The present invention relates to a process for preparation of etoricoxib of Formula I.

Further, the present invention provides a process for preparation of intermediate, ketosulfone and use in preparation of etoricoxib thereof.

BACKGROUND OF THE INVENTION

US 5,861,419 (herein after referred to as US’419) discloses a variety of substituted pyridines, processes for their preparation, pharmaceutical compositions comprising the compounds, and method of use as selective cyclooxygenase-2 (COX-2) inhibitors. A selective COX-2 inhibitor has anti-inflammatory, antipyretic and analgesic properties similar to a conventional non-steroidal anti-inflammatory drug. Among them, Etoricoxib, is a COX-2 inhibitor and it is indicated for the symptomatic relief of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and the pain and signs of inflammation associated with acute gouty arthritis. Etoricoxib is represented by following Formula-I.

US’419 also disclose a process for the preparation of etoricoxib. The process of preparation of etoricoxib involves bromination of 2-amino pyridine derivative to give 2-amino-3-bromo pyridine derivative which upon coupling with 4-(methyl thio) phenyl boronic acid in presence of base followed by oxidation in acetone results into formation of 3-[4-(methylsulfonyl)phenyl]-5-(trifluoromethyl)-2-aminopyridine. The amino compound so obtained is then converted to halide derivative. Pd(II) catalyzed coupling of sulphone halide gives etoricoxib.

The above said method suffers from serious drawback of unsatisfactory purity which is less than 90%.

US 6,040,319 (US’319) discloses process for the preparation of etoricoxib by reacting 2-chloro-N,N-dimethylamino trimethinium hexafluorophosphate with ketosulfone in the presence of equimolar amount of tertiary butoxide in tetrahydrofuran and quenching resultant adduct in a mixture of acetic acid and trifluoroacetic acid. Ring closure is performed by heating in presence of aqueous ammonium hydroxide. The etoricoxib so obtained consist of 5-6% of ketosulphone, 1-(6-methylpyridin-3-yl)-2-(4-(methylsulfonyl) phenyl) ethanone of Formula-II which require removal through crystallization. Also, it is observed that the etoricoxib obtained as per above said method is brownish colored and require multiple purifications to form commercial grade product resulting into loss in terms of yields.

WO2010/097802 (WO’802) describes a process for preparing the drug substance etoricoxib by reacting certain substituted ß-chloro vinamidinium salts with ketosulphone of Formula-II. Adduct of keto sulphone and vinamidinium salt is cyclized using ammonia solution and ammonium acetate in 16h. The resultant etoricoxib is purified in two steps. Firstly, crude etoricoxib is treated with formalin solution and heated at 60oC for 1h and then subjected to crystallization in alcohol like isopropyl alcohol.

The above said method suffers from a major drawback such as the reaction is time engulfing requiring around 16h for completion.

WO2013/105106 (WO’106) describes preparation of etoricoxib by reacting ketosulfone with vinamidinium salts using sodium hydride as a base and dimethyl sulfoxide as a solvent. The cyclisation of adduct is performed using ammonium acetate and ammonia gas. The purification of etoricoxib so obtained is done by heating with formaldehyde followed by crystallization with isopropyl alcohol. In this process, use of reagents like sodium hydride makes the process difficult to be handled at large scale.

WO2012/066570 (WO’570) describes purification of crude etoricoxib in isopropanol containing 4-6% w/w of water.

WO2011/158250 (WO’250) describes purification of crude etoricoxib in either mixture of tetrahydrofuran and water or 1:1 ratio of isopropyl acetate and hexane or in isopropyl alcohol alone.

Similarly, WO2013/144977 (WO’977) described purification of crude etoricoxib by the use of isopropyl alcohol as purifying solvent.

The present invention relates to a process for the preparation of Etoricoxib and purifying etoricoxib having sufficient purity and yield, to meet quality and regulatory standards for commercial use. The present invention encompasses a novel process for preparation of etoricoxib and intermediates thereof.

OBJECT OF THE INVENTION
The main object of the present invention is to provide a process for preparation of highly pure etoricoxib of Formula I
.

In another object, the present invention provides a process for the preparation of intermediate, ketosulfone of Formula II and use of said intermediate in preparation of etoricoxib.

SUMMARY OF THE INVENTION
In main aspect, present invention provides a process for preparation of highly pure etoricoxib of Formula I
.

