FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
The Patent Rules, 2003
COMPLETE SPECIFICATION
[Section 10, and Rule 13]
L-VALINE BENZYL ESTER SALT OF MEDICINAL COMPOUND
Applicant
Name: Torrent Pharmaceuticals Limited
Nationality: Indian
Address: Torrent House, Off Ashram Road,
Near Dinesh Hall,
Ahmadabad 380 009.
Gujarat, India
The following specification particularly describes the nature of the invention and the manner in which it is to be performed:

FIELD OF THE INVENTION
The present invention relates to L-valine benzyl ester salt of statin or sartan, a process for preparation thereof and an intermediate compound L-valine benzyl ester salt of statin or sartan, useful in the synthesis of purified statin or sartan and its salts. Particularly, the present invention relates to L-valine benzyl ester salt of rosuvastatin, a process for preparation thereof and novel intermediate compound L-valine benzyl ester salt of rosuvastatin, useful in the synthesis of purified rosuvastatin and its salts.
BACKGROUND OF THE INVENTION
L-valine benzyl ester salt of medicinal compound i.e. statin or sartan. Statin includes but not limited to rosuvastatin, atrovastatin, and the like and sartan includes valsartan, telmisartan, candeasrtan and the like.
Rosuvastatin is chemically known as (3R, 5S, 6E)-7-[4-(4-fluorophenyl)-6-(l- methyl ethyl)-2-[methyl (methylsulfonyl) amino-5-pyrimidinyl]-3, 5-dihydroxy-6- heptenoic acid, is a synthetic lipid-lowering agent, which is an inhibitor of 3- hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, an early and rate-limiting step in cholesterol biosynthesis.
US RE 37,314 discloses an amorphous form of the calcium salt of rosuvastatin and the sodium salt is obtained therein as powdery crystals. The calcium salt of rosuvastatin is presently available in the market as CRESTOR. Further, this patent describes the preparation of calcium salt of rosuvastatin by dissolving the corresponding sodium salt in water and adding calcium chloride and collecting the resultant precipitate by filtration.
WO 01/60804 describes the preparation of crystalline rosuvastatin salts, namely,
ammonium, methylammonium, ethylammonium, diethanolammonium,tri
(hydroxyrnethyl)- methylammonium, benzylammonium, 4- methoxybenzylammonium, lithium and magnesium salts respectively. This patent publication also describes a process for the preparation of all these salts.
WO 2005/077916 Al discloses various amine salts of rosuvastatin comprising cyclohexyl ammonium salt, diisopropyl ammonium salt, isopropyl ammonium salt, dicyclohexyl ammonium salt and (S) (+)-methylbenzyl ammonium salts.

US 6,838,566 also describes novel salts of HMG-CoA reductase inhibitors with organic amines which include (±)-l,2-dimethylpropylamine, 3-(2-aminoethylamino)- propylamine, n-butylamine, secondary butylamine, tertiary butylamine (TBA), dibutylamine, tertiary amylamine, cyclopentylamine, cyclohexylamine, cycloheptylamine, dicyclohexylamine (DCHA), N-methylcyclohexylamine, N5N'- diisopropylethylenediamine (DIPEDA), N,N-diethylenediamine, N-methyl-1,3- propanediamine, N-methylethylenediamine, N,N,N',N'-tetramethyl-l,2- diaminoethane, N,N,N',N'-tetramethyl- 1 ,4-diaminobutane, N,N,N',N'-tetramethyl- 1 ,6- diaminohexane, 1,2-dipiperidinethane, dipiperidinemethane, 2-amino-3, 3- dimethylbutane, NA-dimethylcyclohexylamine, neopentylarhine, adamantylamine, NjN-diethylcyclohexylamine, N-isopropylcyclohexylamine, N- methylcyclohexylamine, cyclobutylamine and norborylamine. However, this patent also mentions that amines having larger organic groups and especially those having bulky groups generally show a more easy crystallization and to lower extent form salts with unwanted side products when compared with amines having small organic groups.
PCT Pub.No.WO 2008/067440 discloses the dehydroabietylamine salt of rosuvastatin. PCT Pub.No.WO 2008/038132 discloses the crystalline rosuvastatin amine salts
PCT Pub. No. WO 2009113087 ('087) discloses specifically benzhydryl pierazine salt of montelukast and also discloses benzhydryl pierazine salt of statins such as Atorvastatin, simvastatin, Rosuvastatin, sartans like valsartan, candesartan, Telmisartan etc. '087 discloses process which involves further purification of salt to get the pure salt of benzhydryl pierazine salt of compounds i.e.Montelukast.
SUMMARY OF INVENTION
The present invention relates to L-valine benzyl ester salt of statin or sartan, a process for preparation thereof and an intermediate compound L-valine benzyl ester salt of statin or sartan, useful in the synthesis of purified statin or sartan and its salts.
In another embodiment, the specification discloses L-valine benzyl ester salt of statin or sartan, particularly rosuvastatin, atorvastatin, and candesartan, valsartan and Telmisartan respectively.

