DESC:Field of the invention
The present invention relates to pharmaceutical compositions comprising a gonadotropin-releasing hormone antagonist (GnRH antagonist). More particularly, the present invention relates to pharmaceutical compositions comprising Elagolix or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients and process for preparing such compositions.

Background of the invention
Elagolix sodium is a nonpeptide small molecule, GnRH receptor antagonist. Elagolix sodium is chemically described as sodium 4-({(1R)-2-[5-(2-fluoro-3¬ methoxyphenyl)-3-{[2-fluoro-6-(trifluoromethyl)phenyl]methyl}-4-methyl-2,6-dioxo-3,6¬-dihydropyrimidin-1(2H)-yl]-1-phenylethyl}amino)butanoate.
Elagolix in the form of sodium salt is approved in the form of tablets and marketed by Abbvie Inc. under the brand name ORILISSA®. The tablets are approved in the strengths of Eq 150mg base and Eq 200mg base.
Elagolix sodium is indicated for the treatment of moderate to severe pain associated with endometriosis.
ORILISSA 150 mg tablets are light pink, oblong, film-coated tablets with “EL 150” debossed on one side. Each tablet contains 155.2 mg of elagolix sodium (equivalent to 150 mg of elagolix) as the active ingredient and the following inactive ingredients: mannitol, sodium carbonate monohydrate, pregelatinized starch, povidone, magnesium stearate, polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, and carmine high tint.
ORILISSA 200 mg tablets are light orange, oblong, film-coated tablets with “EL 200” debossed on one side. Each tablet contains 207.0 mg of elagolix sodium (equivalent to 200 mg of Reference ID: 4295625 elagolix) as the active ingredient and the following inactive ingredients: mannitol, sodium carbonate monohydrate, pregelatinized starch, povidone, magnesium stearate, polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, and iron oxide red.
WO 01/55119 A2 and WO 2005/007165 A1 discloses elagolix or a stereoisomer, prodrug or pharmaceutically acceptable salt thereof.
WO 2017/040841 A1 discloses a method of treating endometriosis or uterine fibroids, where the method involves the administration of elagolix, and where the method may further involve the co-administration of rifampin or ketoconazole.
WO 2019/036712 A1 discloses a pharmaceutical composition comprising about 150 mg, about 200 mg, or about 300 mg Elagolix (Compound A) or a pharmaceutically acceptable salt thereof; and an anti-gelling agent; wherein the pharmaceutical composition comprises at least 10% by weight of Compound A (Elagolix) or the pharmaceutically acceptable salt thereof.
WO 2019/036712 A1 further discloses that the monosodium salt of Compound A (Elagolix) has a tendency to form a gel, particularly when present at an amount greater than about 10% by weight in the absence of an appropriate anti-gelling agent when administered orally in a solid dosage form. Such gel formation limits the dissolution of API and, ultimately, can lead to highly variable inter- and intra patient bioavailability. Another challenge was that Compound A (Elagolix) can degrade to form a compound having a lactam moiety (referred to herein as Compound B). Reducing conversion of the drug substance into its lactam-containing degradation product is desirable, for example, to maintain safety and efficacy over the life of the product.
WO 2019/036712 A1 also discloses that it has been determined in the present application that a pharmaceutical composition containing an anti-gelling agent reduces gelling of the API and/or reduces generation of the lactam degradation product (i.e., Compound B).
WO 2019/036713 A1 discloses a solid pharmaceutical composition comprising 4-((R)-2-[5-(2-fluoro-3-methoxy- phenyl)-3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-l-yl]-l-phenyl-ethylamino)-butyric acid (Compound A) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable meltable binder.
WO 2019/203870 A1 discloses a method of treating endometriosis associated pain wherein the method further reduces fatigue in a patient with moderate to severe endometriosis, or wherein the method further reduces use of pain medications in patients with moderate to severe endometriosis, the method comprising administering to 4-((R)-2-[5-(2-fluoro-3-methoxy- phenyl)-3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H- pyrimidin-l-yl]-l-phenyl-ethylamino)-butyric acid (Compound A) or a pharmaceutically acceptable salt thereof.
The above prior art reference discloses different compositions comprising Elagolix. None of the prior art discloses Elagolix compositions which are substantially free of an anti-gelling agent. The inventors of the present invention have surprisingly found that a tablet composition comprising Elagolix sodium which is free of an anti-gelling agent showed comparable dissolution with respect to the marketed tablet dosage forms of Elagolix which contain an anti-gelling agent.

