DESC:FIELD OF THE INVENTION
The present invention is related to highly pure amorphous telmisartan sodium of formula I and processes for preparation thereof.

Formula I
BACKGROUD OF INVENTION
Telmisartan is an angiotensin antagonist, particularly an angiotensin- II- antagonist, namely 4'-[[2-n-propyl-4-methyl-6-(1-methylbenzimidazole-2-yl)-benzimidazol-1-yl]-methyl]-biphenyl-2-carboxylic acid and having chemical structure of formula II

Formula II
Telmisartan is used to treat hypertension and cardiac insufficiency, to treat ischemic peripheral circulatory disorders, myocardial ischemia (angina), to prevent the progression of cardiac insufficiency after myocardial infarct, to treat diabetic neuropathy, glaucoma, gastrointestinal diseases, and bladder diseases.
Telmisartan and its pharmaceutically acceptable salts along with its pharmaceutical compositions have been first disclosed in US patent 5,591,762. The said patent discloses preparation of telmisartan by alkylation of 1,7'-dimethyl-2'-propyl-1H, 3'H-[2,5'] bibenzoimidazolyl (BIM) with 4'-[(bromomethyl)[1,1'-biphenyl]-2-carboxylic acid 1,1-dimethylethyl ester followed by hydrolysis.
US patent 6,358,986 discloses polymorphic forms of telmisartan particularly polymorphic form B and mixtures of polymorphs along with the method of preparing those polymorphic forms.
US patent 6,737,432 unveils a crystalline telmisartan sodium process for its preparation and its use for preparation of a pharmaceutical composition. It discloses the process for preparation of crystalline telmisartan sodium which involves the reaction of telmisartan suspension solution in toluene with sodium hydroxide and ethanol at temperature 78°C for about 30 min and then the mixture is filtered. In another vessel, toluene is taken and refluxed. Then filtrate, as obtained above is slowly added in the toluene solution thereto at boiling temperature and simultaneously distilled off azeotropically. The mixture is distilled at up to 103°C and the suspension is allowed to cool to ambient temperature. The crystals are suction filtered, washed with toluene and dried at 60° C in the circulating air drier to obtain crystalline telmisartan sodium.
It further discloses an alternate process for preparation of crystalline telmisartan sodium which involves reaction of telmisartan hydrochloride with sodium methoxide in the presence of toluene, water and isopropanol to obtain the reaction mixture which is subjected for heating along with charcoal to temperature 75°C and then reaction mass is filtered to remove the insoluble and distilled the solvent followed by azeotropic removal of solvent and mixture is left for crystallization, filtration, washing to obtain crystalline telmisartan sodium.
The above processes to prepare crystalline telmisartan sodium are not consistent and complicated, requires higher temperature to perform azeotropic distillation.
US patent publication 2006/0111417 discloses an amorphous form of telmisartan and a process for the preparation thereof. The process involves dissolving telmisartan in dichloromethane followed by filtration through paper and cloth. The obtained residue is spray dried at 40- 45 °C until the solvent is completely removed. Finally, the solid thus obtained is dried under high vacuum to get the desired amorphous form of telmisartan.
Another US patent publication 2006/0293377 discloses an amorphous and crystalline forms (0 to XX) of telmisartan sodium and process of preparing such amorphous and crystalline forms. Specifically, it provides the amorphous form of telmisartan sodium and the preparation thereof. The above said application provides two methods of preparing amorphous form of telmisartan sodium.
The first method involves treatment of telmisartan methyl ester with sodium hydroxide solution in the presence of ethanol followed by heating the mixture to reflux for 10.5 hrs. The resulting mixture is divided into two parts wherein water is added to the first part and ethanol is evaporated. The aqueous solution is lyophilized to obtain amorphous form of telmisartan sodium. In second part the ethanol is added, and the solvents are directly evaporated to obtain amorphous form of telmisartan.
The second method includes treating telmisartan with sodium hydroxide in the presence of ethanol. The obtained solution is stirred at room temperature for half an hour followed by evaporating solvents form the solution to obtain amorphous form of telmisartan.
Organic solvents such as aliphatic alcohols are frequently used during processing of chemical materials, and subsequent removal of those solvents is one of key steps to produce pure chemical products. Drying is typically used, but in some times, it is difficult to remove residual solvents by drying especially if solid material is an amorphous, or when particles are obtained that are big, irregular, and agglomerated. Furthermore, efficient removal of organic solvents by drying is often hampered by thermal instability of the desired chemical product.
