A monolithic tablet composition comprising linagliptin & metformin

Abstract

The present invention relates to a monolithic tablet composition comprising a) first granules comprising linagliptin, meglumine and one or more pharmaceutically acceptable excipients; b) second granules comprising metformin or its pharmaceutically acceptable salts and one or more pharmaceutically acceptable excipients; and c) an extragranular component comprising at least one disintegrant. The present invention further relates to a preparation of said composition and use thereof for adults with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycaemic control.

Description

[0001] A MONOLITHIC TABLET COMPOSITION COMPRISING LINAGLIPTIN & METFORMIN

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to a monolithic tablet composition comprising a) first granules comprising linagliptin, meglumine and one or more pharmaceutically acceptable excipients; b) second granules comprising metformin or its pharmaceutically acceptable salts and one or more pharmaceutically acceptable excipients; and c) an extragranular component comprising at least one disintegrant. The present invention further relates to a preparation of said composition and use thereof for adults with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycaemic control.

[0004] BACKGROUND OF THE INVENTION

[0005] Linagliptin is chemically known 8-[(3R)-3-aminopiperidin-1-yl]-7-but-2-yn-1-yl)-3- methyl-1-[(4- methyl quinazolin-2-yl)methyl]-3,7-dihydro-1 H-purine-2, 6-dione as shown in formula (I):

[0006] Linagliptin is a selective, orally administered, xanthine based dipeptidyl peptidase-4 (DPP-4) inhibitor used as an adjunct to diet and exercise to improve glycemic control. DPP-4 inhibitors work by blocking the action of DPP-4, an enzyme which destroys the hormone incretin. There are two types of incretin hormones found in the body, called glucagon-like peptide-1 (GLP-1 ) and glucose-dependent insulinotropic peptide (GIP). These hormones are naturally produced by the body in response to food intake. Their function is to help the body produce more insulin only when it is needed and reduce the amount of glucose being produced by the liver when it is not needed. Linagliptin works by binding to DPP-4 and preventing it from breaking down the GLP- 1 and GIP. This increases the levels of these hormones in the body and so increases their effect on controlling blood sugar.

[0007] Metformin is chemically known 1 ,1 -dimethylbiguanide hydrochloride as shown in formula (II):

[0008] Metformin is antidiabetics having an orally-administrated biguanide structure. Metformin hydrochloride is a white to off-white crystalline compound and it is freely soluble in water and practically insoluble in acetone, ether and chloroform. Oral doses of metformin are generally recommended in the range of 500 to 2500 mg a day and a single dose may vary from 500 to 850 mg. It is used singly or in combination with sulfonylureas, alpha-glucosidase inhibitors, or insulin.

[0009] The combination of Linagliptin and Metformin is well known combination and marketed under the tradename of Jentadueto® by Boehringer Ingelheim. Jentadueto® film- coated tablets is indicated in adults with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycaemic control in patients inadequately controlled on their maximally tolerated dose of metformin alone. The maximum recommended daily dose of 5 mg linagliptin plus 2,000 mg of metformin hydrochloride for adults with normal renal function (GFR >90 ml / min). The dose of Jentadueto® should be individualized on the basis of the patient’s current regimen, effectiveness, and tolerability. For patients not adequately controlled on metformin alone, the usual starting dose of Jentadueto® should provide linagliptin dosed as 2.5 mg twice daily (5 mg total daily dose) plus the dose of metformin already being taken. Jentadueto® film coated tablet contains arginine, copovidone, magnesium stearate, maize starch and colloidal silica anhydrous in tablet core & hypromellose, titanium dioxide, talc, yellow iron oxide red iron oxide and propylene glycol in film coating.

[0010] According to the European Public Assessment report (EPAR) of Jentadueto®, originator has submitted that active substances showed degradation of linagliptin when combined with metformin hydrochloride. Several concepts to overcome this instability were considered for the final formulation, including physical separation in the pharmaceutical form (bilayer tablets) or addition of a stabilizer. Screening trials with excipients with a potentially stabilizing effect on linagliptin were performed in order to find a suitable stabilizer for the formulation. In short, it is challenging to identify the suitable stabilizing agent, which prevent the degradation of actives when combined.