Objective of the invention
The main objective of the present invention relates to pharmaceutical composition comprising Elagolix or a pharmaceutically acceptable salt thereof.
The present invention also relates to a tablet composition comprising Elagolix or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients.
The present invention also relates to a process for the preparation of tablet composition comprising Elagolix or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients having comparable dissolution properties, content uniformity, stability and equivalent bioavailability w.r.t commercialized Elagolix tablet dosage form.

Summary of the invention
Accordingly, the present invention relates to a tablet composition comprising Elagolix or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients.
The present invention also relates to a tablet composition comprising Elagolix or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients, wherein the composition is free of an anti-gelling agent.
The present invention also relates to a process for the preparation of tablet composition comprising Elagolix or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients.

Detailed description of the invention
The present invention relates to a pharmaceutical composition comprising Elagolix or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients.
The present invention also relates to a process for the preparation of pharmaceutical composition comprising Elagolix or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients.
The present invention relates to a pharmaceutical composition comprising Elagolix or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients, wherein the composition is free of an anti-gelling agent.
The present invention relates to a process for the preparation of a pharmaceutical composition comprising Elagolix or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients, wherein the composition is free of an anti-gelling agent.
The present invention also relates to a tablet composition comprising Elagolix or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients.
The present invention also relates to a process for the preparation of tablet composition comprising Elagolix or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients.
The present invention relates to a tablet composition comprising Elagolix or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients, wherein the composition is free of an anti-gelling agent.
The present invention relates to a process for the preparation of tablet composition comprising Elagolix or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients, wherein the composition is free of an anti-gelling agent.
In an embodiment, “Elagolix” according to the present invention includes but not limited to Elagolix free base and its pharmaceutically acceptable salts, ethers, esters, prodrugs, polymorphs and derivatives thereof.
In another embodiment, the pharmaceutically acceptable salt of Elagolix is a sodium salt.
As used herein, the term “% w/w” refers to the weight of the component based on the total weight of a composition comprising the component.
“Pharmaceutically acceptable excipient/s” are the components added to pharmaceutical formulation to facilitate manufacture, enhance stability, control release, enhance product characteristics, enhance bioavailability, enhance patient acceptability, etc.
In another embodiment, the composition according to the present invention comprises Elagolix or a pharmaceutically acceptable salt thereof in an amount of about 10-90% w/w, preferably about 20-70% w/w and more preferably about 30-60% w/w of the composition.
In another embodiment, the composition according to the present invention further comprises one or more pharmaceutically acceptable excipients which include but not limited to fillers/diluents, disintegrants, binders, glidants and lubricants. These excipients may be present intragranularly or extragranularly.
Fillers/Diluents according to the present invention include but not limited to lactose, lactose monohydrate, lactose anhydrous, fructose, dextrose, dextrates, dextrins, mannitol, lactitol, sorbitol, starch, sucrose, microcrystalline cellulose, silicified microcrystalline cellulose, cellulose powdered, kaolin, isomaltulose derivatives, povidone (polyvinyl pyrrolidone), pre-gelatinized starch and the like or combinations thereof. The Fillers/Diluents can be used in the range of about 0-90% w/w of the composition.
Binders according to the present invention include but not limited to hydroxypropyl methylcellulose (Hypromellose), hydroxypropyl cellulose, polyvinylpyrrolidone, gelatin, ethyl cellulose, polyvinyl alcohol, pregelatinized starch, carboxymethyl cellulose, sodium alginate, povidone (polyvinyl pyrrolidone), copovidone, microcrystalline cellulose, gelatin, polymethacrylates and the like or combinations thereof. The binder can be used in the range of about 0-50% w/w of the composition.
Disintegrants according to the present invention include but not limited to starches or modified starches such as pregelatinized starch, croscarmellose sodium, carmellose sodium, carmellose calcium, povidone (polyvinyl pyrrolidone), copovidone, crospovidone (Crosslinked polyvinyl pyrrolidone), sodium starch glycolate, low substituted hydroxypropyl cellulose, hydroxypropyl cellulose, alginic acid, and the like or combinations thereof. The disintegrant can be used in the range of about 0-25% w/w of the composition.