All of the documents discussed above utilizes spray drying/ evaporation to remove solvents form the solution in order to obtain the amorphous telmisartan sodium. It has been observed by the present inventors that upon repetition of the processes, the residual solvent content in the product obtained after evaporation/ spray drying is quite high than the permissible limits as specified in International Conference for Harmonization (ICH) guidelines.
According to ICH guidelines the level of residual organic solvents should be strictly limited to the prescribed values especially if a solvent belongs to ICH Class 1 or 2. However, Class 3 solvents may be regarded as less toxic and amount of less than 5000 ppm of Class 3 solvents would be acceptable without justification. Additionally, the use of Class 1 solvents should be avoided because of their unacceptable toxicity, or their deleterious environmental effect. Also, the use of Class 2 solvents should be limited in pharmaceutical products because of their inherent toxicity. For example, for Class 2 solvents, the content of tetrahydrofuran (THF) should not be higher than 720 ppm, the content of 1,4-dioxane should not be higher than 380 ppm and the content of methanol should not be higher than 3,000 ppm; for Class 3 solvents such as ethanol, isopropyl alcohol and n-butanol, their content should not be higher than 5,000 ppm.
Usually, the solvents used in the preparation of a drug substance sometimes cannot completely be removed by practical manufacturing techniques, which are employed in the production. Therefore, in the preparation of a drug substance wherein plural steps are serially carried out until the final step, each solvent used in each step can possibly remain present as a residue in the drug substance. Further, solvent residues in a drug substance normally are not useful for the therapeutic benefits of the drug substance and may cause a problem of safety to a patient, depending on the kinds of residual solvents and concentrations thereof. For improving and increasing the safety of drugs, ICH recommendations have been adopted by regulatory authorities in the European Union, Japan, and the USA.
Since a solvent can play an important role in increasing the yield rate or in determination of physical properties of drug substance such as the crystal form, purity, solubility, etc., even if such a solvent is known to be toxic, there may be many cases where the use thereof in the preparation of drug substance cannot be avoided in terms of risk-benefits. In such cases, this guideline requires that a concentration of a residual solvent in drug substance should be not more than a specified value, which is toxicologically acceptable.
Another disadvantage of the above processes is that the development of dull color (yellowish or yellow) at the point when telmisartan is added in sodium hydroxide solution at room temperature due to the generation of exothermicity in the reaction which leads to form dull color material. Such material is not suitable for development of pharmaceutical compositions.
In general, the different physical properties shown by polymorphs affect important pharmaceutical parameters such as storage, stability, compressibility, density and dissolution rates (important in determining bioavailability). Stability differences may result from variations in chemical reactivity, mechanical changes or both. Solubility differences between polymorphs may, in extreme situations, result in transitions to crystalline forms that lack potency or are toxic. In addition, the physical properties of the crystalline form to that of an amorphous form may be important in pharmaceutical processing. For example, an amorphous form may provide better bioavailability than the crystalline form. Thus, a present amorphous form can provide a useful alternative for telmisartan sodium and may be useful for formulations which can have better stability, solubility, storage, compressibility etc. important for formulation and product manufacturing and doesn't degrade to crystalline forms of telmisartan sodium.
So, it is evident from the prior arts that the amorphous telmisartan sodium obtained by the preceding processes is unstable and not suitable for pharmaceutical preparations due to the presence of higher content of the residual solvents. Hence, there is an urgent need to develop an industrial friendly process for the manufacture of highly pure amorphous telmisartan sodium in a consistent manner by controlling the limit of residual solvent, and impurities along with avoiding the dull color formation.

