KR20070022243A - Deferasirox dispersible tablets - Google Patents

Abstract

The present invention provides 42 to 65% by weight of deferasirox 4- [3,5-bis (2-hydroxyphenyl)-[1,2,4] triazol-1-yl] benzoic acid as the active ingredient by weight of the total tablet. Or to a dispersible tablet comprising a pharmaceutically acceptable salt thereof.

Deferasirox, 4- [3,5-bis (2-hydroxyphenyl)-[1,2,4] triazol-1-yl] benzoic acid, dispersible tablets, chelation therapy

Description

Deferasirox dispersible tablet {DEFERASIROX DISPERSIBLE TABLETS}

The present invention includes 4- [3,5-bis (2-hydroxyphenyl)-[1,2,4] triazol-1-yl] benzoic acid or a pharmaceutically acceptable salt thereof, referred to herein as Compound I Dispersible tablets, for example pharmaceutical dispersible tablets.

Compound I is orally active iron kill prescribed in the treatment of blood transfusion dependent anemia, especially thalassemia major, thalassemia intermediate, and sickle cell disease to reduce iron related morbidity and mortality. It is an iron chelator. Compound I can also be used to treat hemochromatosis.

Clinical thalassemia (large and medium) is a genetic disease characterized by a defect in hemoglobin production, leading to decreased production and destruction of red blood cells.

Sickle cell disease is caused by mutations in the hemoglobin-beta gene that cause the production of abnormal hemoglobin S. Normal erythrocytes die after 120 days and sickle cells (red blood cells with hemoglobin S) are destroyed more quickly (10-20 days) causing anemia. Because of this anemia, the disease is commonly referred to as sickle cell anemia, a known name.

Hemochromatosis, the most common form of iron hyperplasia, is a genetic disorder that causes the body to absorb and store too much iron. Excess iron accumulates in the trachea and damages the trachea. If left untreated, the disease can cause the organ to lose its function.

Patients with sickle cell disease or thalassemia and hemochromatosis who receive a large number of blood transfusions require a therapy called chelation therapy to remove iron from the body.

Compound I is represented by the formula

<Compound I>

Compound I in its free acid form, salts thereof and crystalline forms thereof are disclosed in International Patent Application Publication No. WO 97/49395 (published December 31, 1997) which is incorporated herein by reference.

In general, the daily dosage of Compound I prescribed for thalassemia treatment is large, for example 5 to 40 mg / kg body weight per day for adults or children. For children, the dosage is preferably 5 to 30 mg / kg body weight per day. Depending on age, personal condition, mode of administration, and the clinical context in question, an effective daily dose of Compound I, for example 350-2800 mg, is administered to a 70 kg body weight patient. Because of the high daily dose, patients may have to take six or more tablets per day. Thus, there is a need for oral dosage forms with reduced frequency of tablet administration of patients, which are convenient and safe to administer to adults and children and provide a pharmacologically active daily dose of Compound I.

We have found through the present invention that Compound I can be formulated in the form of dispersible tablets which are convenient and stable to administer to children and the elderly, such as, for example, and have a drug load of 1000 mg of Compound I.

"Dispersible tablet" means a tablet that is dispersed in the aqueous phase, eg, water, prior to administration.

Accordingly, the present invention provides an amount of from about 42 to 65% by weight, such as at least about 45, 47, 50, 52 or 55% by weight, preferably more than 45% by weight, based on the total weight of the dispersible tablet as the active ingredient. It provides a dispersible tablet having a high drug load, comprising a compound I present. In particular, the amount of compound I is 42 to 65% by weight, for example 45 to 60% by weight, for example 45 to 60% by weight, for example 45 to 55% by weight, based on the total weight of the dispersible tablet For example 47 to 53% by weight, for example 50% by weight.

The present invention relates to a dispersible tablet comprising a chelating pharmaceutically effective amount of Compound I or a pharmaceutically acceptable salt thereof, present in an amount of 42 to 65% by weight, based on the total weight of the tablet.

In one aspect of the invention, there is provided a dispersible tablet comprising Compound I or a pharmaceutically acceptable salt thereof present in an amount of 42 to 65% by weight, based on the total weight of the tablet.

Compound I may be in free acid form or a pharmaceutically acceptable salt thereof, preferably in free acid form. The active moiety corresponds to compound I in free acid form. In the present disclosure, reference to compound I includes compound I in any of its crystalline form, including its free acid form or its pharmaceutically acceptable salt, or hydrate or solvate, as appropriate and where appropriate, unless stated otherwise. It should be understood that.