Glidants according to the present invention include but not limited to silica, colloidal silicon dioxide, talc and magnesium silicate and mixtures thereof. The glidants can be used in the range of 0-10% w/w of the composition.
Lubricants according to the present invention include but not limited to stearic acid, magnesium stearate, calcium stearate, sodium stearyl fumarate, zinc stearate, glyceryl mono fatty acid, glyceryl monostearate, glyceryl dibehenate, glyceyryl palmito stearic ester, hydrogenated castor oil and mixtures thereof. The Lubricants and/or glidants can be used in the range of 0-10% w/w of the composition.
In one embodiment, the anti-gelling agent according to the present invention include but not limited to a water-soluble salt of a weak acid, a base, a basic amino acid or a basic salt.
In another embodiment of the present invention, Elagolix may be present in crystalline form or amorphous form.
In another embodiment, the present invention relates to a process for the preparation of pharmaceutical composition, comprising the steps of:
(i) blending Elagolix or a pharmaceutically acceptable salt thereof with one or more pharmaceutically acceptable excipients,
(ii) formulating the blend of step (i) into suitable dosage form.
In another embodiment, the present invention relates to a process for the preparation of pharmaceutical composition, comprising the steps of:
(i) blending Elagolix or a pharmaceutically acceptable salt thereof with one or more pharmaceutically acceptable excipients,
(ii) optionally, lubricating the blended material of step (i) with a lubricant, and
(iii) preparing the lubricated material of step (ii) into a suitable dosage form.
In another embodiment, the present invention relates to a process for the preparation of pharmaceutical composition, comprising the steps of:
(i) blending Elagolix or a pharmaceutically acceptable salt thereof with one or more pharmaceutically acceptable excipients, and
(ii) compressing the blend of step (i) into tablet dosage form.
In another embodiment, the present invention relates to a process for the preparation of pharmaceutical composition, comprising the steps of:
(i) blending Elagolix or a pharmaceutically acceptable salt thereof with one or more pharmaceutically acceptable excipients,
(ii) optionally lubricating the blend of step (i) with a lubricant, and
(iii) compressing the blend of step (ii) into a tablet dosage form.
In another embodiment, the present invention relates to a process for the preparation of pharmaceutical composition, comprising the steps of:
(i) blending Elagolix or a pharmaceutically acceptable salt thereof with one or more pharmaceutically acceptable excipients,
(ii) granulating the blend of step (i) into granules,
(iii) blending the granules of step (ii) with one or more pharmaceutically acceptable excipients, and
(iv) compressing the lubricated blend of step (iii) into tablet dosage form.
In another embodiment, the present invention relates to a process for the preparation of pharmaceutical composition, comprising the steps of:
(i) blending Elagolix or a pharmaceutically acceptable salt thereof with one or more pharmaceutically acceptable excipients,
(ii) granulating the blend of step (i) into granules,
(iii) blending the granules of step (ii) with one or more pharmaceutically acceptable excipients,
(iv) compressing the lubricated blend of step (iii) into tablet dosage form, and
(v) optionally film coating the tablets obtained in step (iv).
In another embodiment, the present invention relates to a process for the preparation of pharmaceutical composition, comprising the steps of:
(i) blending Elagolix or a pharmaceutically acceptable salt thereof with one or more pharmaceutically acceptable excipients, and
(iii) filling the blend of step (i) into capsules.
In another embodiment, the present invention relates to a process for the preparation of pharmaceutical composition, comprising the steps of:
(i) blending Elagolix or a pharmaceutically acceptable salt thereof with one or more pharmaceutically acceptable excipients,
(ii) lubricating the blended material of step (iii) with a lubricant, and
(iii) filling the lubricated material of step (ii) into capsules.
In another embodiment, the present invention relates to a process for the preparation of pharmaceutical composition, comprising the steps of:
(i) blending Elagolix or a pharmaceutically acceptable salt thereof with one or more pharmaceutically acceptable excipients,
(ii) granulating the blend of step (i) into granules,
(iii) blending the granules of step (ii) with one or more pharmaceutically acceptable excipients, and
(iv) filling the lubricated blend of step (iii) into capsules.
In another embodiment, the present invention relates to a process for the preparation of pharmaceutical composition, comprising the steps of:
(i) blending Elagolix or a pharmaceutically acceptable salt thereof with one or more pharmaceutically acceptable excipients,
(ii) granulating the blend of step (i) by roller compaction and milling to obtain granules,
(iii) blending the granules of step (ii) with one or more pharmaceutically acceptable excipients, and
(iv) compressing the lubricated blend of step (iii) into tablet dosage form.