[0011] EP 1532149 B1 firstly discloses the Linagliptin compound and its processes for preparation, pharmaceutical compositions and use thereof in the treatment of diseases or conditions associated with increased DPP-IV activity or which can be prevented or alleviated by reduction of DPP-IV activity, in particular diabetes mellitus type I or type II.

[0012] US 3174901 firstly discloses the biguanide antihyperglycemic agent metformin compound and its processes for preparation, pharmaceutical compositions & combinations.

[0013] EP 2023902 B1 discloses the pharmaceutical composition comprising as an active ingredient a DPP IV inhibitor compound (Linagliptin) or a salt thereof, a first diluent which is mannitol, a second diluent which is pregelatinized starch, a binder which is copovidone, a disintegrant which is corn starch, and a lubricant which is magnesium stearate and its manufacturing process.

[0014] WO 2009121945 A2 discloses pharmaceutical composition comprising or made from DPP-4 inhibitor, a partner drug, and one or more pharmaceutical excipients, and a nucleophilic and / or basic agents for stabilizing said DPP-4 inhibitor against degradation. The DPP-4 inhibitor is linagliptin and partner drug is metformin HCI. Furthermore, WO 2009121945 A2 discloses use of a basic amino acid L-arginine, which may be suitable for stabilizing, such as e.g. a suitable buffering agent as stabilizer, to overcome the problems of incompatibility and poor stability, especially decomposition and / or "assay decrease" which may be caused e.g. by reaction of free base type DPP-4 inhibitors when combined with an incompatible partner drug, or its impurity product and / or a pharmaceutical excipient having such functional group (such as a reducing end of a sugar or an acyl group, such as e.g. an acetyl or carbamoyl group).

[0015] WO 2009121945 A2 discloses the preparation of 2.5 / 500 mg, 2.5 / 850 mg and 2.5 / 1000 mg strength mono-layer tablets comprising linagliptin, metformin hydrochloride, L- arginine, a filler (corn starch), a binder (copovidone), a glidant (colloidal anhydrous silica) and a lubricant (magnesium stearate) in the core, and a film coat comprising hypromellose, propylene glycol, talc, titanium dioxide, iron oxide yellow and iron oxide red. The tablets are produced by conventional fluid-bed granulation of all core ingredients, except the glidant and the lubricant, which are added extra-granularly, and subsequent conventional compressing and film-coating. The bi-layer and tablet-in tablet formulations involve the preparation of separate linagliptin granules comprising arginine as stabilizing agent and metformin granules.

[0016] EP 2482812 A1 discloses the pharmaceutical composition comprising or made from a DPP-4 inhibitor which is Linagliptin, metformin, a stabilizer which is a basic amino acid and one or more pharmaceutical excipients for use in treating and / or of metabolic diseases, especially type 2 diabetes mellitus.

[0017] EP 3801539 A2 discloses a solid oral pharmaceutical formulation comprising linagliptin or a pharmaceutically acceptable salt thereof, wherein the composition is free of microcrystalline cellulose, croscarmellose sodium and stearates.

[0018] WO 2021160608 A1 discloses an oral pharmaceutical dosage form comprising linagliptin and metformin, characterized in that it comprises: a) a first type of granule comprising linagliptin or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient; and b) a second type of granule comprising metformin or a pharmaceutically acceptable salt thereof and meglumine. WO 2022173406 A1 discloses a process for the preparation of the film coated tablet comprising linagliptin or a pharmaceutically acceptable salt thereof comprising the following steps a) mixing linagliptin or a pharmaceutically acceptable salt thereof, at least one disintegrant and at least one filler, b) dissolving at least binder in a solvent and obtained a granulation solution, c) granulating the mixture with the granulation solution at step (a) using spray granulation.

[0019] EP 2882424 B1 discloses a pharmaceutical composition comprising linagliptin or a pharmaceutically acceptable salt thereof as active ingredient, mannitol, copovidone, and magnesium stearate, wherein the mannitol is present in an amount of 90% to 95 % by weight, based on the pharmaceutical composition, and the pharmaceutical composition is prepared by direct compression.

[0020] EP 4161525 A1 discloses a process for the preparation of a film coated tablet comprising linagliptin and metformin wherein the process comprises steps of a) preparing a mixture called first mixture comprising metformin HCI and at least one pharmaceutically acceptable excipient b) preparing a mixture called second mixture comprising linagliptin and meglumine c) preparing a granulation solution.