OBJECT OF THE INVENTION
The principal object of the present invention is to provide an efficient and industrial advantageous process for the preparation of highly pure amorphous telmisartan sodium in which the content of residual solvents and impurities are controlled as per ICH guidelines.
Another object of the present invention is to provide an efficient and industrial advantageous process for the preparation of amorphous telmisartan sodium which is free from colored impurities or by products.
One another object of the present invention is to provide highly pure amorphous telmisartan sodium which is stable during drying and storage.
SUMMARY OF INVENTION
Accordingly, the present invention provides highly pure amorphous telmisartan sodium having residual solvent and impurities as per ICH guidelines.
Further the present invention provides a process for the preparation of highly pure amorphous telmisartan sodium on commercial scale using a process which is simple, cost effective and industrial friendly.
According to an embodiment, the present invention provides an efficient process for the preparation of highly pure amorphous telmisartan sodium of formula I,

Formula I
which comprises steps of:
i. dissolving sodium source in an alcoholic solvent at 0-15? to obtain a solution,
ii. adding telmisartan or telmisartan alkyl ester to the solution of step (i) at same a temperature,
iii. stirring the reaction mass till complete dissolution,
iv. optionally filtering the reaction mass,
v. removing the solvent from the reaction mass to obtain the solid material,
vi. drying the resulting product of step (v),
vii. milling of the resulting product of step (vi),
viii. drying the milled material to obtain highly pure amorphous telmisartan sodium.
According to another embodiment of the present invention provides a process for preparing highly pure amorphous telmisartan sodium,
which comprises steps of:
i. dissolving sodium source in a mixture of an alcoholic and ether solvent at 0-15? to obtain a solution,
ii. adding telmisartan or telmisartan alkyl ester to the solution of step (i) at same a temperature,
iii. stirring the reaction mass till complete dissolution,
iv. optionally filtering the reaction mass,
v. removing the solvent from the reaction mass,
vi. drying the resulting product of step (v),
vii. milling of the resulting product of step (vi),
viii. drying the milled material to obtain highly pure amorphous telmisartan sodium.
According to another embodiment of the present invention provides a process for preparing highly pure amorphous telmisartan sodium,
which comprises steps of:
i. providing crude telmisartan sodium,
ii. milling of the product of step (i),
iii. drying the milled material to obtain highly pure amorphous telmisartan sodium.

BRIEF DESCRIPTION OF THE DRAWINGS
1. Figure 1- represents PXRD pattern of amorphous telmisartan sodium.
2. Figure 2- represents PXRD pattern of amorphous telmisartan sodium.
3. Figure 3- represents PXRD pattern of amorphous telmisartan sodium.
4. Figure 4- represents PXRD pattern of amorphous telmisartan sodium.
5. Figure 5- represents PXRD pattern of amorphous telmisartan sodium.
6. Figure 6- represents PXRD pattern of amorphous telmisartan sodium.