In another embodiment, the present invention relates to a process for the preparation of tablet composition, comprising the steps of:
i) blending elagolix with one or more pharmaceutically acceptable excipients,
ii) granulating the blend of step (i) by roller compaction and milling to obtain granules,
iii) blending the granules of step (ii) with one or more pharmaceutically acceptable excipients,
iv) compressing the blend of step (iii) into tablets, and
v) optionally film coating the tablets obtained in step (iv).
In another embodiment, the present invention relates to a process for the preparation of pharmaceutical composition, comprising the steps of:
(i) blending Elagolix or a pharmaceutically acceptable salt thereof with one or more pharmaceutically acceptable excipients,
(ii) granulating the blend of step (i) using purified water/binder solution and drying to obtain granules,
(iii) blending the granules of step (ii) with one or more pharmaceutically acceptable excipients, and
(iv) compressing the lubricated blend of step (iii) into tablet dosage form.
In another embodiment, the present invention relates to a process for the preparation of pharmaceutical composition, comprising the steps of:
(i) blending Elagolix or a pharmaceutically acceptable salt thereof with one or more pharmaceutically acceptable excipients,
(ii) granulating the blend of step (i) using purified water/binder solution and drying to obtain granules,
(iii) blending the granules of step (ii) with one or more pharmaceutically acceptable excipients,
(iv) compressing the lubricated blend of step (iii) into tablet dosage form, and
(v) optionally film coating the tablets obtained in step (iv).

In another embodiment, the present invention relates to a process for the preparation of tablet composition, comprising the steps of:
(i) blending Elagolix Sodium, mannitol, Povidone and Colloidal Silicon dioxide,
(ii) lubricating the blend obtained in step (i) with intragranular Sodium stearyl fumarate,
(iii) granulating the lubricated blend of step (ii) by roller compaction and milling to obtain granules,
(iv) blending the granules of step (iii) with extragranular Crospovidone, Croscarmellose Sodium and Silicon Dioxide,
(v) lubricated the blend of step (iv) with Sodium stearyl fumarate,
(vi) compressing the lubricated blend of step (v) into tablets, and
vii) optionally film coating the tablets obtained in step (iv).
In another embodiment, the present invention relates to a tablet composition comprising:
(a) an intra-granular portion comprising:
(i) elagolix sodium,
(ii) mannitol,
(iii) povidone,
(iv) colloidal silicon dioxide,
(v) sodium stearyl fumarate,
(b) an extra-granular portion comprising:
(i) crospovidone,
(ii) croscarmellose sodium,
(iii) silicon dioxide, and
(iv) sodium stearyl fumarate.

