DESC:FORM 2

THE PATENTS ACT, 1970
(39 of 1970)
&
The Patents Rules, 2003

COMPLETE SPECIFICATION
(Section 10 and Rule 13)

PHARMACEUTICAL COMPOSITIONS OF SIPONIMOD OR ACCEPTABLE SALTS THEREOF

AUROBINDO PHARMA LTD HAVING CORPORATE OFFICE AT
GALAXY, FLOORS: 22-24,
PLOT No.1, SURVEY No.83/1,
HYDERABAD KNOWLEDGE CITY,
RAIDURG PANMAKTHA,
RANGA REDDY DISTRICT,
HYDERABAD – 500 032,
TELANGANA, INDIA
AN INDIAN ORGANIZATION

The following specification describes the invention and the manner in which it is to be performed.
FIELD OF THE INVENTION

This present invention relates to stable pharmaceutical composition comprising siponimod or its pharmaceutically acceptable salts, as an active agent and suitable pharmaceutical excipients. The invention also relates to the methods of preparation of the composition having improved dissolution profile and stability.

BACKGROUND OF THE INVENTION

Siponimod fumaric acid is a sphingosine 1-phosphate (S1P) receptor modulator. Commonly prescribed for the treatment of relapsing forms of multiple sclerosis (MS).

Siponimod fumaric acid is 2:1 co-crystal of siponimod and fumaric acid chemically known as sodium 1-[[4-[(1E)-1-[[[4-Cyclohexyl-3-(trifluoromethyl)phenyl]methoxy]imino]ethyl]-2-ethylphenyl]methyl]-3-azetidine carboxylic acid (2E)-2-butenedioate (2:1) and is represented by the following formula:

Siponimod fumaric acid is white to almost white powder.

Siponimod fumaric acid is commercially available under the brand name MAYZENT® in 0.25 mg, 1 mg and 2 mg film coated tablets and marketed by Novartis pharmaceuticals Corp. Inactive ingredients of MAYZENT® tablets for 0.25mg, 1mg and 2mg are colloidal silicon dioxide, crospovidone, glyceryl dibehenate, lactose monohydrate, microcrystalline cellulose, with a film coating containing iron oxides (black and red iron oxides for the 0.25 mg and 1 mg strengths and red and yellow iron oxides for the 2 mg strength), lecithin (soy), polyvinyl alcohol, talc, titanium dioxide, and xanthan gum.

U.S. Patent No 7,939,519 discloses compound Siponimod or a pharmaceutically acceptable salt thereof and method for treating Multiple sclerosis using siponimod fumaric acid.

US Patent No 8,673,918 discloses pharmaceutical composition comprising siponimod and pharmaceutically acceptable excipients.

U.S. Publication No 20200199069 discloses pharmaceutical composition comprising siponimod fumaric acid and non-basic excipient.

U.S. Publication No 20200290961 discloses Siponimod, polymorphic forms and solid dispersions of siponimod.

U.S. Publication No 20210161860 discloses pharmaceutical composition comprising siponimod fumaric acid, a moisture protective agent and pharmaceutically acceptable excipients.

The above discussed prior art suggests that formulating siponimod into suitable solid oral dosage forms like tablet is challenging from the formulation development perspective due to dissolution issues, compressibility issues, manufacturing process selection, control of process and degradation of product.

Hence, there is an unmet need in the art to develop a simple, reproducible, and cost-effective manufacturing process for pharmaceutical composition of siponimod which also offers desired pharmaceutical technical attributes such as dissolution, stability, bioequivalence and manufactured by simple, reproducible and commercially viable process at industrial scale.

The present inventors have developed solid pharmaceutical composition of siponimod and unexpectedly found that said composition have improved stability and dissolution profile coupled with simple manufacturing process at industrial scale and bioequivalent to commercially available MAYZENT® tablets.

SUMMARY OF THE INVENTION

In one aspect, an invention provides a stable solid pharmaceutical composition comprising:
a) 0.1-10% w/w of siponimod fumaric acid,
b) 60-95% of diluent,
c) 3-10% w/w of disintegrant,
d) 1-6% w/w of lubricant stearic acid, and
e) 5-15% of w/w of stabilizer.

In another aspect, an invention provides a direct compression process for producing a pharmaceutical solid dosage form which comprises steps of:
a) sifting and blending stabilizer, diluent, siponimod fumaric acid, disintegrant and other pharmaceutically acceptable excipients,
b) sifting stearic acid and adding to step (a) and compressing the blend in to tablets and
c) optionally the tablet is film coated.

