FIELD OF THE INVENTION
The present application relates to solid dispersions of Siponimod hemifumarate, their preparative methods and pharmaceutical compositions thereof.

BACKGROUND OF THE INVENTION
The drug compound having the adopted name Siponimod, has a chemical name (E)-1-(4-(1-(((4-cyclohexyl-3-(trifluoromethyl)benzyl)oxy)-imino)ethyl)-2-ethylbenzyl)-azetidine-3-carboxylic acid, and is represented by the structure of formula I.

Siponimod is an investigational selective sphingosine-1-phosphate receptor modulator drug currently in phase III clinical trials for the therapy of secondary progressive multiple sclerosis.
Siponimod base, its synthetic process and its pharmaceutical compositions are described in US patent No. 7,939,519 B2 (US ‘519). Siponimod hemifumarate salt and its pharmaceutical compositions are described in US patent application No. 20150175536 A1 (US ‘536).
The US ‘536 also describes crystalline forms of Siponimod hemifumarate salt and their pharmaceutical compositions.
There remains a need to provide commercially viable and advantageous processes for preparation of pure and stable amorphous form and solid dispersions of Siponimod hemifumarate.
SUMMARY OF THE INVENTION
The present application generally relates to processes for preparation of amorphous Siponimod hemifumarate and solid dispersions thereof.
In the first aspect, the present application provides a process for preparing amorphous form of Siponimod hemifumarate, comprising;
a) providing a solution of Siponimod hemifumarate in a solvent or a mixture of solvents;
b) removing solvent from the solution of Siponimod hemifumarate obtained in step a); and
c) recovering amorphous form of Siponimod hemifumarate.
In the second aspect, the present application provides a solid dispersion comprising Siponimod hemifumarate and one or more pharmaceutically acceptable carrier.
In the third aspect, the present application provides a process for preparing an amorphous solid dispersion comprising siponimod hemifumarate and one or more pharmaceutically acceptable carriers, the process comprising;
a) providing a solution comprising Siponimod hemifumarate and one or more pharmaceutically acceptable excipients,
b) removing solvent from the solution obtained in step (a), and
c) recovering an amorphous solid dispersion comprising Siponimod hemifumarate and one or more pharmaceutically acceptable excipient.
In the fourth aspect, the present application provides pharmaceutical composition comprising amorphous Siponimod hemifumarate and one or more pharmaceutically acceptable excipients.
In the fifth aspect, the present application provides a pharmaceutical composition comprising any one of Siponimod hemifumarate solid dispersion of the present invention and a pharmaceutically acceptable carrier.
In the sixth aspect, the present application provides a method of treating multiple sclerosis, comprising administering to a subject in need thereof an effective amount of any one of Siponimod hemifumarate solid dispersion of the present invention, or a pharmaceutical composition comprising the Siponimod hemifumarate solid dispersion of the present invention.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 is powder X-ray power diffraction ("PXRD") pattern of an amorphous form of Siponimod hemifumarate prepared according to Example 1.
Figure 2 is powder X-ray power diffraction pattern of amorphous solid dispersion comprising Siponimod hemifumarate and Syloid (1:0.5 w/w) prepared according to Example 1.
Figure 3 is powder X-ray power diffraction pattern of amorphous solid dispersion comprising Siponimod hemifumarate and hydroxypropyl methyl cellulose (HPMC) (1:1 w/w) prepared according to Example 2.
Figure 4 is powder X-ray power diffraction pattern of amorphous solid dispersion comprising Siponimod hemifumarate and Polyvinylpyrrolidone K-30 (PVP K-30) (1:1 w/w) prepared according to Example 3.
Figure 5 is powder X-ray diffraction pattern of amorphous solid dispersion comprising Siponimod hemifumarate and Kollidon VA64 (1:1 w/w) prepared according to Example 4.
Figure 6 is powder X-ray diffraction pattern of amorphous solid dispersion comprising Siponimod hemifumarate and Kollidon VA64 (1:2 w/w) prepared according to Example 5.
Figure 7 is powder X-ray diffraction pattern of amorphous solid dispersion comprising Siponimod hemifumarate and Klucel LF (1:1 w/w) prepared according to Example 6.
Figure 8 is powder X-ray diffraction pattern of amorphous solid dispersion comprising Siponimod hemifumarate and hydroxypropyl cellulose (HPC L) (1:1 w/w) prepared according to Example 7.