In addition, the invention provides (a) at least about 42 to 65% by weight, for example at least about 45, 47, 50 or 52% by weight, calculated as the weight ratio of the content of active moiety based on the total weight of the dispersible tablet; Provided are dispersible tablets comprising Compound I or a pharmaceutically acceptable salt thereof, preferably present in an amount greater than 47% by weight, and (b) one or more pharmaceutically acceptable excipients suitable for preparing dispersible tablets. In particular, the amount of compound I as active ingredient may vary from 42 to 65% by weight, for example 45 to 55%, 47 to 53% by weight, based on the total weight of the dispersible tablet.

In a preferred embodiment of the invention, the invention provides dispersible tablets in which compound I is in free acid form (compound I in free acid form).

In the most preferred aspect of the invention, compound I in free acid form is in crystalline form.

One or more pharmaceutically acceptable excipients, for example conventionally used excipients, for example (1.1) one or more fillers such as lactose, Prosolv ^™ SMCC® 90, ethylcellulose, fine Crystalline cellulose, (1.2) at least one disintegrant, for example crosslinked polyvinylpyrrolidinone, for example Crospovidone®, (1.3) at least one binder, for example polyvinyl Pyridone, hydroxypropylmethyl cellulose, (1.4) one or more surfactants such as sodium laurylsulfate, (1.5) one or more lubricants, such as colloidal silicon dioxide, (1.6) one or more Lubricants such as magnesium stearate may be present in the dispersible tablet.

For the above and other pharmaceutically acceptable excipients and processes mentioned herein, reference is made to a number of documents incorporated herein by reference (especially Handbook of Pharmaceutical Excipients, Third Edition, edited by Arthur H. Kibbe, American Pharmaceutical Association, Washington , USA and Pharmaceutical Press, London, and Lexikon der Hilfsstoffe fuer Pharmazie, Kosmetik and angrenzende Gebiete edited by HP Fiedler, 4th Edition, Edito Cantor, Aulendorf, and earlier publications.

Fillers (1.1) according to the invention are lactose, especially lactose monohydrate, preferably lactose monohydrate dried (200 mesh) and sprayed lactose, microcrystalline cellulose, especially PH 102, PH 101 or Pro cellosolve ^TM SMCC (TM ) 90.

Suitable disintegrants (1.2) according to the invention are corn starch, CMC-Ca, CMC-Na, microcrystalline cellulose, crosslinked PVP, for example the trade name crospovidone (trademark) available from the ISP company. ), Known and commercially available as Polyplasdone® or Kollidon® XL, including, but not limited to, alginic acid, sodium alginate and guar gum. Preferably, crosslinked PVP is used, for example crospovidone®.

Binder (1.3) is a starch, for example potato, wheat or corn starch, microcrystalline cellulose, for example a product such as Avicel®, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropylmethyl Celluloses such as hydroxypropylmethyl cellulose-type 2910 USP, hypromellose and polyvinylpyrrolidone, such as povidone® K30 (BASF). Preferably, polyvinylpyrrolidone is used, most preferably PVP K.30.

As suitable surfactants (1.4) according to the invention, sodium laurylsulfate, quaternary ammonium salts, polysorbates, sorbitan esters and poloxamers can be used. Preferably the surfactant is sodium laurylsulfate.

As lubricant (1.5), one or more of silica, colloidal silica, for example colloidal silica anhydride, such as Aerosil® 200, magnesium trisilicate, powdered cellulose, starch and talc, can be used. Can be. Preferably, colloidal silicon dioxide is used.

As lubricant (1.6), Mg-, Al- or Ca-stearate, PEG 4000 to 8000, talc, sodium benzoate, for example glyceryl monofatty acid having a molecular weight of 200 to 800 daltons, for example glyceryl monostearate (E.g. Danisco, UK), glyceryl dibehenate (e.g. Compritol AT0888 ^™ , Gattefosse France), glyceryl palmito-stearic acid ester (e.g. For example, Precirol ^TM , Gatefoss France, Polyoxyethylene glycol (PEG, BASF), Hydrogenated cottonseed oil (Lubitrab, Edward Mendell Co Inc), Castor oil (Curtina) (Cutina HR, Henkel) can be used. Preferably, magnesium stearate is used.

