Crystal polymorph of magnesium glycinate dihydrate and process for its preparation
View Patent ↗Embodiments of the invention provide solid forms of magnesium glycinate dihydrate and compositions thereof, which are useful for treating hyperphosphatemia and which exhibit desirable characteristics for the same. The invention further provides processes for the production of solid forms of magnesium glycinate dihydrate.
1. A crystalline dihydrate form of magnesium glycinate (Formula I)
wherein the form is characterized by an X-ray powder diffraction pattern having one or more peaks selected from those at about 14.6, 16.0, 16.9, 17.6, 19.3, 22.9, 24.4, 25.8, 30.9 or 47.1.
2. The form of claim 1 , wherein the form is characterized by an X-ray powder diffraction pattern having two or more peaks selected from those at about 14.6, 16.0, 16.9, 17.6, 19.3, 22.9, 24.4, 25.8, 30.9 or 47.1.
3. The form of claim 1 , wherein the form is characterized by an X-ray powder diffraction pattern having three or more peaks selected from those at about 14.6, 16.0, 16.9, 17.6, 19.3, 22.9, 24.4, 25.8, 30.9 or 47.1.
4. The form of claim 1 , wherein the form has all of the peaks in its X-ray powder diffraction pattern selected from those at about 14.6, 16.0, 16.9, 17.6, 19.3, 22.9, 24.4, 25.8, 30.9 or 47.1.
5. The form of claim 4 , having all of the peaks in its X-ray powder diffraction pattern selected from those at about:
No.
2-Theta °
Δ 2θ (±)°
d, Å
1
14.6
0.1
6.06
2
16.0
0.1
5.54
3
16.9
0.1
5.25
4
17.6
0.1
5.04
5
19.3
0.1
4.59
6
22.9
0.1
3.88
7
24.4
0.1
3.65
8
25.8
0.1
3.46
9
30.9
0.1
2.89
10
47.1
0.1
1.93.
6. The form of claim 1 , wherein the crystalline magnesium glycinate dihydrate has a space group P21/n.
7. The form of claim 1 , wherein the crystalline magnesium glycinate dihydrate has unit cell dimensions of about a=7.5 Å, b =9.0 Å, and c=13.0 Å.
8. The form of claim 7 , wherein the crystalline magnesium glycinate dihydrate has unit cell dimensions of about a=7.548 Å, b=9.053 Å, and c=12.970 Å.
9. The form of claim 7 , wherein the crystalline magnesium glycinate dihydrate has unit cell dimensions of about a=7.575 Å, b =9.153 Å, and c=13.052 Å.
10. A crystalline magnesium glycinate dihydrate form characterized by one or more of the following crystal structure parameters:
Crystal system
Monoclinic
Space group
P 21/n
Unit cell dimensions
a = 7.5481(3) Å
α = 90°
b = 9.0525(3) Å
β = 98.612(3)°
c = 12.9702(5) Å
γ = 90°
Volume
876.25(6) Å 3
Z
4
Density (calculated)
1.580 Mg/m 3
Absorption coefficient
1.893 mm −1
F(000)
440
Crystal size
0.10 × 0.01 × 0.01 mm 3
Theta range for data collection
5.98 to 66.64°
Index ranges
−8 <= h <= 7, −10 <= k <= 10,
−10 <= l <= 15
Reflections collected
5746
Independent reflections
1501 [R(int) = 0.0279]
Completeness to theta = 66.64°
97.2%
Absorption correction
Semi-empirical from equivalents
Max. and min. transmission
0.7528 and 0.6842
Refinement method
Full-matrix least-squares on F 2
Data/restraints/parameters
1501/0/150
Goodness-of-fit on F 2
1.056
Final R indices [I > 2sigma(I)]
R1 = 0.0269, wR2 = 0.0696
R indices (all data)
R1 = 0.0303, wR2 = 0.0718
Largest diff. peak and hole
0.215 and −0.224 e · Å −3 .
11. A pharmaceutical composition comprising the crystalline form of magnesium glycinate dihydrate as described in claim 1 .
12. The pharmaceutical composition of claim 11 , further comprising an enteric coating.
13. The pharmaceutical composition of claim 12 , wherein the enteric coating comprises acetyltributyl citrate, carbomers, cellulose acetate phthalate, cellulose acetate succinate, ethyl cellulose, guar gum, hypromellose acetate succinate, hypromellose phthalate, polymethacrylates, polyvinyl acetate phthalate, shellac, tributyl citrate, triethyl citrate, white wax and/or zein.
14. The pharmaceutical composition of claim 12 , wherein the enteric coating is stable at pH less than 3 but dissolves at a pH above 5.5.
15. The pharmaceutical composition of claim 12 , wherein the composition further comprises one or more additional therapeutic agents or nutrients.
16. The pharmaceutical composition of claim 15 , wherein the nutrient is selected from vitamins, minerals, fatty acids, and/or amino acids.
17. A method of treating hyperphosphatemia in a subject, the method comprising administering to the subject a form of magnesium glycinate dihydrate according to claim 1 .