DETAILED DESCRIPTION OF THE INVENTION
Accordingly, the present invention provides an efficient process for the preparation of highly pure amorphous telmisartan sodium wherein the contents of residual solvent and impurities are maintained as per ICH guidelines. The process eradicates the problems of the prior art and is convenient to operate for commercial production.
As used herein, the term ‘highly pure’ represents a compound having residual solvent content as per ICH guidelines and purity greater than 99.0 w/w by HPLC, preferably greater than 99.2% w/w by HPLC, more preferably greater than 99.5% w/w by HPLC and any individual impurity present in an amount of less than 0.3% more preferably less than 0.15% w/w by HPLC and total impurities present in an amount less than 0.5% w/w by HPLC.
As used herein, the term ‘crude’ represents a compound having residual solvent content greater than the limits specified as per ICH guidelines.
As used herein, the term “ambient temperature” represents a temperature 25?± 5?.
As used herein, the term “milling” refers to application of mechanical energy to physically break down coarse particles to finer ones.
As used herein, the term “solvent recovery” refers to applying heat/ vacuum to vaporize the solvent present in the reaction or liquid mixture with the desired product.
As used herein, the term “moisture content” refers to amount of moisture or water held in the drug substance.
The present invention relates to an improved and efficient process for the preparation of amorphous telmisartan sodium free from colored impurities, contaminants and controlled of residual solvent within the prescribed limit of ICH guidelines.
The process comprises of the step of treating the telmisartan or telmisartan alkyl ester with a suitable sodium source in a solvent at suitable reaction temperature. The suitable sodium source can be selected from one or more of sodium hydroxide, sodium bicarbonate, sodium carbonate, sodium 2-ethylhexanoate, disodium hydrogen citrate, sodium citrate, sodium acetate, sodium propionate, sodium butyrate, sodium isobutyrate, sodium tartrate, sodium oxalate, sodium benzoate, sodium sorbate, sodium malate, monosodium succinate, disodium succinate, disodium hydrogen phosphate, sodium borate, sodium sulfite, and sodium hydrosulfide. In particular, sodium source may be sodium hydroxide.
Specifically, the process comprises of the step of dissolving sodium hydroxide in an alcoholic solvent, ether solvent or a mixture thereof. The dissolution of sodium hydroxide in alcoholic solvent, ether solvent or a mixture thereof may be attained by stirring the reaction mixture at a temperature range of 0-15?. The alcoholic solvent system can be selected from the group consisting of C1-C4 alcohol such as methanol, ethanol, isopropyl alcohol, n-butanol. The ether solvent is selected from a group consisting of C2-C5 ethers such as dioxane, tetrahydrofuran (THF) and the like and mixture thereof.
In general, alcoholic solvent used herein includes but not limited to methanol, ethanol and isopropyl alcohol. Most preferably the mixture used herein is of tetrahydrofuran (THF) and isopropyl alcohol (IPA). After obtaining the solution, telmisartan or telmisartan alkyl ester is added to the above reaction mass in portion wise manner by maintaining the temperature range between 0-15?. The reaction mass is stirred till complete dissolution of telmisartan for 5 minutes to 3 hrs. Preferably 15 minutes to 2 hrs. Most preferable stirring time may be 30 minutes to 1 hr. The telmisartan alkyl ester can be selected from the group consisting of C1-C4 alkyl ester group which includes but not limited to methyl ester, ethyl ester, isopropyl ester, propyl ester, butyl ester and t-butyl ester. More preferably, the starting material is telmisartan methyl ester.
Optionally, the temperature of reaction mass is allowed to attain an ambient temperature followed by stirring 10 minutes to 3 hrs. Preferably 15 minutes to 2.5 hrs and more preferably 20 minutes to 2 hrs. Most preferable stirring time may be 30 minutes to 1 hr. The reaction mass is filtered from the hyflow bed, and the resulting filtrate is subjected to vacuum under reduced pressure at a temperature range of 40-55? for complete recovery of solvent. Afterward, the solid material is dried in vacuum tray dryer and then material is placed for process of milling. After milling the material is again dried under vacuum to obtain the highly pure amorphous telmisartan sodium. The milled material can be dried at temperature greater than 40°C. Preferable, drying temperature can be 40-90°C. Most preferably, drying temperature can be 45-80°C.
In an alternate embodiment, the present invention provides a process for preparing highly pure amorphous telmisartan sodium wherein content of residual solvent is controlled through milling of crude telmisartan sodium followed by subsequent drying. The limit of residual solvent is controlled as per ICH guidelines.
According to the invention it is also unexpectedly found that a good reproducibility of the amorphous telmisartan sodium can be obtained by using a preferable solvent quantity i.e., three to ten times of the quantity of telmisartan or telmisartan alkyl ester in the process and subjecting the recovered material for milling followed by drying. Most preferable solvent quantity is four to five times.
