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
"AN IMPROVED PROCESS FOR THE PREPARATION OF AMORPHOUS FORM OF PRAVASTATIN CALCIUM"
Enaltcc Labs Pvt. Ltd. an Indian Company, having its Registered Office at 17thFloor, Kesar Solitaire, Plot No.5 Sector-19, Sanpada, Navi Mumbai Maharashtra, India. Pin Code: 400705
1. The following specification particularly describes the invention and the manner in which it is to be performed.

AN IMPROVED PROCESS FOR THE PREPARATION OF AMORPHOUS FORM OF PRAVASTATIN CALCIUM
FIELD OF THE INVENTION
The present invention provides an improved process for the preparation of amorphous form of pitavastatin calcium comprising the steps of
a. providing a solution of pitavastatin calcium in an acetone solvent and
b. isolating amorphous form of the pitavastatin calcium
BACKGROUND OF THE INVENTION
The chemical name for pitavastatin calcium is (+) monocalcium bis {(3R, 5S, 6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-3, 5-dihydroxy-6-heptenoate} and is known from U.S. Patent No. 5,856,336. The pitavastatin calcium (2:1) salt is represented by structural formula I.

The pitavastatin calcium (2:1) salt is commercially available under the brand name of LIVALO and is being marketed by Kowa Pharma.
The pitavastatin calcium (2:1) is indicated for the treatment of primary hyperlipidemia and mixed dyslipidemia as an adjunctive therapy to diet to reduce elevated total cholesterol, low-

density lipoprotein cholesterol, apolipoprotein B, and triglycerides and to increase high density lipoprotein cholesterol.
U.S Patent Publication No. 2009/0182008 discloses amorphous form of pitavastatin calcium (2:1) salt and its processes for the preparation. The process disclosed in the U.S Patent Publication N0. 2009/0182008 involves addition of a non-solvent to a concentrated solution of pitavastatin calcium in an organic solvent. Examples of non-solvent include heptane or methyl tert-butyl ether and examples of organic solvent include 1, 4-dioxane, tetrahydrofuran and ethyl methyl ketone.
U.S Patent Publication No. 2009/0182008 also discloses lyophilization process for the preparation of amorphous form of pitavastatin calcium.
The processes disclosed in the U.S Patent Publication N0. 2009/0182008 suffers from the disadvantages like prolong reaction hours i.e 16 hours for the preparation of amorphous form of pitavastatin calcium and the specific requirement of lyophilization equipment, which is not commercially viable for the large scale production of amorphous form of pitavastatin calcium.
Accordingly there is a need in the art to develop an improved process for the preparation of amorphous form of pitavastatin calcium.
SUMMARY OF THE INVENTION:
A first object of the present invention is to provide a process for the preparation of amorphous form of pitavastatin calcium comprising the steps of
a Providing 3 solution of pitavastatin calcium in an acetone solvent and
b- Isolating amorphous form of the pitavastatin calcium

DETAIL DESCRIPTION OF THE INVENTION
The process of the present invention does not involve specific equipment requirement or prolonged operations and is thus convenient to operate on a commercial scale.
The crystalline pitavastatin calcium used as a starting material may be any of the various polymorphic forms known in the prior art such as polymorphs A, B. C, D, E. F etc as disclosed in the USA patent application 2009/0182008. which is incorporated herein by reference only.
The solution of pitavastatin calcium may be obtained by dissolving crystalline pitavastatin calcium in an acetone solvent or alternatively such a solution may be obtained directly from a reaction mixture in which pitavastatin calcium is formed in an acetone solvent.
The acetone solvent may be used from 5 volume / weight to 150 volume / weight of pitavastatin calcium for forming a solution of pitavastatin calcium.
The pitavastatin acid may be reacted with a source of calcium in an acetone solvent to form a solution of pitavastatin calcium in an acetone solvent.
The acetone solvent may be used from 5 volume / weight to 30 volume / weight of pitavastatin acid and the source of calcium may be calcium chloride or calcium acetate.
The isolation of amorphous form of the pitavastatin calcium may be carried out by distilling acetone solvent from the solution of pitavastatin calcium under reduced pressure at a temperature intherange of 30°Cto 45°C.
The amorphous form of pitavastatin calcium obtained by the present invention may be dried at a temperature in the range of 40°C to 70°C for 30 minutes to 10 hours

