FORMULATIONS COMPRISING OXALATE SALTS OF TENELIGLIPTIN AND SOLVATES THEREOF

FIELD OF INVENTION

[001] The present invention relates to pharmaceutically acceptable formulations comprising oxalate salts of Teneligliptin and solvates thereof, optionally further comprising biguanides class of molecules. Also provided are uses of said formulations and treatment of glucose metabolism disorder in patients in need.

BACKGROUND OF THE INVENTION

[002] Dipeptidyi peptidase-4 (DPP-IV) inhibitors is a class of anti-diabetic drugs act by inhibiting the degradation of the incretins, glucagon-like peptide- 1 (G LP-1) and glucose-dependent insulinotropic peptide (G !P). Genericaily these compounds are termed as "gliptins".

[003] DPP-IV inhibitors are commonly used in a combination therapy along with other antidiabetic drugs,

[004] There is a need in the art to provide novel and stable formulations which are efficacious in nature and exhibit enhanced stability and processability.

SUMMARY OF THE INVENTION

[005] in an embodiment, there is provided pharmaceutical compositions comprising oxalate salts of the compound of Formula (!) and solvates thereof, and at least one or more pharmaceutically acceptable carriers, diluents, binder, lubricant, disintegrant and stabilizing agent. In one aspect of this embodiment, the diluent is selected from group comprising of mannitol, sorbitol, xylitoi, starch, lactose, cellulose, calcium dihydrogen phosphate and like, preferable, mannitol or lactose, in one other aspect, binder is selected from group comprising of hydroxypropy! cellulose, polyvinyl alcohol, povidone, copovidone, ethyl cellulose, hypromellose and like, preferably hypromellose or hydroxypropy! cellulose. in one more aspect of this embodiment, lubricant is glyceryl dibehenate, sodium or calcium stearyl fu ma rate, magnesium stearate, stearic acid, glyceryl palmitostearate and like, preferably glyceryl dibehenate. In other aspect of this embodiment, disintegrant is selected from group comprising of Low- Substituted Hydroxypropyl Cellulose, Crospovidone, Croscarmeilose sodium, Sodium Starch Giycolate and like, preferably Low-Substituted Hydroxypropyl Cellulose, in yet another aspect of this embodiment, stabilizing agent is selected from at least one stabilizer; at least one compiexing agent; at least one polymer; at least one chelating agent; and combinations thereof.

[006] In one aspect of this embodiment, the present invention provides pharmaceutical composition wherein (a) oxalate salt of compound (I) and solvate thereof selected from Teneligliptin 2.5 oxalate or Teneligliptin 3.0 oxalate and solvate thereof

(b) diluent is selected from mannitol or lactose

(c) binder is selected from hydroxypropyl cellulose or hypromellose

(d) Lubricant is selected from glyceryl dibehenate, or magnesium stearate

(e) disintegrant is selected from Low-Substituted Hydroxypropyl Cellulose, Crospovidone, Croscarmellose sodium

(f) stabilizing agent is selected from oxalic acid, beta-cyclodextrin, hydroxypropyl cellulose, EDTA and combinations thereof

[007] In one more aspect of this embodiment, there is provided, a pharmaceutical composition comprising,

(a) oxalate salt of compound (I) and solvate thereof which is Teneligliptin 3.0 oxalate n. hydrate, wherein 1.0 to 4.0

(b) diluent is mannitol

(c) binder is hypromellose

(d) Lubricant is glyceryl dibehenate

(e) disintegrant is Low-Substituted Hydroxypropyl Cellulose

(f) stabilizing agent is selected from oxalic acid, beta-cyclodextrin, hydroxypropyl cellulose, EDTA and combinations thereof

[008] In one more aspect of this embodiment, there is provided, a pharmaceutical composition comprising,

(a) oxalate salt of compound (I) and solvate thereof which is Teneligliptin 3.0 oxalate n. hydrate, wherein 1.0 to 4.0

(b) diluent is lactose

(c) binder is hypromellose

(d) Lubricant is glyceryl dibehenate

(e) disintegrant is Low-Substituted Hydroxypropyl Cellulose

(f) stabilizing agent is selected from oxalic acid, beta-cyclodextrin, hydroxypropyl cellulose, EDTA and combinations thereof.

