PREPARATION METHOD FOR EUTECTIC HYDRATE CRYSTAL FORM II OF AHU-377 AND DIOVAN TRISODIUM SALT
First Claim
1. A preparation method of trisodium AHU-377 and Valsartan co-crystal hydrate Form II, wherein the X-ray powder diffraction pattern (CuKα
- radiation) of said Form II has characteristic peaks at 2theta values of 4.3°
±
0.2°
, 5.0°
±
0.2° and
12.8°
±
0.2°
, said preparation method comprises the following steps;
Step 1;
preparing a clear solution containing trisodium AHU-377 and Valsartan, wherein said clear solution comprises a first solvent and a second solvent;
the first solvent is an anti-solvent of Form II, and can form azeotrope with water, the second solvent is a good solvent of Form II, and the boiling point of the second solvent is lower than that of the first solvent;
Step 2;
evaporating the clear solution obtained in Step 1 under vacuum or under nitrogen purging to remove the second solvent and water from the system; and
Step 3;
mixing the system obtained in Step 2 with water, a third solvent and with or without seed crystals of Form II, then stirring for crystallization, filtering, washing and drying to obtain Form II, wherein said third solvent is an anti-solvent of Form II, which is miscible in the first solvent, and water is soluble in said third solvent.
1 Assignment
0 Petitions
Accused Products
Abstract
The present disclosure relates to a preparation method of a trisodium AHU-377 and Valsartan co-crystal hydrate Form II. The preparation method comprises: firstly, preparing a clear solution of trisodium AHU-377 and Valsartan, the solvent of the clear solution comprises an anti-solvent and a good solvent of the target product Form II, and the boiling point of the good solvent is lower than that of the anti-solvent; secondly, evaporating the solution under vacuum to remove the good solvent and water from the system; and finally, optionally adding seed crystals of Form II or not and replenishing a mixture of water and a carrier solvent for stirring for crystallization. The method of the present disclosure can prepare Form II successfully, and the process is consistent and controllable. The obtained Form II product has high chemical purity, crystalline purity and good flowability; and the process can be scaled up, and meets the requirements of large-scale production.
-
Citations
20 Claims
-
1. A preparation method of trisodium AHU-377 and Valsartan co-crystal hydrate Form II, wherein the X-ray powder diffraction pattern (CuKα
- radiation) of said Form II has characteristic peaks at 2theta values of 4.3°
±
0.2°
, 5.0°
±
0.2° and
12.8°
±
0.2°
, said preparation method comprises the following steps;Step 1;
preparing a clear solution containing trisodium AHU-377 and Valsartan, wherein said clear solution comprises a first solvent and a second solvent;
the first solvent is an anti-solvent of Form II, and can form azeotrope with water, the second solvent is a good solvent of Form II, and the boiling point of the second solvent is lower than that of the first solvent;Step 2;
evaporating the clear solution obtained in Step 1 under vacuum or under nitrogen purging to remove the second solvent and water from the system; andStep 3;
mixing the system obtained in Step 2 with water, a third solvent and with or without seed crystals of Form II, then stirring for crystallization, filtering, washing and drying to obtain Form II, wherein said third solvent is an anti-solvent of Form II, which is miscible in the first solvent, and water is soluble in said third solvent. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20)
- radiation) of said Form II has characteristic peaks at 2theta values of 4.3°
Specification