In another embodiment, the present invention relates to a tablet composition comprising:
(a) an intra-granular portion comprising:
(i) elagolix sodium,
(ii) mannitol,
(iii) povidone,
(iv) colloidal silicon dioxide,
(v) sodium stearyl fumarate,
(b) an extra-granular portion comprising:
(i) crospovidone,
(ii) croscarmellose sodium,
(iii) silicon dioxide,
(iv) sodium stearyl fumarate, and
a film coating over the tablet composition.

In another embodiment, the pharmaceutical composition according to the present invention is in the form of tablets, capsules, granules, powder, pellets and sachets.
In one preferred embodiment, the pharmaceutical composition according to the present invention is in the form of tablets.
In another embodiment, the blend is formulated into a suitable dosage form like tablets or capsules using different techniques which are well known in the prior art.
In another embodiment, the compositions of the present invention may be prepared using any method known in the art, but are not limited to wet granulation, dry granulation, roller compaction, solid dispersion, encapsulation and direct compression.
In another embodiment, the granulation can be done using one pharmaceutically acceptable excipient, a binder, which can be added to the drug substance in a dissolved state (e.g. in an aqueous/non-aqueous solution) or in a powder form and then granulated by adding a granulation liquid. A combination of more than one binder can be used.
In another embodiment, the solvents used for granulation process may be selected from water, isopropyl alcohol, methanol, ethanol, methylene chloride or combination thereof.
In another embodiment, the granulation can be done using any method known in the art, but are not limited to fluidized bed granulation, high-shear granulation, low shear granulation, spray granulation and melt granulation.
The composition according to the present invention may be uncoated or optionally coated with functional coating, film coating, moisture barrier coating or a protective coating composition. The coating may be selected from amongst one or more of those suitable coating materials known in the art. Coating may be performed by applying one or more film forming polymers, with or without other pharmaceutically inert excipients, as a solution/suspension using any conventional coating technique known in the art, such as spray coating in a conventional coating pan or fluidized bed processor or dip coating.
The amount of the film coating may be about 1 to about 10% w/w, preferably, about 1 to about 3% w/w, of the total composition. Any of a variety of film coatings can be used in the present composition. Suitable film coating may include but not limited to polymers, plasticizers, pigments, opacifiers, glidants, binders, antitacking agents, antifoaming agents, surfactants, fillers, extenders, coloring agents and the like.
Examples of film-forming polymers include ethylcellulose, hydroxypropyl methylcellulose, polyvinyl alcohol (PVA), hydroxypropylcellulose, methylcellulose, carboxymethyl cellulose, hydroxymethylcellulose, hydroxyethylcellulose, cellulose acetate, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, cellulose acetate trimellitate; waxes such as polyethylene glycol; methacrylic acid polymers such as Eudragit® RL and RS; and the like. Alternatively, commercially available coating compositions comprising film-forming polymers marketed under various trade names, such as OPADRY® and INSTAMOIST SHIELD® may also be used for coating the tablets. The coating can be obtained as a dry blend concentrate.
The film coating may also optionally include a plasticizer such as triacetin, propylene glycol, diethyl phthalate, tributyl sebacate or polyethylene glycol (PEG), preferably PEG; and an anti-adherent or glidant such as talc, fumed silica or magnesium stearate, an opacifying agent such as titanium dioxide.
Coloring agent may be selected from FDA approved colorants such as Iron Oxide, Lake of Tartrazine, Allura Red, Lake of Quinoline Yellow, Lake of Erythrosine, Titanium Dioxide and the like.
The coating according to the present invention is applied by solubilising or suspending the excipients in solvents such as isopropyl alcohol, water, acetone, ethanol, methylene chloride, hydrochloric acid and the like, or mixtures thereof.
In yet another embodiment, the present invention provides a tablet composition comprising Elagolix or a pharmaceutically acceptable salt thereof in the range of about 1mg to about 1000 mg, preferably 100mg to 500mg.
In another embodiment, the present invention provides a tablet composition comprising Elagolix or a pharmaceutically acceptable salt thereof for the treatment of moderate to severe pain associated with endometriosis.
The invention is further illustrated by the following examples which are provided to be exemplary of the invention and do not limit the scope of the invention. While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.

