Novel pharmaceutical salts of 1-benzyl-4-[ (5,6-dimethoxy-1-indanone)-2-yl] methyl piperidine ( Donepezil)

Abstract

New salts of donepezil, and new polymorphic forms of donepezil and its salts, and methods to prepare both the amorphous form and various polymorphic forms of donepezil or its salts.

Description

BRIEF DESCRIPTION OF FIGURES

FIG. 1 shows a powder X-ray diffraction pattern for Donepezil maleate form (I) crystals.

FIG. 2 shows a powder X-ray diffraction pattern for Donepezil fumarate form (I) crystals.

FIG. 3 shows a powder X-ray diffraction pattern for amorphous form of Donepezil maleate

FIG. 4 shows a powder X-ray diffraction pattern for amorphous form of Donepezil fumarate

FIG. 5 shows a powder X-ray diffraction pattern for amorphous form of Donepezil oxalate

FIG. 6 shows an infrared absorption spectrum for Donepezil maleate form (I) crystals

FIG. 7 shows an infrared absorption spectrum for Donepezil fumarate form (I) crystals

FIG. 8 shows an infrared absorption spectrum for amorphous form for Donepezil Maleate

FIG. 9 shows an infrared absorption spectrum for amorphous form for Donepezil fumarate

FIG. 10 shows an infrared absorption spectrum for amorphous form for Donepezil oxalate

(1) Maleate Form (I) Crystals

Peaks in powder X-ray diffraction pattern (See FIG. 1)

Peaks in infrared absorption spectrum recorded in potassium bromide (See FIG. 6)

(2) Amorphous Maleate Form

Peaks in powder X-ray diffraction pattern (See FIG. 3)

Peaks in infrared absorption spectrum recorded in potassium bromide (See FIG. 8)

(3) Fumarate Form (I) Crystals

Peaks in powder X-ray diffraction pattern (See FIG. 2)

Peaks in infrared absorption spectrum in potassium bromide (See FIG. 7)

(4) Amorphous Fumarate Form

Peaks in powder X-ray diffraction pattern (See FIG. 4)

Peaks in infrared absorption spectrum in potassium bromide (See FIG. 9)

(5) Amorphous Oxalate Form

Peaks in powder X-ray diffraction pattern (See FIG. 5)

Peaks in infrared absorption spectrum in potassium bromide (See FIG. 10)

The processes for preparing novel maleate salts are given below, where in,

Donepezil base is prepared by a process as described in U.S. Pat. No. 6,649,765 B1 and is incorporated here as a reference.

(1) Maleate Form (I) Crystals:

(1-1) Process for preparing Donepezil maleate by addition of maleic acid in (1-1) acetone to Donepezil base in ethyl acetate.

(1-2) Process for preparing Donepezil maleate by addition of maleic acid in Propan-2-ol to Donepezil base in ethyl acetate.

(1-3) Process for preparing Donepezil maleate by addition of maleic acid in methanol to Donepezil base in ethyl acetate.

(1-4) Dissolving Donepezil maleate in Methanol, followed by addition of Diethyl ether.

(1-5) Dissolving Donepezil maleate in Methanol, followed by addition of Diisopropyl ether.

(1-6) Dissolving Donepezil maleate in Ethanol, followed by addition of Diisopropyl ether.

(1-7) Dissolving Donepezil maleate in Ethanol, followed by addition of Diethyl ether.

(1-8) Dissolving Donepezil maleate in Water, followed by addition of acetone.

(1-9) Dissolving Donepezil maleate in Water, followed by addition of propan-2-ol.

(1-10) Dissolving Donepezil maleate in Ethanol, followed by addition of n-hexane.

(1-11) Dissolving Donepezil maleate in Methanol and cooling to RT.

(1-12) Dissolving Donepezil maleate in Methanol, followed by addition of Toluene.

(1-13) Dissolving Donepezil maleate in water, followed by addition of Acetonitrile.

(1-14) Dissolving Donepezil maleate in Tetrahydrofuran, followed by addition of diisopropyl ether.

(1-15) The above-mentioned Donepezil maleate salt was dissolved in respective solvents by heating at 40° C.-60° C.

(2) Donepezil Maleate Amorphous Form

(2-1) Process for isolating the amorphous form which comprises spray drying, a solution of Donepezil Maleate in volatile organic solvent.

(2-2) Concentration of Donepezil maleate used for spray drying is preferably in the range of from 3 to 10% weight/volume. Spray drying is carried out in the inlet temperature range of 120° C.-200° C. and outlet temperature range 60° C.-110° C.