In one aspect, the present invention provides a process for the preparation of etoricoxib,
;
comprising the step of:
a) reacting ketosulfone of Formula II with vinamidinium salt of Formula-III
, ’
in presence of solvent (s), wherein atleast one solvent is dimethyl formamide; and
b) purifying in presence of suitable solvent to give etoricoxib.

In another aspect, the present invention provides a process for the preparation of etoricoxib of Formula I
;
comprising the step of:
a) reacting 3-(6-methylpyridin-3-yl)-2-(4-(methylthio)phenyl)-3-oxopropanenitrile of Formula IV with one or more acid(s) to form 1-(6-methylpyridin-3-yl)-2-(4-(methylthio)phenyl)ethan-1-one of Formula V,
;
wherein 1-(6-methylpyridin-3-yl)-2-(4-(methylthio)phenyl)ethan-1-one of Formula V is optionally isolated;
b) oxidizing the compound of Formula V in presence of suitable oxidizing agent to give ketosulfone of Formula II,
; and
c) converting the ketosulfone of Formula II to etoricoxib of Formula I.

In an additional aspect, the present invention provides the process for purification of etoricoxib wherein said process comprising crystallization of crude etoricoxib in alcohol.

Accordingly, in one another aspect, the present invention provides process for purification of etoricoxib, wherein said process comprising the steps of:
a) adding crude etoricoxib in an alcohol at a temperature in the range of room temperature to reflux temperature of the alcohol;
b) cooling to 0-10oC;
c) filtering and washing with chilled alcohol; and
d) isolating to get pure etoricoxib.

In another aspect, the present invention provides novel crystalline forms of etoricoxib of Formula I wherein said crystalline form is substantially free from amorphous form.

In another aspect, the present invention provides a stable amorphous form of etoricoxib of Formula I substantially free of crystalline form.

In another aspect, the present invention provides a stable solid dispersion of etoricoxib wherein said solid dispersion comprises of etoricoxib with pharmaceutical acceptable excipient and/ or polymer.

In another aspect, the present invention provides pure etoricoxib substantially free of impurities of Formula II, and other related impurities wherein each impurity is less than about 0.3% w/w and total impurities are less than about 1.0% w/w.

DETAILED DESCRIPTION
Definitions:
The term “solvents” or “solvent (s)” or “suitable solvent(s)” as used in the context of the present invention relates to solvent selected from, but not limited to, benzene, toluene, ethylbenzene, m-xylene, o-xylene, p-xylene, trimethylbenzene, chlorobenzene, fluorobenzene, trifluorotoluene, anisole; esters such as ethyl acetate, n-propyl acetate, n-butyl acetate, iso propyl acetate, isobutyl acetate, t-butyl acetate, ethyl formate, methyl acetate, methyl propanoate, ethyl propanoate, methyl butanoate, ethyl butanoate, diethyl ether, diisopropyl ether, methyl t-butyl ether, glyme, diglyme, tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, dibutyl ether, dimethylfuran; halogenated solvents such as dichloromethane, 1,2-dichloroethane, trichloroethylene, perchloroethylene, 1,1,1-trichloroethane, 1,1,2-trichloroethane, chloroform, carbon tetrachloride; ketones such as acetone, ethyl methyl ketone, diethyl ketone, methyl isobutyl ketone; nitriles such as acetonitrile, propionitrile, butanenitrile, sulfoxides, acetamides, dimethyl formamide and other amides, alcohols such as C1-C6 straight or branched chain alcohol, water or mixture thereof.

The term “alcohol” as used in the context of the present invention relates to alcohols selected from the group comprising of methanol, ethanol, tert-butanol, n-butanol, iso-butanol, pentanol, iso-pentanol, and mixture thereof.

The term “pharmaceutically acceptable excipient” as used in the context of the present invention may include, but not limited to an inorganic oxide such as silicon dioxide, titanium dioxide, zinc oxide, zinc dioxide, aluminium dioxide and zeolite; and organic polymers such as polyvinyl pyrrolidinone, cross linked cellulose acetate phthalate, microcrystalline cellulose, polyethylene/polyvinyl alcohol copolymer, polyethyle/polyvinyl pyrrolidinone copolymer, cross-linked carboxymethyl cellulose, povidone, povidone K-30, povidone K-60, Povidone K-90, Co-povidone, polyvinyl pyrrolidone vinyl acetate, polyvinyl alcohol, polysorbate 80, polyethylene glycol, methyl cellulose, Eudragit S-100, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, gelucire 44/14, ethyl cellulose, D-alphatocopheryl polyethylene glycol 1000 succinate, cellulose acetate phthalate, carboxymethylethylcellulose, cellulose derivatives; polyethylene glycol, cyclodextrins, gelatins, hypromellose phthalates, sugars, polyhydric alcohols, mannitol, lactose, fructose, sorbitol, xylitol, maltodextrin, dextrates, dextrins, lactitol and the like.

