PHARMACEUTICALLY ACCEPTABLE SALTS OF QUINOLINONE COMPOUNDS HAVING IMPROVED PHARMACEUTICAL PROPERTIES
A lacate salt of a compound of Formula I or a tautomer of the compound, wherein Formula I has the following structure and R 1 -R 9 and R 12 -R 14 are as defined herein
1 . A lactate salt of 4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]quinolin-2(1H)-one.
2 . The lactate salt of claim 1 , wherein the salt comprises the mono-lactate or bis-lacate salt.
3 . The lactate salt of claim 1 , wherein the salt comprises the mono-lactate salt.
4 . The lactate salt of claim 1 , wherein the solubility of the salt in water at 22° C. is greater than 30 mg/mL.
5 . The lactate salt of claim 1 , wherein the solubility of the salt in water at 22° C. is from about 150 mg/mL to about 250 mg/mL.
6 . The lactate salt of claim 1 , wherein the salt comprises the DL lactate salt.
7 . The lactate salt of claim 1 , wherein the salt comprises the D lactate salt.
8 . The lactate salt of claim 1 , wherein the salt comprises the L lactate salt.
9 . The lactate salt of claim 1 , wherein the salt comprises the D lactate salt, the L lactate salt, or a mixture thereof.
10 . The lactate salt of claim 1 , wherein the salt is crystalline and comprises plate-shaped crystals.
11 . A composition comprising a tablet of the lactate salt of claim 1 .
12 . A method of preparing the lactate salt of claim 1 , comprising:
(a) suspending 4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]quinolin-2(1H)-one in a solvent or mixture of solvents;
(b) contacting lactic acid with 4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]quinolin-2(1H)-one to provide a mixture;
(c) heating the mixture;
(d) cooling the mixture; and
(e) isolating the salt.
13 . The method of claim 12 , wherein the solvent is a protic solvent.
14 . The method of claim 12 , wherein the solvent is selected from the group consisting of methanol, ethanol, water, tetrahydrofuran, and mixtures thereof.
15 . A pharmaceutical formulation, comprising the lactate salt of claim 1 and a pharmaceutically acceptable carrier.