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Crystalline forms of Trisodium Sacubitril Valsartan

IP.com Disclosure Number: IPCOM000246931D
Publication Date: 2016-Jul-15
Document File: 13 page(s) / 1M

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The IP.com Prior Art Database

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Page 01 of 13

The present disclosure relates to novel crystalline forms of Trisodium Sacubitril Valsartan, designated as form-I and form-II.

Trisodium Sacubitril Valsartan hemipentahydrate complex, structurally represented as formula-I.

In one embodiment, crystalline form-I of Trisodium Sacubitril Valsartan is characterized by the powder X-ray diffraction having characteristic peak at about 5.1, 8.5, 13.0, 15.0 and 22.8 (±) 0.2° 2-theta.

In one more embodiment, crystalline form-I of Trisodium Sacubitril Valsartan is further characterized by the Powder X-ray diffraction having peaks at about 4.3, 5.1, 5.5, 5.8, 8.5, 12.6,
13.0, 15.0, 17.0, 17.7, 18.2, 19.1, 19.5, 20.4, 21.3, 22.0, 22.8 and 23.1 (±) 0.2° 2-theta.

In one embodiment, crystalline form-II of Trisodium Sacubitril Valsartan is characterized by the powder X-ray diffraction having characteristic peak at about 5.0, 5.4, 5.9, 7.3, 10.9, 11.5, 12.9,
14.6, 16.5, 17.2, 17.5, 19.0, 19.4, 20.2, 21.0, 21.8, 24.1, 24.5 and 26.4 (±) 0.2° 2-theta.

In one more embodiment, crystalline form-II of Trisodium Sacubitril Valsartan is further characterized by the Powder X-ray diffraction having peaks at about 4.3, 5.0, 5.4, 5.9, 7.3, 9.9,
10.9, 11.5, 12.9, 13.7, 14.6, 15.7, 16.5, 17.2, 17.5, 18.0, 18.5, 19.0, 19.4, 20.2, 21.0, 21.8, 23.0,
24.1, 24.5, 25.2 and 26.4 (±) 0.2° 2-theta.


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Instrumentation:


Powder X-ray Diffraction (PXRD)

The said polymorphs of the present invention is characterized by their X-ray powder difftaction pattern. Thus, the X-ray diffraction patterns of said polymorphs of the invention were measured on PANalytical, X'Pert PRO powder diffractometer equipped with goniometer of θ/θ configuration and X'Celerator detector. The Cu-anode X-ray tube was operated at 40kV and 30mA. The experiments were conducted over the 2 θ range of 2.00-50.00, 0.0300 step size and 50 seconds step time.

DSC
Differential Scanning Calorimetry of form I and form II were measured on TA Q1000 of TA instruments. The samples were heated from 30° to 250°C at heating rate of 10.0°C/min with modulation amplitude ±0.5°C, modulation period 80sec and nitrogen purging at a flow rate of 50m1/min Standard aluminum pans covered by lids with five pin holes were used.

TGA
TGA was recorded using on instrument TA Q5000 of TA instruments. The experiments were performed at a heating rate of 10.0°C/min over a temperature range of 25°C-300°C purging with nitrogen at a flow rate of 25m1/min.

ATR-FTIR
The ATR-FTIR data for form I and form II were collected on Perkin Elmer spectrum 100 instrument in the range of 400-4000 cm-1.

Sodium Content
Sodium content was calculated by Atomic Absorption Spectroscopy (AAS) using Flame Atomization technique. Measurements were performed by Perkin Elmer Pinnacle 900T instrument.

13C-Solid State NMR (13C SSNMR)

Approximately 40-50 mg of the fine powdered sample is filled into 3.2 mm zirconium rotor and submitted for NMR. Sample is oriented at magic angle and a spinning of 10 KHz...