Field of the Invention:-
The present invention relates to a process for the preparation of amorphous valsartan by spray drying.
Background of the Invention:-
Valsartan namely N-l(1-oxopentyl)-N-[[2'-(lH-tetrazol-5yl) [1,1'- biphenyl]-4-yl]methyl].-L-valine has the following structure

VALSARTAN
Valsartan is a well-known nonpeptide angiotensin II AT* . receptor antagonist and is marketed as the free acid under the name DIOVAN.
U.S. Pat. No. 5,399,578 discloses Valsartan, its pharmaceutically acceptable salts and process for their preparation.
PCT publication WO 02/06253 discloses crystalline, partly crystalline, amorphous and polymorphous forms of specific salts of Valsartan such as monopotassium salt, mono sodium salt, bis- diemethylammonium salt and others.
PCT publication WO 2004/06253 discloses amorphous and polymorphic forms of Valsartan. This publication also disclosed a process for the preparation of amorphous valsartan comprising
• Precipitating amorphous valsartan from a solution of valsartan in a solvent selected from the group consisting of methyl t-butyl ether and acetone
• Recovering valsartan amorphous form.
Or
• Preparing a solution of valsartan in a solvent selected from the group consisting of tetrahydrofuran, dioxane, ethanol, isopropanol, diethyl ether and methanol;
• Removing the solvent by evaporation.
In the prior art methods valsartan is being dried by vacuum drying for prolonged time at elevated temperatures. This leads to racemization of the product (increases the content of other unwanted stereo isomer)
PCT publication WO 2004/087681 discloses a novel amorphous form of Valsartan and also discloses a process a process in which the inventors achieved the amorphous form by removing the solvent either by vacuum drying or spray drying. In this publication the inventors did not disclosed the conditions and parameters for the spray drying.
In viewing the entire above prior art methods we invented a process for preparing amorphous Valsartan by spray drying at selected conditions.
Summary of the invention:
The main object of the present invention is to provide a suitable process for preparing amorphous Valsartan by spray drying technique.
Another object of the present invention is to prepare amorphous valsartan with the minimum residual solvent levels and with high optical / chiral purity.
Detailed description of the invention:
The process of the present invention comprises: Dissolving Valsartan in organic solvent(s)
Removing the solvent by spray drying under selected / specific conditions
Thus according to the method of the present invention, valsartan is dissolved in an organic solvent, which is selected from methanol, ethanol, acetone, methyl acetate, ethyl acetate and mixtures thereof at a temperature ranging from room temperature to reflux temperature of the solvent.
The ratio of solvent to the valsartan in the liquid concentrate feeding to the heat exchanger is preferably 1:1 to 1:5 and most preferably 1:2.
The prepared valsartan solution is subjected to the spray drying at a feed rate of 180-720 ml/hr and it depends upon the solvent taken for the dissolution. While drying nitrogen flow rate is adjusted at a rate of 350-750 lts/hr.
During the course of drying aspiration rate is adjusted to 100% and nitrogen pressure is maintained at 6 - 7 Kg/cm2. Inlet temperature is maintained at 100 - 130°C and outlet temperature is adjusted according to the inlet temperature.
In accordance with the present invention valsartan is prepared as per the prior art methods.
The prepared valsartan is dried in a tray drier upto LOD comes to a level of 5-15%(ethyl acetate). The semi-dried material is directly taken for the spray drying. The semi-dried valsartan is dissolved in a suitable solvent and subjected to spray drying and the obtained material shows the residual solvents with in the limits as per the
ICH guidelines and the optical rotation and purity of the material is equivalent to the standard valsartan. XRD difractogram of the amorphous valsartan obtained by spray drying (fig-1) is similar to the standard amorphous valsartan.
The invention is now illustrated with a few non-limiting examples. Reference Example:
Preparation of N-(1-oxopentyl)-N-[[2'-(lH-tetrazol-5-yl)-[1,1'- biphenyl]-methyl]]-L-valine (Valsartan)
Tributyltin azide prepared from Sodium azide (24.4 g) and Tributyltin- chloride (80.5 g) is added to N-Valeryl-N-[(2'- cyanobiphenyl-4-yl)methyl]-L-valine methyl ester (50 g)in o-xylene (400 ml) and maintained at reflux till the reaction substantially completes. The reaction mass cooled to 25 - 35°C and quenched into 15% KOH solution at 25 - 35°C (53.8 g KOH dissolved in 800 ml DM Water) and further maintained at 25 - 35°C for 10 hrs. The aqueous layer was separated and washed with MDC. The pH of the aqueous layer was adjusted to neutral with dilute HC1 and washed with IPE. The pH of the aqueous layer was further lowered to 4.0 with dilute HC1 at 25 - 35°C and extracted the compound into MDC.The final MDC layer was washed with 10% NaCl solution. The solvent is distilled atmospherically and crystallized from Ethyl acetate. The precipitated product is isolated and dried at 40 - 45°C till LOD comes to 5 - 15%. Yield: 35 g
Drying was carried out in various solvents and the results are given in the table-1

We claim:
1. A process for the preparation of amorphous valsartan comprising the steps of,
• dissolving Valsartan in organic solvent(s)
• removing the solvent by spray drying
2. The process as claimed in claim 1, wherein valsartan is dissolved in a solvent, which is selected from methanol, ethanol, acetone, methyl acetate, ethyl acetate and mixtures thereof.
3. The process as claimed in claim 1, wherein the dissolution temperature is ranging from room temperature to reflux temperature of the solvent
4. The process as claimed in claim 1, wherein the ratio of organic solvent to the valsartan is ranging from 1:1 to 5:1
5. The process as claimed in claim 1, wherein the solvent is removed by spray drier.
6. The process as claimed in claim 1, wherein the feed rate is adjusted at a rate of 15 - 30%(100 - 300ml/hr)
7. The process as claimed in claim 1, wherein the nitrogen flow rate is adjusted at a rate of 40 -60 mm Hg and nitrogen pressure is maintained at 6 - 7 Kg/cm2.
8. The process as claimed in claim 1, wherein the drier inlet temperature is maintained at 100 - 130°C