(2-3) Another process to obtain the amorphous form of Donepezil Maleate is evaporation of the solvent under vacuum.

(3) Fumarate Form (I) Crystals

(3-1) Process for preparing Donepezil fumarate by addition of fumaric acid in acetone to Donepezil base in ethyl acetate.

(3-2) Process for preparing Donepezil fumarate by addition of fumaric acid in Propan-2-ol to Donepezil base in ethyl acetate.

(3-3) Process for preparing Donepezil fumarate by addition of fumaric acid in methanol to Donepezil base in ethyl acetate.

(3-4) Dissolving Donepezil fumarate in Methanol, followed by addition of Diethyl ether.

(3-5) Dissolving Donepezil fumarate in Methanol, followed by addition of Diisopropyl ether.

(3-6) Dissolving Donepezil fumarate in Ethanol, followed by addition of Diisopropyl ether.

(3-7) Dissolving Donepezil fumarate in Ethanol, followed by addition of Diethyl ether.

(3-8) Dissolving Donepezil fumarate Water, followed by addition of acetone.

(3-9) Dissolving Donepezil fumarate in Water, followed by addition of propan-2-ol.

(3-10) Dissolving Donepezil fumarate in Ethanol, followed by addition of n-hexane.

(3-11) Dissolving Donepezil fumarate in Methanol and cooling to RT.

(3-12) Dissolving Donepezil fumarate in Methanol, followed by addition of Toluene.

(3-13) Dissolving Donepezil fumarate in water, followed by addition of Acetonitrile.

(3-14) Dissolving Donepezil fumarate in Tetrahydrofuran, followed by addition of diisopropyl ether.

(3-15) The above-mentioned Donepezil fumarate salt was dissolved in respective solvents by heating at 40° C.-60° C.

(4) Donepezil Fumarate Amorphous Form

(4-1) Process for isolating the amorphous form which comprises spray drying, a solution of Donepezil fumarate in volatile organic solvent.

(4-2) Concentration of Donepezil fumarate used for spray drying is preferably in the range of from 1 to 5% weight/volume. Spray drying is carried out in the inlet temperature range of 120° C.-200° C. and outlet temperature range 60° C.-110° C.

(4-3) Another process to obtain the amorphous form of Donepezil fumarate is evaporation of the solvent under vacuum

(5) Doenpezil Oxalate Amorphous Form

(5-1) Process for isolating the amorphous form which comprises spray drying, a solution of Donepezil Oxalate in volatile organic solvent.

(5-2) Concentration of Donepezil oxalate used for spray drying is preferably in the range of from 1 to 5% weight/volume. Spray drying is carried out in the inlet temperature range of 120° C.-200° C. and outlet temperature range 60° C.-110° C.

(5-3) Another process to obtain the amorphous form of Donepezil oxalate is evaporation of the solvent under vacuum.

Donepezil Maleate Form (I)

Peaks in the powder x-ray diffraction pattern are:

	Diffraction Angle	Intensity %
Sr. No	(2θ°)	(I/Io)
1.	7.031	9.57
2.	8.285	7.10
3.	9.858	41.20
4.	11.053	14.05
5.	11.414	54.94
6.	11.688	2.97
7.	11.645	5.85
8.	12.477	12.72
9.	12.980	29.19
10.	13.497	18.20
11.	15.868	7.63
12.	15.159	5.61
13.	15.636	10.18
14.	16.001	20.54
15.	16.517	8.07
16.	16.784	12.55
17.	17.792	25.77
18.	18.586	24.02
19.	18.998	25.71
20.	19.229	12.21
21.	19.573	48.75
22.	20.087	64.22
23.	20.546	100.00
24.	20.680	96.42
25.	21.363	15.95
26.	21.788	9.39
27.	22.146	39.60
28.	22.239	47.76
29.	22.605	93.51
30.	22.786	77.64
31.	24.054	37.99
32.	24.479	11.18
33.	25.362	42.39
34.	25.712	29.47
35.	26.480	32.65
36.	26.814	15.85
37.	27.168	11.70
38.	27.804	18.28
39.	28.437	14.12
40.	28.860	7.68
41.	29.382	23.26
42.	29.947	32.29
43.	30.234	18.50
44.	31.407	11.19
45.	31.838	10.09
46.	32.204	7.34
47.	33.731	11.26
48.	34.761	8.17
49.	35.712	4.40
50.	36.655	2.93
51.	37.408	9.40
52.	39.040	6.72
53.	40.415	5.63
54.	41.834	4.50
55.	43.315	2.41
56.	44.096	5.91
57.	46.338	3.98

