DESC:[001] FIELD OF THE INVENTION

[002] The present invention relates to formulations and dosage forms of lenvatinib i.e. 4-[3­chloro-4-(N’-cyclopropylureido) phenoxy]-7-methoxyquinoline-6-carboxamide, process for preparation thereof and methods of using the formulations and dosage forms.

[003] BACKGROUND OF THE INVENTION

[004] E7080 (also known as lenvatinib) is an active inhibitor of multiple receptor tyrosine kinases (e.g., receptor tyrosine kinases involved in angiogenesis and tumor proliferation) including vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), platelet-derived growth factor receptor a (PDGFRa), KIT, and RET proto-oncogene receptors. Lenvatinib is structurally represented as:

[005] Lenvatinib has been approved by USFDA and is available in the market as 4 mg and 10 mg capsules with the brand name Lenvima®. Each 4 mg Lenvima® capsule contains 4 mg of lenvatinib (equivalent to 4.90 mg of lenvatinib mesylate) as the active ingredient and calcium carbonate, hydroxypropyl cellulose, low-substituted hydroxypropylcellulose, mannitol, microcrystalline cellulose, and talc as the inactive ingredients. Each 10 mg Lenvima® capsule contain 10 mg of lenvatinib (equivalent to 12.25 mg of lenvatinib mesylate) as the active ingredient and calcium carbonate, hydroxypropyl cellulose, low-substituted hydroxypropylcellulose, mannitol, microcrystalline cellulose, and talc as the inactive ingredients.

[006] Lenvima® capsules are used for the treatment of locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC), in combination with everolimus for the treatment of advanced renal cell carcinoma (RCC), unresectable hepatocellular carcinoma (HCC) and in combination with pembrolizumab for the treatment of advanced endometrial carcinoma.

[007] For the treatment of differentiated thyroid cancer (DTC) with Lenvima® the recommended daily dosage is 24 mg orally once daily. As 4 mg and 10 mg capsules are present in the market, a patient using Lenvima® capsules for the treatment of DTC has to administer 2x10 mg capsules and 1x4 mg capsule to make a dose of 24 mg.

[008] For the treatment of advanced renal cell carcinoma (RCC) with Lenvima® the recommended daily dosage is 18 mg orally once daily with everolimus 5 mg orally once daily. As 4 mg and 10 mg capsules are present in the market, a patient using Lenvima® capsules for the treatment of RCC has to administer 1x10 mg capsule and 2x4 mg capsules to make a dose of 18 mg.

[009] For the treatment of hepatocellular carcinoma (HCC) with Lenvima® the recommended daily dosage is 12 mg orally once daily for a patient greater than or equal to 60 kg. As 4 mg and 10 mg capsules are present in the market, a patient using Lenvima® capsules for the treatment of HCC has to administer 3x4 mg capsules to make a dose of 12 mg.

[010] For the treatment of endometrial carcinoma with Lenvima® the recommended daily dosage is 20 mg orally once daily in combination with pembrolizumab 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks. As 4 mg and 10 mg capsules are present in the market, a patient using Lenvima® capsules for the treatment of endometrial carcinoma has to administer 2x10 mg capsules to make a dose of 20 mg.

[011] For the treatment of DTC, HCC, RCC and endometrial cancer with Lenvima® (lenvatinib mesylate as the active ingredient), patients have to administer, multiple capsules of either 4 mg and 10 mg of Lenvima® capsules daily. Among, the other things, a suitable single unit discrete dosage form, such as capsules, caplets, tablets, lozenges, orally disintegrating tablets and orally disintegrating films, comprising the prescribed amount e.g. 12 mg, 18 mg, 20 mg and 24 mg of lenvatinib would be advantageous alternative to the 4 mg and 10 mg lenvatinib capsules.