Example 1: Tablet composition comprising Elagolix sodium
S. No Ingredients Quantity (mg/tab)
1 Elagolix sodium* 206.96
2 Mannitol 215.04
3 Crospovidone 40.00
4 Silicified Microcrystalline cellulose 124.00
5 Colloidal Silicon dioxide 6.00
6 Magnesium stearate 6.00
Extra-granular
7 Crospovidone 40.00
8 Colloidal Silicon dioxide 6.00
9 Magnesium stearate 6.00
Total Core Tablet weight 650.00
Film Coating
12 OPADRY® Coating Composition 32.00
Total Coated Tablet Weight 682.00
*206.96 mg of Elagolix sodium is equivalent to 200 mg of Elagolix

The processing steps involved in manufacturing the tablets were given below:
(i) Elagolix Sodium, Mannitol, Crospovidone, Silicified Microcrystalline cellulose and Colloidal Silicon dioxide were sifted separately and blended,
(ii) the blend obtained in step (i) was lubricated with intragranular magnesium stearate,
(iii) the lubricated blend of step (ii) was roll compacted and milled to obtain granules,
(iv) the granules of step (iii) were mixed with extragranular Crospovidone, Colloidal Silicon dioxide and blended,
(v) the above blend of step (iv) was lubricated with Sodium stearyl fumarate,
(vi) the lubricated blend of step (v) was compressed into tablets, and
(vii) the tablets obtained in step (vi) were coated using OPADRY® film coating composition.

Example 2: Tablet composition comprising Elagolix sodium
S. No Ingredients Quantity (mg/tab)
1 Elagolix sodium* 206.96
2 Povidone 300.00
3 Colloidal Silicon dioxide 10.00
4 Sodium Stearyl fumarate 7.50
Extra-granular
5 Mannitol 81.04
6 Microcrystalline cellulose 50.00
7 Crospovidone 21.00
8 Croscarmellose Sodium 21.00
9 Silicon Dioxide 15.00
10 Sodium Stearyl fumarate 7.50
Total Core Tablet weight 720.00
Film Coating
11 OPADRY® Coating Composition 24.00
Total Coated Tablet Weight 744.00
*206.96 mg of Elagolix sodium is equivalent to 200 mg of Elagolix
The processing steps involved in manufacturing the tablets were given below:
(i) Elagolix Sodium, Povidone and Colloidal Silicon dioxide were sifted separately and blended,
(ii) the blend obtained in step (i) was lubricated with intragranular Sodium stearyl fumarate,
(iii) the lubricated blend of step (ii) was roll compacted and milled to obtain granules,
(iv) the granules of step (iii) were mixed with extragranular Mannitol, Microcrystalline cellulose, Crospovidone, Croscarmellose Sodium, Silicon Dioxide and blended,
(v) the above blend of step (iv) was lubricated with Sodium stearyl fumarate,
(vi) the lubricated blend of step (v) was compressed into tablets, and
(vii) the tablets obtained in step (vi) were coated using OPADRY® film coating composition.
Example 3: Tablet composition comprising Elagolix sodium
S. No Ingredients Quantity (mg/tab)
1 Elagolix sodium* 206.96
2 Mannitol 191.04
3 Povidone 140.00
4 Colloidal Silicon dioxide 10.00
5 Sodium stearyl fumarate 8.00
Extra-granular
6 Crospovidone 20.00
7 Croscarmellose sodium 20.00
8 Silicon dioxide 16.00
9 Sodium stearyl fumarate 8.00
Total Core Tablet weight 620.00
Film Coating
12 OPADRY® Coating Composition 24.00
Total Coated Tablet Weight 644.00
*206.96 mg of Elagolix sodium is equivalent to 200 mg of Elagolix