DETAILED DESCRIPTION OF THE INVENTION

The term “composition”, as in stable solid pharmaceutical composition, is intended to encompass a drug product comprising siponimod or its pharmaceutically acceptable salts thereof, and other inert ingredient(s). The pharmaceutical composition of the invention includes, but is not limited to, granules, tablets, immediate release tablets, caplets, capsules and the like. Preferably, pharmaceutical composition refers to tablets and capsules. More preferably, the pharmaceutical composition refers to immediate release oral tablets, which may be un-coated or film coated.
The term “excipient” means a pharmacologically inactive component such as a filler or diluent, binder, stabilizer, disintegrant, lubricant, glidant, solubilizer, and coloring agent or the like.

According to the present invention, siponimod fumaric acid is present in an amount from 0.1 to 10% by weight based on total weight of the composition, preferably, 0.1% to 8% w/w, more preferably 0.1% to 5%, most preferably 0.1% to 3% w/w.

The term “bulk density” as used herein according to the present invention is bulk density of a powder or granules and is the ratio of the mass of an untapped powder or granules sample and its volume including the contribution of the interparticulate void volume. The bulk density of lubricated blend according to the present invention is from 0.2 g/ml to 1 g/ml, preferably from 0.3 g/ml to 1 g/ml more preferably from 0.3 g/ml to 0.8 g/ml and most preferably the bulk density of lubricated blend is 0.4 g/ml to 0.7 g/ml, 0.46 g/ml to about 0.6 g/ml and more specifically 0.4-0.6 g/ml.

The term “tapped density” as used herein according to the present invention is an increased bulk density attained after mechanically tapping a container containing the powder sample. The tapped density of lubricated blend according to the present invention is from 0.5 g/ml to 1 g/ml, preferably from 0.5 g/ml to 0.9 g/ml, more preferably 0.6 g/ml to 0.9 g/ml and most preferably the tapped density of lubricated blend is 0.6 g/ml to 0.87g/ml, 0.6 g/ml to 0.85g/ml and more specifically 0.6 to 0.8 g/ml.

The term “degradation product” are unwanted chemicals that can develop during the manufacturing, transportation, and storage of drug products and can affect the efficacy of pharmaceutical products.

The dissolution is performed as per conditions mentioned or provided in office of generic drugs dissolution database and as determined by the USP. The dissolution profile of tablets dosage form was measured in 500mL (for 0.25 mg and 1 mg), 900 mL (for 2 mg) phosphate buffer of pH 6.8 at 50 rpm, Paddle.

The term “about” is used herein to mean approximately, roughly, around, or in the regions of. When the term "about" is used in conjunction with a numerical range, it modifies that range by extending the boundaries above and below the numerical values set forth. In general, the term "about" is used herein to modify a numerical value above and below the stated value by a variance of 10 percent.

The term "particle(s)" as used herein refers to individual particles of siponimod or pharmaceutically acceptable salt thereof, whether the particles exist singly or are agglomerated. The term “particle size” of siponimod fumaric acid having a particle size distribution such that more than 90% of the particles are not more than 50µm, preferably not more than 40µm, more preferably not more than 30µm. The particle size of siponimod fumaric acid was measured using a Malvern light scattering technique.

The term “stable” as used herein refers to formulations that substantially retain the label amount of the therapeutically active ingredient during storage for commercially relevant times, and the drug-related impurity contents in the formulations remain within the acceptable limit.

The term "diluent" or "filler" as used herein is defined as an inert agent designed to increase the weight and/or the size of the pharmaceutical composition and to improve dissolution, examples of fillers include but are not limited to dicalcium phosphate, isomalt, microcrystalline cellulose, lactitol, xylitol, silicified MCC, microfine cellulose, lactose, mannitol and mixtures thereof. Diluent is present in an amount from 60-95% and preferably from 70-90%, preferred diluent according to the present invention is mannitol.

The term "disintegrant" as used herein is defined as an accelerating agent of the disintegration of the tablet and the dispersion of the active ingredient in water or gastrointestinal fluids. Examples of disintegrants according to present invention include, but are not limited to croscarmellose sodium, carboxymethyl cellulose calcium, crospovidone, polacrilin potassium, sodium starch glycolate and/or combinations thereof. Disintegrant is present in an amount from 3% to 10% w/w, preferably, the amount of disintegrant is from 3% to 8% w/w, more preferably, the amount of disintegrant is from 4% to 7% w/w, preferred disintegrant according to the present invention is crospovidone.