[0021] WO 2014080383 A1 discloses fixed- dose combination formulations comprising a DPP-4 inhibitor and an additional antidiabetic agent, preferably the combination of linagliptin and metformin. The formulations are in the form of monolayer, bilayer or trilayer tablets and comprise an alkalinizing agent as stabilizer, which is not a basic amino acid. Several suitable alkalinizing agents are cited, and meglumine is said to be preferred.

[0022] The prior art references emphasize on using stabilizing agent, particularly basic agent, to overcome the problem of chemical degradation of free base of linagliptin when combined with metformin hydrochloride. Hence, there is still a need exists which would address the issue relating to degradation of linagliptin and provides a chemically stable pharmaceutical composition of linagliptin in the presence of its partner drug metformin hydrochloride. The inventors of the present invention have surprisingly found an alternative composition in the form of monolithic tablet comprising Linagliptin, metformin hydrochloride and stabilizing agent meglumine with particular arrangement of excipients provides enhanced stability, enhanced dissolution profile and bioavailability of said composition.

[0023] OBJECTS OF THE INVENTION

[0024] The main object of the present invention is to obtain a monolithic tablet composition of linagliptin and metformin hydrochloride eliminating all aforesaid problems and bringing additional advantages to the relevant prior art.

[0025] Another object of the present invention is to develop a monolithic tablet composition of linagliptin and metformin hydrochloride with enhanced stability.

[0026] Another object of the present invention is to obtain a monolithic tablet composition of linagliptin and metformin hydrochloride with increased uniformity.

[0027] Another object of the present invention is to obtain a monolithic tablet composition of linagliptin and metformin hydrochloride with enhanced dissolution profile and bioavailability.

[0028] Another object of the present invention is to obtain a monolithic tablet composition of linagliptin and metformin hydrochloride with desired content uniformity.

[0029] Another object of the present invention is to obtain a monolithic tablet composition of linagliptin and metformin hydrochloride having the desired stability, content uniformity, flowability and compressibility.

[0030] SUMMARY OF THE INVENTION

[0031] In one aspect, the present invention provides a monolithic tablet composition comprising a) first granules comprising linagliptin, meglumine and one or more pharmaceutically acceptable excipients; b) second granules comprising metformin or its pharmaceutically acceptable salts and one or more pharmaceutically acceptable excipients; and c) an extragranular component comprising at least one disintegrant.

[0032] In another aspect, the present invention provides a monolithic tablet composition, wherein first granules comprising linagliptin or its pharmaceutically acceptable salts, meglumine and one or more pharmaceutically acceptable excipients are selected from diluent and / or binder.

[0033] In yet another aspect, the present invention provides a monolithic tablet composition, wherein first granules comprising linagliptin or its pharmaceutically acceptable salts, meglumine and diluent comprising mannitol and / or pregelatinized starch.

[0034] In yet another aspect, the present invention provides a monolithic tablet composition, wherein first granules comprising linagliptin or its pharmaceutically acceptable salts, meglumine and copovidone as binder.

[0035] In yet another aspect, the present invention provides a monolithic tablet composition, wherein first granules comprising linagliptin or its pharmaceutically acceptable salts, meglumine, diluent comprising mannitol and / or pregelatinized starch and copovidone as binder.

[0036] In yet another aspect, the present invention provides a monolithic tablet composition, wherein second granules comprising metformin or its pharmaceutically acceptable salts and one or more pharmaceutically acceptable excipients selected from diluent and / or binder.

[0037] In yet another aspect, the present invention provides a monolithic tablet composition, wherein second granules comprising metformin or its pharmaceutically acceptable salts and pregelatinized starch as diluent.

[0038] In yet another aspect, the present invention provides a monolithic tablet composition, wherein second granules comprising metformin or its pharmaceutically acceptable salts and copovidone as binder. In yet another aspect, the present invention provides a monolithic tablet composition, wherein second granules comprising metformin or its pharmaceutically acceptable salts, pregelatinized starch as diluent and copovidone as binder.

[0039] In yet another aspect, the present invention provides a monolithic tablet composition, wherein an extragranular component comprising crospovidone as a disintegrant.