The processing steps involved in manufacturing the tablets were given below:
(i) Elagolix Sodium, Mannitol, Povidone and Colloidal Silicon dioxide were sifted separately and blended,
(ii) the blend obtained in step (i) was lubricated with intragranular Sodium stearyl fumarate,
(iii) the lubricated blend of step (ii) was roll compacted and milled to obtain granules,
(iv) the granules of step (iii) were mixed with extragranular Croscarmellose sodium, Crospovidone, Silicon dioxide and blended,
(v) the above blend of step (iv) was lubricated with Sodium stearyl fumarate,
(vi) the lubricated blend of step (v) was compressed into tablets, and
(vii) the tablets obtained in step (vi) were coated using OPADRY® film coating composition.

Example 4: Tablet composition comprising Elagolix sodium
S. No Ingredients Quantity (mg/tab)
1 Elagolix sodium* 206.96
2 Mannitol 147.04
3 Povidone 200.00
4 Colloidal Silicon dioxide 10.00
5 Sodium stearyl fumarate 8.00
Extra-granular
6 Crospovidone 12.00
7 Croscarmellose sodium 12.00
8 Silicon dioxide 16.00
9 Sodium stearyl fumarate 8.00
Total Core Tablet weight 620.00
Film Coating
12 OPADRY® Coating Composition 24.00
Total Coated Tablet Weight 644.00
*206.96 mg of Elagolix sodium is equivalent to 200 mg of Elagolix
The processing steps involved in manufacturing the tablets were given below:
(i) Elagolix Sodium, Mannitol, Povidone and Colloidal Silicon dioxide were sifted separately and blended,
(ii) the blend obtained in step (i) was lubricated with intragranular Sodium stearyl fumarate,
(iii) the lubricated blend of step (ii) was roll compacted and milled to obtain granules,
(iv) the granules of step (iii) were mixed with extragranular Croscarmellose sodium, Crospovidone, Silicon dioxide and blended,
(v) the above blend of step (iv) was lubricated with Sodium stearyl fumarate,
(vi) the lubricated blend of step (v) was compressed into tablets, and
(vii) the tablets obtained in step (vi) were coated using OPADRY® film coating composition.

Dissolution Data: Table-1 given below provides the comparative dissolution profile of Elagolix tablets prepared according to Examples 3-4 and ORILISSA® (Elagolix sodium) Tablets 200 mg using the following dissolution conditions:
Dissolution Conditions:
Media : pH 6.8 sodium phosphate buffer
Volume: 900 mL
Apparatus: Paddle
Speed : 500 RPM

Table 1: Comparative dissolution profile of Elagolix tablets prepared according to Examples 3-4 and ORILISSA® (Elagolix sodium) Tablets 200 mg
Time
(Minutes) Cumulative % drug released
ORILISSA® (Elagolix sodium) Tablets 200 mg Tablets prepared using
Example-3 Tablets prepared using
Example-4
0 0.00 0.00 0.00
5 10.00 3.00 2.00
10 32.00 17.00 13.00
15 52.00 31.00 25.00
20 69.00 44.00 38.00
30 92.00 67.00 57.00
45 105.00 88.00 82.00
60 107.00 96.00 96.00
90 107.00 99.00 102.00
,CLAIMS:We Claim:

1. A tablet composition comprising Elagolix or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients, wherein the composition is free of an anti-gelling agent.