Figure 9 is powder X-ray diffraction pattern of amorphous solid dispersion comprising Siponimod hemifumarate and Soluplus (1:3 w/w) prepared according to Example 8.
Figure 10 is powder X-ray diffraction pattern of amorphous solid dispersion comprising Siponimod hemifumarate and Soluplus (1:2 w/w) prepared according to Example 9.
Figure 11 is powder X-ray diffraction pattern of amorphous solid dispersion comprising Siponimod hemifumarate and Soluplus (1:1 w/w) prepared according to Example 10.
DETAILED DESCRITPION
In the first aspect, the present application provides a process for preparing amorphous form of Siponimod hemifumarate, comprising:
a) providing a solution of Siponimod hemifumarate in a solvent or a mixture of solvents;
b) removing the solvent from the solution of Siponimod hemifumarate obtained in step a); and
c) recovering amorphous form of Siponimod hemifumarate.
Siponimod hemifumarate used as the input in the process for preparation of amorphous form of the present application can be prepared by any process known in the art or the process described in this application.
Providing a solution of Siponimod hemifumarate in step a) includes direct use of a reaction mixture containing Siponimod hemifumarate that is obtained in the course of its synthesis; or dissolving Siponimod hemifumarate in a solvent.
Any physical form of Siponimod hemifumarate may be utilized for providing the solution of Siponimod hemifumarate in step a).
Suitable solvents which can be used for dissolving Siponimod hemifumarate include but are not limited to: alcoholic solvents such as methanol, ethanol, isopropyl alcohol, and the like; halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane, and the like; and any mixtures of two or more thereof.
After dissolution in step (a), the obtained solution may optionally be filtered to remove any insoluble particles. Suitable techniques to remove insoluble particles are filtration, centrifugation, decantation, and any other known techniques in the art. The solution can be filtered by passing through paper, glass fiber, or other membrane material, or a clarifying agent such as Celite. Depending upon the equipment used and the concentration and temperature of the solution, the filtration apparatus may need to be preheated to avoid premature precipitation of solid.
Step (b) involves removing solvent from the solution of Siponimod hemifumarate.
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, agitated thin-film drying, Rotary vacuum paddle dryer, agitated nutsche filter drying, pressure nutsche filter drying, freeze-drying or any other suitable technique known in the art. The drying may be carried at normal pressure or under reduced pressure.
Step (c) involves recovering an amorphous form of Siponimod hemifumarate. The said recovery can be done by using the processes known in the art.
In an embodiment, the isolation of amorphous form of Siponimod hemifumarate may be carried out by employing any of the techniques known to a person skilled in art. Techniques for the isolation of amorphous form of Siponimod hemifumarate include, but not limited to: decantation, filtration by gravity or suction, centrifugation, and the like, and optionally washing with a solvent.
The resulting compound in step (c) may optionally be further dried. Drying can be carried out in a tray dryer, vacuum oven, air oven, cone vacuum dryer, rotary vacuum dryer, fluidized bed dryer, spin flash dryer, flash dryer, or the like. The drying can be carried out at temperatures of less than about 100°C, less than about 60°C, less than about 40°C, or any other suitable temperatures; at atmospheric pressure or under a reduced pressure; as long as the Siponimod hemifumarate is not degraded in its quality. The drying can be carried out for any desired times until the required product quality is achieved. Suitable time for drying can vary from few minutes to several hours for example from about 30 minutes to about 24 or more hours.
In another aspect, the present application provides amorphous form of Siponimod hemifumarate characterized by powder X-ray diffraction (PXRD) substantially as illustrated in Figure 1.
In another aspect, the present application provides a solid dispersion comprising Siponimod hemifumarate and one or more pharmaceutically acceptable carrier.
In another aspect, the present application provides a process for preparing an amorphous solid dispersion comprising siponimod hemifumarate and one or more pharmaceutically acceptable carriers, the process comprising;
a) providing a solution comprising Siponimod hemifumarate and one or more pharmaceutically acceptable excipients,
b) removing solvent from the solution obtained in step (a), and
c) recovering an amorphous solid dispersion comprising Siponimod hemifumarate and one or more pharmaceutically acceptable excipient.
Providing a solution in step (a) includes direct use of a reaction mixture containing Siponimod hemifumarate that is obtained in the course of its synthesis or dissolving Siponimod hemifumarate and pharmaceutically acceptable carrier in a solvent or a mixture of solvents.