In another embodiment, the specification discloses L-valine benzyl ester salt of rosuvastatin of formula (IV).

In another aspect, there is provided a process for preparation of statin or sartan, particularly rosuvastatin L-valine benzyl ester salt of rosuvastatin includes the steps of: a) providing a solution or suspension of free acid of statin or sartan, particularly rosuvastatin; b) treating the solution or suspension with L-valine benzyl ester to form a L-valine benzyl ester salt of statin or sartan, particularly rosuvastatin.
In another aspect, there is provided a process of preparation of salt of statin or sartan, particularly calcium salt of rosuvastatin, the process includes: a) providing a solution or suspension of free acid of statin or sartan, particularly rosuvastatin; b) treating the solution or suspension with L-valine benzyl ester to form a L-valine benzyl ester salt of statin or sartan, particularly rosuvastatin and c) converting L-valine benzyl ester salt of statin or sartan, particularly rosuvastatin to the salt of statin or sartan, particularly calcium salt of rosuvastatin.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1: An X-ray powder diffraction pattern of crystalline L-valine benzyl ester salt of rosuvastatin.
DETAILED DESCRIPTION OF THE INVENTION

The term "statin" includes but not limited to rosuvastatin, atrovastatin, and the like and "sartan" includes valsartan, telmisartan, candeasrtan and the like.
The present invention relates to L-valine benzyl ester salt of statin or sartan, a process for preparation thereof and an intermediate compound L-valine benzyl ester salt of statin or sartan, useful in the synthesis of purified statin or sartan and its salts.
In another embodiment, the specification discloses L-valine benzyl ester salt of statin or sartan, particularly rosuvastatin of formula (IV).

In an aspect of the invention, the specification discloses L-valine benzyl ester salt of satin or sartan, particularly L-valine benzyl ester salt of rosuvastatin of formula (IV).


The L-valine benzyl ester salt of statin or sartan, particularly rosuvastatin may be in crystalline or amorphous forms. Preferably, L-valine benzyl ester salt of rosuvastatin is in crystalline form.
The crystalline L-valine benzyl ester salt of rosuvastatin is characterized by its X-Ray Powder Diffraction ("XRPD") pattern. Figure 1 shows the XRPD pattern of the crystalline L-valine benzyl ester salt of rosuvastatin. It has significant peaks at about 6.1, 10.7, 10.9, 12.9, 15.9, 19.3, 19.4,21.0, 21.2, 21.4 ± 0.2 °θ.
The present application provides L-valine benzyl ester salt of statin or sartan, particularly rosuvastatin which makes the purification of statin or sartan, particularly rosuvastatin simpler. The crystalline salt of statin or sartan, particularly L-valine benzyl ester salt of rosuvastatin may be converted to its hemi-calcium salt.
It has been observed that when rosuvastatin ester of formula (V),

(Wherein R1 is C1-C6 alkyl) is converted to rosuvastatin hemi-calcium via its corresponding sodium salt by conventional methods, the purity of the product obtained is not satisfactory. The main impurity that is observed is the anti-isomers of rosuvastatin calcium.
It was observed surprisingly that when rosuvastatin tert-butyl ester is converted to L-valine benzyl ester salt of rosuvastatin and then converted to rosuvastatin hemi-calcium, the product obtained is pure and the amount of anti-isomer present in rosuvastatin hemi-calcium is almost insignificant.