[012] Therefore, there exists a need to develop a single unit discrete dosage form suitable for oral administration to a human comprising: an amount equal or greater than about 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, 16 mg, 17 mg, 18 mg, 19 mg, 20 mg, 21 mg, 22 mg, 23 mg, 24 mg, 25 mg, 26 mg, 27 mg, 28 mg, 29 mg and 30 mg of lenvatinib as an active ingredient and a pharmaceutically acceptable excipient.

[013] DETAILED DESCRIPTION

[014] The present invention provides a pharmaceutical dosage form of lenvatinib, or a pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, hydrate or clathrate, thereof. Most preferable used salt in the present invention is lenvatinib mesylate. In some embodiments, the dosage forms provided herein, exhibit advantageous physical and/or pharmacological properties. Such properties include, but are not limited to, ease of administration, ease of assay, content uniformity, flow properties for manufacture, dissolution, bioavailability and stability. In certain embodiments, the dosage forms provided herein have a shelf life of at least about 12 months, at least about 24 months, or at least about 36 without refrigeration.

[015] Also provided herein are kits comprising pharmaceutical compositions and dosage forms provided herein. Also provided herein are methods of treating, managing, and/or preventing a disease or condition, which comprising administering to a patient in need thereof a pharmaceutical composition or a dosage form provided herein.

[016] In one embodiment, provided herein is a single unit dosage form suitable for oral administration to a human comprising, an amount equal to or greater than about 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, 16 mg, 17 mg, 18 mg, 19 mg, 20 mg, 21 mg, 22 mg, 23 mg, 24 mg, 25 mg, 26 mg, 27 mg, 28 mg, 29 mg and 30 mg of lenvatinib or a pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, hydrate or clathrate, thereof; and a pharmaceutically acceptable excipient.

[017] In one specific embodiment, the single unit dosage form contains 12 mg of lenvatinib or a pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, hydrate or clathrate, thereof.

[018] In another embodiment, the single unit dosage form contains 18 mg of lenvatinib or a pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, hydrate or clathrate, thereof.

[019] In a further embodiment, the single unit dosage form contains 20 mg of lenvatinib or a pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, hydrate or clathrate, thereof.

[020] In a still further embodiment, the single unit dosage form contains 24 mg of lenvatinib or a pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, hydrate or clathrate, thereof.

[021] Pharmaceutical compositions and formulations provided herein can be presented as single unit discrete dosage form, such as capsules (soft gelatin and hard gelatin), caplets, tablets, lozenges, orally disintegrating tablets and orally disintegrating films.

[022] Tablets, capsules, caplets, orally disintegrating tablets and orally disintegrating films contain from about 100 mg to 300 mg of the pharmaceutical composition. (i.e active ingredient and pharmaceutically acceptable excipients). Capsules can be of any size. Examples of standard sizes include #000, #00, #0, #1, #2, #3, #4, and #5. In some embodiments, capsules provided herein are of size #1 or larger, size #2 or larger, size # 3 or larger, or #4 or larger.

[023] In one embodiment, lenvatinib or a pharmaceutically acceptable salt thereof as used in the present invention is lenvatinib mesylate.

[024] In one embodiment of the invention lenvatinib comprises of about 11 mg to about 30 mg in the single unit dosage form.

[025] In another embodiment, the present invention provides a single unit dosage form comprising lenvatinib and a pharmaceutically acceptable excipient. The pharmaceutically acceptable excipients are selected from group consisting of stabilizers, diluent, binder, disintegrating agent and a lubricant.

[026] In one embodiment, the present invention provides a single unit dosage form comprising lenvatinib and stabilizer. The stabilizer as used in the present invention is combination of calcium hydroxide and potassium hydroxide.

[027] In further embodiment, the present invention provides a single unit dosage form comprising lenvatinib, calcium hydroxide, potassium hydroxide, diluent, binder, disintegrating agent and a lubricant.