Any physical form of Siponimod hemifumarate may be utilized for providing the solution of step (a).
Suitable pharmaceutically acceptable carriers which can be used in step (a) include, but are not limited to: diluents such as starches, pregelatinized starches, lactose, powdered celluloses, microcrystalline celluloses, dicalcium phosphate, tricalcium phosphate, Polyethylene glycol, Copovidone, Soluplus, Silicified microcrystalline cellulose mannitol, sorbitol, sugar and the like; binders such as acacia, guar gum, tragacanth, gelatin, polyvinylpyrrolidones, hydroxypropyl celluloses, hydroxypropyl methylcelluloses such as HPMC-Phthalate, HPMC-AS, HPMC-15 CPS; pregelatinized starches and the like; disintegrants such as starches, sodium starch glycolate, pregelatinized starches, crospovidones, croscarmellose sodium, colloidal silicon dioxide and the like; lubricants such as stearic acid, magnesium stearate, zinc stearate and the like; glidants such as colloidal silicon dioxide and the like; solubility or wetting enhancers such as anionic or cationic or neutral surfactants; complex forming agents such as various grades of cyclodextrins and resins; release rate controlling agents such as hydroxypropyl celluloses, hydroxymethyl celluloses, hydroxypropyl methylcelluloses, ethylcelluloses, methylcelluloses, various grades of methyl methacrylates, waxes and the like. Other pharmaceutically acceptable excipients that are of use include but are not limited to film formers, plasticizers, colorants, flavoring agents, sweeteners, viscosity enhancers, preservatives, antioxidants, and the like.
In a preferred embodiment, the pharmaceutically acceptable carriers are PVP-K30, hydroxypropyl methylcellulose (HPMC), Kollidon VA64, Klucel LF, hydroxypropyl cellulose (HPC L) and Soluplus.
Suitable solvent that can be used for dissolving the Siponimod hemifumarate include but are not limited to: alcohol solvents such as methanol, ethanol, isopropyl alcohol, n-propanol, 2-butanol and the like; halogenated hydrocarbons such as dichloromethane, 1 ,2-dichloroethane, and the like; ketones such as acetone, ethyl methyl ketone, methyl isobutyl ketone and the like; esters such as ethyl acetate, n-propyl acetate, n-butyl acetate, t-butyl acetate and the like; ethers such as diethyl ether, dimethyl ether, di-isopropyl ether, 1 ,4-dioxane and the like; hydrocarbons such as toluene, xylene and the like; nitriles such as acetonitrile, propionitrile and the like; dimethylformamide, dimethylacetamide and dimethylsulfoxide, and any mixtures of two or more thereof.
In a specific aspect the solvent used in step (a) is selected form the group comprising methanol, ethanol, IPA and dichloromethane.
After dissolution in step (a), optionally undissolved particles, if any, may be removed suitably by filtration, centrifugation, decantation, and any other known techniques. The solution can be filtered by passing through paper, glass fiber, or other membrane material, or a clarifying agent such as celite. Depending upon the equipment used and the concentration and temperature of the solution, the filtration apparatus may need to be preheated to avoid premature crystallization.
Step (b) involves removing solvent from the solution obtained in step (a);
Suitable techniques which can be used for the removal of solvent include but not limited to evaporation, flash evaporation, simple evaporation, rotational drying such as drying using a rotavapor, spray drying, agitated thin-film drying, agitated nutsche filter drying, pressure nutsche filter drying, freeze-drying, filtration or any other technique known in the art.
Step (c) involves recovering an amorphous solid dispersion comprising Siponimod hemifumarate and one or more pharmaceutically acceptable carriers. The said recovery can be achieved by using the processes known in the art.
The resulting compound obtained in step (c) may optionally be further dried. Drying can be carried out in a tray dryer, vacuum oven, air oven, cone vacuum dryer, rotary vacuum dryer, fluidized bed dryer, spin flash dryer, flash dryer, or the like. The drying can be carried out at temperatures of less than about 75°C, less than about 50°C, or any other suitable temperatures; at atmospheric pressure or under a reduced pressure; as long as the Siponimod hemifumarate is not degraded in its quality. The drying can be carried out for any desired time until the required product quality is achieved. Suitable time for drying can vary from few minutes to several hours for example from about 30 minutes to about 24 or more hours.
