MXPA06011592A - deferasirox DISPERSIBLE TABLETS - Google Patents

Abstract

The invention pertains to dispersible tablets comprising as active ingredient deferasirox 4-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-l-yl]benzoic acid or pharmaceutically acceptable salt thereof in an amount of from 42%to 65%in weight by weight of the total tablet.

Description

DEFERASIROX D1SPERSIBLE TABLETS The present invention relates to dispersible tablets, e.g. dispersible pharmaceutical tablets, comprising 4- [3,5-bis (2-hydroxyphenyl) - [1,2,4] triazoI-1-yl] benzoic acid or a pharmaceutically acceptable salt thereof, and is referred to hereafter as Compound I Compound I is an orally active iron chelating agent that is indicated in the treatment of iron overload in transfusion-dependent anemias, in particular thalassemia major, thalassemia intermedia and in sickle-cell disease to reduce iron-related morbidity and mortality . Compound I can also be used in the treatment of hemochromatosis. Clinical thalassemia (major and intermediate) are hereditary disorders characterized by the abnormal production of hemoglobin, which leads to decreased production and increased destruction of red blood cells. . Sickle cell disease is caused by a mutation in the hemoglobin-beta gene that leads to the production of abnormal hemoglobin S. Normal red blood cells die after 120 days and sickle cells (red blood cells with hemoglobin S) are destroyed more rapidly (10 to 20 days) causing anemia. This anemia is what gives the disease its commonly known name - sickle cell anemia. Hemochromatosis, the most common form of iron overload disease, is an inherited disorder that causes the body to absorb and store much more iron. The extra iron builds up in the organs and damages them. Without treatment, the disease can cause these organs to fail. Patients with sickle cell anemia or thalassemia, who receive numerous blood transfusions and patients with hemochromatosis, require therapy to remove iron from the body, called chelation therapy. Compound I has the following formula: Compound I in the free acid form, salts thereof and their crystalline forms are described in International Patent Publication WO 97/49395, which is hereby incorporated by reference (published December 31, 1997). Typically, the prescribed daily doses of compound I for the treatment of thalassemia are high, e.g. 5 to 40 mg / kg of body weight / day in adults or children. In children, the dose is preferably 5 to 30 mg / kg of body weight / day. Depending on the age, the individual condition, mode of administration and the clinical picture in question, the effective daily dosage, 350 to 2800 mg of Compound I, are administered to patients of 70 Kg of body weight. Due to the high daily dosage, patients may have to take 6 or more tablets per day. Thus, there is a need for an oral dosage form that allows the patient to take a reduced number of tablets, which is convenient and safe to administer to adults and children and which provides a pharmacologically active daily dosage amount of Compound I. The present inventors have now surprisingly found that Compound I can be formulated in the form of a dispersible tablet having a drug loading of 1000 mg of Compound I and which is convenient to administer to, for example children and the elderly, and is stable. By "dispersible tablet" is defined a tablet that is dispersed in aqueous phase, e.g. in water, before being administered. Accordingly, the present invention provides a dispersible tablet with a high load of the drug comprising Compound I as an active ingredient, the active ingredient is present in an amount of from 42% to 65%, e.g. at least 45, 47, 50, 52 or 55%, preferably more than 45% by weight based on the total weight of the dispersible tablet. In particular, the amount of compound I can vary from 42% to 65%, e.g. 45% to 60%, e.g. 45 to 55%, e.g. 47% to 53%, e.g. 50%, by weight based on the total weight of the tablet dispersible. The present invention relates to a dispersible tablet comprising a pharmacologically effective chelating