In one embodiment, step a) includes i) synthesizing the free acid of statin or sartan, particularly rosuvastatin in situ, ii) separating a solution of the free acid of statin or sartan, particularly rosuvastatin as an organic phase from the reaction mixture of the step i), as well as iii) using the separated solution of the step ii) directly in said step b) without isolating the free acid. The starting mass is a solution or a suspension depending on the choice of the solvent. Temperatures which are adopted for preparation of the mixture may range from about 25 °C to about 100 °C.
Solvents may be used for dissolving or suspending statin or sartan, particularly rosuvastatin include, but are not limited to, nitriles such as acetonitrile and propionitrile; alcohols, such as methanol, ethanol, isopropyl alcohol, and n-propanol; ketones, such as acetone, ethyl methyl ketone, and methyl isobutyl ketone; esters such as ethyl acetate, n-propyl acetate, n-butyl acetate, and t-butyl acetate; ethers, such as diethyl ether, dimethyl ether, diisopropyl ether, and 1 ,4-dioxane; hydrocarbons such as toluene, xylene, n-heptane, cyclohexane, n-hexane; or mixtures thereof or their combinations with water. The preferred solvent is ethyl acetate.
When the starting mass is in the form of a solution, it may be filtered to remove the undissolved particles followed by further processing. The undissolved particles may be removed, for example, by filtration, centrifugation, decantation, and other techniques. The solution is filtered by passing through paper, glass fiber, or other membrane material, or a clarifying agent such as celite. Depending upon the equipment used and the concentration and temperature of the solution, the filtration apparatus may need to be preheated to avoid premature crystallization.
The solution of free acid of statin or sartan, particularly rosuvastatin can be obtained by dissolving or suspending statin or sartan, particularly rosuvastatin ester of formula (V) in suitable solvent followed by addition of base and acid. Rosuvastatin ester of formula (V) may be tertiary butyl ester of Rosuvastatin.
Solvents may be used for dissolving or suspending ester of statin or sartan,perticlularly rosuvastatin ester of formula (V) include, but are not limited to, nitriles such as acetonitrile and propionitrile; alcohols, such as methanol, ethanol, isopropyl alcohol, and n-propanol; ketones, such as acetone, ethyl methyl ketone, and methyl isobutyl ketone; esters such as ethyl acetate, n-propyl acetate, n-butyl acetate, and t-butyl acetate;

ethers, such as diethyl ether, dimethyl ether, diisopropyl ether, and 1 ,4-dioxane; hydrocarbons such as toluene, xylene, n-heptane, cyclohexane, n-hexane; or mixtures thereof or their combinations with water.
Bases include lithium hydroxide, sodium hydroxide, sodium carbonate, sodium bicarbonate, potassium hydroxide, potassium carbonate, and potassium bicarbonate. Sodium hydroxide is preferred. These bases may be used in the form of solids or in the form of aqueous solutions. The acid includes hydrochloric acid. Hydrochloric acid may be used as aqueous acid.
In step b), the solution or suspension of statin or sartan, particularly rosuvastatin is treated with L-valine benzyl ester.
In one embodiment, the L-valine benzyl ester may be added at temperatures ranging from about 20° C to about 70° C.The L-valine benzyl ester may be used in the form of a solid or in the form of its aqueous solution or in the form of its solution in an organic solvent.
The process may begin with an isolated L-valine benzyl ester salt of statin or sartan, particularly rosuvastatin, which is then provided in a solvent for further processing, or may be used directly after step b).
Organic solvents which are used for preparing the solution include, but are not limited to, alcohols such as methanol, ethanol, isopropanol, n- butanol; ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran; nitrile solvents, such as acetonitrile, propionitrile; lower carboxylic acids solvents such as acetic acid; and mixtures thereof, preferably ethyl acetate.
The L-valine benzyl ester salt of statin or sartan, particularly rosuvastatin may be isolated by known technique in the arts i.e.filtration, washing and drying.
The L-valine benzyl ester salt of statin or sartan may further be isolated by using antisolvent. Preferably L-valine benzyl ester salt of rosuvastatin is isolated using antioslvent.