Alternatively the amorphous solid dispersion of Siponimod hemifumarate can be prepared by mixing Siponimod hemifumarate with a suitable pharmaceutically acceptable carrier such as Syloid, PVP-K30, hydroxypropyl methylcellulose (HPMC), optionally in presence of a suitable solvent, followed by isolating and drying the amorphous solid dispersion of Siponimod hemifumarate.
When the active ingredient is hygroscopic or the formulation contains a hygroscopic ingredient, and to increase the stability of the amorphous form or a solid dispersion comprising Siponimod hemifumarate, addition of other carriers such as syloid, methyl cellulose, colloidal silicon dioxide, Eudragit, amorphous silica, micro crystalline cellulose, and the like, in the formulation has been found to be of particular value. Therefore these ingredients may be combined during the preparation of solid dispersion or after the preparation of amorphous Siponimod hemifumarate or solid dispersion to control hygroscopicity and to improve stability.
In another aspect, the present application provides pharmaceutical composition comprising amorphous Siponimod hemifumarate and one or more pharmaceutically acceptable excipients.
In another aspect, the present application provides a pharmaceutical composition comprising any one of Siponimod hemifumarate solid dispersion of the present invention and a pharmaceutically acceptable carrier.
In another aspect, the present application provides a method of treating multiple sclerosis, comprising administering to a subject in need thereof an effective amount of any one of Siponimod hemifumarate solid dispersion of the present invention, or a pharmaceutical composition comprising the Siponimod hemifumarate solid dispersion of the present invention.
Certain specific aspects and embodiments of the present application will be explained in greater detail with reference to the following examples, which are provided only for purposes of illustration and should not be construed as limiting the scope of the application in any manner. Variations of the described procedures, as will be apparent to those skilled in the art, are intended to be within the scope of the present application.
DEFINITIONS
The following definitions are used in connection with the present invention unless the context indicates otherwise. The term “amorphous” refers to a solid lacking any long-range translational orientation symmetry that characterizes crystalline structures although; it may have short range molecular order similar to a crystalline solid.
Celite is flux-calcined diatomaceous earth. Hyflo is flux-calcined diatomaceous earth treated with sodium carbonate.
An “alcohol solvent” is an organic solvent containing a carbon bound to a hydroxyl group. “Alcoholic solvents” include, but are not limited to, methanol, ethanol, 2-nitroethanol, 2-fluoroethanol, 2,2,2-trifluoroethanol, hexafluoroisopropyl alcohol, ethylene glycol, 1-propanol, 2-propanol (isopropyl alcohol), 2- methoxyethanol, 1-butanol, 2-butanol, i-butyl alcohol, t-butyl alcohol, 2- ethoxyethanol, diethylene glycol, 1-, 2-, or 3-pentanol, neo-pentyl alcohol, t-pentyl alcohol, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, cyclohexanol, benzyl alcohol, phenol, glycerol, or the like.
The term "about" when used in the present application preceding a number and referring to it, is meant to designate any value which lies within the range of ±10%, preferably within a range of ±5%, more preferably within a range of ±2%, still more preferably within a range of ±1 % of its value. For example "about 10" should be construed as meaning within the range of 9 to 11 , preferably within the range of 9.5 to 10.5, more preferably within the range of 9.8 to 10.2, and still more preferably within the range of 9.9 to 10.1.
All percentages and ratios used herein are by weight of the total composition and all measurements made are at about 25°C and about atmospheric pressure, unless otherwise designated. All temperatures are in degrees Celsius unless specified otherwise. As used herein, “comprising” means the elements recited, or their equivalents in structure or function, plus any other element or elements which are not recited. The terms “having” and “including” are also to be construed as open ended. All ranges recited herein include the endpoints, including those that recite a range “between” two values. Whether so indicated or not, all values recited herein are approximate as defined by the circumstances, including the degree of expected experimental error, technique error, and instrument error for a given technique used to measure a value.
Certain specific aspects and embodiments of the present application will be explained in greater detail with reference to the following examples, which are provided only for purposes of illustration and should not be construed as limiting the scope of the application in any manner. Reasonable variations of the described procedures are intended to be within the scope of the present invention. While particular aspects of the present invention have been illustrated and described, it would be obvious to those skilled in the art that various other changes and modifications can be made without departing from the spirit and scope of the invention. It is therefore intended to cover in the appended claims all such changes and modifications that are within the scope of this invention.

