DESC:FIELD OF THE INVENTION
The present invention relates to amorphous form of daclatasvir dihydrochloride and processes for its preparation.

BACKGROUND OF THE INVENTION
Daclatasvir is an inhibitor of HCV nonstructural protein 5A (NS5A). It is used for the treatment of patients with chronic hepatitis C virus (HCV) genotype 3 infection. It is developed and marketed by Bristol-Myers Squibb under the trade name Daklinza® in USA. It is on the World Health Organization's List of Essential Medicines. The chemical name for drug substance daclatasvir dihydrochloride is N,N'-[[1,1'-biphenyl]-4,4'-diylbis[1H-imidazole-5,2-diyl-(2S)-2,1-pyrrolidinediyl[(1S)-1-(1-methylethyl)-2-oxo-2,1-ethanediyl]]]bis-carbamic acid, C,C'-dimethyl ester, hydrochloride (1:2). Daclatasvir dihydrochloride has the following structural formula:

(I)
Daclatasvir is described in the PCT publication number WO 2008021927.

The PCT publication number WO2009020828 describes crystalline form N-2 of daclatasvir dihydrochloride.

SUMMARY OF THE INVENTION:
The present invention relates to an amorphous form of daclatasvir dihydrochloride having one or more spectra selected from the group consisting of (a) to (c):
(a) PXRD pattern as depicted in Figure 1;
(b) TGA as depicted in Figure 2; and
(c) IR spectrum as depicted in Figure 3.

The present invention further relates to a process for the preparation of an amorphous form of daclatasvir dihydrochloride comprising dissolving daclatasvir dihydrochloride in a suitable solvent, removing the solvent and isolating an amorphous form of daclatasvir dihydrochloride.

BRIEF DESCRIPTION OF THE FIGURE
Figure 1 – PXRD diffractogram of amorphous form of daclatasvir dihydrochloride
Figure 2—TGA thermogram of amorphous form of daclatasvir dihydrochloride
Figure 3—IR spectrum of amorphous form of daclatasvir dihydrochloride

DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to an amorphous form of daclatasvir dihydrochloride and processes for its preparation.

In one embodiment, the present invention provides amorphous form of daclatasvir dihydrochloride.

The amorphous form of daclatasvir dihydrochloride of the present invention can be characterized by PXRD pattern as depicted in Figure 1.

The amorphous form of daclatasvir dihydrochloride of the present invention can be characterized by TGA as depicted in Figure 2.

The amorphous form of daclatasvir dihydrochloride of the present invention can be characterized by IR spectrum as depicted in Figure 3.

In another embodiment, the present invention provides a process for the preparation of amorphous form of daclatasvir dihydrochloride comprising dissolving daclatasvir dihydrochloride in a suitable solvent, removing the solvent and isolating the amorphous form of daclatasvir dihydrochloride.

‘Dissolving daclatasvir dihydrochloride in a suitable solvent’ includes the mixture of daclatasvir and hydrogen chloride in a suitable solvent.

Daclatasvir dihydrochloride used in the present invention may be in any polymorphic form for example, crystalline form N-2 which described in PCT publication number WO2009020828.

Solvent used in the present invention may be selected form the water, alcohol, ether and mixtures thereof.

Alcohol solvent may be selected from methanol, ethanol, and isopropanol.

Ether may be selected from tetrahydrofuran (THF), dioxane.

Solvent used in the present invention may be preferably methanol.

Quantity of solvent may be 5 to 50 volumes with respect to quantity of daclatasvir.

Solvent may be removed by concentrating under reduced pressure (thin film drying and agitated thin film drying), spray drying or freeze drying.

The X-ray powder diffraction spectrum (XRPD) was recorded at room temperature using PANalytical X’Pert PRO diffractogram with Cu Ka radiation (? = 1.54060 Å), running at 45 kV and 40 mA.
Thermogravimetric analysis (TGA) was done using Pyris-1 TGA Perkin Elmer instrument. The scans were recorded between 20 and 250 °C at a constant heating rate of 10°C/min.

FTIR spectrum was obtained using a Perkin Elmer Precisely Spectrum 400 instrument using KBr pellet method.

The present invention is described in the following examples, however it should be noted that the scope of present invention is not limited by the examples.

Example
Preparation of amorphous form of daclatasvir dihydrochloride
Daclatasvir dihydrochloride (5 g) was dissolved in methanol (150 ml). The mixture was concentrated under reduced pressure on rotary evaporator to obtain amorphous form of daclatasvir dihydrochloride. Yield: 4.96 g.
,CLAIMS:Claim 1. A process for the preparation of an amorphous form of daclatasvir dihydrochloride comprising dissolving daclatasvir dihydrochloride in a suitable solvent, removing the solvent and isolating an amorphous form of daclatasvir dihydrochloride.

Claim 2. The process as claimed in claim 1, wherein the solvent is selected form the water, alcohol, ether and mixtures thereof.

Claim 3. The process as claimed in claim 2, wherein alcohol solvent is selected from methanol, ethanol, and isopropanol.

Claim 4. The process as claimed in claim 2, wherein ether is selected from tetrahydrofuran and dioxane.

Claim 5. The process as claimed in claim 1, wherein the solvent is methanol.

Claim 6. The process as claimed in claim 1, wherein the solvent is removed by concentrating under reduced pressure, spray drying or freeze drying.

Claim 7. An amorphous form of daclatasvir dihydrochloride, obtainable by the process as claimed in claim 1.