[009] In an embodiment of the present invention, there is provided pharmaceutical compositions comprising about 0.5 % to about 80.0 % by weight of oxalate salt of compound (I) and solvate thereof, about 10 % to about 95 % by weight of diluent, about 0.1% to about 10.0 % by weight of binder, about 0.1 % to about 20.0 % by weight of lubricant, about 0.1 % to about 30 % by weight of disintegrant and about 0.05 % to about 30 % by weight stabilizing agent. . In one aspect, the oxalate salt of compound (I) and solvate thereof is Teneligliptin 2.5 oxalate or Teneligliptin 3.0 oxalate and solvate thereof. In one more aspect of this embodiment, solvate is n. hydrate. In yet another aspect of this embodiment, oxalate salt of compound (I) and solvate thereof is Teneligliptin 2.5 oxalate n. hydrate or Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0.

[0010] In an embodiment of the present invention, there is provided pharmaceutical compositions comprising about 5 % to about 40.0 % by weight of oxalate salt of compound (I) and solvate thereof, about 15 % to about 95 % by weight of diluent, about 0.1% to about 10 % by weight of binder, about 0.1 % to about 20.0 % by weight of lubricant, about 0.1 % to about 30 % by weight of disintegrant and about 0.1 % to about 20 % by weight stabilizing agent. . In one aspect, the oxalate salt of compound (I) and solvate thereof is Teneligliptin 2.5 oxalate or Teneligliptin 3.0 oxalate and solvate thereof. In one more aspect of this embodiment, solvate is n. hydrate. In yet another aspect of this embodiment, oxalate salt of compound (I) and solvate thereof is Teneligliptin 2.5 oxalate n. hydrate or Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0

[0011] In an embodiment of the present invention, there is provided pharmaceutical compositions comprising about 5 % to about 40.0 % by weight of oxalate salt of compound (I) and solvate thereof, about 30 % to about 80 % by weight of diluent, about 0.1% to about 10 % by weight of binder, about 0.1 % to about 20.0 % by weight of lubricant, about 0.1 % to about 30 % by weight of disintegrant and about 0.1 % to about 20 % by weight stabilizing agent. . In one aspect, the oxalate salt of compound (I) and solvate thereof is Teneligliptin 2.5 oxalate or Teneligliptin 3.0 oxalate and solvate thereof. In one more aspect of this embodiment, solvate is n. hydrate. In yet another aspect of this embodiment, oxalate salt of compound (I) and solvate thereof is Teneligliptin 2.5 oxalate n. hydrate or Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0

[0012] In an embodiment of the present invention, there is provided pharmaceutical compositions comprising about 5 % to about 15.0 % by weight of Teneligliptin 3.0 oxalate n. hydrate, about 30 % to about 80 % by weight of diluent, about 0.1% to about 10 % by weight of binder, about 1.0 % to about 15.0 % by weight of lubricant, about 1.0 % to about 20 % by weight of disintegrant and about 0.5 % to about 15 % by weight stabilizing agent.

[0013] In an embodiment of the present invention, there is provided pharmaceutical compositions comprising about 0.5 % to about 10.0 % by weight of Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, about 5 % to about 40 % by weight of diluent, about 0.1% to about 10 % by weight of binder, about 0.5 % to about 5.0 % by weight of lubricant, about 0.5 % to about 10 % by weight of disintegrant and about 0.1 % to about 10 % by weight stabilizing agent and one or more anti-diabetic agent.