EXAMPLES
Example-1: Preparation of amorphous Siponimod hemifumarate
Siponimod hemifumarate (4.0 g) and methanol (200 mL) were charged into a 500 mL rotavapor flask. The mixture was heated to 66 °C under stirring, and the clear solution was concentrated under vacuum at 66 °C to yield 2.5 g of amorphous Siponimod hemifumarate. PXRD as shown in Figure 1.
The amorphous Siponimod hemifumarate (1.0 g) and Syloid (0.5 g) were mixed in a rotavapor flask (rpm of rotavapor is 40) for 30 minutes. The resulted solid was isolated and analyzed. PXRD of the resulted solid is shown in Figure 2.
Example-2: Preparation of amorphous solid dispersion of Siponimod hemifumarate and hydroxy propyl methyl cellulose (HPMC).
Siponimod hemifumarate (1.5 g), methanol (100 mL) and Hydroxy propyl methyl cellulose (HPMC, 1.5 g) were charged into a 500 mL rotavapor flask at 27°C. The resulted mixture was heated to 65°C and stirred for 10 min. at 65°C. The heterogeneous mixture was completely evaporated under reduced pressure at 65°C. To the solid added a mixture of dichloromethane and methanol (50 mL of dichloromethane and 100 mL of methanol) and heated to 65 °C. The resulted gel like material was concentrated under reduced pressure at 65°C. 1.7 g of flakes like material was obtained. PXRD pattern: Fig. 3.
Example 3: Preparation of amorphous solid dispersion of Siponimod hemifumarate and Polyvinylpyrrolidone K-30 (PVP K-30).
Siponimod hemifumarate (1.5 g), Polyvinylpyrrolidone K-30 (PVP K-30, 1.5 g), and methanol (100 mL) were charged into a 500 mL rotavapor flask at 27°C. The mixture was heated to 65 °C and stirred for 5 min. at 65°C. The resulted clear solution was concentrated under reduced pressure at 65°C. The material was dried at 65 °C under reduced pressure. 2.1 g of amorphous solid dispersion was obtained. PXRD pattern: Fig. 4.
Example-4: Preparation of amorphous solid dispersion of Siponimod hemifumarate and Kollidon VA64 (1:1 w/w).
Kollidon VA64 (500 mg) and acetone (50 mL) were added to a 500 mL Buchi flask and stirred for 5 minutes. To the clear solution Siponimod hemifumarate (500 mg) and acetone (50 mL) were charged at 27°C. The Buchi flask containing the resulted mixture was kept for rotation and heated to 50°C and stirred for 10 min. To the mixture methanol (10 mL) was added and stirred for 10 minutes at 50 °C. The reaction mass was completely evaporated under reduced pressure at 50 °C. 800 mg of solid material was obtained. PXRD pattern: Fig. 5.
Example 5: Preparation of amorphous solid dispersion of Siponimod hemifumarate and Kollidon VA64 (1:2 w/w).
Kollidon VA64 (1000 mg) and acetone (150 mL) were added to a 500 mL Buchi flask and stirred for 5 minutes. To the clear solution Siponimod hemifumarate (500 mg) was charged at 27°C. The Buchi flask containing the resulted mixture was kept for rotation and stirred for 10 min at 27 °C. To the mixture methanol (15 mL) was added and stirred for 10 minutes. The reaction mass was completely evaporated under reduced pressure at 55 °C. 1000 mg of solid material was obtained. PXRD pattern: Fig. 6.
Example 6: Preparation of amorphous solid dispersion of Siponimod hemifumarate and Klucel LF (1:1 w/w).
Klucel LF (500 mg) and acetone (50 mL) were added to a 500 mL Buchi flask and stirred for 5 minutes. To the clear solution Siponimod hemifumarate (500 mg) was charged at 27°C. The Buchi flask containing the resulted mixture was kept for rotation and stirred for 10 min. To the mixture methanol (50 mL) was added and stirred for 10 minutes. The reaction mass was completely evaporated under reduced pressure at 60 °C. 750 mg of solid material was obtained. PXRD pattern: Fig. 7.
Example 7: Preparation of amorphous solid dispersion of Siponimod hemifumarate and Hydroxy Propyl Cellulose (HPC L) (1:1 w/w).