While the invention is susceptible to various modifications and alternative forms, specific embodiment thereof will be described in detail below. It should be understood, however that it is not intended to limit the invention to the particular forms disclosed, but on the contrary, the invention is to cover all modifications, equivalents, and alternative falling within the scope of the invention as defined by the appended claims.

The steps of a method may be providing more details that are pertinent to understanding the embodiments of the present invention and so as not to obscure the disclosure with details that will be readily apparent to those of ordinary skill in the art having benefit of the description herein.

Further characteristics and advantages of the process according to the invention will result from the description herein below of preferred exemplary embodiments, which are given as indicative and non-limiting examples.

The present invention is providing a solution to the problems associated with the prior known processes.

Accordingly in one embodiment, the present invention provides a novel process for the preparation of highly pure etoricoxib,
;
comprising the step of:
a) reacting ketosulfone of Formula II with vinamidinium salt of Formula-III,
, ,
in presence of solvent (s) wherein atleast one solvent is dimethyl formamide; and
b) purifying in presence of suitable solvent to give etoricoxib.

In another embodiment, the reaction of ketosulfone of Formula II with vinamidinium salt of Formula-III is carried out in presence of base selected from organic and inorganic base wherein said organic base is selected from trialkylamine, dimethyl amino pyridine, diisopropyl amine, ammonia, diisopropyl ethyl amine, pyridine and the like and said inorganic base is selected from, but not limited to, alkali and alkaline earth metal hydroxides, alkali and alkaline earth metal carbonates, alkali and alkaline earth metal bicarbonates, alkali metal alkoxides, and the like.

In another embodiment, the ketosulfone of Formula II is either procured from any commercial source or can be prepared by the process of the present invention or by any known conventional methods.

In another embodiment, the present invention provides a process for the preparation of etoricoxib of Formula I,
;
comprising the step of:
a) reacting 3-(6-methylpyridin-3-yl)-2-(4-(methylthio)phenyl)-3-oxopropanenitrile of Formula IV with one or more acid(s) to form 1-(6-methylpyridin-3-yl)-2-(4-(methylthio)phenyl)ethan-1-one of Formula V,
;
wherein 1-(6-methylpyridin-3-yl)-2-(4-(methylthio)phenyl)ethan-1-one of Formula V is optionally isolated;
b) oxidizing the compound of Formula V in presence of suitable oxidizing agent to give ketosulfone of Formula II,
; and
c) converting the ketosulfone of Formula II to etoricoxib of Formula I.

In a preferred embodiment, the step of conversion of compound of Formula IV to ketosulfone is carried out in situ in presence of acid without isolation of compound of Formula V.

In another preferred embodiment, the compound of Formula V may be isolated, purified and then oxidized to ketosulfone of Formula II.

In another embodiment, the acids used for preparation of ketosulfone are selected from acetic acid, sulfuric acid, hydrochloric acid, and mixture thereof.

In further embodiment, the ketosulfone of Formula II can be converted to etoricoxib by any known conventional methods.

In another embodiment, the present invention provides a process for the preparation of etoricoxib of Formula I,
;
comprising the step of:
a) reacting 3-(6-methylpyridin-3-yl)-2-(4-(methylthio)phenyl)-3-oxopropanenitrile of Formula IV with one or more acid(s), to form 1-(6-methylpyridin-3-yl)-2-(4-(methylthio)phenyl)ethan-1-one of Formula V,
;
wherein said compound of Formula V is optionally isolated;
b) oxidizing the compound of Formula V in presence of suitable oxidizing agent to give ketosulfone of Formula II,
;
c) purifying the ketosulfone of Formula II in presence of suitable solvent (s); and
d) converting the ketosulfone of Formula II to etoricoxib of Formula I.

In another embodiment, the present invention provides a process for purification of etoricoxib wherein said etoricoxib is optionally treated with para-toluene sulfonic acid proceeding with treatment with alcohol.