The term "lubricant” as used herein is defined as an agent able to decrease adhesion of a powder to punches and friction between particles. Examples of lubricants according to the present invention include, but are not limited to stearic acid, Zinc stearate, sodium stearyl fumarate, calcium stearate, talc and magnesium stearate. Lubricant is present in an amount from 1 to 6%, preferably, the amount of lubricant is from 1-4% w/w, preferred lubricant according to the present invention is stearic acid.

The term "stabilizer" as used herein is defined as an agent able to make stable pharmaceutical composition. Examples of stabilizers according to the present invention include, but are not limited to citric acid, adipic acid, maleic acid, magnesium aluminometasilicate, fumaric acid, beta cyclodextrin, calcium hydroxide and aluminum hydroxide. Stabilizer is present in an amount from 5% to 15% w/w, preferably, the amount of stabilizer is from 5% to 10% w/w, more preferably, the amount of stabilizer is from 6% to 9% w/w, preferred stabilizer according to the present invention is fumaric acid.

The term "coated tablet" as used herein is defined as a tablet provided with a coating layer is preferable to achieve long-term storage stability and prevent degradation due to light and the like. The coating layer comprises pharmaceutical additives, such as a coating agent, plasticizer, dispersant, defoaming agent, and the like, usually used for coating (for providing a coat to) orally administrable pharmaceutical preparations. Colorants are added to the coating agent for coating the tablet. Examples of film coating material include Wincoat green, wincoat blue, wincoat grey, one-step film coating system which combines polymer, plasticizer, opacifier and pigment, as required, in a dry concentrate. Examples of Wincoat coating material according to present invention include, but not limited to moisture barrier film coating.

The composition of wincoat green contains polyvinyl alcohol, soya lecithin, xanthan gum, titanium dioxide, talcum and aluminium lake of quinoline yellow and aluminium lake of brilliant blue. wincoat blue contains polyvinyl alcohol, soya lecithin, xanthan gum, titanium dioxide, talcum and aluminium lake of brilliant blue. wincoat grey contains polyvinyl alcohol, soya lecithin, xanthan gum, titanium dioxide, talcum and black iron oxide.

In one embodiment, an invention provides a stable solid pharmaceutical composition comprising:
a) 0.1-10% w/w of siponimod fumaric acid,
b) 60-95% of diluent comprising mannitol,
c) 3-10% w/w of disintegrant comprising crospovidone,
d) 1-6% w/w of lubricant comprising stearic acid,
wherein 90% of the particles of siponimod fumaric acid have size between 5 µm to 50µm.

In addition to the above embodiment, the composition has w/w ratio of crospovidone to stearic acid is 1:0.33 to 1:0.42.

In addition to the above embodiment, the composition may also comprise 5-15% of w/w of stabilizer comprising fumaric acid.

In addition to the above embodiment, the lubricated blend composition has a bulk density ranging from about 0.3 mg/mL to about 0.6 mg/mL and tapped density ranging from about 0.5 mg/mL to about 0.8mg/mL.

In addition to the above embodiment, wherein the particle size distribution of siponimod fumaric acid is such that more than 90% of the particles of siponimod fumaric acid are not more than 50µm.

In addition to the above embodiment, more than 50% of the siponimod fumaric acid dissolves in 10 minutes and at least 90% dissolves within 30 minutes in pH 6.8 Phosphate buffer + 0.1% Tween 80, Paddle, 50 RPM, 500mL (for 0.25 mg and 1 mg), 900 mL (for 2 mg).

In one embodiment, an invention provides a process for the preparation of stable tablet composition comprising Siponimod fumaric acid and stearic acid as lubricant prepared by direct compression.

In another embodiment, an invention provides a process for producing a pharmaceutical solid dosage form with direct compression which comprises steps of:
a) sifting and blending mannitol, siponimod fumaric acid, crospovidone and other pharmaceutically acceptable excipients,
b) sifting stearic acid and adding to step (a) and compressing the blend in to tablets and,
c) optionally the tablet is film coated.

It has been found that the stable pharmaceutical composition of the present invention has been found to have improved dissolution profile and stability coupled with simple manufacturing process at industrial scale and it is bioequivalence to commercially available counterpart tablets MAYZENT®.

