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1. (WO2019025600) SOFOSBUVIR HYDRATE
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CLAIMS

1) A hydrate of sofosbuvir according to formula (II)


nH20 (Π),

wherein n is in the range of from 0.9 to 1.1, characterized by having a powder X-ray diffractogram comprising reflections at 2-theta angles of (7.6 ± 0.2)°, (12.7 ± 0.2)° and (17.0 ± 0.2)°, when measured at a temperature in the range of from 20 to 30 °C with Cu-Kalphai,2 radiation having a wavelength of 0.15419 nm.

The hydrate of claim 1 characterized by having a powder X-ray diffractogram comprising additional reflections at 2-theta angles of (10.4 ± 0.2)° and (11.5 ± 0.2)°, when measured at a temperature in the range of from 20 to 30 °C with Cu-Kalphai,2 radiation having a wavelength of 0.15419 nm.

The hydrate of claim 1 or 2 characterized by having a powder X-ray diffractogram comprising no reflection at 2-theta angles in the range of from 2.0 to 7.3°, when measured at a temperature in the range of from 20 to 30 °C with Cu-Kalphai,2 radiation having a wavelength of 0.15419 nm.

The hydrate according to any one of the preceding claims characterized by having a Fourier transform infrared spectrum comprising peaks at wavenumbers of (3512 ± 2) cm"1, (1740 ± 2) cm"1 and (1673 ± 2) cm"1, when measured at a temperature in the range of from 20 to 30 °C with a diamond ATR cell.

The hydrate according to claim 4 characterized by having a Fourier transform infrared spectrum comprising additional peaks at wavenumbers of (3402 ± 2) cm"1 and (946 ± 2) cm"1, when measured at a temperature in the range of from 20 to 30 °C with a diamond ATR cell.

The hydrate according to any one of the preceding claims characterized by having a differential scanning calorimetry curve comprising an endotherm with a peak

temperature in the range of from 77 to 80 °C, when measured at a heating rate of 10 K/min.

7) A composition comprising the hydrate according to any one of the preceding claims and at most 20 weight%, 10 weight%, 5 weight%, 2 weight% or 1 weight% of any other physical form of sofosbuvir, based on the weight of the composition.

8) A process for the preparation of the sofosbuvir hydrate as defined in any one of claims 1 to 6 or the composition as defined in claim 7 comprising:

(a) providing sofosbuvir in crystalline form 1 characterized by having a powder X-ray diffractogram comprising reflections at 2-theta angles of (5.0 ± 0.2)°, (7.3 ± 0.2)°, (9.4 ± 0.2)° and (18.1 ± 0.2)°, when measured at a temperature in the range of from 20 to 30 °C with
radiation having a wavelength of 0.15419 nm, in crystalline form 8 characterized by having a powder X-ray diffractogram comprising reflections at 2-theta angles of (8.6 ± 0.2)°, (9.2 ± 0.2)°, (14.2 ± 0.2)°, (15.6 ± 0.2)°, (16.0 ± 0.2)°, (17.1 ± 0.2)°, (17.5 ± 0.2)°, (18.1 ± 0.2)°, (19.8 ± 0.2)° and (25.6 ± 0.2)°, when measured at a temperature in the range of from 20 to 30 °C with
radiation having a wavelength of 0.15419 nm and/or in amorphous form;

(b) suspending the sofosbuvir provided in (a) in water, wherein the sofosbuvir provided in (a) is present in the suspension in an amount in the range of from 100 to 700 g/L;

(c) slurrying the suspension provided in step (b).

9) Use of the hydrate as defined in any one of claims 1 to 6 or the composition as defined in claim 7 for the preparation of a pharmaceutical composition.

10) A pharmaceutical composition comprising the hydrate as defined in any one of claims 1 to 6 or the composition as defined in claim 7 and at least one pharmaceutically acceptable excipient.

11) The pharmaceutical composition of claim 10, further comprising one or more additional active pharmaceutical ingredient(s).

12) The pharmaceutical composition of claim 11, wherein the one or more additional active pharmaceutical ingredient(s) is/are selected from the group consisting of ledipasvir, velpatasvir and voxilaprevir.

13) The pharmaceutical composition according to any one of claims 10 to 12, wherein the pharmaceutical composition is an oral solid dosage form.

14) The pharmaceutical composition of claim 13, wherein the oral solid dosage form is a tablet.

15) The pharmaceutical composition according to anyone of claims 10 to 14 comprising a predetermined and/or effective amount of the sofosbuvir hydrate according to any one of claims 1 to 6 wherein the predetermined and/or effective amount of the sofosbuvir hydrate is 400 mg calculated as water-free sofosbuvir.

16) The hydrate as defined in any one of claims 1 to 6 or the pharmaceutical composition according to any one of claims 10 to 15 for use in the treatment of viral hepatitis C infections.