[0040] In yet another aspect, the present invention provides a process for the preparation of monolithic tablet composition comprises steps of: a) granulating the linagliptin, meglumine and one or more pharmaceutically acceptable excipients with a granulation solution comprising a binder to obtain granules and drying the granules; b) granulating the metformin or its pharmaceutically acceptable salts and one or more pharmaceutically acceptable excipients with a granulation solution comprising a binder to obtain granules and drying the granules; c) blending the granules obtained in step (a) and step (b) with at least one disintegrant; and d) compressing the granules obtained in step (c) to obtain tablet. e) optionally, coating the tablets.

[0041] In yet another aspect, the present invention provides use of a monolithic tablet composition for adults with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycemic control.

[0042] The details of one or more embodiments of the present invention are set forth in the description below. Other features, objects and advantages of the invention will be apparent from the description.

[0043] DETAILED DESCRIPTION OF THE PRESENT INVENTION

[0044] The present invention will now be more specifically illustrated as hereunder. In the present invention, unless indicated otherwise, all ingredient concentrations are presented in units of % weight or % volume .

[0045] The term "about" can indicate a difference of 10 percent of the value specified. Numerical ranges as used herein are meant to include every number and subset of numbers enclosed within that range, whether particularly disclosed or not. Further, these numerical ranges should be construed as providing support for a claim directed to any number or subset of numbers in that range.

[0046] The term “intragranular” as used in the present invention refer to the excipients or ingredients, which are incorporated prior to granulation i.e. , within the granule.

[0047] The term “extragranular” as used in the present invention refer to the excipients or ingredients, which are incorporated after granulation.

[0048] The term “composition” as used in the present invention means pharmaceutical composition includes, without limitation, capsules, tablets, caplets, pellets, granules, beads, etc.

[0049] The term “Linagliptin” as used in the present invention includes, but is not limited to, linagliptin per se, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs (crystalline and amorphous) and pharmaceutically acceptable prodrugs thereof.

[0050] The term “Metformin” as used in the present invention includes, but is not limited to, metformin per se, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs (crystalline and amorphous) and pharmaceutically acceptable prodrugs thereof. The term “meglumine” as used in the present invention includes, but is not limited to, meglumine, meglumine amidodrizoate, meglumine iotalamate, meglumine iotroxate, meglumine iodoxamate or meglumine sulfate. Meglumine chemically known as A / - methylglucamine, a derivative of sorbitol in which the hydroxyl group in position 1 is replaced by methylamino group.

[0051] In general embodiment, the present invention provides a monolithic tablet composition comprising first granules comprising linagliptin or its pharmaceutically acceptable salts, meglumine and one or more pharmaceutically acceptable excipients; second granules comprising metformin or its pharmaceutically acceptable salts and one or more pharmaceutically acceptable excipients; and an extragranular component comprising at least one disintegrant.

[0052] In embodiments, a monolithic tablet composition of the present invention comprising first granules comprising linagliptin or its pharmaceutically acceptable salts, meglumine and one or more pharmaceutically acceptable excipients are selected from diluent and binder.

[0053] In embodiments, a monolithic tablet composition of the present invention comprising second granules comprising metformin or its pharmaceutically acceptable salts and one or more pharmaceutically acceptable excipients are selected from diluent and binder.

[0054] Diluents are selected from the group comprising microcrystalline cellulose, powdered cellulose, dibasic calcium phosphate, tribasic calcium phosphate, calcium carbonate, mannitol, sucrose, sorbitol, xylitol, corn starch, pregelatinised starch, maltodextrin or mixtures thereof. The diluent can be used in amount from 5 % to 30 % by weight of the total weight of the tablet core composition. In the present invention mannitol & pregelatinised starch are preferred diluents.

[0055] Binders are selected from the group comprising povidone, copovidone, hydroxypropyl methyl cellulose, hydroxyethylcellulose, xanthan gum, sorbitol, sucrose, gum arabic, pullulan, gelatin, sodium alginate, com syrup, carbomers or mixtures thereof. The binder can be used in an amount from 5 % to 20% by weight of the total weight of the tablet core composition. In the present invention copovidone is preferred as binder.

[0056] A suitable grade of meglumine is present in an amount of about 0.25% to about 10% by weight of the total weight of the tablet core composition.

[0057] In specific embodiments, a monolithic tablet composition of the present invention comprises first granules comprising linagliptin, meglumine, pregelatinized starch and mannitol as a diluent and copovidone as binder.