The following examples serve to illustrate the embodiments of the present invention. However, they do not intend to limit the scope of the invention. It is obvious to those skilled in the art to find out the composition for other dosage forms and substitute the equivalent excipients as described in this specification or with the one known to the industry.
Examples: The following examples further illustrate the invention and do not limit the scope of the invention.

Example 1: Siponimod fumaric acid tablets composition given in Table 1.
Table – 1:

S. No Ingredients Function 0.25 mg 1 mg 2 mg
Qty. per unit (mg) %w/w Qty. per unit (mg)
%w/w Qty. per unit (mg) %w/w
1 Siponimod Fumaric Acid API 0.28 0.31 1.11 1.23 2.22 2.48
2 Mannitol Diluent/Filler 77.5 86.42 76.67 85.49 75.56 84.26
3 Crospovidone Disintegrant 5.10 5.69 5.10 5.68 5.10 5.69
Lubrication
4 Stearic Acid Lubricant 2.12 2.36 2.12 2.36 2.12 2.36
Film Coating
5 Moisture Barrier Film Coating Film Coating material 4.68 5.22 4.68 5.21 4.68 5.22
6 Purified Water -- Qs -- Qs --
Film coated Tablet Weight 89.68 100.00 89.68 100 89.68 100.00

Manufacturing process

a) sifted mannitol, siponimod fumaric acid and crospovidone through 425 ?m sieve and blended for 10 minutes,
b) passed the materials of step (a) through mill and later blended the materials in a blender for 10 minutes,
c) sifted stearic acid through 250 ?m sieve and added to step (b) and blended for 5 minutes and compressed the blend into tablets,
d) the tablets were further film coated.

Example 2: Siponimod fumaric acid tablets composition given in Table 2.
Table -2:

S. No Ingredients Function 0.25 mg 1 mg 2 mg
Qty. per unit (mg) %w/w Qty. per unit (mg)
%w/w Qty. per unit (mg) %w/w
1 Siponimod Fumaric Acid API 0.28 0.28 1.11 1.12 2.22 2.25
2 Mannitol Diluent/Filler 85.25 86.45 84.33 85.58 83.11 84.45
3 Crospovidone Disintegrant 5.61 5.68 5.61 5.69 5.61 5.70
Lubrication
4 Stearic Acid Lubricant 2.33 2.36 2.33 2.36 2.33 2.36
Film Coating
5 Moisture Barrier Film Coating Film Coating material 5.14 5.21 5.14 5.22 5.14 5.21
6 Purified Water -- Qs -- Qs -- Qs --
Film coated Tablet Weight 98.61 100 98.53 100 98.41 100

Manufacturing process:
The tablets were prepared using the process similar to the one described in example 1.

Example 3: Siponimod fumaric acid tablets composition given in Table 3.
Table 3:
S. No Ingredients Function 0.25 mg 1 mg 2 mg
Qty. per unit (mg) %w/w Qty. per unit (mg)
%w/w Qty. per unit (mg) %w/w
1 Siponimod Fumaric Acid API 0.28 0.34 1.11 1.37 2.22 2.74
2 Mannitol Diluent/Filler 69.75 86.39 69.00 85.37 68.00 84.03
3 Crospovidone Disintegrant 4.59 5.68 4.59 5.67 4.59 5.67
Lubrication
4 Stearic Acid Lubricant 1.90 2.35 1.90 2.35 1.90 2.34
Film Coating
5 Moisture Barrier Film Coating Film Coating material 4.21 5.21 4.21 5.20 4.21 5.20
6 Purified Water -- Qs -- Qs -- Qs --
Film coated Tablet Weight 80.73 100 80.82 100 80.92 100

Manufacturing process: The tablets were prepared using the process similar to the one described in example 1.

Example 4: Siponimod fumaric acid tablets composition given in Table 4.
Table 4:

S. No Ingredients Function 0.25 mg 1 mg 2 mg
Qty. per unit (mg) %w/w Qty. per unit (mg)
%w/w Qty. per unit (mg) %w/w
1 Siponimod Fumaric Acid API 0.28 0.31 1.11 1.23 2.22 2.48
2 Mannitol Diluent/Filler 70.5 78.61 69.67 77.68 68.56 76.45
3 Crospovidone Disintegrant 5.1 5.69 5.10 5.68 5.1 5.69
4 Fumaric Acid Stabilizer 7 7.81 7.00 7.80 7 7.81
Lubrication
5 Stearic Acid Lubricant 2.12 2.36 2.12 2.36 2.12 2.36
Film Coating
6 Moisture Barrier Film Coating Film Coating material 4.68 5.22 4.68 5.21 4.68 5.22
7 Purified Water -- Qs -- Qs -- Qs --
Film coated Tablet Weight 89.68 100.00 89.68 100.00 89.68 100.00