Wave numbers (cm⁻¹) of infrared absorption spectra recorded in potassium bromide are:

3375.2, 3207.4, 3016.5, 2997.2, 2947.0, 2912.3, 2723.3, 2358.8, 1697.2, 1589.2, 1569.9, 1552,6, 1500.5, 1460.0, 1355.9, 1317.3, 1303.8, 1265.2, 1218.9, 1191.9, 1161.1, 1130.2, 1105.1, 1087.8, 1066.6, 1035.7, 1010.6, 979.8, 945.1, 920.0, 898.8, 873.7, 860.2, 833.2, 806.2, 754.1, 705.9, 638.4, 605.6, 561.2, 497.6, 461.0 & 430.1

Donepezil Maleate Amorphous

Wave numbers (cm⁻¹) of infrared absorption spectra recorded in potassium bromide are:

2918, 2837.1, 1689.5, 1577.7, 1500.5, 1458.4, 1450.4, 1355.9, 1315.4, 1265.2, 1191.9, 1035.7, 945.1, 864.1, 806.1, 750.3, 702.0, 650.0, 559.3.

Fumarate Form (I)

Peaks in the powder x-ray diffraction pattern are:

	Diffraction Angle	Intensity %
Sr. No	(2θ°)	(I/Io)
1.	4.210	6.17
2.	8.222	19.58
3.	11.887	44.64
4.	12.303	100.00
5.	12.558	65.52
6.	13.909	34.31
7.	14.367	58.10
8.	17.026	76.00
9.	18.591	20.56
10.	19.536	20.22
11.	20.433	60.76
12.	21.201	35.43
13.	21.795	27.65
14.	22.560	10.17
15.	23.596	33.43
16.	24.003	56.55
17.	24.285	43.44
18.	25.046	36.93
19.	26.645	50.71
20.	27.230	23.42
21.	27.721	22.58
22.	28.593	15.28
23.	29.573	8.02
24.	31.028	10.24

Wave numbers (cm⁻¹) of infrared absorption spectra recorded in potassium bromide are:

2997.2, 2939.3, 2920.0, 2864.1, 2530.4, 2360.7, 1681.8, 1658.7, 1641.3, 1552.6, 1500.5, 1473.5, 1454.2, 1442.7, 1380.9, 1317.3, 1265.2, 1224.7, 1168.8, 1107.1, 1085.8, 1037.6, 1012.6, 983.6, 941.2, 920.0, 856.3, 810.0, 785.0, 744.5, 698.2, 634.5, 603.7, 586.3, 559.3, 449.5 and 466.7

Donepezil Fumarate Amorphous

Wave numbers (cm⁻¹) of infrared absorption spectra recorded in potassium bromide are:

1689.5, 1676.0, 1589.2, 1500.5, 1544.9, 1436.9, 1363.6, 1315.4, 1265.2, 1217.0, 1118.6, 981.7, 947, 921.9, 862.1, 804.3, 785.0, 750.3, 702.0, 646.1, 559.3

Donepezil Oxalate Amorphous

Wave numbers (cm⁻¹) of infrared absorption spectra recorded in potassium bromide are:

2929.7, 2839.0, 1685.7 1498.6, 1458.1, 1363.6, 1315.4, 1265.2, 1217.0, 1118.6, 1037.6, 862.1, 806.2, 750.3, 700.1

EXAMPLES

Examples 1 to 13: Production of Polymorphic crystals of Donepezil maleate form (I).

Example 14 to 15: Production of amorphous form of Donepezil maleate

Examples 16 to 28: Production of Polymorphic crystals of fumarate form (I).

Example 29 to 30: Production of amorphous form of Donepezil Fumarate

Example 31 to 32: Production of amorphous form of Donepezil oxalate

The present invention will now be described in more detail with reference to the following examples. It is needless to say that the technical scope of the present invention is not limited to these examples.

Example 1

To Donepezil base (obtained after benzylation¹) (10 gms.) in ethyl acetate (200 ml) was added maleic acid (5 gms dissolved in 100 ml acetone slowly with stirring. After addition the reaction mass was concentrated in vacuum. The solid separated was filtered and washed with acetone and dried at 60° C. afforded the title compound with a yield of 12 gms (90.2%) and melting point 176-77° C.