[0014] In one aspect, one or more anti-diabetic agents comprised in pharmaceutical composition of present invention is selected from the group consisting of sulfonyl urea class of compounds and salts thereof, glitazone class of compounds and salts thereof, biguanide class of compounds and salts thereof, alpha-glucosidase inhibitor class of compounds and salts thereof, SG LT2 inhibitor class of compounds and salts thereof, and combinations thereof. In one aspect [0015] In an embodiment of present invention, the pharmaceutical compositions comprises stabilizing agent, wherein stabilizing agent is oxalic acid is present in an amount about 0.5% to about 5.0 % by weight

[0016] In an embodiment of present invention, the pharmaceutical compositions comprises stabilizing agent, wherein stabilizing agent is beta-cyclodextrin present in an amount about 0.5 % to about 5.0% by weight

[0017] In an embodiment of present invention, the pharmaceutical compositions comprises stabilizing agent, wherein stabilizing agent is hydroxy-propyl cellulose present in an amount about 0.1 % to about 5.0 % by weight

[0018] In an embodiment of present invention, the pharmaceutical compositions comprises stabilizing agent, wherein stabilizing agent is EDTA present in an amount about 0.5% to about 5.0% by weight [0019] In an embodiment, oxalate salts of the compound of Formula (I) in pharmaceutical composition of present invention is Teneligliptin 2.5 oxalate n. hydrate, wherein n is 1.0 to 4.0, characterized by X ray powder diffraction pattern comprising reflections at 5.68°, 6.56°, 16.44°, 17.72°, 18.34°, 21.12°, 21.67°, 23.15°, 23.86°, 24.99° ± 26

[0020] In an embodiment, oxalate salts of the compound of Formula (I) in pharmaceutical composition of present invention is Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, characterized by X ray powder diffraction pattern comprising reflections at 5.69°, 6.57°, 16.43°, 17.71°, 21.66°, 23.15°, 23.86°, 24.99°± 26

[0021] In one embodiment, Pharmaceutical compositions comprising oxalate salts of the compound of Formula (I)

[0022] In one aspect of present invention, pharmaceutical compositions said oxalate salts of the compound of Formula (I) and solvates thereof comprised in pharmaceutical composition of present invention, are substantially pure.

[0023] In one embodiment, the present invention provides, pharmaceutical composition comprising oxalate salt of compound of formula (I)

[0024] and solvate thereof; and at least one or more anti-diabetic agents selected from the group consisting of sulfonyl urea class of compounds and salts thereof, glitazone class of compounds and salts thereof, biguanide class of compounds and salts thereof, alpha-glucosidase inhibitor class of compounds and salts thereof, SGLT2 inhibitor class of compounds and salts thereof, and combinations thereof. In one aspect of this embodiment, pharmaceutical compositions comprise sulfonyl urea class of compounds comprises glimepiride, glipiride, tolbutamide, tolazamide, glibenclamide, gliclazide and the like. In another aspect of this embodiment, pharmaceutical compositions comprise glitazone class of compounds comprising pioglitazone, rosiglitazone and the like. In one more aspect, of this embodiment, pharmaceutical compositions comprise biguanide class of compounds comprises metformin, buformin, phenformin and like or pharmaceutically acceptable salt thereof. In yet another aspect of this embodiment, pharmaceutical compositions comprise alpha-glucosidase inhibitor class of compounds comprising voglibose, acarbose, miglitol and the like. In one more aspect of this embodiment, pharmaceutical compositions comprise SG LT2 inhibitor class of compounds comprises remogliflozin, dapagliflozin, canagliflozin, empagliflozin, luseogliflozin and the like, salt, ester or solvate thereof.

[0025] In an embodiment, the present invention provides a pharmaceutical composition comprising Teneligliptin 2.5 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0 and extended release metformin, wherein Teneligliptin 2.5 oxalate n. hydrate to metformin or w/w ratio is in the range of 1:10-1:50.

[0026] In an embodiment, the present invention provides a pharmaceutical composition comprising Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0 and metformin, wherein Teneligliptin 3.0 oxalate n. hydrate to metformin w/w ratio is in the range of 1:10-1:50.

[0027] In an embodiment, the present invention provides a pharmaceutical composition comprising a mixture of Teneligliptin 2.5 oxalate n. hydrate and Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0; and metformin, wherein mixture to metformin w/w ratio is in the range of 1:10-1:50.

