FIELD OF THE INVENTION
The present invention relates to a new crystalline form of l-Cyclopropyl-6-fluoro-l,4-diydro-8-methoxy-7-[(4ai5,7aS)-octahydro-6/^pyrrolo[3,4-6]pyriclin-6-yl]-4-oxo-3-quinoline carboxylic acid hydrochloride of the Formula I with a moisture content of 1.5 % w/w. The present invention also relates to a process of preparing the new crystalline form.

BACKGROUND OF THE INVENTION
1 -Cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[(4a5',7aS)-octahydro-6//-pyrrolo[3,4-6]pyridin-6-yl]-4-oxo-3-quinoline carboxylic acid hydrochloride is generically known as moxifloxacin hydrochloride. Moxifloxacin hydrochloride, a fluoroquinolone, is a synthetic broad-spectrum anti-bacterial agent and has a methoxy function at the 8-position.
The present invention describes a new crystalline form of moxifloxacin hydrochloride. Polymorphism is the property of some molecules and molecular complexes to assume more than one crystalline or amorphous form in solid state. A molecule such as moxifloxacin of formula I may give rise to a variety of solids having distinct physical properties like solubility, melting point, powder X-ray dlffractogram (XRD) etc. The differences in the physical properties of polymorphs resuh from the orientation and intermolecular interactions of adjacent molecules (complexes) in the bulk solid. Accordingly, polymorphs are distinct solids sharing the same molecular formula, which may be thought of as analogous

to unit cell metallurgy, yet having distinct advantageous and or disadvantageous physical properties compared to other forms in the polymorph family.
Moxifloxacin and its derivatives have been disclosed for the first time in US Patent 4,990,517 by Bayer. It is more specifically claimed in US Patent 5,607,942.
US Patent 5,849,752, incorporated by reference, claims monohydrated moxifloxacin monohydrochloride. The monohydrate form, which crystallizes as prisms, can be prepared by suspending anhydrous crystalline moxifloxacin in ethanol/water mixtures, preferably in ethanol/water at room temperature. The monohydrated moxifloxacin monohydrochloride as disclosed in US Patent 5,849,752 has a moisture content of about 3.9 % w/w. In this patent, it is also mentioned that the form of moxifloxacin hydrochloride reported as of the date of filing of US Patent 5,849,752 is anhydrous.
An amorphous form of moxifloxacin hydrochloride is disclosed in WO 2004/039804 along with a process to prepare the same. The inventors have used the spray drying or freeze-drying technique utilizing the moxifloxacin hydrochloride solution to prepare amorphous moxifloxacin hydrochloride.
In WO 2004/091619, a new polymorphic form of anhydrous moxifloxacin monohydrochloride has been described and the inventors have designated this polymorphic form as Form III.
SUMMARY OF INVENTION
The present invention provides a new crystalline form of moxifloxacin hydrochloride with a moisture content in the range of about 1 to 2 % w/w, but typically close to 1.5 % w/w.

The present invention provides a new crystalline form of moxifloxacin hydrochloride having a moisture content of 1 to 2 % w/w amounting closely to hemihydrate and is herein referred to as moxifloxacin hydrochloride Form A.
The new crystalline polymorphic Form A of the present invention shows X-ray diffraction peaks at the diffraction angles of about 6.36 ± 0.2, 8.39 ± 0.2, 10.02 ± 0,2, 12.28 ± 0.2, 13.28 ± 0.2, 13.64 ± 0.2, 14.90 ± 0.2, 15.39 ± 0.2, 15.79 ± 0.2, 16.71 ± 0.2, 17.69 ± 0.2, 18.23 ± 0.2, 19.09 ± 0.2, 20.07 ± 0.2, 20.71 ± 0.2, 21.44 ± 0.2, 22.25 ± 0.2, 23.60 ± 0.2, 24.18 ± 0.2, 24.61 ± 0.2, 25.98 ± 0.2, 26.90 ± 0.2, 27.83 ± 0.2, 28.67 ± 0.2, 29.90 ± 0.2, 30.40 ± 0.2, 31.17 ± 0.2, 32.01 ± 0.2, 32.85 ±0.2, 38.24 ±0.2
Further, the new crystalline polymorphic Form A can be characterized by an endotherm at about 64.9 °C and a melting endotherm with a peak temperature at about 241.7 °C in the Differential Scanning Calorimetry (DSC) thermogram.
The new crystalline polymorphic Form A can be characterized by infrared absorption spectrum pattern having characteristic peaks at 1455, 1515, 1621, 1701,3521 and 3354 cm-1
According to an embodiment, the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of the new crystalline moxifloxacin hydrochloride Form A and a pharmaceutically acceptable carrier. In addition, the invention relates to a process for preparing the present new crystalline moxifloxacin hydrochloride Form A.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 is an X-ray powder diffraction pattern of new crystalline moxifloxacin hydrochloride Form A.