Example 2

To Donepezil base (obtained after benzylation¹) (10 gms.) in ethyl acetate (200 ml) was added maleic acid (5 gms dissolved in 100 ml propan-2-ol) slowly with stirring. After addition the reaction mass was concentrated in vacuum. The solid separated was filtered and washed with acetone and dried at 60° C. afforded the title compound with a yield of 12.5 gms (96.9%) and melting point 176-78° C.

Example 3

To Donepezil base (obtained after benzylation¹) (10 gms.) in ethyl acetate (200 ml) was added maleic acid (5 gms dissolved in 100 ml Methanol) slowly with stirring. After addition the reaction mass was concentrated in vacuum. To the residue was added 50 ml propan-2-ol. The solid separated was filtered and washed with propan-2-ol and dried at 70° C. afforded the title compound with a yield of 12 gms, 90.2%.

Example 4

Donepezil maleate (crude) 5 gms was dissolved in Methanol 50 ml under heating at 50° C. Under stirring, at room temperature 50 ml diethyl ether was added. Stirring was continued for 1 hour after the separation of the crystals. Filtration of the crystals and drying at 60° C. afforded the title compound with a yield of 4.5 gms (90%) and melting point 177-78° C.

Example 5

Donepezil maleate (crude) 5 gms was dissolved in Methanol 50 ml under heating at 50° C. Under stirring, at room temperature 50 ml diisopropyl ether was added. Stirring was continued for 1 hour after the separation of the crystals. Filtration of the crystals and drying at 60° C. afforded the title compound with a yield of 4.0 gms (80%) and melting point 177-78° C.

Example 6

Donepezil maleate (crude) 5 gms was dissolved in Ethanol 50 ml under heating at 50° C. Under stirring, at room temperature 50 ml diethyl ether was added. Stirring was continued for 1 hour after the separation of the crystals. Filtration of the crystals and drying at 60° C. afforded the title compound with a yield of 4.2 gms (84%) and melting point 176-78° C.

Example 7

Donepezil maleate (crude) 5 gms was dissolved in water 50 ml at room temperature. Under stirring, at 50° C. 100 ml acetone was added. Stirring was continued for 1 hour after the separation of the crystals. Filtration of the crystals and drying at 60° C. afforded the title compound with a yield of 4.1 gms (82%) and melting point 177-78° C.

Example 8

Donepezil maleate (crude) 5 gms was dissolved in water 50 ml at room temperature. Under stirring, at 50° C. 100 ml propan-2-ol was added. Stirring was continued for 2 hour after the separation of the crystals at 15° C. Filtration of the crystals and drying at 60° C. afforded the title compound with a yield of 4.6 gms (92%) and melting point 176-78° C.

Example 9

Donepezil maleate (crude) 5 gms was dissolved in ethanol 50 ml under heating at 50° C. Under stirring, at 50° C. 50 ml n-hexane was added. Stirring was continued for 1 hour after the separation of the crystals. Filtration of the crystals and drying at 60° C. afforded the title compound with a yield of 4.4 gms (88%) and melting point 177-78° C.

Example 10

Donepezil maleate (crude) 5 gms was dissolved in methanol 25 ml under heating at 50° C. Stirring was continued for 1 hour with gradual cooling. Stirring was further continued for 1 hour after the separation of the crystals at room temperature. Filtration of the crystals and drying at 60° C. afforded the title compound with a yield of 4.0 gms (80%) and melting point 177-78° C.

Example 11

Donepezil maleate (crude) 5 gms dissolved in methanol 50 ml under heating at 50° C. Under stirring, at 50° C. 100 ml toluene was added. Stirring was continued for 1 hour with gradual cooling. Stirring was further continued for 1 hour after the separation of the crystals. Filtration of the crystals and drying at 60° C. afforded the title compound with a yield of 4.4 gms (88%) and melting point 177-78° C.

Example 12

Donepezil maleate (crude) 5 gms was dissolved in water 50 ml at room temperature. Under stirring, at 50° C. 100 ml acetonitrile was added. Stirring was continued for 2 hour with gradual cooling. Stirring was further continued for 1 hour after the separation of the crystals. Filtration of the crystals and drying at 60° C. afforded the title compound with a yield of 4.0 gms (80%) and melting point 176-78° C.

Example 13

Donepezil maleate (crude) 5 gms was dissolved in tetrahydrofuran 50 ml under heating at 50° C. Under stirring, at 40° C. 100 ml diisopropyl ether was added. Stirring was continued for 1 hour after the separation of the crystals at 15° C. Filtration of the crystals and drying at 60° C. afforded the title compound with a yield of 4.2 gms (86%) and melting point 177-78° C.