Antisolvent used may be aliphatic ester hydrocarbons or acetones: more preferably heptane, hexane or acetone.
When a solution is prepared by dissolving L-valine benzyl ester salt of statin or sartan, particularly rosuvastatin in a suitable solvent, any form of L-valine benzyl ester salt of statin or sartan, particularly rosuvastatin, such as any crystalline form including solvates and hydrates may be utilized.
In one embodiment, L-valine benzyl ester salt of statin or sartan, particularly rosuvastatin is further dissolved in the suitable organic solvents solvent to form L-valine benzyl ester salt of statin or sartan, particularly rosuvastatin.
Organic solvents which.are used for preparing the solution include, but are not limited to, alcohols such as methanol, ethanol, isopropanol, n- butanol; ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran; nitrile solvents, such as acetonitrile, propionitrile; lower carboxylic acids solvents such as acetic acid; and mixtures thereof, preferably mixture of methanol and ethyl acetate.
In step c), the L-valine, benzyl ester salt of statin or sartan, particularly rosuvastatin is converted to the salt of statin or sartan, particularly rosuvastatin calcium salt of rosuvastatin.The converting step involves treating the L-valine benzyl ester salt of statin or sartan, particularly rosuvastatin with acid, like hydrochloric acid, followed by extraction in organic solvent. The extracted salt of statin or sartan, particularly rosuvastatin acid is treated with an alkali base to obtain an alkali salt of statin or sartan, particularly rosuvastatin and treating the resulting intermediate alkali salt of statin or sartan, particularly rosuvastatin with a source of calcium cations. Non-limiting examples of alkali bases include lithium hydroxide, sodium hydroxide, sodium carbonate, sodium bicarbonate, potassium hydroxide, potassium carbonate, and potassium bicarbonate. Sodium hydroxide is preferred. These bases may be used in the form of solids or in the form of aqueous solutions. The intermediate base addition salt is in an aqueous solution and may be further made free of its organic impurities by washing the aqueous layer with a less polar solvents like esters such as ethyl acetate, n-propyl acetate, n-butyl acetate, t-butyl acetate; ethers such as diethyl ether, diisopropyl ether; hydrocarbons such as toluene, xylene, n-heptane, cyclohexane, n-hexane or mixtures thereof.

The intermediate alkali salt is then converted to salt of statin or sartan by the way of processes known in the prior art.
The intermediate alkali salt is then converted to rosuvastatin calcium salt of rosuvastatin by a treatment with a source of calcium cations. The calcium ions may be generated, for example, by using calcium compounds such as calcium chloride, calcium hydroxide, calcium carbonate, calcium acetate, calcium sulfate, calcium borate, calcium tartarate, calcium bromide, or other compound capable of generating calcium ion. The preferred sources of calcium ions are calcium acetate and hydrates of calcium acetate. Rosuvastatin calcium may be isolated by maintaining the reaction mixture at temperatures of from below about 10° C to about 25° C, for a period of time required for a more complete formation of the solid product. Isolation may be enhanced by methods such as cooling, partial removal of the solvent from the mixture, The method by which the solid material is recovered from the final mixture, with or without cooling below the operating temperature, can be any of techniques such as filtration by gravity, or by suction, centrifugation. The crystals so isolated will carry a small proportion of occluded mother liquor containing a higher percentage of impurities. If desired the crystals are washed on the filter with a solvent to wash out the mother liquor. The wet cake obtained In step c) may optionally be further dried. Drying is carried out In a tray dryer, vacuum oven, air oven, fluidized bed drier, spin flash dryer, flash dryer, preferably air tray dryer. Drying is carried out at temperatures of about 35° C to about 70° C, and is carried out for periods ranging from about 1 to about 20 hours.
L-valine benzyl ester salt of rosuvastatin is converted to the calcium salt of rosuvastatin can be converted to rosuvastatin calcium by the way of processes known in the prior art.
L-valine benzyl ester salt of statin or sartan, particularly rosuvastatin prepared as described herein preferably have purity greater than 98%, more preferably greater than about 99%, yet more preferably, greater than about 99.5%.
The salt of this invention may used to prepare salt of present invention with stains such as Atorvastatin, sartans like valsartan, candesartan, Telmisartan etc.
Starting rosuvastatin or rosuvastatin ester of formula (V) (Rosuvastatin ester of formula (V) is tertiary butyl ester of Rosuvastatin) for the purpose of use in the