Accordingly, in a preferred embodiment, the present invention provides a process for purification of etoricoxib comprising the steps of:
a) adding crude etoricoxib in an alcohol at a temperature in the range of room temperature to reflux temperature of the alcohol;
b) cooling to 0-10oC;
c) filtering and washing with chilled alcohol; and
d) isolating to get pure etoricoxib.

In another embodiment, the present invention provides a process for purification of etoricoxib comprising the steps of:
a) adding crude etoricoxib in a mixture of isopropyl alcohol and t-butanol at a temperature in the range of room temperature to reflux temperature of the alcohol, wherein the mixture of isopropyl alcohol to t-butanol is in the ratio of 2-8:8-2;
b) gradually cooling to 10-25oC;
c) filtering and washing with chilled isopropyl alcohol; and
d) isolating to get pure etoricoxib.

In one another embodiment, the solution of etoricoxib in isopropyl alcohol and t-butanol is cooled at a temperature of 10-25oC for precipitation of pure etoricoxib.

In one another embodiment, the mixture of isopropyl alcohol to t-butanol is in the ratio of 2-8:8-2; preferably 7:3, and most preferably 5:5.

In one another embodiment, the etoricoxib obtained by the process of the present invention is characterized by purity of 99.0% and above, preferably 99.5% and above, and most preferably 99.95% and above.

In another embodiment, the present invention provides novel crystalline forms of etoricoxib of Formula I wherein said crystalline form is substantially free from amorphous form.

In another embodiment, the present invention provides a stable amorphous form of etoricoxib of Formula I substantially free of crystalline form.

In another embodiment, the present invention provides a stable amorphous solid dispersion of etoricoxib wherein said solid dispersion comprises of etoricoxib with pharmaceutical acceptable excipient and/ or polymer.

In one another embodiment, the present invention provides a process for the preparation of an amorphous solid dispersion of etoricoxib, comprising the steps of:
a) providing a solution of etoricoxib in a suitable solvent;
b) adding atleast one pharmaceutically acceptable excipient to the solution obtained in step a); and
c) isolating the amorphous solid dispersion of etoricoxib.

In further embodiment, the etoricoxib described herein, for the preparation various amorphous solid dispersion are either amorphous, or crystalline in nature. Even the reaction mixture containing etoricoxib can be used for preparing solid dispersions.

In another embodiment, the isolation in step c) above may be done using techniques such as direct filtration or by scraping, or by shaking the container, removal of the solvent include using a rotational distillation device such as a buchi rotavapor, spray drying, agitated thin film drying, freeze drying (lyophilization), and the like, or other techniques specific to the equipment used.

In another embodiment, the present invention provides pure etoricoxib substantially free of impurities of Formula II, and other related impurities wherein each impurity is less than about 0.3% w/w and total impurities are less than about 1.0% w/w.

In another embodiment, the present invention provides pure etoricoxib substantially free of impurities of Formula VI and VII,
, and .

In one another embodiment, the present invention provides a pharmaceutical composition comprising etoricoxib along with at least one pharmaceutical acceptable excipient thereof, wherein said pharmaceutical acceptable salt is prepared as per the process of the present invention.

In another preferred embodiment, the compound of Formula I, i.e. etoricoxib is characterized by the particle size distribution wherein, d90 is between 0.1µm to 200µm.

In a preferred embodiment, the compound of Formula I, i.e. etoricoixib is characterized by particle size distribution wherein, d90 is between 2.0 µm to 150µm.

EXAMPLES
EXAMPLE 1: Preparation of Etoricoxib
Ketosulphone and 2-chloro-1,3-bis(dimethylamino) trimethenium hexafluophosphate is reacted with potassium tertiary butoxide in DMF and toluene. After completion of reaction, reaction mass was quenched in acetic acid followed by addition of ammonia is added to the reaction mass and ammonium acetate. Cooled the mass, settled and separated the layers and extracted with toluene from aqueous layer. Combined the total toluene layer and washed with sodium hydroxide solution followed by washing of toluene layer with DM water. Treated the toluene layer with activated carbon at 60-65°C. Filtered through hyflo bed and washed the bed with toluene. Mother liquor is treated with p-toluene sulphonic acid and DM water followed by addition of aqueous ammonia to adjust pH 9-10. Separated the layers and washed the toluene layer with DM water. Treated the toluene layer with activated carbon and filtered through hyflo bed and washed the bed with toluene. Distilled out toluene under vacuum and chased out traces of toluene by isopropyl alcohol at 45-50°C to get etoricoxib.