amount of iron of Compound I or a pharmaceutically acceptable salt thereof present in an amount of from 42% to 65% by weight per 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 from 42% to 65% by weight based on the total weight of the tablet. The compound I can be in the free acid form or pharmaceutically acceptable salts thereof, preferably in the free acid form. The active portion corresponds to Compound I in the free acid form. Within the context of this disclosure, reference to Compound I is understood to include Compound I in its free acid form or a pharmaceutically acceptable salt thereof or any of the crystal forms thereof which includes hydrates or solvates, if not Indicates otherwise and where appropriate and convenient. The present invention also provides a dispersible tablet comprising: (a) Compound I or a pharmaceutically acceptable salt thereof, and (b) at least one pharmaceutically acceptable excipient suitable for the preparation of dispersible tablets wherein the amount of the compound I or a pharmaceutically acceptable salt thereof, calculated as the percentage of the weight content of the active portion based on the total weight of the dispersible tablet, is from about 42% to 65%, eg at least 45, 47, 50 or 52% preferably more than 47% by weight based on the total weight of the dispersible tablet. In particular, the amount of compound I as active ingredient can vary from 42% to 65%, e.g. 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 present invention provides a dispersible tablet wherein Compound I is in the free acid form (Compound I in free acid form). In a more preferred aspect of the invention, Compound I in the free acid form is in a crystalline form. One or more pharmaceutically acceptable excipients may be present in the dispersible tablets, e.g. those conventionally used, e.g. (1.1) at least one filling material, e.g. , lactose, Prosolv ™ SMCC® 90, ethyl cellulose, microcrystalline cellulose, (1.2) at least one disintegrant, e.g. crosslinked polyvinylpyrrolidone, e.g. Crospovidone®, (1.3) at least one binder, e.g. polyvinylpyridone, hydroxypropylmethyl cellulose, (1.4) at least one surfactant, e.g. sodium laurisulfate, (1.5) at least one glidant or glidant, e.g. colloidal silicon dioxide, (1.6), at least one lubricant, e.g. magnesium stearate. With reference to the extensive literature in the field of these and other pharmaceutically acceptable excipients and methods mentioned herein, see in particular Handbook of Pharmaceutical Excipients, 3rd Edition, edited by Arthur H. Kibbe, American Pharmaceutical Association, Washington, USA and Pharmaceutical Press, London; and Lexikon der Hilfsstoffe für Pharmazie, Kosmetik and Angrenzende Gebiete edited by H. P. Fiedler, 4th Edition, Edito Cantor, Aulendorf and previous editions which are incorporated herein by reference. The filling materials (1 .1) according to the invention are lactose especially lactose monohydrate, preferably lactose monohydrate (200 mesh) and lactose dehydrated by spraying, microcrystalline cellulose especially PH 102, PH 1 01 or Prosolv ™ SMCC® 90. Suitable disintegrants (1 .2) according to the invention include but are not limited to corn starch, CMC-Ca, CMC-Na, microcrystalline cellulose, cross-linked PVP, e.g. as known and commercially available under the tradenames Crospovidone®, Polyplasdone®, commercially available from the ISP Company, or Kollidon® XL, alginic acid, sodium alginate, and guar gum. Preferably cross-linked PVP is used, e.g. Crospovidone®. Binders (1 .3) include but are not limited to starches, e.g. potato, wheat or corn starch, microcrystalline cellulose, e.g. products such as Avicel®; hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, e.g. hydroxypropylmethyl cellulose Type 291 0 USP, hypromellose and polyvinylpyrrolidone, e.g. Povidone® K30 from BASF. Preferably polyvinylpyrrolidone is used, more preferably PVP K30. An appropriate surfactant (1.4) according to the invention can be used: sodium laurisulfate, quaternary ammonium salts, polysorbates, sorbitan esters and poloxamer.

