CRYSTALINE FORM OF OZENOXACIN FIELD OF THE INVENTION
The present invention relates to crystalline form of Ozenoxacin and its process for the preparation.
BACKGROUND OF THE INVENTION
Ozenoxacin (INN; trade names Ozaenex and Xepi) is a quinolone antibiotic being approved for the treatment of impetigo. 1% topical cream is approved for treatment of impetigo in Canada and in the United States. Ozenoxacin is active against some bacteria that have developed resistance to currently used quinolone and fluoroquinolone antibiotics. It is a non-fluorinated quinolone with dual inhibitory activity against bacterial DNA replication enzymes, DNA gyrase A and topoisomerase IV. Ozenoxacin is chemically known as 1-cyclopropyl-8-methyl-7-(5-methyl-6-methylamino-pyridin-3-yl)-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid of formula (I) has the following structure.
Polymorphism is defined as "the ability of a substance to exist as two or more crystalline phases that have different arrangement and/or conformations of the molecules in the crystal Lattice. Thus, in the strict sense, polymorphs are different crystalline forms of the same pure substance in which the molecules have different arrangements and/or different configurations of the molecules". Different polymorphs may differ in their physical properties such as melting point, solubility, X-ray diffraction patterns, etc. Although those differences disappear once the compound is dissolved, they can appreciably influence pharmaceutically relevant properties of the solid form, such as handling properties, dissolution rate and stability. Such properties can significantly influence the

processing, shelf life, and commercial acceptance of a polymorph. It is therefore important to investigate all solid forms of a drug, including all polymorphic forms, and to determine the stability, dissolution and flow properties of each polymorphic form. Polymorphic forms of a compound can be distinguished in the laboratory by analytical methods such as X-ray diffraction (XRD), Differential Scanning Calorimetry (DSC) and Infrared spectrometry (IR).
US 8,507,684 B2 specifically covered crystalline forms of pharmaceutical salts of Ozenoxacin. such as the salts are citrate, hemi-fumarate, maleate, L-tartrate, mesylate, hydrochloride monohydrate, potassium and sodium.
The present inventors have found a crystalline form of Ozenoxacin. The said crystalline form has been more stable over the time and reproducible. Hence it is suitable for pharmaceutical preparations.
The object of the present invention to prepare a novel crystalline form of Ozenoxacin.
SUMMARY OF THE INVENTION
The present invention relates to crystalline form of Ozenoxacin and its process for the preparation.
One embodiment of the present invention provides a crystalline form of Ozenoxacin, which is characterized by an X-ray powder diffraction (XRPD) spectrum having peak reflections at about 7.26, 9.37, 11.32, 13.97, 17.35, 22.65 and 25.27 ±0.2 degrees 2θ.
In another embodiment of the present invention provides a process for the preparation of crystalline form of Ozenoxacin, comprising:
a. Ozenoxacin was dissolved in an organic solvent,
b. heating the obtained suspension,
c. cooling the solution obtained in step b), and
d. isolating the crystalline form of Ozenoxacin.

BRIEF DESCRIPTION OF THE DRAWINGS:
Figure 1: X-ray powder diffraction (PXRD) crystalline form of Ozenoxacin.
Figure 2: Differential scanning calorimetry (DSC) crystalline form of Ozenoxacin.
DETAILED DESCRIPTION OF THE INVENTION
The present invention relates crystalline form of Ozenoxacin and its process for the preparation.
One embodiment of the present invention, the crystalline form of Ozenoxacin is characterized by X-Ray powder diffraction spectrum as depicted in Figure 1.
The second embodiment of the present invention provides the crystalline form of Ozenoxacin characterized by an X-ray powder diffraction (XRPD) spectrum having peak reflections at about 7.26, 9.37, 11.32, 13.97, 17.35, 22.65 and 25.27 ±0.2 degrees 2θ.
The third embodiment of the crystalline form of Ozenoxacin is further characterized by an X-ray powder diffraction (XRPD) spectrum having peak reflections at about 7.26, 9.37, 11.32, 12.61, 13.97, 14.40, 15.58, 16.85,17.35, 18.79, 19.23, 20.57, 21.14, 22.65, 23.88, 24.97, 26.06, 27.53, 28.36, 30.89, 33.43 and 39.33 ±0.2 degrees 2θ.
The fourth embodiment of the present invention, the crystalline form of Ozenoxacin differential scanning calorimetry (DSC) as depicted in Figure 2.
The fifth embodiment of the present invention provides a process for the preparation of crystalline form of Ozenoxacin, comprising:
a. Ozenoxacin was dissolved in an organic solvent,
b. heating the obtained suspension,
c. cooling the solution obtained in step b), and
d. isolating the crystalline form of Ozenoxacin.

