Polymorphs of 1-cyclopropyl-7-([s,s])-2,8-diazadicyclo[4.3.0]non-8-yl)-6-fluoro-1,4-dihydro -8-methoxy-4-oxo-3-quinoline carboxylic acid hydrochloride and methods for the preparation thereof
Abstract
Two novel crystalline forms, designated form A and form B of the antibacterial agent 1-cyclopropyl-7-([S,S])-2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinoline carboxylic acid hydrochloride of formula, the preparation thereof, and their pharmaceutical compositions are described. These crystalline forms, which are characterized by greater stability and ease of preparation and of formulation, can be produced by industrially applicable methods which comprise the steps of: a) suspending 1-cyclopropyl-7-([S,S])-2,8-diazabicyclo-[4.3.0]non-8-yl)-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinoline carboxylic acid hydrochloride in a solvent selected from an alcohol and a polyalcohol, b) heating the mixture under reflux, c) cooling, d) isolating the product which is separated, (form A) and, additionally, e) reslurrying the solid at reflux in a solvent selected from alcohols and polyols or mixtures thereof, in which the resulting mixture has an overall water content of between 2.5% and 0.01% by weight, f) isolating the product (form B).
Claims
exact text as granted — not AI-modified1 . Moxifloxacin hydrochloride form B, characterized by an X-ray diffraction spectrum having the following principal peaks:
Rel. Intens.
Angle (2Θ)
D (Å)
(I/I 0 )
5.700
15.4919
24.0
7.200
12.2675
100.0
8.470
10.4307
18.9
8.820
10.0176
91.6
10.505
8.4142
44.0
11.405
7.7522
14.6
12.220
7.2369
5.9
13.200
6.7018
16.2
13.925
6.3544
18.1
14.415
6.1395
26.6
14.740
6.0049
49.9
15.395
5.7508
4.9
16.600
5.3360
20.7
17.180
5.1571
13.7
17.705
5.0054
68.7
18.710
4.7387
13.7
19.105
4.6416
26.2
19.865
4.4657
11.8
20.155
4.4021
7.6
21.055
4.2159
2.4
21.545
4.1211
16.9
22.155
4.0090
17.3
22.690
3.9157
11.8
22.905
3.8794
10.5
24.610
3.6144
18.7
24.955
3.5652
10.0
25.385
3.5058
7.0
25.815
3.4483
14.5
26.195
3.3992
16.3
26.605
3.3477
18.4
26.960
3.3044
28.7
27.265
3.2681
37.0
28.045
3.1790
9.0
28.730
3.1047
22.2
29.110
3.0651
8.5
29.745
3.0011
9.6
30.170
2.9598
6.2
31.440
2.8430
4.1
31.795
2.8121
1.9
32.145
2.7823
3.1
32.410
2.7601
2.5
33.385
2.6817
1.8
2 . Moxifloxacin hydrochloride form B, characterized by an X-ray diffraction spectrum as shown in FIG. 6.
3 . Moxifloxacin hydrochloride form B, characterized by an IR spectrum as shown in FIG. 7.
4 . Moxifloxacin hydrochloride form B, characterized by a DSC graph as shown in FIG. 8.
5 . A method for the preparation of moxifloxacin hydrochloride form B, which comprises the steps the steps of:
a) suspending moxifloxacin hydrochloride in a solvent selected from alcohols and polyols or mixtures thereof, in which the resulting mixture has an overall water content of between 2.5% and 0.01% by weight, b) heating the mixture under reflux, c) cooling, d) isolating the product, e) reslurrying the solid in a solvent selected from alcohols and polyols or mixtures thereof, in which the resulting mixture has an overall water content of between 2.5% and 0.01% by weight and f) isolating the product.
6 . A method according to claim 5 in which the moxifloxacin hydrochloride in step a) is in anhydrous or monohydrate crystalline form.
7 . A method according to claim 6 in which the moxifloxacin hydrochloride is in an anhydrous form having a water content of less than 0.3%.
8 . A method according to claim 5 in which the solvent of steps a) and e) is a C 1 -C 6 alcohol or polyol, preferably ethanol or isopropanol.
9 . A method according to claim 5 in which the solvent of steps a) and e) has a water content of between 1% and 0.01%, preferably between 0.3% and 0.01%, more preferably between 0.1% and 0.01%.
10 . A method according to claim 5 in which the mixture is cooled to room temperature.
11 . A method according to claim 5 in which the solvent is used in a ratio of between 50:1 and 2:1, preferably between 30:1 and 5:1, more preferably about 10:1, the ratio being expressed as ml of solvent per gram of moxifloxacin hydrochloride.
12 . A method according to claim 5 in which step e) is performed by heating the mixture under reflux for 1 to 4 hours, preferably for about 2 hours.
13 . A method for treating bacterial infections which comprises administering moxifloxacin hydrochloride form B according to claim 1 to a patient in need of such a treatment.
14 . A method for treating bacterial infections which comprises administering moxifloxacin hydrochloride form B according to claim 2 to a patient in need of such a treatment.
15 . A method for treating bacterial infections which comprises administering moxifloxacin hydrochloride form B according to claim 3 to a patient in need of such a treatment.
16 . A method for treating bacterial infections which comprises administering moxifloxacin hydrochloride form B according to claim 4 to a patient in need of such a treatment.
17 . Pharmaceutical compositions comprising moxifloxacin hydrochloride form B according to claim 1 and at least one pharmaceutically acceptable excipient.
18 . Pharmaceutical compositions comprising moxifloxacin hydrochloride form B according to claim 2 and at least one pharmaceutically acceptable excipient.
19 . Pharmaceutical compositions comprising moxifloxacin hydrochloride form B according to claim 3 and at least one pharmaceutically acceptable excipient.
20 . Pharmaceutical compositions comprising moxifloxacin hydrochloride form B according to claim 4 and at least one pharmaceutically acceptable excipient.Join the waitlist — get patent alerts
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