By routine experimentation one or more of the above pharmaceutically acceptable excipients having the desired specific properties of the dispersible tablet can be selected and used.

According to the invention, the amount of filler (1.1) may vary within about 30 to 50% by weight, in particular 35 to 45% by weight, based on the total weight of the dispersible tablet. The amount of disintegrant (1.2) may vary within 2 to 25% by weight, for example 2 to 15% by weight, based on the total weight of the dispersible tablet. The amount of binder (1.3) may vary from 1 to 10% by weight, preferably 1.5 to 5% by weight, based on the total weight of the dispersible tablet. The amount of surfactant (1.4) may vary from 0.1 to 3% by weight, preferably from 0.2 to 1.5% by weight. The amount of lubricant (1.5) can vary within 0 to 5% by weight, in particular 0.1 to 2.5% by weight, for example 0.1 to 0.5% by weight, based on the total weight of the dispersible tablet. The amount of lubricant (1.6) is less than 1% by weight, preferably less than 0.5% by weight, most preferably less than 0.4% by weight, even more preferably 0.01 to 0.4% by weight, based on the total weight of the dispersible tablet. Very preferably, the amount of lubricant is greater than 0.02 weight percent and less than 0.4 weight percent based on the total weight of the dispersible tablet.

It will be appreciated that any given excipient may function as two or more functions, for example fillers, disintegrants, binders, lubricants and / or lubricants.

The lubricant may be present at less than 1 weight percent, preferably less than 0.4 weight percent based on the total weight of the dispersible tablet.

The present invention also relates to a dispersible tablet wherein the lubricant is magnesium stearate.

In a preferred aspect of the invention, the dispersible tablet is based on the total weight of the at least one filler, the dispersible tablet, in total amount of about 40-50% by weight based on the total weight of the pharmaceutically acceptable excipient, ie, the dispersible tablet. At least one binder in total amount of from about 1.5 to 5% by weight, based on the total weight of dispersible tablets in total of at least one disintegrant, dispersible tablets in total from about 2 to 35% by weight of total amount of about At least one lubricant and from 0.1 to 0.5% by weight of one or more lubricants and / or from about 0.01 to 0.4% by weight of total amount based on the total weight of the dispersible tablet.

In a preferred aspect of the invention, the dispersible tablet is based on the total weight of the at least one filler, the dispersible tablet, in total amount of about 40-50% by weight based on the total weight of the pharmaceutically acceptable excipient, ie, the dispersible tablet. At least one binder in total amount of about 1.5 to 5% by weight, based on the total weight of dispersible tablets, at least one disintegrant, in total amount of about 10 to 35% by weight, One or more surfactants in an amount of from 0.2 to 1% by weight, based on the total weight of the dispersible tablets in an amount of about 0.1 to 0.5% by weight in total, based on the total weight of one or more lubricants and / or dispersible tablets. At least one lubricant that is 0.01 to 0.4 wt%.

The absolute amount of each pharmaceutically acceptable excipient and the relative amount to other pharmaceutically acceptable excipients are similarly determined depending on the required properties of the dispersible tablet and may be selected by routine experimentation.

The inventors have faced difficulties in the preparation of dispersible tablets comprising Compound I, which may be caused by low density of the active ingredient, electrostatic properties which can cause low fluidity, and stickiness.

In accordance with the present invention, the present invention relates to the preparation of tablets by the compression method in a pharmaceutically acceptable oral solid dosage form in the form of a dispersible tablet which is convenient for administration to a patient and can be dispersed within 5 minutes, preferably within 3 minutes. It was unexpectedly found that it could be produced by More specifically, the dispersible tablets of the present invention may be prepared by a compression method after granulation, preferably wet granulation, preferably under spray lubrication.

In general, wet granulation can be used to improve flow and adhesion, but wet granulation processes are undesirable when the pharmaceutical composition is a dispersible tablet. Indeed, wet granulation does not comply with European pharmacopoeia, which increases the adhesion of the active ingredient particles and increases the disintegration time of the final tablet, requiring disintegration times of less than 3 minutes for the patient's conformable or dispersible tablets. In addition, the present inventors faced the problem that when a large amount of microcrystalline cellulose was used, the dissolution was very late and incomplete. We have found that by reducing the amount of insoluble excipients, dissolution can be improved. In order rather than maintaining the technical characteristics of the tablet while using less water-insoluble excipients, and it may be necessary to replace the microcrystalline cellulose into a silicate Chemistry microcrystalline cellulose (prop cellosolve ^TM SMCC (R) 90), which, in some cases, It shows more good compressibility. Avicel and colloidal silicon dioxide can also be used.