[028] In a still further embodiment, the present invention provides a single unit dosage form comprising lenvatinib, calcium hydroxide, potassium hydroxide, microcrystalline cellulose and mannitol as a diluent, hydroxypropyl cellulose as a binder, low substituted hydroxypropyl cellulose as a disintegrant and talc as a lubricant.

[029] In one embodiment of the present invention, the single unit dosage form comprises about 14.7 mg, 22.05 mg, 24.5 mg or 29.4 mg of lenvatinib mesylate.

[030] In a further embodiment of the present invention, the single unit dosage form comprises about 13.2 mg, 19.8 mg, 22 mg or 26.4 mg of calcium hydroxide.

[031] In another embodiment of the present invention, the single unit dosage form comprises about 3.6 mg, 5.4 mg, 6 mg or 7.2 mg of potassium hydroxide.

[032] In a further embodiment of the present invention, the single unit dosage form comprises about 24 mg, 36 mg, 40 mg and 48 mg of microcrystalline cellulose.

[033] In another embodiment of the present invention, the single unit dosage form comprises about 28.5 mg, 42.75 mg, 47.5 mg and 57 mg of mannitol.

[034] In another embodiment of the present invention, the single unit dosage form comprises about 30 mg, 45 mg, 50 mg and 60 mg of low substituted hydroxypropyl cellulose.

[035] In still another embodiment of the present invention, the single unit dosage form comprises about 3.6 mg, 5.4 mg, 6.0 mg and 7.2 mg of hydroxypropyl cellulose.

[036] In another embodiment of the present invention, the single unit dosage form comprises about 2.4 mg, 3.6 mg, 4 mg and 4.8 mg of talc.

[037] In one embodiment, provided herein is a single unit dosage form comprising
(a) about 12 mg, 18 mg, 20 mg and 24 mg of lenvatinib,
(b) about 13.2 mg, 19.8 mg, 22 mg or 26.4 mg of calcium hydroxide,
(c) about 3.6 mg, 5.4 mg, 6 mg or 7.2 mg of potassium hydroxide,
(d) about 24 mg, 36 mg, 40 mg and 48 mg of microcrystalline cellulose,
(e) about 28.5 mg, 42.75 mg, 47.5 mg and 57 mg of mannitol,
(f) about 30 mg, 45 mg, 50 mg and 60 mg of low substituted hydroxypropyl cellulose,
(g) about 3.6 mg, 5.4 mg, 6 mg and 7.2 mg of hydroxypropyl cellulose, and
(h) about 2.4 mg, 3.6 mg, 4 mg and 4.8 mg of talc.

[038] In one embodiment provided herein, wherein the total weight of the dosage form is 120 mg. In a specific embodiment, the dosage form with the total weight of 120 mg is administered in a size 3 capsule or larger capsule.

[039] In a further embodiment provided herein, wherein the total weight of the dosage form is 180 mg. In a specific embodiment, the dosage form with total weight of 180 mg is administered in a size 2 capsule or larger capsule.

[040] In a still further embodiment provided herein, wherein the total weight of dosage form is 200 mg. In a specific embodiment, the dosage form with total weight of 200 mg is administered in a size 2 capsule or larger capsule.

[041] In a further embodiment provided herein, wherein the total weight of the dosage form is 240 mg. In a specific embodiment, the dosage form with total weight of 240 mg is administered in a size 1 capsule or a larger capsule.

[042] In one embodiment, the present invention provides a capsule which weighs 120 mg and comprises
(a) 12 mg of lenvatinib (equivalent to 14.7 mg of lenvatinib mesylate),
(b) 24 mg of microcrystalline cellulose,
(c) 28.5 mg of mannitol,
(d) 30 mg of low substituted hydroxypropyl cellulose,
(e) 13.2 mg of calcium hydroxide,
(f) 3.6 mg of potassium hydroxide,
(g) 3.6 mg of hydroxypropyl cellulose and
(h) 2.4 mg of talc.