The amorphous telmisartan sodium obtained by the process of the present invention is highly pure, having good solubility and high stability, wherein content of residual solvent is within the prescribed limit of ICH guidelines. For example, for Class 2 solvents, the content of tetrahydrofuran (THF) should not be higher than 720 ppm, the content of 1,4-dioxane should not be higher than 380 ppm and the content of methanol should not be higher than 3,000 ppm; for Class 3 solvents such as ethanol, and isopropyl alcohol, their content should not be higher than 5,000 ppm. Also, amorphous telmisartan sodium does not convert to any other solid form when stored at a temperature of up to about 40ºC and at a relative humidity of about 25% to about 75% for about three months or more and containing less than about 0.5% (w/w) total impurities.
The process of the present invention provides amorphous telmisartan sodium wherein the level of individual specified, and unspecified impurities is controlled at a level of equal to or less than 0.15% and 0.1% respectively and total impurities at a level of less than 0.5% as per regulatory guidelines. The amorphous telmisartan sodium obtained by the process of the present invention have moisture content between 2.0-3.0%. The moisture content can be determined by titration according to Karl-Fischer. The amorphous telmisartan sodium obtained by the process of the present invention is highly pure having white to off-white color material, thermodynamically stable, and flow properties remaining essentially unchanged over a period of time. Moreover, the process for the preparation of amorphous telmisartan sodium is simple and easy to adopt on a commercial scale.
The starting material i.e., telmisartan can be prepared by the methods reported in prior art or by the process as given in the present specification.
X-ray powder diffraction analyses were carried out on a PANalytical X'Pert Pro diffractometer using Cu K alpha radiation. The instrument was equipped with a line focus X-ray tube, and the voltage and amperage were set to 45kV and 40mA respectively. The scanning rate was set as 10 second per step and step size is set as 0.01º. The diffractometer was equipped with X’celerator detector and rotating sample stage. X-ray diffractometer was used to record diffractogram from 4º to 50º (2-theta).
Although, the following examples illustrate the practice of the present invention in some of its embodiments, the examples should not be construed as limiting the scope of invention. Other embodiments will be apparent to one skilled in the art from consideration of the specification and examples.
EXAMPLES:
Example 1: Process for the preparation of amorphous telmisartan sodium
Sodium hydroxide (4 g) was dissolved in methanol (250 mL) at 0-10?. To the solution, telmisartan (50 g) was added by maintaining the same temperature. The reaction mass was stirred till complete dissolution of telmisartan. The reaction mass was then filtered through hyflow bed. The resulting filtrate was then subjected for complete recovery of solvent under vacuum at 45- 50?. Thereafter, the resulting solid material was dried at vacuum tray dryer followed by milling of dried material. The milled material was again dried in vacuum tray dryer to obtain the amorphous telmisartan sodium (51 g).
Moisture content: 2.90%.
HPLC purity: 99.88%
XRD of resulting product is shown in Figure 1.
Example 2: Process for the preparation of amorphous telmisartan sodium
Sodium hydroxide (5.2 g) was dissolved in methanol (325 mL) at 0- 10?. To the solution telmisartan (65 g) was added by maintaining the same temperature. The reaction mass was stirred till complete dissolution of telmisartan. The reaction mass was then filtered through hyflow bed. The resulting filtrate was then subjected for complete recovery of solvent under vacuum at 45- 50?. Thereafter, the resulting solid material was dried at vacuum tray dryer followed by milling of that dried material. The milled material was again dried in vacuum tray dryer to obtain the white amorphous telmisartan sodium (65 g).
Moisture content: 2.17%.
HPLC purity: 99.98%
XRD of resulting product is shown in Figure 2.
Example 3: Process for the preparation of amorphous telmisartan sodium
Sodium hydroxide (8 g) was dissolved in methanol (500 mL) at 0- 10?. To the solution telmisartan (100 g) was added in a portion wise manner by maintaining the temperature between 0-10?. The reaction mass was stirred till complete dissolution of telmisartan. Afterwards the reaction mass was allowed to attain an ambient temperature and stirred for 30-60 minutes then filtered from hyflow bed. The resulting filtrate was then subjected for complete recovery of solvent under vacuum at 45- 50?. Thereafter, the resulting solid material was dried at vacuum tray dryer followed by milling of that dried material. The milled material was again dried in vacuum tray dryer to obtain the off-white amorphous telmisartan sodium (102 g).
Moisture content: 2.26%.
HPLC purity: 100%
XRD of resulting product is shown in Figure 3.
Example 4: Process for the preparation of amorphous telmisartan sodium
Sodium hydroxide (0.8 g) was dissolved in ethanol (50 mL) at 0- 10?. To the solution telmisartan (10 g) was added by maintaining the temperature between 0-10?. The reaction mass was then stirred till complete dissolution of telmisartan. Afterwards, the reaction mass was allowed to attain an ambient temperature and stirred for 30-60 minutes then filtered through hyflow bed. The resulting filtrate was then subjected for complete recovery of solvent under vacuum at 45- 50?. Thereafter, the resulting solid material was dried at vacuum tray dryer followed by milling of that dried material. The milled material was again dried in vacuum tray dryer to obtain the amorphous telmisartan sodium (9.8 g).