EXAMPLE 2: Purification of Etoricoxib
To a stirred suspension of etoricoxib in isopropyl alcohol was heated to 80-85°C till clarity of mass followed by sudden cooling of reaction mass to 0°C-10oC. Stirred for 2 hours and filtered the product. Washed the product with chilled isopropyl alcohol and dried the product to get pure etoricoxib.

EXAMPLE 3: Purification of Etoricoxib
To a stirred suspension of etoricoxib in isopropyl alcohol was heated to 80-85°C till clarity of mass. Gradually cooled the mass to room temperature and then cooled to 0-10°C. Stirred for 2 hours and filtered the product. Washed the product with chilled isopropyl alcohol and dried the product to get pure etoricoxib.

EXAMPLE 4: Purification of Etoricoxib
To a stirred suspension of etoricoxib charged in isopropyl alcohol and t-butanol (1:1) and heated to 80-85°C till clarity of mass. Gradually cooled the mass to below room temperature. Stirred for 2 hours and filtered the product. Washed the product with chilled isopropyl alcohol and dried the product to get pure etoricoxib.

EXAMPLE 5: Preparation of 2-chloro-1,3-bis(dimethylamino)trimethinium hexafluoro phosphate of Formula III
Phosphorous oxy chloride (135.8 gm) is to add in mixture of N,N-dimethylformamide (420 gm) in the presence of Chloroacetyl chloride (100 gm) at 45-60°C, stirred for 4 hours and cooled to 25-30°C. Added sodium hydroxide solution (70 gm in 250 ml DM water) simultaneously in previously prepared DM water (250 ml), sodium hydroxide solution (70 gm in 250 ml DM water) and hexafluoro phosphoric acid (233.0 gm) at 0-10°C to get precipitate and filtered to get 2-chloro-1,3-bis(dimethylamino)trimethinium hexafluorophosphate.

EXAMPLE 6: Preparation of 3-(6-methylpyridin-3-yl)-2-(4-(methylthio)phenyl)-3-oxopropanenitrile of Formula IV
Charged toluene (800.0 ml) in 3.0 litre 4 neck round bottom flask, and added 4-Methylthio benzyl cyanide (100.0g) and Methyl-6-methyl nicotinate (111.12 g) at 25-30°C. Heated the reaction mass to 80-90°C, added 30.0% of sodium methoxide solution (213.91 g) within 1-1.5 hours at 80-90°C. Distilled out methanol and toluene mixture to achieve temperature 85-90°C. Stirred the reaction mass for 2-3 hours at 85-90°C. After completion of reaction, cooled the reaction mass to 10-15°C. Charged DM water (600.0 ml) to the mass at 10-20°C and adjusted the pH 6.5-7.0 with hydrochloric acid. Stirred the mass for 1-1.5 hours at 10-15°C and filtered the product and dried the product under vacuum at 45-50°C for 10-15 hours, yield (1.5-1.7w/w).

EXAMPLE 7: Preparation of ketosulfone of Formula II
Charged acetic acid (100.0 ml) in 4 neck round bottom flask, Charged step-01(150.0 g) 4 neck round bottom flask at 25-30°C. Charged concentrated hydrochloric acid (500.0 ml) at 25-30°C. Slowly heated the mass to 65-70°, Stirred the mass for 1hour at 65-70°C. Raised the temperature to 85-90°C. Stirred the mass for 2-5 hours at 85-90°C. Send the sample for HPLC or TLC. After reaction complies, cooled the mass to 10-15°C. Charged DM water (150.0 ml) at 10-15 and adjusted pH 7-8 with aqueous ammonia. Stirred the mass for 1.5-2 hours at 10-20°C, filtered the product under vacuum and washed with chilled DM water (150.0 ml) to get a wet cake. Charged acetic acid (400.0 ml) to the wet cake at 25-30°C, then charged sulphuric acid (30.0 g) at 25-30°C and catalyst (1.5 g) at 25-30°C. Cooled the mass to 10-20°C and slowly added hydrogen peroxide (180.62 g) at 10-20°C followed by raising the temperature to 25-30°C. Stirred the mass for 2-3 hours and added the solution of sodium thiosulphate [sodium thiosulphate (15.0 g) in DM water (150.0 ml)] at 10-15°C. Adjusted the pH with pH to 8-8.5. Stirred the mass 2 hours at 10-20°C and filtered the product under vacuum and wash with chilled DM water (150 ml). Dried the product under vacuum at 45-50°C for 10-15 hours to get ketosulfone.

