DESC:CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims the benefit of the earlier filing date of Indian Provisional Patent Application No. IN202041016425 filed on April 16, 2020.
FIELD OF THE INVENTION
The present invention relates to amorphous form of cabotegravir sodium and a process for the preparation of amorphous cabotegravir sodium.
BACKGROUND OF THE INVENTION
Cabotegravir is a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor (INSTI) currently under development for the treatment of HIV-1 infection in combination with other antiretroviral agents. It is chemically designated as (3S,11aR)-N[2,4- Difluorophenyl)methy1]-6-hydroxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1,3]oxazolo [3,2-a]pyrido[1,2-d]pyrazine-8-carboxamide and can be represented by the following chemical structure according to Formula (I).

Formula-I
PCT Publication No. WO2006/116764A1 discloses a process for the preparation of cabotegravir.
PCT Publication No. WO2018/149608A1 discloses different crystalline forms of cabotegravir sodium.
PCT Publication No. WO2018/109786A1 discloses different crystalline forms of cabotegravir and its sodium salt. This patent publication also discloses cabotegravir potassium salt and its crystalline forms.
The present invention provides amorphous cabotegravir sodium and a process for the preparation of cabotegravir sodium thereof.
SUMMARY OF THE INVENTION
A first aspect of the present invention is to provide amorphous cabotegravir sodium.

Another aspect of the present invention is to provide a process for the preparation of amorphous cabotegravir sodium, which comprises:
a) providing cabotegravir sodium in a solvent;
b) optionally heating the suspension of step (a) to get clear solution; and
c) removing the solvent to get the amorphous cabotegravir sodium.

BRIEF DESCRIPTION OF THE FIGURES
Further aspects of the present disclosure together with additional features contributing thereto and advantages accruing there from will be apparent from the following description of embodiments of the disclosure which are shown in the accompanying drawing figures wherein:

Figure. 1 is an X-ray powder diffractogram of amorphous cabotegravir sodium.

DETAILED DESCRIPTION OF THE INVENTION
It is to be understood that the description of the present invention has been simplified to illustrate elements that are relevant for a clear understanding of the invention, while eliminating, for purposes of clarity, other elements that may be well known.

The polymorph of the present disclosure is characterized by its X-ray powder diffraction pattern. Thus, the X-ray diffraction patterns of the polymorphs of the disclosure were measured on PANalytical, X'Pert PRO powder diffractometer equipped with goniometer of ?/? configuration and X'Celerator detector. The Cu-anode X-ray tube was operated at 40kV and 30mA. The experiments were conducted over the 2? range of 2.0°-50.0°, 0.030° step size and 50 seconds step time.

The present disclosure relates to amorphous cabotegravir sodium and a process for the preparation thereof.

In one embodiment the present invention provides a process for the preparation of amorphous cabotegravir sodium, which comprises:
a) providing cabotegravir sodium in a solvent;
b) optionally heating the suspension of step (a) to get clear solution; and
c) removing the solvent to get the amorphous cabotegravir sodium.

According to the present invention, cabotegravir sodium is provided in a solvent and the reaction mixture is heated at a temperature of 60±5 °C to obtain a clear solution. The solvent was removed and dried to get amorphous cabotegravir sodium.

Within the context of this embodiment of the present invention, the input cabotegravir sodium may be prepared by any prior art process for example as disclosed in WO2006/116764A1.

Within the context of this embodiment of the present invention, the solvent employed may include, organic solvents such as methanol, ethanol, isopropanol, 2-acetonitrile, 1,4-dioxane, THF, water, trifluoroethanol, hexafluoro-2-propanol, 1,1,1,3,3,3-hexafluoro-2-propanol or mixtures thereof. In particular useful embodiments of the present invention 1,1,1,3,3,3-hexafluoro-2-propanol is used.

Within the context of this embodiment of the present invention, suitable techniques which can be used for the removal of solvent include but not limited to evaporation, flash evaporation, simple evaporation, rotational drying, spray drying, freeze-drying or any other suitable technique known in the art. In particular useful embodiments of the present invention the solvent is removed by spray drying.

In view of the above description and the examples below, one of ordinary skill in the art will be able to practice the invention as claimed without undue experimentation. The foregoing will be better understood with reference to the following examples that detail certain procedures for the preparation of molecules, compositions, and formulations according to the present invention. All references made to these examples for the purpose of illustration. The following examples should not be considered exhaustive, but merely illustrative of only a few of the many aspects and embodiments contemplated by the present invention.
Example 1: Preparation of amorphous cabotegravir sodium
Cabotegravir Sodium (5 g) was dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol (30 mL) at 60±3°C. The resulting clear solution was filtered through hyflo to remove any undissolved particulates and subjected to spray-drying in a laboratory spray-dryer (Model: Buchi B-290) with feed rate of solution 5 mL/min and inlet temperature at 90°C with 100% aspiration to yield cabotegravir Sodium amorphous form.
Example 2: Preparation of amorphous cabotegravir sodium
Cabotegravir Sodium (5g) was dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol (30mL) at 50±3°C. The resulting clear solution was filtered through hyflo to remove any undissolved particulates and subjected to spray-drying in a laboratory spray-dryer (Model: Buchi B-290) with feed rate of solution 5ml/min and inlet temperature at 70°C with 100% aspiration to yield cabotegravir Sodium amorphous form.
,CLAIMS:We claim
1) Amorphous cabotegravir sodium.
2) A process for the preparation of amorphous cabotegravir sodium, which comprises:
a) providing cabotegravir sodium in a solvent;
b) optionally heating the suspension of step (a) to get clear solution; and
c) removing the solvent to get the amorphous cabotegravir sodium.

3) The process as claimed in claim 2, wherein the solvent is selected from methanol, ethanol, isopropanol, 2-acetonitrile, 1,4-dioxane, THF, water, trifluoroethanol, 1,1,1,3,3,3-hexafluoro-2-propanol or mixtures thereof.

4) The process as claimed in claim 2, wherein the solvent is removed by evaporation, flash evaporation, rotational drying, spray drying, freeze-drying.