Example 15

3% weight/volume solution of Donepezil maleate in methylene dichloride is Spray dried at inlet temperature range of 120-200° C. and outlet temperature range 60-110° C. to yield amorphous Donepezil maleate (64%).

Example 16

3% weight/volume solution of Donepezil maleate in methylene dichloride is evaporated under vacuum at temperature range of 50-70° C. to yield amorphous Donepezil maleate (72%).

Example 17

To Donepezil base (obtained after benzylation¹) (10 gms.) in ethyl acetate (200 ml) was added maleic acid (5 gms dissolved in 100 ml propan-2-ol) slowly with stirring. After addition the reaction mass was concentrated in vacuum. The solid separated was filtered and washed with acetone and dried at 60° C. afforded the title compound with a yield of 12.3 gms (95.4%) and melting point 172-75° C.

Example 18

To Donepezil base (obtained after benzylation¹) (10 gms) in ethyl acetate (200 ml) was added fumaric acid (5 gms dissolved in 100 ml Methanol) slowly with stirring. After addition the reaction mass was concentrated in vacuum. To the residue was added 50 ml propan-2-ol. The solid separated was filtered and washed with propan-2-ol and dried at 70° C. afforded the title compound with a yield of 12.2 gms 92%.

Example 19

Donepezil fumarate (crude) 5 gms was dissolved in Methanol 50 ml under heating at 50° C. Under stirring, at room temperature 50 ml diethyl ether was added. Stirring was continued for 1 hour after the separation of the crystals. Filtration of the crystals and drying at 60° C. afforded the title compound with a yield of 4.55 gms (91%) and melting point 172-75° C.

Example 20

Donepezil fumarate (crude) 5 gms was dissolved in Methanol 50 ml under heating at 50° C. Under stirring, at room temperature 50 ml diisopropyl ether was added. Stirring was continued for 1 hour after the separation of the crystals. Filtration of the crystals and drying at 60° C. afforded the title compound with a yield of 4.2 gms (84%) and melting point 172-75° C.

Example 21

Donepezil fumarate (crude) 5 gms was dissolved in Ethanol 50 ml under heating at 50° C. Under stirring, at room temperature 50 ml diethyl ether was added. Stirring was continued for 1 hour after the separation of the crystals. Filtration of the crystals and drying at 60° C. afforded the title compound with a yield of 4.1 gms (82%) and melting point 172-75° C.

Example 22

Donepezil fumarate (crude) 5 gms was dissolved in water 50 ml at room temperature. Under stirring, at 50° C. 100 ml acetone was added. Stirring was continued for 1 hour after the separation of the crystals. Filtration of the crystals and drying at 60° C. afforded the title compound with a yield of 4.25 gms (85%) and melting point 172-75° C.

Example 23

Donepezil maleate (crude) 5 gms was dissolved in water 50 ml at room temperature. Under stirring, at 50° C. 100 ml propan-2-ol was added. Stirring was continued for 2 hour after the separation of the crystals at 15° C. Filtration of the crystals and drying at 60° C. afforded the title compound with a yield of 4.5 gms (90%) and melting point 172-75° C.

Example 24

Donepezil fumarate (crude) 5 gms was dissolved in water 50 ml under heating at 50° C. Under stirring, at 50° C. 50 ml n-hexane was added. Stirring was continued for 1 hour after the separation of the crystals. Filtration of the crystals and drying at 60° C. afforded the title compound with a yield of 4.5 gms (90%) and melting point 172-75° C.

Example 25

Donepezil fumarate (crude) 5 gms was dissolved in methanol 25 ml under heating at 50° C. Stirring was continued for 1 hour with gradual cooling. Stirring was further continued for 1 hour after the separation of the crystals at room temperature. Filtration of the crystals and drying at 60° C. afforded the title compound with a yield of 4.3 gms (86%) and melting point 172-75° C.

Example 26

Donepezil fumarate (crude) 5 gms was dissolved in methanol 50 ml under heating at 50° C. Under stirring, at 50° C. 100 ml toluene was added. Stirring was continued for 1 hour with gradual cooling. Stirring was further continued for 1 hour after the separation of the crystals. Filtration of the crystals and drying at 60° C. afforded the title compound with a yield of 4.3 gms (86%) and melting point 172-75° C.