Manufacturing process:

a) sifted fumaric acid, mannitol, siponimod fumaric acid and crospovidone through 425 ?m sieve and blended for 10 minutes,
b) passed the materials of step (a) through mill and later blended the materials in a blender for 20 minutes,
c) sifted stearic acid and added to step (b) blended and compressed the blend into tablets,
d) the tablets were further film coated.

Example 5: Siponimod fumaric acid tablets composition given in Table 5.

Table 5:

S. No Ingredients Function 0.25 mg 1 mg 2 mg
Qty. per unit (mg) %w/w Qty. per unit (mg)
%w/w Qty. per unit (mg) %w/w
1 Siponimod Fumaric Acid API 0.28 0.28 1.11 1.12 2.22 2.25
2 Mannitol Diluent/Filler 77.55 78.63 76.63 77.77 75.41 76.62
3 Crospovidone Disintegrant 5.61 5.68 5.61 5.69 5.61 5.70
4 Fumaric Acid Stabilizer 7.7 7.80 7.7 7.81 7.7 7.82
Lubrication
5 Stearic Acid Lubricant 2.33 2.36 2.33 2.36 2.33 2.36
Film Coating
6 Moisture Barrier Film Coating Film Coating material 5.14 5.21 5.14 5.21 5.14 5.22
7 Purified Water -- Qs -- Qs -- Qs --
Film coated Tablet Weight 98.62 100 98.53 98.42 100

Manufacturing process: The tablets were prepared using the process similar to the one described in example 4.

Example 6: Siponimod fumaric acid tablets composition given in Table 6.

Table 6:

S. No Ingredients Function 0.25 mg 1 mg 2 mg
Qty. per unit (mg) %w/w Qty. per unit (mg)
%w/w Qty. per unit (mg) %w/w
1 Siponimod Fumaric Acid API 0.28 0.34 1.11 1.37 2.22 2.74
2 Mannitol Diluent/Filler 63.45 78.58 62.70 77.58 61.70 76.23
3 Crospovidone Disintegrant 4.59 5.68 4.59 5.67 4.59 5.67
4 Fumaric Acid Stabilizer 6.30 7.80 6.3 7.79 6.30 7.78
Lubrication
5 Stearic Acid Lubricant 1.90 2.35 1.90 2.35 1.90 2.34
Film Coating
6 Moisture Barrier Film Coating Film Coating material 4.21 5.21 4.21 5.19 4.21 5.20
7 Purified Water -- Qs -- Qs --
Film coated Tablet Weight 80.74 100 80.81 100 80.93 100

Manufacturing process: The tablets were prepared using the process similar to the one described in example 4.

Dissolution study:
Dissolution profile of commercially marketed siponimod fumaric acid tablets (MAYZENT®) and Example 1 for 0.25mg, 1mg and 2mg tablets is shown in table 7.

Dissolution parameters: pH 6.8 Phosphate buffer + 0.1% Tween 80, Paddle, 50 RPM, 500mL (for 0.25 mg and 1 mg), 900 mL (for 2 mg).

Table 7:

Strength 0.25 mg 1 mg 2 mg
Product MAYZENT® Example 1 Example 1 MAYZENT® Example 1
Time points (minutes) % Siponimod fumaric acid released (±5%)
5 38 85 92 42 90
10 77 90 95 75 94
15 86 93 99 84 95
20 89 94 97 89 94
30 91 94 98 93 95
45 - 96 98 - 96
60 - 98 - - 96

Dissolution profile of commercially marketed siponimod fumaric acid tablets (MAYZENT®) and Example 4 for 0.25 mg, 1 mg and 2 mg tablets is shown in table 8.

Dissolution parameters: pH 6.8 Phosphate buffer + 0.1% Tween 80, Paddle, 50 RPM, 500mL (for 0.25 mg and 1 mg), 900 mL (for 2 mg).