processes described herein may be prepared by known processes in the art. Starting rosuvastatin can be prepared by following the method disclosed in US patent No.RE 37,314.
In an embodiment, the present patent application also provides pharmaceutical compositions that include statin or sartan, particularly rosuvastatin or its salts prepared according to the processes described herein along with one or more pharmaceutically acceptable carriers, excipients or diluents
The pharmaceutical compositions of statin or sartan, particularly rosuvastatin or its pharmaceutically acceptable salts along with one or more pharmaceutically acceptable carriers of this invention may further formulated as: solid oral dosage forms such as, but not limited to, powders, granules, pellets, tablets, and capsules; liquid oral dosage forms such as but not limited to syrups, suspensions, dispersions, and emulsions; and injectable preparations such as but not limited to solutions, dispersions, and freeze dried compositions. Formulations may be in the form of immediate release, delayed release or modified release. Further, immediate release compositions may be conventional, dispersible, chewable, mouth dissolving, or flash melt preparations, and modified release compositions that may comprise hydrophilic or hydrophobic, or combinations of hydrophilic and hydrophobic, release rate controlling substances to form matrix or reservoir or combination of matrix and reservoir systems. The compositions may be prepared by direct blending, dry granulation or wet granulation or by extrusion and spheronization. Compositions may be presented as uncoated, film coated, sugar coated, powder coated, enteric coated or modified release coated. Compositions of the present invention may further comprise one or more pharmaceutically acceptable excipients. Pharmaceuticaliy acceptable excipients that find use in the present invention include, but are not limited to: diluents such as starch, pregelatinized starch, lactose, powdered cellulose, microcrystalline cellulose, dicalcium phosphate, tricalcium phosphate, mannitol, sorbitol, sugar; binders such as acacia, guar gum, tragacanth, gelatin, polyvinyl pyrrolidone, hydroxypropyl cellulose, hydroxypropyl methylcellulose, pregelatinized starch; disintegrants such as starch, sodium starch glycolate, pregelatinized starch, crospovidone, croscarmellose sodium, colloidal silicon dioxide; lubricants such as stearic acid, magnesium stearate, zinc stearate; glidants such as colloidal silicon dioxide; solubility or wetting enhancers such as anionic or cationic or neutral surfactants; complex forming agents such as various grades of cyclodextrins, resins; release rate

controlling agents such as hydroxypropyl cellulose, hydroxymethyl cellulose, hydroxypropyl methylcellulose, ethyl cellulose, methyl cellulose, various grades of methyl methacrylates, waxes. Other pharmaceutically acceptable excipients that are of use include but are not limited to film formers, plasticizers, colorants, flavoring agents, sweeteners, viscosity enhancers, preservatives, antioxidants.
In the compositions of present invention statin or sartan, particularly rosuvastatin or its pharmaceutical acceptable salts is a useful active ingredient in the range of 0.5 mg to 100 mg, or 1 mg to 50 mg.
Certain specific aspects and embodiments of this invention are described in further detail by the examples below, which are provided only for the purpose of illustration and are not intended to limit the scope of the invention in any manner.
Example 1
PREPARATION OF TERTIARY BUTYL ROSUVASTATIN ESTER
To a 500 ml 4 neck flask was equipped with thermo pocket, stopper, moisture guard, ice bath etc., keto ester 10g and 350 ml of tetrahydrofuran and 90ml of methanol were charged. Reaction mass was cooled to -78°C. 18.7ml 1M diethyl methoxy borane was added at -78°C. Reaction mass was stirred for 30 min.at -78°C.1.07g of sodium borohydride was charged slowly at -78°C.Reaction mass was stirred for 3hrs at-78°C16 ml of acetic acid was added slowly. Temperature was raised to 5-10°C and pH 8 was adjusted using Sat bicarbonate solution. Temperature was allowed to 25-30°C300 ml of ether was charged & stirred for 5-10min.Layers were separated, org layer kept a side. Aq.layer was again extracted with ether (50ml).Organic layer was combined and washed with 2X100ml of RO water.Seperated organic layer was distilled out completely to give the title product as syrup.
Example 2
PREPARATION OF L-VALINE BENZYL ESTER SALT OF ROSUVASTATIN