Preferably the surfactant is sodium laurisulfate. As glidants (1.5), one or more of the following can be used: silica, colloidal silica, e.g. anhydrous colloidal silica, e.g. Aerosil® 200, magnesium trisilicate, cellulose powder, starch and talc. Preferably, the colloidal silicon dioxide is used. As lubricants (1 .6), one or more of the following can be used: Mg stearate, AI or Ca, PEG 4000-8000, talc, sodium benzoate, glyceryl fatty monoacid, e.g. having a molecular weight of from 200 to 800 Daltons, e.g. glyceryl monostearate (eg Danisco, UK), glyceryl dibehenate (eg Compritol ATO888 ™, Gattefossé France), glyceryl palmito-stearic ester (eg Precirol ™, Gattefossé France), polyoxyethylene glycol (PEG, BASF), seed oil hydrogenated cotton (Lubitrab, Edward Mendell Co Inc.), castor bean oil (Cutina HR, Henkel). Preferably, magnesium stearate is used. One or more of these pharmaceutically acceptable excipients can be selected and used with reference to the desired properties in particular of the dispersible tablet by routine experimentation. According to the present invention, the amount of the filling material (1.1) can vary within a range of from about 30 to 50%, in particular 35 to 45% by weight based on the total weight of the dispersible tablet. . The amount of disintegrant (1.2) can vary within a range of 2 to 25%, e.g. 2 to 15% by weight based on the total weight of the dispersible tablet. The amount of binder (1.3) can vary from 1 to 10%, preferably from 1.5 to 5% by weight based on the total weight of the dispersible tablet. The amount of the surfactant (1 .4) can vary from 0.1 to 3%, preferably from 0.2 to 1.5%. The amount of the slider (1 .5) can vary within the range of from 0 to 5%, in particular 0.1 to 2.5%, e.g. 0.1 to 0.5% by weight based on the total weight of the dispersible tablet. The amount of the lubricant (1.6) can be less than 1% by weight based on the total weight of the dispersible tablet, preferably less than 0.5%, more preferably less than 0.4% and even more preferably the amount of lubricant varies between 0.01 % and 0.4%. Most preferably the amount of lubricant is above 0.02% and below 0.4% by weight based on the total weight of the dispersible tablet. It will be appreciated that any given excipient can serve more than one function e.g. as filler, disintegrant, binder, glidant and / or lubricant material. A lubricant may be present in an amount less than 1% by weight based on the total weight of the dispersible tablet, preferably less than 0.4%. The invention also relates to a dispersible tablet wherein the lubricant is magnesium stearate. In a preferred aspect of the invention, the dispersible tablet comprises the following pharmaceutically acceptable excipients: one or more fillers in a total amount of about 40% to 50% by weight based on the total weight of the dispersible tablet, one or more binders in a total amount of about 1.5% to 5% by weight based on the total weight of the dispersible tablet, one or more disintegrants in a total amount of about 2 to 35% by weight based on the total weight of the dispersible tablet, one or more slides in a total amount of about 0.1% to 0.5% by weight based on the total weight of the dispersible tablet and / or one or more lubricants in a total amount of about 0.01% to 0.4% by weight based on the total weight of the tablet. the dispersible tablet. In a preferred aspect of the invention, the dispersible tablet comprises the following pharmaceutically acceptable excipients: one or more fillers in a total amount of about 40% to 50% by weight based on the total weight of the dispersible tablet, one or more binders in a total amount of about 1.5% to 5% by weight based on the total weight of the dispersible tablet, one or more disintegrants in a total amount of about 1.0 to 35% by weight based on the total weight of the tablet. dispersible tablet, one or more surfactants in a total amount of about 0.2% to 1% by weight based on the total weight of the dispersible tablet, one or more glidants in a total amount of about 0.1% to 0.5% by weight based on the total weight of the dispersible tablet and / or one or more lubricants in a total amount of about 0.01% to 0.4% by weight based on the total weight of the dispersible tablet. The absolute amounts of each pharmaceutically acceptable excipient and the amounts relative to other pharmaceutically acceptable excipients depend in a similar manner on the desired properties of the dispersible tablet and can also be selected by routine experimentation. The present inventors have encountered difficulties in the production of the dispersabie tablets comprising Compound I which may be due to the low density of the active ingredient, its electrostatic characteristics which may lead to poor fluidity and its tendency to adhere. In accordance with the present invention, it has unexpectedly been found that the pharmaceutically acceptable oral solid dosage form in the form of dispersible tablets suitable for administration to patients and dispersible in 5 minutes or less, preferably 3 minutes or less, can be obtained at Prepare the tablets by compression methods. More specifically, the dispersible tablets of the invention can be prepared by granulation, preferably wet granulation, followed by compression methods, preferably under nebulization lubrication. In general, wet granulation can be used to improve the flowability and tendency to adhere, however the wet granulation process is not preferred when the pharmaceutical composition is to be a dispersible tablet. In fact, wet granulation increases the cohesion of the particles of the active ingredient and increases the disintegration time of the final tablet, which is not in accordance with the compliance of the patient or the European Pharmacopoeia which requires a disintegration time of 3 days. minutes or less for a dispersible tablet. In addition, the present inventors have encountered the problem that when large amounts of microcrystalline