[043] In another embodiment, the present invention provides a capsule which weighs 180 mg and comprises
(a) 18 mg of lenvatinib (equivalent to 22.05 mg of lenvatinib mesylate),
(b) 36 mg of microcrystalline cellulose,
(c) 42.75 mg of mannitol,
(d) 45 mg of low substituted hydroxypropyl cellulose,
(e) 19.8 mg of calcium hydroxide,
(f) 5.4 mg of potassium hydroxide,
(g) 5.4 mg of hydroxypropyl cellulose and
(h) 3.6 mg of talc.

[044] In a further embodiment, the present invention provides a capsule which weighs 200 mg and comprises
(a) 20 mg of lenvatinib (equivalent to 24.5 mg of lenvatinib mesylate),
(b) 40 mg of microcrystalline cellulose,
(c) 47.5 mg of mannitol,
(d) 50 mg of low substituted hydroxypropyl cellulose,
(e) 22 mg of calcium hydroxide,
(f) 6 mg of potassium hydroxide,
(g) 6 mg of hydroxypropyl cellulose and
(h) 4 mg of talc.

[045] In a still further embodiment, the present invention provides a capsule which weighs 240 mg and comprises
(a) 24 mg of lenvatinib (equivalent to 29.4 mg of lenvatinib mesylate),
(b) 48 mg of microcrystalline cellulose,
(c) 57 mg of mannitol,
(d) 60 mg of low substituted hydroxypropyl cellulose,
(e) 26.4 mg of calcium hydroxide,
(f) 7.2 mg of potassium hydroxide,
(g) 7.2 mg of hydroxypropyl cellulose,
(h) 4.8 mg of talc

[046] In one embodiment, the present invention provides a capsule which weighs 120 mg and comprises
(a) 12 mg of lenvatinib (equivalent to 14.7 mg of lenvatinib mesylate),
(b) 24 mg of microcrystalline cellulose,
(c) 28.5 mg of mannitol,
(d) 30 mg of low substituted hydroxypropyl cellulose,
(e) 13.2 mg of calcium hydroxide,
(f) 3.6 mg of potassium hydroxide,
(g) 3.6 mg of hydroxypropyl cellulose,
(h) 2.4 mg of talc and wherein the capsule suitable for administration is in a size 3 or larger capsule.

[047] In another embodiment, the present invention provides a capsule which weighs 180 mg and comprises
(a) 18 mg of lenvatinib (equivalent to 22.05 mg of lenvatinib mesylate),
(b) 36 mg of microcrystalline cellulose,
(c) 42.75 mg of mannitol,
(d) 45 mg of low substituted hydroxypropyl cellulose,
(e) 19.8 mg of calcium hydroxide,
(f) 5.4 mg of potassium hydroxide,
(g) 5.4 mg of hydroxypropyl cellulose,
(h) 3.6 mg of talc and wherein the capsule suitable for administration is in a size 2 or larger capsule.

[048] In a further embodiment, the present invention provides a capsule which weighs 200 mg and comprises
(a) 20 mg of lenvatinib (equivalent to 24.5 mg of lenvatinib mesylate),
(b) 40 mg of microcrystalline cellulose,
(c) 47.5 mg of mannitol,
(d) 50 mg of low substituted hydroxypropyl cellulose,
(e) 22 mg of calcium hydroxide,
(f) 6 mg of potassium hydroxide,
(g) 6 mg of hydroxypropyl cellulose,
(h) 4 mg of talc and wherein the capsule suitable for administration is in a size 2 or larger capsule.

[049] In a still further embodiment, the present invention provides a capsule which weighs 240 mg and comprises
(a) 24 mg of lenvatinib (equivalent to 29.4 mg of lenvatinib mesylate),
(b) 48 mg of microcrystalline cellulose,
(c) 57 mg of mannitol,
(d) 60 mg of low substituted hydroxypropyl cellulose,
(e) 26.4 mg of calcium hydroxide,
(f) 7.2 mg of potassium hydroxide,
(g) 7.2 mg of hydroxypropyl cellulose,
(h) 4.8 mg of talc and wherein the capsule suitable for administration is in a size 1 or larger capsule.