The amorphous form of pitavastatin calcium prepared according to the process of the present invention was characterized by its X-ray powder diffraction, as shown in Figure 1. pattern which gave a plain halo and showed no peaks, thus demonstrating the amorphous nature of the product.
A pharmaceutical composition of amorphous form of pitavastatin calcium, wherein amorphous form of pitavastatin calcium is formed from a solution of pitavastatin calcium in an acetone solvent.
Description of the Drawing:
Figure 1 depicts characteristic X-ray powder diffraction pattern for the amorphous form of pitavastatin calcium
Method of analysis: XRD:
Instrument: PANalytical Xrpert PRO
X-ray source: Cu (1.5406A)
Filter for Kp Nickel
Scanning range: 2-40° (29)

EXAMPLES
In the following examples, the preferred embodiments of the present invention are described only by way of illustrating the process of the invention. However, these are not intended to limit the scope of the present invention in any way.
Example 1: Preparation of amorphous form of pitavastatin calcium
Crystalline pitavastatin calcium (7 gm) was dissolved in acetone (1050 ml) at 25-30°C and
resulting solution was filtered through hyflow bed. The solution of pitavastatin calcium was
distilled under reduced pressure at 40°C and resulting precipitate of pitavastatin calcium was
isolated and dried at 50°C for 10 hours.
Yield: 5.5 gm
Purity: 99.89% (By HPLC)
Example 2: Preparation of amorphous form of pitavastatin calcium
Crystalline pitavastatin calcium (5 gm) was taken in acetone (125 ml) at 25-30°C and resulting
solution was refluxed for 20 minutes. The resulting solution of pitavastatin calcium was filtered
through hyflow bed and distilled under reduced pressure at 40°C and resulting precipitate of
pitavastatin calcium was isolated and dried at SOX for 5 hours.
Yield: 3 gm
Purity: 99.95% (By HPLC)

WE CLAIM:
1. A process for the preparation of amorphous form of pitavastatin calcium comprising the steps
of
a. providing a solution of pitavastatin calcium in an acetone solvent and
b. isolating amorphous form of the pitavastatin calcium.
2. The process according to claim no. 1, wherein solution of pitavastatin calcium is obtained by dissolving crystalline pitavastatin calcium in an acetone solvent.
3. The process according to claim no. 1, wherein a solution of pitavastatin calcium is obtained by reacting pitavastatin acid with a source of calcium in an acetone solvent.
4. The process according to claim nos. 1 or 2 wherein acetone solvent is used from 5 volume / weight to 150 volume / weight of pitavastatin calcium for forming a solution of pitavastatin calcium.
5. The process according to claim no. 3, wherein acetone solvent is used from 5 volume / weight to 30 volume / weight of pitavastatin acid for forming a solution of pitavastatin calcium.
6. The process according to claim no. 3, wherein source of calcium is calcium chloride or calcium acetate.
7. The process according to claim no. 1, wherein isolation of amorphous form of the pitavastatin calcium is carried out by distilling acetone solvent from the solution of pitavastatin calcium under reduced pressure at a temperature in the range of 30°C to 45°C.
8. The process according to claim no. 1, wherein amorphous form of pitavastatin calcium is dried at a temperature in the range of 50°C to 60°C for 30 minutes to 10 hours.

9. The process according to claim nos. 1, 7 or 8 wherein amorphous form of pravastatin calcium
is characterized by X-ray diffraction pattern depicted in figure no. 1.
10. A pharmaceutical composition of amorphous form of pravastatin calcium, wherein
amorphous form of pravastatin calcium is formed from a solution of pitavastatin calcium in an
acetone soJvent