Residual solvent content: Ethanol: 3200 ppm
Moisture content: 2.35%.
XRD of resulting product is shown in Figure 4.
Example 5: Process for the preparation of amorphous telmisartan sodium
Sodium hydroxide (0.8 g) was dissolved in a mixture of tetrahydrofuran (THF) (50 mL) and isopropyl alcohol (30 mL) at 0- 10?. To the solution telmisartan (10 g) was added portion wise by maintaining the temperature between 0-10?. The reaction mass was then stirred till complete dissolution of telmisartan. Afterwards the reaction mass was allowed to attain an ambient temperature and stirred for 30-60 minutes then filtered from hyflow bed. The resulting filtrate was then subjected for complete recovery of solvent under vacuum at 45- 50?. Thereafter, the resulting solid material was dried at vacuum tray dryer followed by milling of that dried material. The milled material was again dried in vacuum tray dryer to obtain the amorphous telmisartan sodium (9.5 g).
Residual solvent content: tetrahydrofuran: not detected; isopropyl alcohol: 3000 ppm Moisture content: 2.88%.
XRD of resulting product is shown in Figure 5.
Example 6: Process for the preparation of amorphous telmisartan sodium
Sodium hydroxide (0.8 g) was dissolved in methanol (50 mL) at 0- 10?. To the solution telmisartan methyl ester (10 g) was added portion wise by maintaining the temperature between 0-10?. The reaction mass was then stirred for 7-8 hours till complete dissolution of telmisartan methyl ester. Afterwards the reaction mass was allowed to attain an ambient temperature and stirred for 30-60 minutes then filtered from hyflow bed. The resulting filtrate was then subjected for complete recovery of solvent under vacuum at 45- 50?. Thereafter, the resulting solid material was dried at vacuum tray dryer followed by milling of that dried material. The milled material was dried in vacuum tray dryer to obtain the amorphous telmisartan sodium (8.5 g).
Moisture content: 2.64%.
XRD of resulting product is shown in Figure 6.
Example 7: Process for the preparation of amorphous telmisartan sodium
Sodium hydroxide (0.8 g) was dissolved in methanol (50 mL) at 0- 10?. To the solution telmisartan (10 g) was added by maintaining the same temperature. The reaction mass was stirred till complete dissolution of telmisartan. The reaction mass was then filtered through hyflow bed. The resulting filtrate was then subjected for complete recovery of solvent under vacuum at 45- 50?. Thereafter, the resulting solid material was dried at vacuum tray dryer followed by milling of that dried material. The milled material was again dried in vacuum tray dryer to obtain the off-white amorphous telmisartan sodium (10.2 g).
Moisture content: 2.35%.
HPLC purity: 99.97%
Example 8: Process for the preparation of amorphous telmisartan sodium
Sodium hydroxide (16 g) was dissolved in methanol (1000 mL) at 0- 10?. To the solution telmisartan (200 g) was added in a portion wise manner by maintaining the temperature between 0-10?. The reaction mass was stirred till complete dissolution of telmisartan. Afterwards the reaction mass was allowed to attain an ambient temperature and stirred for 30-60 minutes then filtered from hyflow bed. The resulting filtrate was then subjected for complete recovery of solvent under vacuum at 45- 50?. Thereafter, the resulting solid material was dried at vacuum tray dryer to get crude product wherein content of residual solvent (methanol: 4847 ppm) and then the crude product was milled. The milled material was again dried in vacuum tray dryer to obtain the amorphous telmisartan sodium (206 g).
Residual solvent content: methanol: 2167 ppm.
Moisture content: 2.91%.
Comparative Examples
Example 1: Process for the preparation of amorphous telmisartan sodium
Sodium hydroxide (0.8 g) was dissolved in methanol (500 mL) at 0-10?. The obtained reaction mass was allowed to attain ambient temperature followed by addition of telmisartan (10 g) to the reaction mass. The reaction mass was then stirred till complete dissolution of telmisartan. The reaction mass was then filtered through hyflow bed. The obtained filtrate was then subjected for complete recovery of solvent under vacuum at a temperature of 45- 50? to get the amorphous telmisartan sodium. The resulting product was having a dull color (yellowish or yellow).
Example 2: Process for the preparation of amorphous telmisartan sodium
Sodium hydroxide (0.8 g) was dissolved in methanol (50 mL) at 0- 10?. The obtained reaction mass was allowed to attain ambient temperature followed by addition of telmisartan (10 g) to the reaction mass. The reaction mass was stirred till complete dissolution of telmisartan. Thereafter, the reaction mass was filtered through hyflow bed. The obtained filtrate was then subjected for complete recovery of the solvent under vacuum at a temperature of 45- 50? to obtain amorphous telmisartan sodium (10.2 g). The resulting product was having a dull color (yellowish or yellow) and the content of residual solvent (methanol: 42077 ppm).
It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention and specific examples provided herein without departing from the spirit and scope of the invention. Thus, it is intended that the present invention covers the modifications and variations of this invention that come within the scope of any claims and their equivalents.
,CLAIMS:WE CLAIM:
1. A process for preparing highly pure amorphous telmisartan sodium of formula I,