[0058] In specific embodiments, a monolithic tablet composition of the present invention comprises second granules comprising Metformin, pregelatinized starch as diluent and copovidone as a binder.

[0059] In specific embodiments, a monolithic tablet composition of the present invention comprising extragranular component comprising at least one disintegrant.

[0060] Disintegrants are selected from the group comprising low substituted hydroxypropyl cellulose (L-HPC), crospovidone, croscarmellose sodium, alginic acid, sodium starch glycolate, carboxymethyl starch, carboxymethyl cellulose, gums and mixtures thereof. The disintegrant can be used in an amount from 1 % to 5 % by weight of the total weight of the tablet core composition. In the present invention crospovidone is preferred disintegrant.

[0061] Lubricants / glidants are selected from the group comprising hydrogenated vegetable oil, glyceryl behenate, stearic acid, sodium stearyl fumarate, magnesium stearate, talc, colloidal silica, aluminium silicate, zinc stearate, silica gel or mixtures thereof. The lubricant can be used in an amount from 1 % to 3% by weight of the total weight of the tablet core composition.

[0062] The monolithic tablet composition of the present invention was prepared by wet granulation of linagliptin & metformin seperately then both the granules were mixed with extragranular component. Dried granules were compressed with tablet compression machine and compressed tablets were coated with coating agent. In specific embodiments, the present invention provides a process for the preparation of monolithic tablet composition comprises steps of: a) granulating the linagliptin, meglumine and one or more pharmaceutically acceptable excipients with a granulation solution comprising a binder obtain granules and drying the granules; b) granulating the metformin or its pharmaceutically acceptable salts and one or more pharmaceutically acceptable excipients with a granulation solution comprising a binder obtain granules and drying the granules; c) blending the granules obtained in step (a) and step (b) with at least one disintegrant; d) compressing the granules obtained in step (c) to obtain tablet; and e) optionally coating the tablets.

[0063] During the preparation of monolithic tablet of the present invention, it has been observed that addition of meglumine in granulation solution while granulating the linagliptin components create a problem of compressibility and flowing of granules and therefore it has been added to the intragranular dry mix along with other excipients.

[0064] The monolithic table composition as described herein above may further be coated with a film forming polymer and one or more pharmaceutically acceptable excipients, using techniques well known in the art e.g., spray coating in a conventional coating pan, or a fluidized bed processor, or dip coating. Alternatively, coating can also be performed using a hot melt technique.

[0065] The film coating may contain one or more film forming polymers, and optionally one or more pharmaceutically acceptable excipients. A suitable film-forming polymer is selected from the group comprising hydroxypropylmethyl cellulose, ethyl cellulose, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, cellulose acetate, hydroxypropylmethyl cellulose phthalate, cellulose acetate trimellitate, methacrylic acid copolymers e.g., Eudragit®, polyvinylpyrrolidone, polyvinylalcohol, polyethylene glycol, or mixtures thereof. A preferred film- forming polymer is hydroxypropylmethyl cellulose. Other suitable filmforming polymers which are known in the art may also be used.

[0066] The monolithic tablet composition of the present invention is used thereof for adults with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycaemic control.

[0067] The following examples are intended to illustrate the scope of the present invention but not to limit it thereto. EXAMPLES

[0068] Example-1: Preparation of Monolithic tablet composition

[0069] Table-1: Unit composition of Monolithic Tablet

[0070] Opadry Pink: hypromellose, talc, iron oxide yellow (E172), titanium dioxide (E171), macrogol 400, iron oxide red (E172).

[0071] Manufacturing process:

[0072] Metformin granules:

[0073] 1 . Metformin and pregelatinized starch were sieved through 1 mm screen.

[0074] 2. Copovidone was dissolved in purified water.

[0075] 3. The mixture obtained in step-1 was granulated using the copovidone solution in fluid bed granulator.

[0076] 4. The granules were dried.

[0077] 5. The obtained granules were sieved through 1 .2 mm screen.

[0078] Linagliptin granules:

[0079] 1 . Copovidone was dissolved in purified water.

[0080] 2. Linagliptin, mannitol, meglumine and pregelatinized starch were sifted through 0.8 mm screen, then the blend was mixed.

[0081] 3. The dry mix obtained in Step-2 was granulated using the copovidone solution in fluid bed granulator.