[0028] In an embodiment, the present invention provides, pharmaceutical compositions comprising oxalate salt of compound of formula (I) and solvate thereof, wherein said oxalate salt is at least 99% pure and content of compound of formula (I I) is less than 1.0 %.

[0029] In an aspect of the present invention, there is provided pharmaceutical compositions comprising: (i) at least one of (a) oxalate salts of the compound of Formula (I) and solvates thereof; (b) Teneligliptin 2.5 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0; (c) Teneligliptin 3.0 oxalate, wherein n is 1.0 to 4.0, preferably 1.0; (ii) at least one or more anti-diabetic agents selected from the group consisting of sulfonyl urea class of compounds and salts thereof, glitazone class of compounds and salts thereof, biguanide class of compounds and salts thereof, alpha-glucosidase inhibitor class of compounds and salts thereof, SGLT2 inhibitor class of compounds and salts thereof, and combinations thereof; and (iii) at least one or more pharmaceutically acceptable carriers, diluents and excipients.

[0030] In another aspect of the present invention, there is provided pharmaceutical compositions comprising (i) comprising oxalate salts of the compound of Formula (I) and solvates thereof; or (ii), Teneligliptin 2.5 oxalate n. hydrate wherein n is 1.0 to 4.0, preferably 1.0; or (iii) Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0; or (iv) Teneligliptin 2.5 oxalate n. hydrate and Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0; or (v) any one of (i) to (iv) and ) at least one or more anti-diabetic agents selected from the group consisting of sulfonyl urea class of compounds and salts thereof, glitazone class of compounds and salts thereof, biguanide class of compounds and salts thereof, alpha-glucosidase inhibitor class of compounds and salts thereof, SG LT2 inhibitor class of compounds and salts thereof, and combinations thereof for use in prophylactic or curative treatment of glucose metabolism disorder in a patient.

[0031] In yet another aspect of the present invention, there is provided a method of prophylactic or curative treatment of a patient with glucose metabolism disorder comprising administering a physiologically relevant amount of pharmaceutical compositions comprising (i) comprising oxalate salts of the compound of Formula (I) and solvates thereof; or (ii) Teneligliptin 2.5 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0; or (iii) Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0; or (iv) Teneligliptin 2.5 oxalate n. hydrate and Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0; or (v) any one of (i) to (iv) and at least one or more anti-diabetic agents selected from the group consisting of sulfonyl urea class of compounds and salts thereof, glitazone class of compounds and salts thereof, biguanide class of compounds and salts thereof, alpha-glucosidase inhibitor class of compounds and salts thereof, SGLT2 inhibitor class of compounds and salts thereof, and combinations thereof.

[0032] This summary is not intended to identify essential features of the claimed subject matter not is it intended for use in determining or limiting the scope of the claimed subject matter.

OBJECTS OF THE INVENTION

[0033] An object of the present invention is to provide pharmaceutically acceptable formulations comprising oxalate salts of Teneligliptin and solvates thereof with superior processability.

[0034] An object of the present invention is to provide pharmaceutically acceptable formulations comprising oxalate salts of Teneligliptin and solvates thereof with superior stability.

[0035] Yet another object of the present invention is to provide pharmaceutically acceptable formulations comprising oxalate salts of Teneligliptin and solvates thereof and at least one or more antidiabetic agents selected from the group consisting of sulfonyl urea class of compounds and salts thereof, glitazone class of compounds and salts thereof, biguanide class of compounds and salts thereof, alpha-glucosidase inhibitor class of compounds and salts thereof, SG LT2 inhibitor class of compounds and salts thereof, and combinations thereof with superior characteristics such as processability, and stability.