Formula I
which comprises steps of:
i. providing crude telmisartan sodium,
ii. milling of the product of step (i),
iii. drying the milled material to obtain highly pure amorphous telmisartan sodium.

2. A process for the preparation of highly pure amorphous telmisartan sodium of formula I,

Formula I
which comprises steps of:
i. dissolving sodium source in an alcoholic solvent at 0-15? to obtain a solution,
ii. adding telmisartan or telmisartan alkyl ester to the solution of step (i) at same a temperature,
iii. stirring the reaction mass till complete dissolution,
iv. optionally filtering the reaction mass,
v. removing the solvent from the reaction mass to obtain the solid material,
vi. drying the resulting product of step (v),
vii. milling of the resulting product of step (vi),
viii. drying the milled material to obtain highly pure amorphous telmisartan sodium.
3. The process as claimed in claim 2, wherein in step i), the alcoholic solvent is selected from the group consisting of C1-C4 alcohol such as methanol, ethanol, isopropyl alcohol, n-butanol.

4. The process as claimed in claim 2, wherein in step ii), telmisartan alkyl ester is selected from C1-C4 alkyl ester the group consisting of methyl ester, ethyl ester, isopropyl ester, propyl ester, butyl ester and t-butyl ester; in step ii), sodium source is selected from one or more of sodium hydroxide, sodium bicarbonate, sodium carbonate, sodium 2-ethylhexanoate, disodium hydrogen citrate, sodium citrate, sodium acetate, sodium propionate, sodium butyrate, sodium isobutyrate, sodium tartrate, sodium oxalate, sodium benzoate, sodium sorbate, sodium malate, monosodium succinate, disodium succinate, disodium hydrogen phosphate, sodium borate, sodium sulfite, and sodium hydrosulfide.

5. The process as claimed in claim 2, wherein the quantity of solvent is three to ten times of the quantity of telmisartan or telmisartan alkyl ester used in the process.

6. A process for preparing highly pure amorphous telmisartan sodium of formula I,

Formula I
which comprises steps of:
i. dissolving sodium source in a mixture of an alcoholic and ether solvent at 0-15? to obtain a solution,
ii. adding telmisartan or telmisartan alkyl ester to the solution of step (i) at same a temperature,
iii. stirring the reaction mass till complete dissolution,
iv. optionally filtering the reaction mass,
v. removing the solvent from the reaction mass,
vi. drying the resulting product of step (v),
vii. milling of the resulting product of step (vi),
viii. drying the milled material to obtain highly pure amorphous telmisartan sodium.
7. The process as claimed in claim 5, wherein in step i), the alcoholic solvent is selected from the group consisting of C1-C4 alcohol such as methanol, ethanol, isopropyl alcohol, n-butanol; the ether solvent is selected from the group consisting of C2-C5 ethers such as dioxane, tetrahydrofuran and mixture thereof.

8. The process as claimed in claim 5, wherein in step ii), telmisartan alkyl ester is selected from C1-C4 alkyl ester the group consisting of methyl ester, ethyl ester, isopropyl ester, propyl ester, butyl ester and t-butyl ester; sodium source is selected from one or more of sodium hydroxide, sodium bicarbonate, sodium carbonate, sodium 2-ethylhexanoate, disodium hydrogen citrate, sodium citrate, sodium acetate, sodium propionate, sodium butyrate, sodium isobutyrate, sodium tartrate, sodium oxalate, sodium benzoate, sodium sorbate, sodium malate, monosodium succinate, disodium succinate, disodium hydrogen phosphate, sodium borate, sodium sulfite, and sodium hydrosulfide.

9. The process as claimed in claim 5, wherein the quantity of solvent or a mixture of solvent, is three to ten times of the quantity of telmisartan or telmisartan alkyl ester used in the process.

10. Highly pure amorphous telmisartan sodium prepared by the process of any of proceeding claims.