To a 250ml_ 4 neck flask was equipped with thermopocket, stopper, moisture guard, water bath etc., tertiary butyl rosuvastatin ester 5g and 70 ml methanol were charged.37ml of 0.5N sodium hydroxide solution was charged. Reaction mass was heated up to 40-45°C.Reaction mass was stirred for 30min.at 40-45oC.Methanol was distilled out completely up to aqueous layer was remained.5 pH was adjusted using 7.5%w/w HCI solution.50 ml of ethyl acetate was charged.Reaction mass was stirred for 5-10min.Layers were separated; organic Layer was kept a side. Aqueous Layer was again extracted with 50ml of ethyl acetate. Layers were separated. Organic layer was kept a side, aqueous layer was discarded. Organic layers were combined and taken into 250ml roundbottomflask Free base of L-valine benzyl ester (prepared from 2.72 gm of its hydrochloride salt, oil was obtained) was dissolved in 10ml of ethyl acetate and charged to above 250ml of RBF.Reaction mass was heated to 60-65°C.Reaction mass was stirred for 90 minute at 60-65°C.Reaction mass was cooled to 40-45°C.Ethyl acetate was distilled out completely to get thick oil. Oil was dissolved in 15ml of methanol and 60ml of ethyl acetate. Reaction mass was heated to 60°C.Reaction mass was stirred up to complete clear solution.(15-20minute).Reaction mass was cooled to 20-25°C60 ml of hexane was added to reaction mass. To a reaction mass, 30 ml of hexane was added. Reaction mass was stirred for 2 hours. Solid was filtered and washed with 2X10 ml of hexane. Solid was dried in air tray dryer at 40-45°C for 12-16 hours. Purity: 99.2%
Example 3
PREPARATION OF ROSUVASTATIN CALCIUM FROM L-VALINE BENZYL ESTER SALT OF ROSUVASTATIN
To a 250mL 4 neck flask was equipped with thermopocket.stopper, moisture guard, water bath etc., L-valine benzyl ester salt of Rosuvastatin 4.5g ,RO Water 50ml and 50ml of Ethyl acetate were charged. Reaction mass was cooled to 0-5°C.Acetic acid (3.91g) was added drop wise at 0-5°C.Temperature was raised up to 15°C.Reaction mass was stirred for 60 minute at 15°C.Layers were separated; Org. Layer was kept a side. Aqueous Layer was again extracted with 50ml of ethyl acetate Layers were separated. Aqueous Layer was discarded. Organic layers were combined and Ethyl acetate was distilled up to thick oil.50ml 1N NaOH solution was added to the residue.30 ml ethyl acetate +30 ml of toluene was charged to reaction mass. Reaction mass was

stirred for 30 minute. Layers were separated; Organic Layer was discarded. Aqueous Layer was again washed with 60 ml of ethyl acetate + toluene (1:1) mixture. Layers were separated; Organic Layer was discarded. Aqueous layer was degassed under reduced pressure to remove traces of organic volatile in Aqueous Layer. 1.15g calcium caetate was dissolved in 5 ml of RO Water and added drop wise to the above Aqueous Layer. Reaction mass was stirred for 2 hours. Solid was filtered and washed with 2 X 10ml of RO Water. Solid was dried in air tray dryer at 45-50°C for 12-16 hours Purity: 99.85 by HPLC. Content of antiisomer (3R, 5R):0.05% Content of Enantiomer (3S, 5R): not detected.

We claim:
1. L-valine benzyl ester salt of statin or sartan.
2. The salt according to claim 1, wherein L-valine benzyl ester salt of statin or sartan is L-valine benzyl ester salt of rosuvastatin of formula (IV).

3. The salt according to claim 2, which is crystalline or amorphous.
4. The salt according to claim 3, which is characterized by an XRPD pattern having peaks at 6.1, 10.7, 10.9, 12.9, 15.9, 19.3, 19.4, 21.0, 21.2, 21.4 ± 0.2 °9.
4. A process for preparation of L-valine benzyl ester salt of statin or sartan includes the
steps of: a) providing a solution or suspension of free acid of statin or sartan; b) treating
the solution or suspension with L-valine benzyl ester to form L-valine benzyl ester salt of
statin or sartan.
5. The process according to claim 4, wherein statin includes rosuvastatin, atrovastatin, and sartan includes valsartan, telmisartan, candesartan.
6. The process according to claim 5, wherein statin includes rosuvastatin.
7. The process according to claim 4 to 6, wherein a solution or suspension is provided in organic solvent.

8. The process according to claim 4 to 6, wherein organic solvent is nitriles, alcohols, ketones, esters ethers, hydrocarbons or mixtures thereof or their combinations with water.
9. The process according to claim 4 to 6, wherein antisolvent is an aliphatic ester hydrocarbon or acetones: more preferably heptane, hexane or acetone.
10. The process according to claim 4 to 6, further comprises the preparation of salt of
statin or sartan, particularly calcium salt of rosuvastatin.