[050] In embodiments of the present invention, the dosage forms herein can be prepared by any methods of pharmacy, but all methods include the step of bringing lenvatinib active ingredient in association with pharmaceutically acceptable excipients, which constitute one or more necessary ingredients. In general, the compositions are prepared by uniformly mixing (i.e direct blend) the lenvatinib active ingredient with pharmaceutically acceptable excipients and then if necessary, granulating the lenvatinib active ingredient with pharmaceutically acceptable excipients (e.g., wet granulation, compaction such as roller compaction) and compression into tablets. If desired, the tablets can be coated by standard aqueous or non-aqueous techniques.

[051] A dosage form provided herein can be prepared by compression or molding, optionally with one or more accessory ingredients. Compressed tablets can be prepared by compressing in a suitable machine the active ingredient in a free-flowing form such as powder or granules, optionally mixed with an excipient as above and/or a surface active or dispersing agent. Molded tablets can be made by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent. Encapsulation of the dosage forms provided herein can be done using capsules of methylcellulose, calcium alginate, or gelatin.

[052] In embodiment of the present invention, the single unit dosage form comprising 12 mg of lenvatinib is used for treatment of unresectable hepatocellular carcinoma, single unit dosage form comprising 18 mg of lenvatinib is used for treatment of renal cell carcinoma, single unit dosage form comprising 20 mg of lenvatinib is used for treatment of endometrial carcinoma and single unit dosage form comprising 24 mg of lenvatinib is used for the treatment of differentiated thyroid cancer.

[053] The following examples are provided to illustrate the present invention. It is understood, however, that the invention is not limited to the specific conditions or details described in the examples below. The examples should not be construed as limiting the invention as the examples merely provide specific methodology useful in the understanding and practice of the invention and its various aspects. While certain preferred and alternative embodiments of the invention have been set forth for purposes of disclosing the invention, modification to the disclosed embodiments can occur to those who are skilled in the art.

[054] Example 1: 12 mg strength of lenvatinib dosage capsule

[055] Table 1 illustrates a single dosage formulation for 12 mg strength lenvatinib single dosage unit in a size # 3 capsule.
Table 1
Material Quantity (mg/Capsule)
Lenvatinib Mesylate 14.7*
Microcrystalline Cellulose 24
Mannitol 28.5
Low substituted hydroxypropyl cellulose 30
Calcium hydroxide 13.2
Potassium hydroxide 3.6
Hydroxypropyl cellulose 3.6
Talc 2.4
Total 120
*denote the amount of lenvatinib mesylate that corresponds to the amount that provides the potency of 12 mg of lenvatinib.

[056] Process for Preparation: Lenvatinib mesylate was co-sifted with mannitol, calcium hydroxide, microcrystalline cellulose, intragranular low substituted hydroxypropyl cellulose (12mg of total 30mg per capsule weight), and dry mixed in a blender. The above dry mixed blend was loaded into the fluid bed processor and the dry mixed blend was wet granulated with the solution containing potassium hydroxide and hydroxypropyl cellulose to form the granules in fluid bed processor. The granules are dried and mixed with extragranular low substituted hydroxypropyl cellulose (18 mg per capsule) and further lubricated with talc and filled into capsules of Size # 3 and further packed into blisters of Aluminum/Aluminum by blister packaging machine.

[057] Example 2: 18 mg strength of lenvatinib dosage capsule

[058] Table 2 illustrates a single dosage formulation for 18 mg strength lenvatinib single dosage unit in a size # 2 capsule.
Table 2
Material Quantity (mg/Capsule)
Lenvatinib Mesylate 22.05*
Microcrystalline Cellulose 36
Mannitol 42.75
Low substituted hydroxypropyl cellulose 45
Calcium hydroxide 19.8
Potassium hydroxide 5.4
Hydroxypropyl cellulose 5.4
Talc 3.6
Total 180
*denote the amount of lenvatinib mesylate that corresponds to the amount that provides the potency of 18 mg of lenvatinib.