[0036] Still another object of the present invention is to provide pharmaceutically acceptable formulations comprising oxalate salts of Teneligliptin and solvates thereof, optionally further comprising at least one or more anti-diabetic agents selected from the group consisting of sulfonyl urea class of compounds and salts thereof, glitazone class of compounds and salts thereof, biguanide class of compounds and salts thereof, alpha-glucosidase inhibitor class of compounds and salts thereof, SG LT2 inhibitor class of compounds and salts thereof, and combinations thereof, useful in treatment or control of glucose metabolism disorders in patients. BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWINGS

[0037] The following drawings form part of the present specification and are included to further illustrate aspects of the present invention. The invention may be better understood by reference to the drawings in combination with the detailed description of the embodiments presented herein.

[0038] FIG. 1 depicts the X ray powder diffraction pattern of crystalline Teneligliptin 2.5 oxalate n. hydrate, in accordance with an embodiment of the present invention.

[0039] FIG. 2 depicts the differential scanning calorimetry of crystalline Teneligliptin 2.5 oxalate n. hydrate, in accordance with an embodiment of the present invention.

[0040] FIG. 3 depicts the FT-I R spectrum of crystalline Teneligliptin 2.5 oxalate n. hydrate, in accordance with an embodiment of the present invention.

[0041] FIG. 4 depicts the depicts the X ray powder diffraction pattern of crystalline Teneligliptin 3.0 oxalate n. hydrate, in accordance with an embodiment of the present invention.

[0042] FIG. 5A-B depicts the differential scanning calorimetry of crystalline Teneligliptin 3.0 oxalate n. hydrate, in accordance with an embodiment of the present invention.

[0043] FIG.6 depicts the FT-IR spectrum of crystalline Teneligliptin 3.0 oxalate n. hydrate, in accordance with an embodiment of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

[0044] Those skilled in the art will be aware that the invention described herein is subject to variations and modifications other than those specifically described. It is to be understood that the invention described herein includes all such variations and modifications. The invention also includes all such steps, features, compositions and methods referred to or indicated in this specification, individually or collectively, and any and all combinations of any two or more said steps or features.

Definitions

[0045] For convenience, before further description of the present invention, certain terms employed in the specification, examples are collected here. These definitions should be read in light of the remainder of the disclosure and understood as by a person of skill in the art. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by a person of ordinary skill in the art. The terms used throughout this specification are defined as follows, unless otherwise limited in specific instances. [0046] The terms used herein are defined as follows. If a definition set forth in the present application and a definition set forth later in a non-provisional application claiming priority from the present provisional application are in conflict, the definition in the non-provisional application shall control the meaning of the terms.

[0047] The term "solvate" means an aggregate consisting of a solute ion or molecule with one or more solvent molecules. Solvates can be, but are not limited to, acetone solvate, etanol solvate, methanol solvate, butanol solvate, TBA solvate, chloroform solvate, and other organic and inorganic solvates.

[0048] The term "hydrate" means a compound, typically a crystalline one, in which one or more water molecules are chemically bound to another compound or molecule or element.

[0049] As used in the specification and the claims, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise.

[0050] The present disclosure is not to be limited in scope by the specific embodiments described herein, which are intended for the purposes of exemplification only.

[0051] The term "salt" or "pharmaceutically acceptable salt" as used herein, is intended to mean those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, and allergic response, commensurate with a reasonable benefit to risk ratio, and effective for their intended use.

[0052] The term "crystalline" as used herein, means having a regularly repeating arrangement of molecules or external face planes.

[0053] The term "amorphous" as used herein, means essentially without regularly repeating arrangement of molecules or external face planes.

[0054] Unless stated otherwise, percentages stated throughout this specification are weight/weight (w/w) percentages.

[0055] The term stabilizing agents as used herein, means a pharmaceutically acceptable excipient which stabilizes the pharmaceutical composition and restricts or prevents chemical degradation of active pharmaceutical ingredient comprised in the said composition.

[0056] The term "therapeutically effective amount" is intended to mean the amount of oxalate salt of compound of Formula (I) or solvate thereof, which will elicit a biological response in tissue of a patient.

[0057] The term "prophylactic" in the context of treatment is intended to mean the amount of oxalate salt of compound of Formula (I) or solvate thereof, which will prevent or reduce occurrence of glucose metabolism disorder in a patient or onset of clinical symptoms of glucose metabolism disorder in a patient.