cellulose are used, the dissolution is very slow and incomplete. The inventors have now found that by decreasing the amount of insoluble excipients, the solution can be improved. To maintain the technical characteristics of the tablets with less insoluble excipients, it may be necessary to replace the microcrystalline cellulose with silica microcrystalline cellulose (Prosolv ™ SMCC® 90), which, in some cases, shows better compression characteristics. Avicel and colloidal silicon dioxide can also be used. The dispersible tablets of the invention have a disintegration time, e.g. in aqueous medium, e.g. in water, 5 minutes or less than 5 minutes. The dispersible tablets of the invention are, in spite of the very high drug loading, dispersible, e.g. in aqueous medium, e.g. in water, in less than 5 minutes, preferably less than 3 minutes and, therefore, convenient to administer, e.g. to children or the elderly. In another embodiment, this invention provides a dispersible tablet comprising more than 800 mg of Compound I as an active ingredient, e.g. from 900 mg to approximately 1 1 00 mg. e.g. 1000 mg. More preferably, the dispersible tablets according to the invention are dispersible tablets containing 1000 mg of Compound I as the active ingredient. Accordingly, the present invention provides dispersible tablets, e.g. dispersible tablets, which contains an amount of Compound I, equal to 1000 mg of Compound I in the free acid form. More preferably, Compound I in the free acid form used for the dispersible tablet according to the invention is in the crystalline form, especially the crystalline form, the preparation of which is described in Example 5 of WO 97/49395, which is incorporated herein by reference. According to the invention, the process for the preparation of the dispersible tablets consists of granulating an internal phase, mixing it (together) with one or more pharmaceutically acceptable excipient (s) and compressing the mixture obtained, optionally under lubrication conditions. by nebulization. The internal phase comprises Compound I. Preferably, the parent phase comprises Compound I and one or more pharmaceutically acceptable excipients. Preferably, the pharmaceutically acceptable excipients of the internal phase are one or more fillers, one or more disintegrants, one or more binders and one or more surfactants. Preferably, the amount of one or more fillers in the internal phase ranges from about 5 to 35% by weight based on the total weight of the dispersible tablet, more preferably 10 to 30% and more preferably 15 to 25%. The amount of lactose can be in the range of 0-1 0% or 0-15%. The filling material according to the invention is preferably lactose monohydrate. The disintegrant is preferably Crospovidone XL. The amount of disintegrant present in the internal phase can be in the range of 0-20% by weight, or preferably range from 5 to 30%, more preferably 7 to 25% by weight based on the total weight of the dispersible tablet. Compound I and one or more filler materials and one or more disintegrants are mixed together with a wetting solution comprising one or more surfactants, water and one or more binders. The preferred binder is PVP K.30. The mixture is processed for granulation, e.g. using a high-cut wet granulator to form wet granulates. The wet granulates can be subsequently dried, e.g. using a fluid bed dryer, and calibrated, e.g. using an oscillating granulator. The external phase consists of one or more pharmaceutically acceptable excipient (s) and is mixed with the internal phase using e.g. a free fall mixer. Preferably, one or more filler materials and / or one or more glidants are added. More preferably, silicified microcrystalline cellulose (Prosolv ™ SMCC® 90) is added or microcrystalline cellulose and lactose are added as fillers. Even more preferably, the microcrystalline cellulose is added in the range of 5 to 20% by weight based on the total weight of the dispersible tablet and the lactose is added in the range of 15 to 35% by weight based on the total weight of the tablet. dispersible tablet. The external phase according to the invention may also contain one or more sliders, more preferably colloidal silicon dioxide. In a preferred embodiment, the amount of slider in the external phase ranges from about 0.1 to 5%, preferably 0.1 to 2.5%, more preferably 0.1 to 0.5% by weight based on the total weight of the tablet. Optionally, in accordance with the present invention, one or more lubricants, instead of being incorporated into the mixture of the internal and external phase, can be deposited in the punches of the tablet-forming machine before compression. According to the invention, one or more lubricants can be sprayed onto the material that is in contact with the surfaces of the compression tools, e.g. punches and / or dies, of the tablet-forming machine before compression. Preferably, one or more lubricants are sprayed onto the material in contact with the surfaces of the compression tools, e.g. punches and dies, of the tablet-forming machine before compression. In one embodiment of the invention, the process for the preparation of a dispersible tablet comprises a) forming an internal phase comprising (i) mixing Compound I together with the pharmaceutically acceptable excipients, (ii) wet granulating the mixture obtained in ( i); b) forming an outer phase moon comprising (iii) adding more phceutically acceptable excipients to the internal phase obtained in (ii) and mixing; (x) optionally lubricate the final mixture by (...) adding one or more lubricants to the mixture obtained in (iii) and mixing c) forming the dispersible tablet by (iv) compressing the mixture obtained in step (iii), optionally under lubrication conditions by nebulization. In a further aspect the present invention provides a process comprising: (i) mixing the compound I and the phceutically acceptable excipients, e.g. one or more filler materials, e.g. lactose, and one or more