Dispersible tablets of the invention have a disintegration time of up to 5 minutes, for example in a suitable medium, for example water. The dispersible tablets of the present invention can be dispersed, for example, in less than 5 minutes, preferably less than 3 minutes, in an aqueous medium, for example water, in spite of a high drug load, and therefore for example administered to a child or elderly person. It is convenient.

In another embodiment, the present invention provides a dispersible tablet comprising greater than 800 mg, for example 900 mg to about 1100 mg, for example 1000 mg of Compound I as the active ingredient. Most preferably, the dispersible tablet according to the invention is a dispersible tablet comprising 1000 mg of compound I as active ingredient.

The present invention therefore provides dispersible tablets, for example dispersible tablets comprising an amount of Compound I equivalent to Compound I in the form of 1000 mg of free acid. Most preferably, the compound I in free acid form used in the dispersible tablet according to the invention is in crystalline form, in particular the crystalline form described for its preparation in Example 5 of WO 97/49395, incorporated herein by reference.

According to the present invention, a process for preparing dispersible tablets comprises granulating the inner phase, mixing it with (at least) one or more pharmaceutically acceptable excipient (s), and spraying the resulting mixture with spray lubrication conditions. Compression step.

The internal phase comprises compound I. Preferably, the internal phase comprises compound I and one or more pharmaceutically acceptable excipients. Preferably, the pharmaceutically acceptable excipients in the inner phase are at least one filler, at least one disintegrant, at least one binder and at least one surfactant. Preferably, the amount of at least one filler included in the inner phase is about 5 to 35 weight percent, more preferably 10 to 30 weight percent, most preferably 15 to 25 weight percent based on the total weight of the dispersible tablet. to be. The amount of lactose may range from 0 to 10% or 0 to 15%. The filler according to the invention is preferably lactose monohydrate. The disintegrant is preferably crospovidone XL. The amount of disintegrant present in the inner phase is 0 to 20% by weight, preferably 5 to 30% by weight and more preferably 7 to 25% by weight, based on the total weight of the dispersible tablet. Compound I and at least one filler and at least one disintegrant are mixed with a wet solution containing at least one surfactant, water and at least one binder. Preferred binder is PVP K.30. The mixture is granulated, for example using a wet high shear granulator to form wet granules. The wet granules are then dried, for example using a fluid bed dryer, and then calibrated in size using, for example, an oscillating granulator.

The outer phase consists of one or more pharmaceutically acceptable excipient (s) and is mixed with the inner phase using, for example, a free-fall mixer. Preferably, at least one filler and / or at least one glidant is added. Most preferably, the silicate Chemistry microcrystalline cellulose ^(TM Pro cellosolve SMCC (R) 90), or cellulose microcrystalline and lactose are added as fillers. Even more preferably, microcrystalline cellulose is added in an amount of 5 to 20% by weight based on the total weight of the dispersible tablet and lactose is added in an amount of 15 to 35% by weight based on the total weight of the dispersible tablet. do. The outer phase according to the invention may also contain at least one lubricant, most preferably colloidal silicon dioxide. In a preferred embodiment, the amount of lubricant included in the outer phase is about 0.1 to 5% by weight, preferably 0.1 to 2.5% by weight and most preferably 0.1 to 0.5% by weight, based on the total weight of the tablet.

In one aspect of the invention, one or more lubricants may optionally be deposited on the punch of the tableting machine prior to compression instead of being included in a mixture of the inner and outer phases. According to the invention, the one or more lubricants may be sprayed onto the material contacting surface of the compaction tool, such as a punch and / or die, of the tableting machine prior to pressing. Preferably, the one or more lubricants are sprayed onto the material contacting surfaces of the compactor, such as punches and dies, of the tableting machine prior to pressing.

In one embodiment of the invention, the method of making the dispersible tablet is

(a) (i) compound I is mixed with a pharmaceutically acceptable excipient,

(ii) forming an internal phase comprising wet granulating the mixture obtained in step (i);

(b) an external phase forming step comprising (iii) adding and mixing additional pharmaceutically acceptable excipients into the internal phase obtained in step (ii);

(x) optionally, adding and mixing one or more lubricants to the blend obtained in step (iii) to lubricate the final blend;

(c) (iv) compressing the mixture obtained in step (iii), optionally under spray lubrication conditions, to form a dispersible tablet.