Figure 2 is an infrared spectrum in KBr of crystalline moxifloxacin hydrochloride Form A.
Figure 3 is differential scanning calorimetry thermogram of crystalline moxifloxacin hydrochloride Form A
BRIEF DESCRIPTION OF THE INVENTION
This new crystalline form of moxifloxacin hydrochloride of the present invention may be prepared by suspending or dissolving moxifloxacin in a suitable solvent, passing hydrogen chloride gas into the reaction medium, and separation of the solvent from the moxifloxacin hydrochloride by conventional techniques such as distillation and filtration.
In general, a suitable solvent may be selected from the group consisting of hydrocarbons, halogenated hydrocarbons, ethereal solvents, lower alkyl esters, lower alkanols preferably for example methanol, ethanol, isopropanol and the like.
The purging of hydrogen chloride gas is done at 0-25 °C or preferably at 0-5 °C because of the high exothermicity of the reaction. The isolation of the compound may be done by conventional techniques such as filtration if the crystallisation is complete or by drying of the material by solvent evaporation under reduced pressure at 20-70°C preferably at 50-60 °C.
The isolation of the new form may be done by stirring the solid in toluene and filtering the solid.
The powder X-ray diffraction of new crystalline form of moxifloxacin hydrochloride form were determined on Seifert XRD 3003 TT system using a copper X-ray tube, a nickel filter and the sample was placed in a pyrex glass

holder. The scan rate was 1.8 degrees, two theta per minute, the step size of 0.03 degrees two theta over the range from 5 to 50 degrees.
This new crystalline form of moxifloxacin hydrochloride was characterized by an X-ray powder diffraction pattern. The X-ray diffraction analysis of Form A is shown in Table 1.
Comparison of XRD data of Form A with anhydrous form and the monohydrate form reported in literature.



This new crystalline form has a moisture content of about 1.5% w/w as analysed by Karl Fisher method (determined on 0.1 g, w/w) which shows it to be different from the monohydrate (moisture content 3.9 % w/w). This form was also characterized by IR spectrum measured by KBr transmission. The absorption bands in the region of OH vibrations differ from that of the monohydrate and anhydrous forms (Figure 2).
Comparing XRD data in the Table 1, it is apparent that certain peaks provide the best way of characterizing the new crystalline moxifloxacin hydrochloride Form A and of differentiating it from the monohydrate and anhydrous forms. Very few of such peaks are needed to allow for such characterization and differentiation. Thus, the crystalline moxifloxacin hydrochloride Form A may be characterized by an X-ray powder diffraction pattern with characteristic peaks at 6.36 ± 0.2, 8.39 ± 0.2, 10.02 ± 0.2. These prominent peaks are absent in the previously reported monohydrate and anhydrous forms.

The differential scanning calorimetry (DSC) thermogram of monohydrate as described by the inventors shows a broad endothermal peak at 260 °C that are absent in the new crystalline form of moxifloxacin hydrochloride (Figure 3).
The new crystalline form of moxifloxacin hydrochloride of the present invention exhibits infrared absorption peaks tabulated in Table 2. The infrared absorption pattern clearly differentiates the present form with the forms reported in the prior art references.
Comparitive table of IR data of Form A, anhydrous form and monohydrate



It is evident from the above data that the new crystalline form of moxifloxacin hydrochloride of the present invention is different from the polymorphic forms reported in the prior-art.
Further the new crystalline polymorph showed good handling properties and stability that are desirable for formulation.
The invention is further described by the following example and is not intended to limit the scope of the invention.
EXPERIMENTAL
EXAMPLE 1
PREPARATION OF l-CYCLOPROPYL-6-FLUORO-l,4-DIYDRO-8-METHOXY-7-[(4AS,7AS)-OCTAHYDRO-6^-PYRROLO[3,4-5]PYRIDIN-6-YL1-4-OXO-3-QUINOLINE CARBOXYLIC ACID HYDROCHLORIDE (MOXIFLOXACIN HYDROCHLORIDE FORM A)
Moxifloxacin (1 g) was suspended in absolute alcohol (20 ml) and cooled to 0-5 °C with stirring. Dry hydrogen chloride gas was bubbled into the reaction mixture till saturation upon which a clear solution resulted. After stirring for 1 hour at 0-10 °C the reaction mixture turned hazy and crystallization of product was observed. The reaction was maintained for another hour at 0-10 °C, the solution

concentrated under reduced pressure and further dried for 12 hours at 75-80 °C under reduced pressure (-10 mm Hg) to yield a new crystalline form of moxifloxacin hydrochloride (1.1 g).

WE CLAIM
1. A new crystalline Form A of l-Cyclopropyl-6-fluoro-l,4-diydro-8-methoxy-7-[(4a5',7aS)-octahydro-6//-pyrrolo[3,4-Z?]pyridin-6-yl]-4-oxO"3-quinoline having water content in the range of 1 to 2% w/w.

3. Crystalline moxifloxacin hydrochloride Form A of claim 1 which is
characterized by infrared absorption spectrum pattern having characteristic peaks
at 1455, 1515, 1621, 1701, 3521 and 3354 cm-1
4. Crystalline moxifloxacin hydrochloride Form A of claim 1, having an
endotherm at 64.9 °C and melting endotherm at 241.7 °C.
5. A process for the preparation of the new crystalline form of moxifloxacin hydrochloride with a moisture content of 1 to 2% w/w, comprising of treating the moxifloxacin base with hydrogen chloride in solvents such as lower alkanols, hydrocarbons, chlorinated hydrocarbons or lower alkyl esters and isolating the crystalline form a of moxifloxacin hydrochloride
6. The process of claim 4 wherein the lower alkanol comprises one or more of methanol, ethanol, isopropanol, n-butanol, tert-butanol, industrial methylated spirit.

7. The process of claim 5 in which gaseous hydrogen chloride has been used to
produce the salt.
8. The process of claim 5 wherein the salt prepared is carried out at a temperature
in the range of 0-25 X.
9. A pharmaceutical composition comprising a therapeutically effective amount
of the crystalline form of crystalline moxifloxacin hydrochloride according to
claim 1 and a pharmaceutically acceptable carrier.