disintegrants, e.g. Crospovídona XL, in a high cut mixer; (ii) adding a solution of one or more surfactants and one or more binders, subjecting the mixture to humidification / kneading, e.g. in a high cut, wet granular mixer using, e.g. a rotary impeller, drying, e.g. in a fluidized bed dryer, then calibrating in an oscillating granulator, and; (iii) adding phceutically acceptable excipients, e.g. sifted excipients, such as one or more filler materials, e.g. silicified microcrystalline cellulose, microcrystalline cellulose or lactose, if necessary one or more glidants, e.g. colloidal silicon dioxide, e.g. in a free fall mixer; add one or more lubricants, e.g. magnesium stearate, and mixing, e.g. in a free fall mixer. (iv) tabletting the mixture obtained in step (iii) by compression, e.g. in a conventional tablet press, preferably a rotating machine and optionally spraying the lubricant on the material that is in contact with the compression tools. The methods that may be used may be conventional or known in the art or based on such procedures, e.g. those described in 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 fas latest editions. "Internal phase" refers to the granulated phase (steps (i) and (ii)) which includes the active ingredient Compound I and one or more of the pharmaceutically acceptable excipients. "External phase" refers to one or more pharmaceutically acceptable excipients added to the internal phase (granules) stage (iii). "Total weight of the dispersible tablet" refers to the weight of a tablet being the internal and external phase. The physical and chemical stability can be evaluated in a conventional manner, e.g. Dispersible tablets can be evaluated as such by measuring dissolution, friability, disintegration time, test for degradation products of Compound I, appearance and / or microscopy, e.g. after being stored at room temperature, i.e. 25 ° C and / or stored at 40 ° C. Dispersible tablets can vary in shape and are, for example, round, oval, oblong, cylindrical or any other suitable shape. In one aspect, the dispersible tablet according to the invention contains small amounts of magnesium stearate, e.g. approximately 0.01% to 0.4% by weight based on the total weight of the dispersible tablet, with reference to the amount of compound I contained therein, thus allowing a disintegration time, which complies with the specifications of the European Pharmacopoeia. In a preferred embodiment of the invention, the dispersible tablets obtained by the compression method described above are of elongated shape. The edges of the dispersible tablets may be beveled or rounded. More preferably, the dispersible tablets are elongated with beveled edges. The dispersible tablets according to the invention can be marked, embossed or printed. The dispersible tablet according to the invention is preferably elongated, flat, optionally with beveled edges. The 1000 mg dispersible tablet has a diameter that varies between 10 and 20 mm, more preferably between 10 and 15 mm. The proposed size is 24 x 12mm. The interval could be from 20 to 26 for the length, and 10 to 18 for the width. The thickness will vary from 5.5 to 8.5mm, depending on the shape and hardness. The preferred diameter of the 125 mg dispersible tablet is 12mm. Its thickness is in the range of 2.5 to 4.5 mm, preferably between 3.2 and 3.9 mm. Dispersible tablets of the invention comprising about 1000 mg of Compound I as the active portion may have a hardness of about 120 to 200 N, preferably 140 to 180 N. Preferably, the disintegration time is not more than 5 minutes, more preferably the disintegration time is less than 3 minutes as measured using a disintegration time apparatus. "Disintegration time" refers to the time that the dispersible tablet needs to disintegrate in water at room temperature in a disintegration time device. The dispersible tablet of the present invention is dispersible in an aqueous phase, preferably water. The dispersible tablets of the invention may be colored or marked to impart an individual appearance and make them instantly recognizable. The use of dyes can serve to improve the appearance as well as to identify the dispersible tablets. Colorants suitable for use in pharmacy typically include carotinoids, oxides of iron or chlorophyll. The dispersible tablets of the invention can be marked using a printing code. The dispersible tablets of the invention are useful for the treatment of iron overload in transfusion-dependent anemias, in particular thalassemia major, thalassemia intermedia and sickle cell disease and in the treatment of hemochromatosis. The activity and characteristics of the dispersible tablets of the invention can be indicated in standard clinical tests and / or animal tests. The dispersible tablets of the invention are expected to be stable during storage, e.g. for at least 2 years, or 3 years, in conventional packaging, e.g. Blister packs or HDPE bottles. Less than about 5%, e.g. 2 or 3% or less of Compound I as an active ingredient may degrade during this time as determined in conventional tests. The invention furthermore also relates to a method of administration to a mammal, preferably a human subject, in need of such treatment, Compound I in the form of a dispersible tablet. The invention especially relates to such a method wherein a daily dose of 5 to 40 mg / kg of body weight of compound I as an active ingredient is administered to a patient. It will be understood that the specific dose level for any particular patient will depend on a variety of factors including age, body weight, general health, combination of the drug with one or more active drugs, type and severity of the disease. The invention further provides a package of the medicament comprising the dispersible tablets according to the invention and printed instructions directed to which one or more dispersible tablets of Compound I are administered orally. The following non-limiting examples illustrate the invention.