[059] Process for Preparation: Lenvatinib mesylate was co-sifted with mannitol, calcium hydroxide, microcrystalline cellulose, intragranular low substituted hydroxypropyl cellulose (18mg of total 45mg per capsule weight), and dry mixed in a blender. The above dry mixed blend was loaded into the fluid bed processor and the dry mixed blend was wet granulated with the solution containing potassium hydroxide and hydroxypropyl cellulose to form the granules in fluid bed processor. The granules are dried and mixed with extragranular low substituted hydroxypropyl cellulose (27 mg per capsule) and further lubricated with talc and filled into capsules of Size# 2 and further packed into blisters of Aluminum/Aluminum by blister packaging machine.

[060] Example 3: 20 mg strength of lenvatinib dosage capsule
[061] Table 3 illustrates a single dosage formulation for 20 mg strength lenvatinib single dosage unit in a size # 2 capsule.
Table 3
Material Quantity (mg/Capsule)
Lenvatinib Mesylate 24.5*
Microcrystalline Cellulose 40
Mannitol 47.5
Low substituted hydroxypropyl cellulose 50
Calcium hydroxide 22
Potassium hydroxide 6
Hydroxypropyl cellulose 6
Talc 4
Total 200
*denote the amount of lenvatinib mesylate that corresponds to the amount that provides the potency of 20 mg of lenvatinib.

[062] Process for Preparation: Lenvatinib mesylate was co-sifted with mannitol, calcium hydroxide, microcrystalline cellulose, intragranular low substituted hydroxypropyl cellulose (20 mg of total 50 mg per capsule weight), and dry mixed in a blender. The above dry mixed blend was loaded into the fluid bed processor and the dry mixed blend was wet granulated with the solution containing potassium hydroxide and hydroxypropyl cellulose to form the granules in fluid bed processor. The granules are dried and mixed with extragranular low substituted hydroxypropyl cellulose (30 mg per capsule) and further lubricated with talc and filled into capsules of Size # 2, and further packed into blisters of Aluminum/Aluminum by blister packaging machine.

[063] Example 4: 24 mg strength of lenvatinib dosage capsule

[064] Table 4 illustrates a single dosage formulation for 24 mg strength lenvatinib single dosage unit in a size # 1 capsule.
Table 4
Material Quantity (mg/Capsule)
Lenvatinib Mesylate 29.4*
Microcrystalline Cellulose 48
Mannitol 57
Low substituted hydroxypropyl cellulose 60
Calcium hydroxide 26.4
Potassium hydroxide 7.2
Hydroxypropyl cellulose 7.2
Talc 4.8
Total 240
*denote the amount of lenvatinib mesylate that corresponds to the amount that provides the potency of 24 mg of lenvatinib.

[065] Process for Preparation: Lenvatinib mesylate was co-sifted with mannitol, calcium hydroxide, microcrystalline cellulose, intragranular low substituted hydroxypropyl cellulose (24mg of total 60mg per capsule weight), and dry mixed in a blender. The above dry mixed blend was loaded into the fluid bed processor and the dry mixed blend was wet granulated with the solution containing potassium hydroxide and hydroxypropyl cellulose to form the granules in fluid bed processor. The granules are dried and mixed with extragranular low substituted hydroxypropyl cellulose (36 mg per capsules) and further lubricated with talc and filled into capsules of Size # 1, and further packed into blisters of Aluminum/Aluminum by blister packaging machine.
,CLAIMS:1. A single unit dosage form suitable for oral administration to a human comprising, an amount equal to or greater than about 11 mg to about 30 mg of lenvatinib or a pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, hydrate or clathrate, thereof; and a pharmaceutically acceptable excipient.

