FORM 2
THE PATENT ACT, 1970
(39 of 1970)
&
The Patents Rules, 2003 COMPLETE SPECIFICATION
(See section 10 and rule 13)
Title of the invention
"NOVEL CRYSTALLINE FORM C OF FLUDIAZEPAM"
Centaur Pharmaceutical Private Limited, an Indian Company, having its Registered Office at Centaur House, Near Grand Hyatt, Shanti Nagar, Vakola, Santacruz (East), Mumbai- Maharashtra, 400055, India
1. The following specification describes the invention.
DESCRIPTION
FIELD OF THE INVENTION
The present invention relates to a crystalline form C of Fludiazepam. The present invention further relate to a processes of preparing crystalline form C of Fludiazepam.

BACKGROUND OF THE INVENTION
Chemically Fludiazepam is 7-Chloro-5-(2-fluorophenyI)1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one and is known from German patent no. DE1136709 and is represented by compound of structural formula I.

Fludiazepam is a drug which is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant and sedative and skeletal muscle relaxant properties.
U.S. Patent 3,371,085 described novel process in example no. 74, 7-Chloro-5-(2-fluorophenyl)1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one is eluted with ether from column chromatography and obtained as viscous colorless oil.
The synthesis and pharmacology of a novel benzodiazepine derivatives by Y. Asami et. al. published in Arzneim.-Forsch, 24, 1563-1568 (1974) discloses that the Fludiazepam is colorless prisms from n-hexane/isopropanol with melting point 88-92°C. However, XRPD and DSC are not reported in this literature.
Quinazoline and 1,4-benzodiazepine by L.H. Sternbach et. al. published in E. Reeder, 27, 3788-3796 (1962) where 7-Chloro-5-(2-fluorophenyl)1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one (Fludiazepam) crystallized from methanol and water mixture to give product having melting point 69-74°C. However, XRPD and DSC are not reported in this literature.
Polymorphism is the property of some molecules and molecular complexes to assume more than one crystalline or amorphous form in the solid state. A single molecule, like the

Fludiazepam in formula (I) may give rise to a variety of solids having distinct physical properties like solubility, X-ray diffraction pattern and melting point.
These polymorphs are thus distinct solid forms which share the molecular formula of the compound from which the crystals are made up, however they may have distinct advantageous physical properties which can have a direct effect on the ability to process and/or manufacture the drug substance, like flowability, and the drug product, like flowability, as well as on drug product stability, dissolution, and bioavailability.
These distinct physical properties of different polymorphs of the same compound can render different polymorphs more, or less, useful for a particular purpose, such as for pharmaceutical formulation.
The discovery of new polymorphic forms and solvates of a pharmaceutically useful compound provides a new opportunity to improve the performance characteristics of a pharmaceutical product. It enlarges the repertoire of materials that a formulation scientist has available for designing, for example, a pharmaceutical dosage form of a drug with a targeted release profile or other desired characteristic.
SUMMARY OF THE INVENTION:
The present invention provides novel crystalline form C of Fludiazepam which is stable and different than reported in the literature. The present invention also provides a process for preparing new polymorph.
A first aspect of the present invention is to provide a novel crystalline form of Fludiazepam herein after referred as crystalline form C may be characterized by its X-ray powder diffraction pattern comprises characteristic peaks at 13.2,13.4,17.6,18.4,18.8,21.1 and 25.2 ± 0.2 degrees 2θ.