[0082] 4. The obtained wet granules were sieved through 3 mm screen.

[0083] 5. The granules obtained in step-4 were loaded to the fluid bed system and dried.

[0084] 6. The dried granules were passed through 0.6 mm screen.

[0085] Extragranular:

[0086] 1. Linagliptin and metformin granules obtained herein above were mixed proportionally.

[0087] 2. Crospovidone and colloidal Silica 200 were passed through a 0.63 mm sieve and added into the granules mixture obtained in step-1.

[0088] 3. Talc and Magnesium stearate were passed through a 0.63 mm sieve and added into the above granules mixture of step-2 sequentially. 4. Blend obtained in step-3 was compressed to tablets by using tablet compression machine.

[0089] 5. The compressed tablets were coated with Opadry® Pink. Example-2: Stability of Monolithic tablet composition of Example-1

[0090] The impurity profiles of the composition of Table-1 have been checked at below mentioned conditions:

[0091] Table-2: Impurity results - Tablets of Example-1

[0092] It is evident from the Table-2 that the composition of the present invention is stable.

[0093] Example-3: Dissolution Profiles of Monolithic tablet composition of Example-1

[0094] Table-3: Dissolution profile of Linagliptin as per the composition of Table-1

[0095] Table-4: Dissolution profile of Metformin as per the composition of Table-1

[0096] Dissolution of tablet composition of Example-1 and reference product Jentadueto® tablets were performed using standard USP apparatus II, paddles, at 50 rpm in 0.1 N HCI.

[0097] As seen in Table-3 & Table-4, Linagliptin and Metformin has similar or equivalence dissolution profile with respect to reference product.

Claims

CLAIMS1. A monolithic tablet composition comprising: a) first granules comprising linagliptin, meglumine and one or more pharmaceutically acceptable excipients; b) second granules comprising metformin or its pharmaceutically acceptable salts and one or more pharmaceutically acceptable excipients; and c) an extragranular component comprising at least one disintegrant.

2. The monolithic tablet composition according to claim 1 , wherein one or more pharmaceutically acceptable excipients used in first granules is selected from diluent and binder.

3. The monolithic tablet composition according to claim 1 , wherein one or more pharmaceutically acceptable excipients used in second granules is selected from diluent and binder.

4. The monolithic tablet composition according to claim 2 or 3, wherein the diluent is selected from the group comprising microcrystalline cellulose, powdered cellulose, dibasic calcium phosphate, tribasic calcium phosphate, calcium carbonate, mannitol, sucrose, sorbitol, xylitol, corn starch, pregelatinised starch, maltodextrin and mixtures thereof.

5. The monolithic tablet composition according to claim 2 or 3, wherein the binder is selected from the group comprising povidone, copovidone, hydroxypropyl methyl cellulose, hydroxyethylcellulose, xanthan gum, sorbitol, sucrose, gum arabic, pullulan, gelatin, sodium alginate, com syrup, carbomers and mixtures thereof.

6. The monolithic tablet composition according to claim 1 , wherein the diluent used in first granules is mixture of pregelatinized starch and mannitol.

7. The monolithic tablet composition according to claim 1 , wherein the diluent used in second granules is pregelatinized starch.

8. The monolithic tablet composition according to claim 1 , wherein the binder used in first or second granules is copovidone.

9. The monolithic tablet composition according to claim 1 , wherein the disintegrant used in extragranular component is selected from the group comprising hydroxypropyl cellulose, crospovidone, croscarmellose sodium, alginic acid, sodium starch glycolate, carboxymethyl starch, carboxymethyl cellulose, gums and mixtures thereof.

10. The monolithic tablet composition according to claim 9, wherein the disintegrant is crospovidone.

11. A process for the preparation of monolithic tablet according to the claim 1 comprising the steps of: a) granulating the linagliptin, meglumine and one or more pharmaceutically acceptable excipients with a granulation solution comprising a binder to obtain granules and drying the granules; b) granulating the metformin or its pharmaceutically acceptable salts and one or more pharmaceutically acceptable excipients with a granulation solution comprising a binder to obtain granules and drying the granules; c) blending the granules obtained in step (a) and step (b) with at least one disintegrant; d) compressing the granules obtained in step (c) to obtain tablet; and e) optionally coating the tablets.

12. The monolithic tablet composition according to claim 1 is used for adults with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycemic control.

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