2. The tablet composition as claimed in claim 1, wherein one or more pharmaceutically acceptable excipients is selected from the group consisting of fillers/diluents, disintegrants, binders, glidants, lubricants and combination thereof.

3. The tablet composition as claimed in claim 2, wherein the filler/diluent is selected from the group consisting of lactose, lactose monohydrate, lactose anhydrous, fructose, dextrose, dextrates, dextrins, mannitol, lactitol, sorbitol, starch, sucrose, microcrystalline cellulose, silicified microcrystalline cellulose, cellulose powdered, kaolin, isomaltulose derivatives, povidone (polyvinyl pyrrolidone), pre-gelatinized starch and combinations thereof.

4. The tablet composition as claimed in claim 2, wherein the binder is selected from the group consisting of hydroxypropyl methylcellulose (Hypromellose), hydroxypropyl cellulose, gelatin, ethyl cellulose, polyvinyl alcohol, pregelatinized starch, carboxymethyl cellulose, sodium alginate, povidone (polyvinyl pyrrolidone), copovidone, microcrystalline cellulose, gelatin, polymethacrylates and the like or combinations thereof.

5. The tablet composition as claimed in claim 2, wherein the disintegrant is selected from the group consisting of starch, pregelatinized starch, croscarmellose sodium, carmellose sodium, carmellose calcium, povidone (polyvinyl pyrrolidone), copovidone, crospovidone (Crosslinked polyvinyl pyrrolidone), sodium starch glycolate, low substituted hydroxypropyl cellulose, hydroxypropyl cellulose, alginic acid, and the like or combinations thereof.
6. The tablet composition as claimed in claim 1, wherein the composition comprises:
(a) an intra-granular portion comprising:
(i) Elagolix sodium,
(ii) mannitol,
(iii) povidone,
(iv) colloidal silicon dioxide,
(v) sodium stearyl fumarate,
(b) an extra-granular portion comprising:
(i) crospovidone,
(ii) croscarmellose sodium,
(iii) silicon dioxide, and
(iv) sodium stearyl fumarate.

7. A process for the preparation of the tablet composition as claimed in claim 1, comprising the steps of:
(i) blending Elagolix or a pharmaceutically acceptable salt thereof with one or
more pharmaceutically acceptable excipients,
(ii) granulating the blend of step (i) into granules,
(iii) blending the granules of step (ii) with one or more pharmaceutically
acceptable excipients,
(iv) compressing the lubricated blend of step (iii) into tablet dosage form, and
(v) optionally film coating the tablets obtained in step (iv).

8. The tablet composition as claimed in claim 1, wherein the composition is prepared by roller compaction.

9. A process for the preparation of the tablet composition as claimed in claim 1, comprising the steps of:
(i) blending Elagolix sodium with one or more pharmaceutically acceptable
excipients,
(ii) granulating the blend of step (i) by roller compaction and milling to obtain
granules,
(iii) blending the granules of step (ii) with one or more pharmaceutically
acceptable excipients,
(iv) compressing the blend of step (iii) into tablets, and
(v) optionally film coating the tablets obtained in step (iv).

10. A process for the preparation of the tablet composition as claimed in claim 1, comprising the steps of:
(i) blending Elagolix Sodium, mannitol, Povidone and Colloidal Silicon dioxide,
(ii) lubricating the blend obtained in step (i) with intragranular Sodium stearyl
fumarate,
(iii) granulating the lubricated blend of step (ii) by roller compaction and milling
to obtain granules,
(iv) blending the granules of step (iii) with extragranular Crospovidone,
Croscarmellose Sodium and Silicon Dioxide,
(v) lubricated the blend of step (iv) with Sodium stearyl fumarate,
(vi) compressing the lubricated blend of step (v) into tablets, and
(vii) optionally film coating the tablets obtained in step (vi).