A second aspect of the present invention is to provide a process for the preparation of crystalline form C of Fludiazepam comprising the steps of:
a. dissolving Fludiazepam in an organic solvent selected from ether under heating;
b. optionally filtering the solution;
c. slowly cooling the solution in order to induce crystallization;
d. isolating crystalline form C of Fludiazepam;
e. optionally drying the crystals.
In the context of the present invention the following abbreviations have the indicated meaning, unless explicitly stated otherwise; XRPD: Powder X-ray diffraction DSC: Differential scanning calorimetry
BRIEF DESCRIPTION OF THE DRAWING:
Figure 1 depicts X-ray powder diffraction pattern of crystalline form C of Fludiazepam. Figure 2 depicts DSC thermogram of crystalline form C of Fludiazepam.
X-Ray Powder Diffraction (XRPD) pattern of the product of Examples 1 was obtained on D 8 - Advance, PANalytical X'Pert PRO 2636, diffractometer equipped with Scintillation detector using Copper Ka (A= 1.5406 A) radiation with scanning range between 2.00-39.98°26 at scanning speed of 27min.
DETAIL DESCRIPTION OF THE INVENTION:
A first aspect of the present invention is to provide a novel crystalline form of Fludiazepam herein after referred as crystalline form C. A crystalline form C of Fludiazepam may be characterized by X-ray powder diffraction pattern as depicted in Figure 1.
A crystalline form C of Fludiazepam may be characterized by its X-ray powder diffraction pattern having peaks at 13.2, 13.4, 17.6, 18.4, 18.8, 21.1 and 25.2 ± 0.2 degrees 2θ.

A crystalline form C of Fludiazepam may be characterized by DSC thermogram as depicted in Figure 2.
A crystalline form C of Fludiazepam may be characterized by its differential scanning calorimetry showing endothermic peak at about 78°C.
A solution of Fludiazepam in an organic solvent selected from ether may be prepared by dissolving Fludiazepam in an organic solvent at a temperature in the range of 30°C to 80°C. Alternatively, such a solution may be obtained directly from a reaction in which Fludiazepam is formed.
The examples of ether solvents may include but not limited to diethyl ether, diethylene glycol diethyl ether, cyclopentyl methyl ether, di-n-butyl ether, di-tert.-butyl ether, diisopropyl ether, ethyl tert-butyl ether, methyl tert-butyl ether and tetrahydrofuran,
The solution of Fludiazepam may be refluxed for a period of 30 minutes to 3 hours, filter and excess organic solvent may be distilled out from the reaction mixture.
The crystalline form C of Fludiazepam may be isolated by the steps of cooling and filtering of reaction mixture.
The crystalline form C of Fludiazepam may be washed with chilled organic solvent selected from the group of ether solvent.
The crystalline form C of Fludiazepam may be dried under reduced pressure at a temperature in the range of 40°C to 60°C.

EXAMLES:
In the following examples, the preferred embodiments of the present invention are described only by way of illustrating the processes of the invention. However, these are not intended to limit the scope of the present invention in any way.
Example: 1:
A solution of Fludiazepam (10 gm) in di-isopropyl ether (50 ml) was heated at 60-65°C for 30 minutes. The di-isopropyl ether (20 ml) was distilled out from the reaction mixture and resulting solution was cooled to 0-5°C and stirred for an hour. The resulting solids were filtered, washed with chilled di-isopropyl ether (10 ml) and dried at 55°C under reduced pressure. Yield= 9.2 gm, Melting point: about 78°C.
XRD: As depicted in Figure 1 DSC: As depicted in Figure 2

WE CLAIM:
1. A crystalline form C of Fludiazepam characterized by its X-ray powder diffraction pattern as depicted in figure no.1.
2. A crystalline form C of Fludiazepam characterized by its DSC thermogram as depicted in figure no.2.
3. A crystalline form C of Fludiazepam characterized by its X-ray powder diffraction pattern having peaks at 13.2, 13.4, 17.6, 18.4, 18.8, 21.1 and 25.2 ±0.2 degrees 20.
4. A crystalline form C of Fludiazepam characterized by its differential scanning calorimetry showing endothermic peak at about 78°C.
5. A process for the preparation of crystalline form C of Fludiazepam comprising the steps of:
a. dissolving Fludiazepam in an organic solvent selected from ether under
heating;
b. optionally filtering the solution;
c. slowly cooling the solution in order to induce crystallization;
d. isolating crystalline form C of Fludiazepam;
e. optionally drying the crystals.
6. The process according to claim no. 5, wherein ether solvent is selected from the
group comprising of organic solvent selected from diethyl ether, diethylene glycol
diethyl ether, cyclopentyl methyl ether, di-n-butyl ether, di-tert-butyl ether, diisopropyl
ether, ethyl tert-butyl ether, methyl tert-butyl ether and tetrahydrofuran solvents.