Example 1: Compound I 1000 mg, Polyvinylpyrrolidone K30 60 mg Sodium lauryl sulfate 20 mg Prosolv SMCC 90 200 mg Crospovidone 100 mg Lactose dehydrated by spray 600 mg Magnesium stearate 20 mg Example 2: Compound I 1000 mg, Polyvinylpyrrolidone K30 60 mg Sodium laurisulfate 20 mg Avicel PH 1 02 300 g Crospovidone 200 mg Lactose dehydrated by aspersion 400 mg Magnesium stearate 20 mg

Claims (9)

1 . A dispersible tablet characterized in that it comprises the compound I of the formula or a pharmaceutically acceptable salt thereof present in an amount of from 42% to 65% by weight based on the total weight of the tablet.

2. The dispersible tablet according to claim 1, characterized in that it comprises: (a) the compound I or a pharmaceutically acceptable salt thereof, and (b) at least one pharmaceutically acceptable excipient suitable for the preparation of tablets.

3. The dispersible tablet according to claim 1 or 2, characterized in that the compound I is in the free acid form.

4. The dispersible tablet according to any of claims 1 to 3, characterized in that the compound I is in a crystalline form.

5. The dispersible tablet according to any of claims 1 to 4, characterized in that a lubricant is present in less than 1% by weight based on the total weight of the tablet.

6. The dispersible tablet according to claim 5, characterized in that the lubricant is present at less than 0.4% by weight based on the total weight of the tablet.

7. The dispersible tablet according to any of claims 1 to 6, characterized in that the disintegration time of the tablet is 5 minutes or less.

8. The dispersible tablet according to any of claims 1 to 7, characterized in that the disintegration time of the tablet is 3 minutes or less. The dispersible tablet according to any of claims 2 to 8, characterized in that the pharmaceutically acceptable excipients comprise: (i) at least one filler material in a total amount of about 35 to 55% by weight based on the weight total tablet, (ii) at least one disintegrant in a total amount of about 10% to 35% by weight based on the total weight of the tablet, (iii) at least one binder in a total amount of about 1 .5% to 5% by weight based on the total weight of the tablet, (iv) at least one surfactant in a total amount of about 0.2% to 1% by weight based on the total weight of the tablet, (v) ) at least one slider in a total amount of about 0.1% to 0.5% by weight based on the total weight of the tablet, and / or (vi) at least one lubricant in a total amount less than about 0.4% by weight based on the total weight of the tablet. 1 0. The dispersible tablet according to any of claims 5 to 9, characterized in that the lubricant is magnesium stearate. eleven . The dispersible tablet according to any of claims 1 to 10, characterized in that it contains the compound I in its free acid form in an amount of about 900 mg to 1 100 mg. 12. A process for the preparation of the dispersible tablet according to any of the preceding claims, the process characterized in that it comprises: (i) wet granulating the compound I or a pharmaceutically acceptable salt thereof; (ii) mixing the granulates obtained in (i) with at least one pharmaceutically acceptable excipient to form a mixture; and (iii) spraying the lubricant onto the materials that are in contact with the surfaces of the compression tools of the tablet forming machine and compressing the mixture obtained in step (iii) to form a tablet. 13. The process according to claim 12, characterized in that the lubricant is magnesium stearate.