GEMCABENE, PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, COMPOSITIONS THEREOF AND METHODS OF USE THEREFOR

1 . A pharmaceutically acceptable salt of gemcabene, the pharmaceutically acceptable salt having a PSD90 ranging from 40 μm to about 75 μm as measured by laser light diffraction and providing a plasma gemcabene AUC (0-24) ranging from about 200 μg·hr/mL at steady state to about 6000 μg·hr/mL at steady state when administered to a human subject at a dose of about 50 mg to about 900 mg.

2 . The pharmaceutically acceptable salt of claim 1 , wherein the pharmaceutically acceptable salt has a dissolution profile characterized by a % dissolution value of (1) at least 80% in pH 5.0 potassium acetate buffer at 37° C.±5° C. in no more than 45 minutes as measured by high-performance liquid chromatography using a detection wavelength of 210 μm or (2) at least 70% in pH 5.0 potassium acetate buffer at 37° C.±5° C. in no more than 30 minutes as measured by high-performance liquid chromatography using a detection wavelength of 210 μm.

3 . The pharmaceutically acceptable salt of claim 1 , wherein the pharmaceutically acceptable salt is a calcium salt.

4 . A pharmaceutically acceptable salt of gemcabene, the pharmaceutically acceptable salt having a PSD90 ranging from 40 μm to about 75 μm as measured by laser light diffraction and providing a plasma gemcabene AUC last ranging from about 50 μg·hr/mL to about 7500 μg·hr/mL after a single dose administration of about 50 mg to about 900 mg to a human subject.

5 . The pharmaceutically acceptable salt of claim 4 , wherein the pharmaceutically acceptable salt has a dissolution profile characterized by a % dissolution value of (1) at least 80% in pH 5.0 potassium acetate buffer at 37° C.±5° C. in no more than 45 minutes as measured by high-performance liquid chromatography using a detection wavelength of 210 μm or (2) at least 70% in pH 5.0 potassium acetate buffer at 37° C.±5° C. in no more than 30 minutes as measured by high-performance liquid chromatography using a detection wavelength of 210 μm.

6 . The pharmaceutically acceptable salt of claim 4 , wherein the pharmaceutically acceptable salt is a calcium salt.

7 . A method for purifying crude gemcabene, wherein the crude gemcabene comprises no more than 3% w/w of 2,2,7,7-tetramethyl-octane-1,8-dioic acid as determined by high-performance liquid chromatography, comprising:

dissolving the crude gemcabene in heptane to provide a heptane solution of the crude gemcabene; and

cooling the heptane solution to a temperature ranging from 10° C. to 15° C. to precipitate gemcabene, wherein the gemcabene comprises 0.5% w/w or less of 2,2,7,7-tetramethyl-octane-1,8-dioic acid as determined by high-performance liquid chromatography.

8 . The method of claim 7 , further comprising:

dissolving the gemcabene in heptane to provide a heptane solution of the gemcabene; and

cooling the heptane solution to a temperature ranging from 10° C. to 15° C. to precipitate recrystallized gemcabene.

9 . The method of claim 7 , further comprising:

allowing two or more molar equivalents of an enolate of an alkali metal salt of isobutyric acid to react with one molar equivalent of a bis-(4-halobutyl)ether to provide crude gemcabene salt and acidifying the crude gemcabene salt to provide the crude gemcabene.

10 . Gemcabene made by the method of claim 7 .

11 . A pharmaceutically acceptable salt of the gemcabene of claim 10 .

12 . The pharmaceutically acceptable salt of claim 11 , wherein the pharmaceutically acceptable salt is a calcium salt.

13 . A composition comprising an effective amount of the pharmaceutically acceptable salt of claim 1 and a pharmaceutically acceptable carrier or vehicle.

14 . A composition comprising an effective amount of the pharmaceutically acceptable salt of claim 4 and a pharmaceutically acceptable carrier or vehicle.

15 . A composition comprising an effective amount of the pharmaceutically acceptable salt of claim 11 and a pharmaceutically acceptable carrier or vehicle.