It includes.

In another aspect, the invention

(i) mixing Compound I in a high shear mixer with a pharmaceutically acceptable excipient such as at least one filler such as lactose and at least one disintegrant such as crospovidone XL;

(ii) adding a solution of at least one surfactant and at least one binder to wet / mix the mixture, for example in a high shear mixer, wet granulation using, for example, a rotating impeller, eg After drying in a fluid bed dryer, for example, correcting the size in a vibrating granulator;

(iii) pharmaceutically acceptable excipients, for example sieved excipients, for example one or more fillers, for example silicified microcrystalline cellulose, microcrystalline cellulose or lactose, if necessary one or more glidants, for example Adding colloidal silicon dioxide, for example, mixing in a free-fall mixer, adding one or more lubricants, such as magnesium stearate, and mixing, for example, in a free-fall mixer; And

(iv) compressing the mixture obtained in step (iii) by compression in a conventional tableting machine, preferably a rotary tableting machine, optionally spraying lubricant onto the material contacting surface of the compacting tool;

It provides a method comprising a.

Processes that can be used are conventional or known in the art or described in, for example, L. Lachman et al. The Theory and Practice of Industrial Pharmacy, 3rd Ed, 1986, H. Sucker et al, Pharmazeutische Technologie, Thieme, 1991 , Hagers Handbuch der pharmazeutischen Praxis, 4th Ed. (Springer Verlag, 1971) and Remington's Pharmaceutical Sciences, 13th Ed., (Mack Publ., Co., 1970) or its successor). Can be done with

"Internal phase" means a granular form (steps (i) and (ii)) comprising the active ingredient Compound I and at least one pharmaceutically acceptable excipient.

"External phase" means one or more pharmaceutically acceptable excipients (step (iii)) added to the internal phase (granule).

"Total weight of dispersible tablet" means the weight of a tablet consisting of an inner phase and an outer phase.

Physical and chemical stability can be tested by conventional methods, and dispersible tablets are for example soluble, crushable, disintegration time, Compound I degradation products after storage at room temperature, i. On its own by analysis, appearance and / or microscopy.

The shape of the dispersible tablet can vary and can be, for example, round, oval, elliptical, columnar or any other suitable form. In one aspect, the dispersible tablet according to the invention contains a small amount of magnesium stearate (e.g. from about 0.01 to 0.4% by weight based on the total weight of the dispersible tablet) relative to the amount of compound I included in the tablet Therefore, the disintegration time is in compliance with the European Pharmacopoeia regulations.

In a preferred embodiment of the present invention, the dispersible tablets obtained by the compression method described above are in elongated form. The edge of the dispersible tablet may be beveled or curved. Most preferably, the dispersible tablets are elongated with slanted edges. Dispersible tablets according to the invention may be lined, embossed or engraved.

The dispersible tablets according to the invention are preferably in the form of flat, elongated edges in some cases. The diameter of the 1000 mg dispersible tablet is 10-20 mm, most preferably 10-15 mm. The suggested size is 24 x 12 mm. The range may be 20 to 26 length and 10 to 18 width. The thickness will be 5.5 to 8.5 mm depending on form and hardness. The preferred diameter of the 125 mg dispersible tablet is 12 mm. Its thickness is 2.5 to 4.5 mm, preferably 3.2 to 3.9 mm. The hardness of the dispersible tablets of the present invention comprising about 1000 mg of compound I as active ingredient may be about 120 to 200 N, preferably 140 to 180 N.

Preferably, the disintegration time is 5 minutes or less, and most preferably the disintegration time is less than 3 minutes as measured by the disintegration time measuring device.

"Disintegration time" means the time required for the dispersible tablet to disintegrate in water at room temperature in the disintegration time measuring apparatus.

The dispersible tablets of the present invention are dispersible in an aqueous phase, preferably in water.

Dispersible tablets of the present invention may be colored and / or marked to give an individual appearance and be readily recognizable. Dyestuffs may be used to improve appearance and identify dispersible tablets. Pharmaceutically suitable dyes generally include carotenoids, iron oxide or chlorophyll. The dispersible tablet of the present invention can be indicated using a stamping code.

The dispersible tablets of the present invention are useful for the treatment of iron hyperemia and for the treatment of hemochromatosis in transfusion dependent anemia, in particular gland thalassemia, thalassemia anemia and sickle cell disease.