Table 8:

Strength 0.25 mg 1 mg 2 mg
Product MAYZENT® Example 4 Example 4 MAYZENT® Example 4
Time points (minutes) % Siponimod fumaric acid released (±5%)
5 38 92 83 42 91
10 77 93 88 75 95
15 86 94 88 84 95
20 89 96 90 89 95
30 91 96 91 93 97
45 - 96 91 - 98
60 - 97 - - 98

Stability studies:
The tablet dosage form prepared in Example 4 was subjected to Accelerated stability testing as per the ICH guidelines at temperature 25°±2°C and relative humidity of 60%±5% for 3 months and evaluated the data at 3 months. The tablet dosage form was placed in a high density polyethylene (HDPE) bottles exposed to above mentioned condition and then evaluated for Assay %, Water by KF, Related substances and Dissolution which is shown in Table 9.

Table 9: Results of Assay, Water by KF, Related substances and Dissolution data on stability samples for Example 4:
Condition RT 25°C±2°C/60% RH±5%RH RT 25°C±2°C/60% RH±5%RH RT 25°C±2°C/60% RH±5%RH
Period Initial 3 M Initial 3 M Initial 3 M
0.25 mg 1 mg 2 mg
1 Assay (%) 100 95.2 96.05 91.80 99.9 96.30
2 Water by KF % 0.76 - 0.73 -- 0.68 --
3 Related substances %
Z-Siponimod(D) 0.05 0.06 0.00 0.03 0.05 0.03
Siponimod N-Oxide(D) 0.00 0.00 0.00 0.00 0.01 0.00
AAC Acid(D) 0.02 0.02 0.02 0.00 0.00 0.00
CTH Amine(D) - - ND 0.00 0.03 0.00
Any unspecified degradation product 0.04 0.12 0.05 0.06 0.08 0.09
Total degradation products 0.15 0.46 0.19 0.18 0.24 0.32
4 Dissolution % Siponimod released (±5%)
5 min 85 78 83 87 91 82
10 min 90 86 88 90 95 89
15 min 93 87 88 94 95 91
20 min 94 89 90 93 95 92
30 min 94 93 91 94 97 95
45 min 96 93 91 95 98 94

The present formulation clearly indicates excellent chemical stability upon storage at accelerated stability conditions at 25°±2°C and 60%±5% relative humidity for 3 months.
,CLAIMS:WE CLAIM

1. A stable solid oral pharmaceutical composition in the form of tablet comprising:
a) 0.1-10% w/w of siponimod fumaric acid,
b) 60-90% of diluent,
c) 3-10% w/w of disintegrant,
d) 1-6% w/w of lubricant stearic acid, and
e) 5-15% w/w of stabilizer.

2. The stable tablet composition according to claim 1, wherein diluent comprises mannitol, disintegrant comprises crospovidone and stabilizer comprising fumaric acid.

3. The stable tablet composition according to claim 1, wherein 90% of the particles of siponimod fumaric acid has a particle size not more than 50µm.

4. The stable tablet composition according to claim 1, wherein composition contains not more than 0.5% of any unspecified degradation product and not more than 1% of total degradation product by weight relative to siponimod fumaric acid when measured by HPLC after storage for 3 months at 25°C/60% relative humidity.

5. A stable tablet composition comprising:
a) 0.25-3 mg of siponimod fumaric acid,
b) 55-90 mg of diluent comprising mannitol,
c) 3-7 mg of disintegrant comprising crospovidone,
d) 1-3 mg of lubricant comprising stearic acid, and
e) 5-9 mg of stabilizer comprising fumaric acid; wherein the tablet is optionally film coated.

6. The stable tablet composition according to claim 5, wherein 90% of the particles of siponimod fumaric acid has a particle size between 15-40µm in size.

7. The stable tablet composition according to claim 5, wherein film coating comprises polyvinyl alcohol, soya lecithin, xanthan gum, titanium dioxide, talcum, aluminium lake and black iron oxide.

8. The stable tablet composition according to claim 5, wherein at least 90% of Siponimod fumaric acid dissolves within 30 minutes in a 900ml of pH 6.8 Phosphate buffer + 0.1% Tween 80 using a USP apparatus-l1 at a paddle rotation of about 50 rpm.

9. A process for the preparation of stable tablet composition comprising Siponimod fumaric acid and stearic acid as lubricant prepared by direct compression.

10. The process according to claim 9, comprising the steps of:
a) sifting mannitol, siponimod fumaric acid and crospovidone through sieve and blend,
b) passing and blending the materials of step (a) in a blender,
c) sifting stearic acid and adding to step (b) and blend for 5 minutes and compress the blend into tablets,
d) the tablet is optionally film coated.