2. The single unit dosage form as claimed in claim 1 comprising of 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, 16 mg, 17 mg, 18 mg, 19 mg, 20 mg, 21 mg, 22 mg, 23 mg, 24 mg, 25 mg, 26 mg, 27 mg, 28 mg, 29 mg and 30 mg of lenvatinib or a pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, hydrate or clathrate, thereof.

3. The single unit dosage form as claimed in claim 1 is selected from the group consisting of capsules, caplets, tablets, lozenges, orally disintegrating tablets and orally disintegrating films.

4. A single unit dosage form comprising
(a) about 12 mg, 18 mg, 20 mg and 24 mg of lenvatinib or a pharmaceutically acceptable salt thereof,
(b) about 13.2 mg, 19.8 mg, 22 mg or 26.4 mg of calcium hydroxide,
(c) about 3.6 mg, 5.4 mg, 6 mg or 7.2 mg of potassium hydroxide
(d) about 24 mg, 36 mg, 40 mg and 48 mg of microcrystalline cellulose,
(e) about 28.5 mg, 42.75 mg, 47.5 mg and 57 mg of mannitol,
(f) about 30 mg, 45 mg, 50 mg and 60 mg of low substituted hydroxypropyl cellulose,
(g) about 3.6 mg, 5.4 mg, 6 mg and 7.2 mg of hydroxypropyl cellulose, and
(h) about 2.4 mg, 3.6 mg, 4 mg and 4.8 mg of talc.

5. The single unit dosage form as claimed in claim 4 selected from the group consisting of capsules, caplets, tablets, lozenges, orally disintegrating tablets and orally disintegrating films.

6. The capsule dosage form as claimed in claim 5, wherein the capsule dosage from weighs 120 mg and comprises
(a) 12 mg of lenvatinib (equivalent to 14.7 mg of lenvatinib mesylate),
(b) 24 mg of microcrystalline cellulose,
(c) 28.5 mg of mannitol,
(d) 30 mg of low substituted hydroxypropyl cellulose,
(e) 13.2 mg of calcium hydroxide,
(f) 3.6 mg of potassium hydroxide,
(g) 3.6 mg of hydroxypropyl cellulose and
(h) 2.4 mg of talc.

7. The capsule dosage form as claimed in claim 5, wherein the capsule dosage form weighs 180 mg and
(a) 18 mg of lenvatinib (equivalent to 22.05 mg of lenvatinib mesylate),
(b) 36 mg of microcrystalline cellulose,
(c) 42.75 mg of mannitol,
(d) 45 mg of low substituted hydroxypropyl cellulose,
(e) 19.8 mg of calcium hydroxide,
(f) 5.4 mg of potassium hydroxide,
(g) 5.4 mg of hydroxypropyl cellulose and
(h) 3.6 mg of talc.

8. The capsule dosage form as claimed in claim 5, wherein the capsule dosage form weighs 200 mg and comprises
(a) 20 mg of lenvatinib (equivalent to 24.5 mg of lenvatinib mesylate),
(b) 40 mg of microcrystalline cellulose,
(c) 47.5 mg of mannitol,
(d) 50 mg of low substituted hydroxypropyl cellulose,
(e) 22 mg of calcium hydroxide,
(f) 6 mg of potassium hydroxide,
(g) 6 mg of hydroxypropyl cellulose and
(h) 4 mg of talc.

9. The capsule dosage form as claimed in claim 5, wherein the capsule dosage form weighs 240 mg and comprises
(a) 24 mg of lenvatinib (equivalent to 29.4 mg of lenvatinib mesylate),
(b) 48 mg of microcrystalline cellulose,
(c) 57 mg of mannitol,
(d) 60 mg of low substituted hydroxypropyl cellulose,
(e) 26.4 mg of calcium hydroxide,
(f) 7.2 mg of potassium hydroxide,
(g) 7.2 mg of hydroxypropyl cellulose,
(h) 4.8 mg of talc