The activity and properties of the dispersible tablets of the invention can be presented in standard clinical trials and / or animal tests.

Dispersible tablets of the present invention are expected to be stable for at least two or three years in conventional packaging, such as blister packs or HDPE bottles, during storage. Less than about 5%, for example 2 or 3% or less of Compound I as the active ingredient can degrade during this period of time as determined by conventional testing.

The invention also relates to a method of administering Compound I in the form of a dispersible tablet to a mammal, preferably a human, in need thereof. The invention particularly relates to the above method of administering to the patient a daily dose of 5 to 40 mg / kg of body weight of compound I as active ingredient. It will be appreciated that the specific dosage level for any particular patient will depend on a variety of factors including age, weight, general state of health, one or more of the combinations with the active drug, the type and severity of the disease.

The invention further relates to a pharmaceutical package comprising a dispersible tablet according to the invention and a printed instruction directing oral administration of one or more dispersible tablets of compound I.

The invention is illustrated by the following non-limiting examples.

Example 1: 1000 mg of compound I, 60 mg of polyvinylpyrrolidone K30, 20 mg of sodium laurylsulfate, 200 mg of prosolve SMCC 90, 100 mg of crospovidone, 600 mg of spray dried lactose, 20 mg of magnesium stearate.

Example 2: 1000 mg of compound I, 60 mg of polyvinylpyrrolidone K30, 20 mg of sodium laurylsulfate, 300 mg of Avicel PH 102, 200 mg of crospovidone, 400 mg of spray dried lactose, 20 mg of magnesium stearate.

Claims (14)

A dispersible tablet comprising Compound I of the formula: or a pharmaceutically acceptable salt thereof, present in an amount of 42 to 65% by weight, based on the total weight of the tablet. <Compound I>

(a) a compound comprising Compound I, or a pharmaceutically acceptable salt thereof, present in an amount of 42 to 65 percent by weight based on the total weight of the tablet, and (b) one or more pharmaceutically acceptable excipients suitable for the manufacture of the tablet. Acid tablets. A dispersible tablet comprising an iron chelating pharmacologically effective amount of Compound I, or a pharmaceutically acceptable salt thereof, present in an amount of 42 to 65 percent by weight based on the total weight of the tablet. 4. The dispersible tablet according to claim 1, wherein compound I is in free acid form. 5. The dispersible tablet according to claim 1, wherein compound I is in crystalline form. 6. The dispersible tablet according to any one of claims 1 to 5, wherein the lubricant is present in less than 1% by weight based on the total weight of the tablet. The dispersible tablet of claim 6 wherein the lubricant is present at less than 0.4 weight percent based on the total weight of the tablet. The dispersible tablet according to any one of claims 1 to 7, wherein the disintegration time of the tablet is 5 minutes or less. The dispersible tablet according to any one of claims 1 to 8, wherein the disintegration time of the tablet is 3 minutes or less. The excipient of claim 2, wherein the pharmaceutically acceptable excipient is (i) at least one filler in an amount of about 35 to 55% by weight, based on the total weight of the tablet, (ii) at least one disintegrant, wherein the total amount is from about 10 to 35 weight percent based on the total weight of the tablet, (iii) at least one binder in total amount of from about 1.5 to 5 weight percent based on the total weight of the tablet, (iv) at least one surfactant in total amount of from about 0.2 to 1 weight percent based on the total weight of the tablet, (v) one or more glidants, wherein the total amount is from about 0.1 to 0.5 weight percent based on the total weight of the tablet, and / or (vi) at least one lubricant with a total amount of less than about 0.4 weight percent based on the total weight of the tablet Dispersible tablet comprising a. The dispersible tablet according to any one of claims 6 to 10, wherein the lubricant is magnesium stearate. The dispersible tablet according to any one of claims 1 to 11 containing Compound I in free acid form in an amount of about 900 mg to 1100 mg. (i) wet granulating Compound I or a pharmaceutically acceptable salt thereof; (ii) mixing the granules obtained in step (i) with one or more pharmaceutically acceptable excipients to form a mixture; And (iii) spraying lubricant on the material contacting surface of the compaction tool in the tableting machine and compressing the mixture obtained in step (ii) to form tablets A method for producing a dispersible tablet according to any one of claims 1 to 12 comprising. The method of claim 13, wherein the lubricant is magnesium stearate.