EXAMPLE 8: Preparation of amorphous solid dispersion of etoricoxib with hydroxypropyl methyl cellulose
Etoricoxib (300 mg), hydroxypropyl methyl cellulose (300 mg) and methanol (30 ml) were charged into a round bottom flask at 25°C. The reaction mass was stirred for 15 minutes at 50°C. The reaction mass temperature cooled to 25°C. The reaction mass was filtered to remove any insoluble particles. The reaction mass was evaporated under vacuum at 50°C for over 60 minutes to give amorphous solid dispersion of etoricoxib with hydroxypropyl methyl cellulose.

EXAMPLE 9: Preparation of amorphous solid dispersion of etoricoxib with Co-povidone
Etoricoxib (500 mg), Co-povidone (500 mg) and methanol (50 ml) were charged into a round bottom flask at 25°C. The reaction mass was stirred for 15 minutes at 50°C. The reaction mass temperature cooled to 25°C. The reaction mass was filtered to remove any insoluble particles. The reaction mass was evaporated under vacuum at 55°C for over 20 minutes to give amorphous solid dispersion of etoricoxib with Co-povidone.

EXAMPLE 10: Preparation of amorphous form of etoricoxib
Charged etoricoxib (1 g) in water (20 mL) and heated at 50oC. Cooled the solution to room temperature and lyophilized to get the title compound.

CLAIMS:WE CLAIM
1. A process for the preparation of etoricoxib,
;
comprising the step of:
a) reacting ketosulfone of Formula II with vinamidinium salt of Formula-III,
, ,
in presence of solvent (s) wherein atleast one solvent is dimethyl formamide; and
b) purifying in presence of suitable solvent to give etoricoxib.

2. A process for the preparation of etoricoxib of Formula I,
;
comprising the step of:
a) reacting 3-(6-methylpyridin-3-yl)-2-(4-(methylthio)phenyl)-3-oxopropanenitrile of Formula IV with one or more acid(s) to form 1-(6-methylpyridin-3-yl)-2-(4-(methylthio)phenyl)ethan-1-one of Formula V,
;
wherein the 1-(6-methylpyridin-3-yl)-2-(4-(methylthio)phenyl)ethan-1-one of Formula V is optionally isolated;
b) oxidizing the compound of Formula V in presence of suitable oxidizing agent to give ketosulfone of Formula II,
; and
c) converting the ketosulfone of Formula II to etoricoxib of Formula I.

3. The process as claimed in claim 2, wherein said acid is selected from acetic acid, sulfuric acid, hydrochloric acid, and mixture thereof.

4. A process for purification of etoricoxib comprising the steps of:
a) adding crude etoricoxib in an alcohol at a temperature in the range of room temperature to reflux temperature of the alcohol;
b) sudden cooling to 0-10oC;
c) filtering and washing with chilled alcohol; and
d) isolating to get pure etoricoxib.

5. The process as claimed in claim 4, wherein said crude etoricoxib in step a) is optionally treated with para-toluene sulfonic acid before adding to an alcohol.

6. The process as claimed in claim 4, wherein said alcohol is selected from the group comprising of methanol, ethanol, tert-butanol, n-butanol, iso-butanol, pentanol, iso-pentanol and mixture thereof.

7. The process as claimed in claim 4, wherein said etoricoxib is isolated with purity of 99.0% and above.

8. The process as claimed in claim 4, wherein said etoricoxib is substantially free of impurities of Formula II, and other related impurities wherein each impurity is less than about 0.3% w/w and total impurities are less than about 1.0% w/w.

9. A process for the preparation of an amorphous solid dispersion of etoricoxib, comprising the steps of:
a) providing a solution of etoricoxib in a suitable solvent;
b) adding atleast one pharmaceutically acceptable excipient to the solution obtained in step a); and
c) isolating the amorphous solid dispersion of etoricoxib.

10. A process for the purification of etoricoxib, wherein said process comprising the steps of:
a) adding crude etoricoxib in a mixture of isopropyl alcohol and t-butanol at a temperature in the range of room temperature to reflux, wherein the mixture of isopropyl alcohol to t-butanol is in the ratio of 1-4:4-1;
b) gradually cooling to 10-25oC;
c) filtering and washing with chilled isopropyl alcohol; and
d) isolating to get pure etoricoxib.