Salts of fenofibric acid and pharmaceutical formulations thereof

• US 7,259,186 B2
• Filed: 06/30/2004
• Issued: 08/21/2007
• Est. Priority Date: 12/17/2002
• Status: Active Grant

• Current Assignee: Abbvie Incorporated
• Original Assignee: Abbott Laboratories Incorporated
• Inventors: Zhang, Geoff G. Z., Rosenberg, Joerg, Gao, Yi, Morris, John B., Long, Michelle A., Cink, Russell Drew, Paterson, Joseph B. Jr.
• Primary Examiner(s): Badio; Barbara P.
• Application Number:
  US10/880,851
• Publication Number:
  US 20050148594A1
• Time in Patent Office: 1,147 Days
• Field of Search: 562/460, 544/358, 514/571, 514/252.12
• US Class Current: 514/571
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/205 Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
• CPC Class Codes: A61K 31/216 of acids having aromatic rings, e.g. benactizyne, clofibrate
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• 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 9/146 with organic macromolecular compounds
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• 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: C07C 215/08 with only one hydroxy group and one amino group bound to the carbon skeleton
• CPC Class Codes: C07C 215/12 the nitrogen atom of the amino group being further bound to hydrocarbon groups substituted by hydroxy groups
• CPC Class Codes: C07C 51/412 by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part
• CPC Class Codes: C07C 59/88 containing halogen

Abstract

In one aspect, the present invention relates to a formulation in the form of molecular dispersion comprising i) fenofibric acid, a physiologically acceptable salt or derivative thereof and optionally other active substances, ii) a binder component comprising at least one enteric binder, and optionally iii) other physiologically acceptable excipients.

In a second aspect, the present invention relates to novel salts of fenofibric acid that are photostable when compared to other salts of fenofibric acid.

Claims

1. A salt of fenofibric acid selected from the group consisting of choline, ethanolamine, diethanolamine, piperazine, calcium and tromethamine.

2. The salt of claim 1 wherein said salt is choline.

3. The salt of claim 1 wherein said salt is ethanolamine.

4. The salt of claim 1 wherein said salt is diethanolamine.

5. The salt of claim 1 wherein said salt is piperazine.

6. The salt of claim 1 wherein said salt is calcium.

7. The salt of claim 1 wherein said salt is tromethamine.

8. A pharmaceutical formulation in a form of a molecular dispersion comprising:

i. a salt of fenofibric acid selected from the group consisting of choline, ethanolamine, diethanolamine, piperazine, calcium and tromethamine; and

ii. a binder component comprising at least one enteric binder.

9. The formulation of claim 8 further comprising a physiologically acceptable excipient.

10. The formulation as claimed in claim 8, wherein the enteric binder is an enteric polymer.

11. The formulation as claimed in claim 10, wherein the enteric polymer is selected from hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, carboxymethylethylcellulose, cellulose acetate phthalate, cellulose acetate trimellitate and carboxymethylcellulose sodium.

12. The formulation as claimed in claim 10, wherein the enteric polymer is a copolymer of (meth)acrylic acid and at least one alkyl (meth)acrylic acid ester.

13. The formulation as claimed in claim 12, wherein the alkyl (meth)acrylic acid ester is methyl methacrylate.

14. The formulation as claimed in claim 8, wherein the formulation comprises about 5 to about 60% by weight of said salt and about 20 to about 95% by weight of a binder component.

15. The formulation of claim 9, wherein the formulation comprises about 1 to about 60% of a physiologically acceptable excipient.