Hydroxy Propyl Cellulose L (500 mg) and acetone (100 mL) were added to a 500 mL Buchi flask and stirred for 5 minutes. To the mixture Siponimod hemifumarate (500 mg) and methanol (10 mL) were charged at 27°C. The Buchi flask containing the resulted mixture was kept for rotation and stirred for 20 min at 50 °C. The clear solution obtained was completely evaporated under reduced pressure at 55 °C. 700 mg of solid material was obtained. PXRD pattern: Fig. 8.
Example 8: Preparation of amorphous solid dispersion of Siponimod hemifumarate and Soluplus (1:3 w/w).
Soluplus (1500 mg) and methanol (100 mL) were added to a 500 mL Buchi flask and stirred for 5 minutes. To the mixture Siponimod hemifumarate (500 mg) was added at 27°C. The Buchi flask containing the resulted mixture was kept for rotation and stirred for 20 min at 60 °C. The clear solution obtained was completely evaporated under reduced pressure at 65 °C. 1400 mg of solid material was obtained. PXRD pattern: Fig. 9.
Example 9: Preparation of amorphous solid dispersion of Siponimod hemifumarate and Soluplus (1:2 w/w).
Soluplus (1000 mg) and methanol (100 mL) were added to a 500 mL Buchi flask and stirred for 5 minutes. To the mixture Siponimod hemifumarate (500 mg) was added at 27°C. The Buchi flask containing the resulted mixture was kept for rotation and stirred for 20 min at 60 °C. The clear solution obtained was completely evaporated under reduced pressure at 65 °C. 1000 mg of solid material was obtained. PXRD pattern: Fig. 10.
Example 10: Preparation of amorphous solid dispersion of Siponimod hemifumarate and Soluplus (1:1 w/w).
Soluplus (500 mg) and methanol (50 mL) were added to a 500 mL Buchi flask and stirred for 5 minutes. To the mixture Siponimod hemifumarate (500 mg) was added at 27°C. The Buchi flask containing the resulted mixture was kept for rotation and stirred for 20 min at 60 °C. The clear solution obtained was completely evaporated under reduced pressure at 65 °C. 600 mg of solid material was obtained. PXRD pattern: Fig. 11.
,CLAIMS:CLAIMS
We claim
1. Amorphous solid dispersion comprising Siponimod hemifumarate and one or more pharmaceutically acceptable carrier.
2. The solid dispersion according to claim 2. Wherein the pharmaceutically acceptable carrier is selected from the group comprising pregelatinized starch, lactose, powdered cellulose, microcrystalline cellulose, dicalcium phosphate, tricalcium phosphate, Polyethylene glycol, Copovidone, Soluplus, Silicified microcrystalline cellulose, mannitol, sorbitol, acacia, guar gum, tragacanth, gelatin, polyvinylpyrrolidone, hydroxymethyl celluloses, ethylcellulose, methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, HPMC-Phthalate, HPMC-AS, HPMC-15 CPS, sodium starch glycolate, crospovidone, croscarmellose sodium, colloidal silicon dioxide stearic acid, magnesium stearate, zinc stearate, colloidal silicon dioxide and mixtures thereof.
3. The solid dispersion according to claim 1. Wherein the pharmaceutically acceptable carrier is selected from the group comprising Syloid, PVP-K30, hydroxypropyl methylcellulose (HPMC), Kollidon VA64, Klucel LF, hydroxypropyl cellulose (HPC L) and Soluplus.
4. A process for preparing an amorphous solid dispersion comprising siponimod hemifumarate and one or more pharmaceutically acceptable carriers, the process comprising;
(a) providing a solution comprising Siponimod hemifumarate and one or more pharmaceutically acceptable excipients,
(b) removing solvent from the solution obtained in step (a), and
(c) recovering an amorphous solid dispersion comprising Siponimod hemifumarate and one or more pharmaceutically acceptable excipient.
5. A pharmaceutical composition comprising any one of Siponimod hemifumarate solid dispersion described in the present application and a pharmaceutically acceptable carrier.
6. A process for preparing amorphous form of Siponimod hemifumarate, comprising;
(a) providing a solution of Siponimod hemifumarate in a solvent or a mixture of solvents;
(b) removing solvent from the solution of Siponimod hemifumarate obtained in step a); and
(c) recovering amorphous form of Siponimod hemifumarate.
7. The process according to claim 6, the solvent used in step (a) is methanol.
8. A pharmaceutical composition comprising amorphous Siponimod hemifumarate prepared by the process of the present application and a pharmaceutically acceptable carrier.