According to the embodiment of the present invention, Ozenoxacin was dissolved in an organic solvent and the mixture was heated to 100-200º C for 1-5 hrs, preferably 100-170°C for 2-3 hrs. The obtained reaction mixture was cooled to 25-30°C and it was stirred for 2 hrs at the same temperature. The resultant solid was filtered, washed with water and dried at 80-90°C for 5-6 hrs to obtained crystalline form of Ozenoxacin.
According to the embodiment of the present invention, the organic solvent is polar aprotic solvents; where in the polar aprotic solvents are selected from group consisting of dimethyl sulfoxide (DMSO), tetrahydrofuran (THF), dimethylformamide (DMF), acetonitrile and ethyl acetate and water or mixture thereof. Preferably DMF.
In yet another embodiment of the present invention, there is provided pharmaceutical compositions comprising a therapeutically effective amount of crystalline form solid dispersion of Ozenoxacin in combination with a pharmaceutically acceptable carrier and along with pharmaceutically acceptable excipients, and at least one pharmaceutically acceptable excipient. The crystalline form of Ozenoxacin in combination with a pharmaceutically acceptable carrier may preferably be formulated into cream, tablets, capsules, suspensions, dispersions, injectables or other pharmaceutical forms.
The process details of the invention are provided in the examples given below, which are provided by way of illustration only and therefore should not be construed to limit the scope of the invention.

EXAMPLES
Example-1:
Purification of crystalline form of Ozenoxacin:
Ozenoxacin crude 50 g was dissolved in DMF at ambient temperature and heat the reaction mass at 100-170 °C for 2-3 hrs and gradually cooled to 25-50°C filter the solid and wash the cake with DMF and suck dry under vacuum for 3-4 hrs, unload the material and further dry under vacuum at 60-70°C for 10-12 hrs to give the crystalline form of Ozenoxacin as pale yellow solid.
HPLC purity: 99.89%
Example-2:
Preparation of crystalline form of Ozenoxacin:
Ozenoxacin crude 50 g was dissolved in DMSO at ambient temperature and heat the reaction mass at 100-189 °C for 2-3 hrs and gradually cooled to 25-50°C filter the solid and wash the cake with DMSO and suck dry under vacuum for 3-4 hrs, unload the material and further dry under vacuum oven at 60-70°C for 10-12 hrs to give the crystalline form of Ozenoxacin as pale yellow solid.
HPLC purity: 99.89%
Example-3:
Preparation of crystalline form of Ozenoxacin:
Ozenoxacin crude 50 g was dissolved in THF at ambient temperature and heat the reaction mass at 50-70 °C for 2-3 hrs and gradually cooled to 25-50°C filter the solid and wash the cake with THF and suck dry under vacuum for 3-4 hrs, unload the material and further dry under vacuum oven at 60-70°C for 10-12 hrs to give the crystalline form of Ozenoxacin as pale yellow solid.
HPLC purity: 99.89%

Example-4:
Preparation of crystalline form of Ozenoxacin:
Ozenoxacin crude 50 g was dissolved in ethyl acetate at ambient temperature and heat the reaction mass at 50-80 °C for 2-3 hrs and gradually cooled to 25-50°C filter the solid and wash the cake with THF and suck dry under vacuum for 3-4 hrs, unload the material and further dry under vacuum oven at 60-70°C for 10-12 hrs to give the crystalline form of Ozenoxacin as pale yellow solid.
HPLC purity: 99.89%

WE CLAIM:
1. Crystalline form of Ozenoxacin.
2. A crystalline form of Ozenoxacin as claimed in claim 1, characterized by an X-ray powder diffraction pattern (XRPD) spectrum having peak reflection at about 7.26, 9.37, 11.32, 13.97, 17.35, 22.65 and 25.27 ±0.2 degrees 2θ.
3. A crystalline form of Ozenoxacin as claimed in claim 2 and 3, further characterized by an X-ray powder diffraction pattern (XRPD) spectrum having peak reflections at about 7.26, 9.37, 11.32, 12.61, 13.97, 14.40, 15.58, 16.85,17.35, 18.79, 19.23, 20.57, 21.14, 22.65, 23.88, 24.97, 26.06, 27.53, 28.36, 30.89, 33.43 and 39.33 ±0.2 degrees 2θ.
4. A crystalline form of Ozenoxacin as claimed in claim 1, having a differential scanning calorimetry (DSC) substantially in accordance with Figure-2.
5. A process for preparing crystalline form of Ozenoxacin comprising:

a) Ozenoxacin was dissolved in an organic solvent,
b) heating the obtained suspension,
c) cooling the solution obtained in step b), and
d) isolating the crystalline form of Ozenoxacin.

6. The process as claimed in claim 6, wherein the organic solvent is selected from polar aprotic solvents.
7. The process as claimed in claim 7, wherein the suitable polar aprotic solvents are selected from group consisting of dimethyl sulfoxide (DMSO), tetrahydrofuran (THF), dimethyl formamide (DMF), acetonitrile and ethyl acetate and water or mixture thereof. Preferably DMF.

8. The process as claimed in claim 6, wherein the step-b) stirring at about 100-200º C for 1-5 hrs, preferably 100-170°C for 2-3 hrs.