REACTIVE GRANULATION OF CALCIUM CITRATE MALATE, DICALCIUM MALATE, AND DIMAGNESIUM MALATE
The present invention provides compositions comprising granules of calcium citrate malate, compositions comprising granules of dicalcium malate, compositions comprising granules of dimagnesium malate, methods for preparing these compositions, and dosage formulations of these compositions.
1 . A composition comprising:
(a) granules of calcium citrate malate having a mole ratio of calcium:malate:citrate of about 6:3:2 and a water content of at least 5.0 weight % (wt %); or
(b) granules of dicalcium malate having a mole ratio of calcium:malate of about 2:1 and a water content of at least 5.0 wt %.
2 - 16 . (canceled)
17 . A composition comprising granules of dimagnesium malate having a mole ratio of magnesium:malate of about 2:1 and a water content of at least 2.0 wt %.
18 . (canceled)
19 . The composition of claim 17 , wherein the granules have a magnesium weight percentage of at least 18 wt %.
20 . The composition of claim 17 , wherein the granules of dimagnesium malate have a particle size ranging from about 50 microns to about 1500 microns.
21 . The composition of claim 17 , wherein 75% of the granules of dimagnesium malate have a particle size ranging from about 90 microns to about 1000 microns.
22 . The composition of claim 17 , wherein the granules have a bulk density of at least 0.70 g/mL.
23 . The composition of claim 17 , wherein the composition comprises no more than 5.0 wt % silica.
24 . The composition of claim 17 , wherein the composition is free of silica.
25 . A method for preparing granules of calcium citrate malate, the method comprising:
contacting citric acid and malic acid forming a particulate mixture;
adding water to the particulate mixture from step (a) forming a slurry;
contacting a calcium base with the slurry from step (b);
reacting to form the granules of calcium citrate malate; and
isolating the granules of calcium citrate malate;
wherein the granules of calcium citrate malate have a water content of at least 5.0 wt %.
26 - 31 . (canceled)
32 . A method for preparing granules of dicalcium malate, the method comprising:
adding water to a calcium base forming a slurry;
contacting the slurry from step (a) with malic acid causing a reaction between the malic acid and the calcium base forming a second slurry;
repeating step (b) until the calcium base and malic acid fully react forming granules of dicalcium malate; and
isolating the granules of dicalcium malate;
wherein the granules of dicalcium malate have a water content of at least 5.0 wt %.
33 - 38 . (canceled)
39 . A method for preparing granules of dimagnesium malate, the method comprising:
contacting a magnesium base and a malic acid forming a particulate mixture;
adding water to the particulate mixture from step (a) causing a partial reaction between the malic acid and the magnesium base forming a slurry;
repeating step (b) until the malic acid and the magnesium base fully react forming granules; and
isolating the granules of dimagnesium malate;
wherein the granules of dimagnesium malate have a water content of at least 2.0 wt %.
40 . The method of claim 39 , wherein adding the water to the particulate mixture from step (a) produces an exotherm; and wherein the rate at which water is added controls the exotherm.
41 . The method of claim 39 , wherein the granules of dimagnesium malate have a mole ratio of magnesium:malate of about 2:1, and/or a magnesium weight percentage (Mg %) of at least 18 wt %, and/or a particle size ranging from about 50 microns to about 1500 microns.
42 - 43 . (canceled)
44 . The method of claim 41 , wherein at least 75% of the granules of dimagnesium malate have a particle size ranging from about 90 microns to about 1000 microns after milling.
45 . The method of claim 39 , wherein the granules have a bulk density of at least 0.70 g/mL.
46 . (canceled)
47 . The dosage formulation of claim 48 , wherein the dosage formulation is a tablet comprising compressed granules of calcium citrate malate.
48 . A dosage formulation comprising granules of the composition of claim 1 .
49 . The dosage formulation of claim 48 , wherein the dosage formulation is a tablet comprising compressed granules of dicalcium malate.
50 . A dosage formulation comprising granules of the composition of claim 17 .
51 . The dosage formulation of claim 50 , wherein the dosage formulation is a tablet comprising compressed granules of dimagnesium malate.