Example 27

Donepezil fumarate (crude) 5 gms was dissolved in water 50 ml at room temperature. Under stirring, at 50° C. 100 ml acetonitrile was added. Stirring was continued for 2 hour with gradual cooling. Stirring was further continued for 1 hour after the separation of the crystals. Filtration of the crystals and drying at 60° C. afforded the title compound with a yield of 4.1 gms (82%) and melting point 176-78° C.

Example 28

Donepezil fumarate (crude) 5 gms was dissolved in water 50 ml under heating at 50° C. Under stirring, at 40° C. 100 ml diisopropyl ether was added. Stirring was continued for 1 hour after the separation of the crystals at 15° C. Filtration of the crystals and drying at 60° C. afforded the title compound with a yield of 4.4 gms (88%) and melting point 172-75° C.

Example 29

2% weight/volume solution of Donepezil Fumarate in methanol is Spray dried at inlet temperature range of 120-200° C. and outlet temperature range 60-110° C. to yield amorphous Donepezil Fumarate (66%).

Example 30

2% weight/volume solution of Donepezil Fumarate in methanol is evaporated under vacuum at temperature range of 50-70° C. to yield amorphous Donepezil Fumarate (68%).

Example 31

1.5% weight/volume solution of Donepezil oxalate in methylene is Spray dried at inlet temperature range of 120-200° C. and outlet temperature range 60-110° C. to yield amorphous Donepezil oxalate (73%).

Example 32

1.5% weight/volume solution of Donepezil oxalate in methanol is evaporated under vacuum at temperature range of 50-70° C. to yield amorphous Donepezil oxalate (82%).

Claims

1. A donepezil salt selected from the group consisting of: donepezil oxalate, donepezil maleate and donepezil fumarate.

2. The invention of claim 1, comprising donepezil maleate.

3. The invention of claim 1, comprising donepezil fumarate.

4. The invention of claim 1, comprising donepezil oxalate.

5. A process for making the invention of claim 1, said process comprising: a. dissolving donepezil base in ethyl acetate to make a donepezil base solution;b. dissolving a suitable acid in a second solvent to make an organic acid solution;c. combining said donepezil base solution with said organic acid solution to make a donepezil salt solution; andd. isolating donepezil salt from said donepezil salt solution.

6. The process of claim 5, said suitable acid comprising maleic acid.

7. The process of claim 5, said suitable acid comprising fumaric acid.

8. The process of claim 5, said isolating performed by adding an anti-solvent to said donepezil salt solution in an amount sufficient to cause said donepezil salt to form a precipitate.

9. The process of claim 8, wherein the anti-solvent comprises a compound selected from the group consisting of: tetrahydrofuran: diethyl ether; diisopropyl ether; n-hexane; propan-2-ol; acetonitrile; and toluene.

10. A process for obtaining a salt of Donepezil of amorphous crystalline structure, the process comprising evaporating a solvent from a solution containing a donepezil salt.

11. The process as claimed in claim 10 wherein the solvent comprises a lower chain alcohol and wherein said donepezil salt comprises donepezil fumarate.

12. The process as claimed in claim 11 wherein the solvent comprises a chlorinated hydrocarbon and wherein said donepezil salt is selected from the group consisting of donepezil maleate and donepezil oxalate.

13. Donepezil or a pharmaceutically acceptable salt thereof having a powder X-ray diffraction angle (2θ) selected from the group consisting of 9.858±0.4; 11.053±0.2; 11.414±0.2; 13.909±0.2; 14.367±0.4; 17.792±0.4; 20.680±0.2; and 25.712±0.4.

14. The invention of claim 13, having a powder X-ray diffraction angle (2θ) of 14.367±0.4.

15. The invention of claim 14, having powder X-ray diffraction angles (2θ) of 14.367±0.4 and 13.909±0.2.

16. The invention of claim 13, having a powder X-ray diffraction angle of (2θ) of 9.858±0.4.

17. The invention of claim 13, having a powder X-ray diffraction angle of (2θ) of 17.792±0.4.

18. The invention of claim 13, having a powder X-ray diffraction angle of (2θ) of 25.712±0.4.

19. The invention of claim 13, having a powder X-ray diffraction angle of (2θ) of 9.858±0.4, 17.792±0.4 and 25.712±0.4.

20. The invention of claim 13, having at least three powder X-ray diffraction angles (2θ) selected from the group consisting of 9.858±0.4; 11.053±0.2; 11.414±0.2; 17.792±0.4; 20.680±0.2; and 25.712±0.4.