agglomerating the dried mixture;

d) adding a flow regulator to the resulting mixture;

e) adding a lubricant to the resulting mixture; and

f) blending the resulting mixture for uniformity of granules.

14. The fluid-bed granulation process according to claim 13 further comprising the step of tabletting the resulting, blended granules.

15. Fluid-bed granulation process according to claim 13, comprising the steps:

a) spraying an aqueous solution of pimobendan and povidone onto a solid support comprising lactose, starch, flavor and citric acid anhydride and

b) drying the resulting mixture;

c) sieving and de-agglomerating the resulting dried mixture;

d) adding a flow regulator to the resulting mixture;

e) adding a lubricant to the resulting mixture; and

f) blending the resulting mixture to obtain uniform granules.

16. The fluid-bed granulation process according to claim 15 further comprising the step of tabletting the resulting, blended granules.

18. A method of treating congestive heart failure in a small mammal, comprising:

administering a therapeutically effective amount of a solid formulation to a small mammal in need thereof, wherein the solid formulation comprises a homogenous dispersion of

pimobendan or a pharmaceutically acceptable salt thereof;

a polyvalent acid selected from the group consisting of citric acid, tartaric acid, an anhydride thereof and mixtures thereof, and;

a flavor suitable for small animals, wherein the flavor is present in an amount of 5 to 30 percent by weight of said solid formulation.

19. The method of claim 18, wherein the solid formulation is a tablet or a granule.

20. The method of claim 18, wherein the small mammal is selected from the group consisting of dogs, cats and rabbits.

21. The method of claim 18, wherein the solid formulation further comprises starch and lactose.

22. The method of claim 21, wherein the starch is selected from the group consisting of native starch, gelatinized starch, partly gelatinized starch, starch powder, starch granules, chemically modified starch, swellable physically modified starch and mixtures thereof.

23. The method of claim 21, wherein the starch is corn starch.

24. The method of claim 21, wherein the lactose consists of coarse particles greater than 200 μ

m in size.

25. The method of claim 18, wherein 0.5 to 20 mg of pimobendan are present in the solid formulation.

26. The method of claim 18, wherein the solid formulation comprises 1.25 mg, 2.5 mg, 5 mg or 10 mg pimobendan, the polyvalent acid is 50 mg/g citric acid, the flavor suitable for small animals is artificial beef flavor, and the solid formulation further comprises lactose, corn starch, croscarmellose-sodium, polyvidone, colloidal anhydrous silica and magnesium stearate.

27. A method of treating congestive heart failure in a small mammal, comprising:

administering a therapeutically effective amount of a solid formulation to a small mammal in need thereof, wherein the solid formulation comprises a homogenous dispersion of

pimobendan or a pharmaceutically acceptable salt thereof;

a polyvalent acid selected from the group consisting of citric acid, tartaric acid, an anhydride thereof and mixtures thereof, wherein the polyvalent acid is present in an amount of 2.5 to 10 percent by weight of said solid formulation;

starch in an amount of 25 to 50 percent by weight of said solid formulation;

lactose in an amount of 25 to 50 percent by weight of said solid formulation; and

a flavor suitable for small animals, wherein the flavor is present in an amount of 5 to 30 percent by weight of said solid formulation.

28. The method of claim 27, wherein 1.25 mg, 2.5 mg, 5 mg or 10 mg of pimobendan is present in the solid formulation.

29. The method of claim 27, wherein the solid formulation is a tablet or a granule.

30. The method of claim 27, wherein the small mammal is selected from the group consisting of dogs, cats and rabbits.