[0058] The term "curative" in the context of treatment is intended to mean the amount of oxalate salt of compound of Formula (I) or solvate thereof, which will cure or manage glucose metabolism disorder in a patient. [0059] The term "metformin" as used herein, unless mentioned otherwise, means metformin, its pharmaceutically acceptable salt or hydrate thereof.

[0060] The term "excipients" refers generally to substances other than pharmaceutically active ingredients which are included in the manufacturing process or are contained in a finished pharmaceutical product dosage form.

[0061] The term "carriers" refers generally to any substance or substrate used in the process of drug delivery which serves to improve the selectivity, effectiveness and/or safety of drug administration.

[0062] The term "glucose metabolism disorder" is intended to cover various metabolic disorders involving glucose in human beings like diabetes mellitus, hyperglycemia, hypoglycemia, glycosuria and like. Further, diabetes mellitus includes Type I and Type I I diabetes mellitus.

[0063] The term "diluents" refers generally to filler/diluents which can be used to increase the bulk volume or improve flow properties.

[0064] 3-{(2S,4S)-4-[4-(3-methyi-l^henyi-lH^yrazol-5-yl)piperazin-l -yi]pyrrolidin-2- yIcarbonyl}thiazo!idine, also known as Tene!igliptin is represented by Formula (I), and referred to as Tenelig!iptin or compound of Formula (I) interchangeably throughout the disclosure.

[0065] In an embodiment, the present invention provides pharmaceutical compositions comprising oxalate salts of the compound of Formula (I)

or solvate thereof and at least one or more pharmaceutically acceptable carriers, diluents, binder, lubricant, disintegrant and stabilizing agent In an embodiment, the solvate is preferably n. hydrate, wherein n is 1.0 to 4.0. In a preferred embodiment, n is 1.0. In one aspect of this embodiment, the diluent is selected from group comprising of mannitol, sorbitol, xyiitol, starch, lactose, cellulose, calcium dihydrogen phosphate and like, preferable, mannitol or lactose, in one other aspect, binder is selected from group comprising of hydroxypropyi cellulose, polyvinyl alcohol, povidone, copovidone, ethyl cellulose, hypromeilose and like, preferably hypromellose or hydroxypropyi cellulose. In one more aspect of this embodiment, lubricant is glyceryl dibehenate, sodium or calcium stearyl fumarate, magnesium stearate, stearic acid, glyceryl pa!mitostearate and like, preferably glyceryl dibehenate. in other aspect of this embodiment, disintegrant is selected from group comprising of Low-Substituted Hydroxypropyi Cellulose, Crospovidone, Croscarmellose sodium, Sodium Starch Glycolate and like, preferably Low-Substituted Hydroxypropyi Cellulose. In yet another aspect of this embodiment, stabilizing agent is selected from at least one stabilizer; at least one complexing agent; at least one polymer; at least one chelating agent; and combinations thereof.

[0066] In an embodiment, the pharmaceutical composition comprises Teneligliptin 2.5 oxalate n. hydrate, wherein n is 1.0 to 4.0. In a preferred embodiment, the pharmaceutical composition comprises Teneligliptin 2.5 oxalate 1.0 hydrate.

[0067] In another embodiment, the pharmaceutical composition comprises Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0. In a preferred embodiment, the pharmaceutical composition comprises Teneligliptin 3.0 oxalate 1.0 hydrate.

[0068] In yet another embodiment, the pharmaceutical composition comprises Teneligliptin 2.5 oxalate n. hydrate, wherein n is 1.0 to 4.0 and Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0. In a preferred embodiment, the pharmaceutical composition comprises Teneligliptin 2.5 oxalate monohydrate and Teneligliptin 3.0 oxalate monohydrate.

[0069] In an embodiment, the solvated oxalate salt of Teneligliptin comprised in pharmaceutical composition is 10-100% pure. In another embodiment, the purity level is 20-100%. In another embodiment, the purity is 30-100%. In another embodiment, the purity is 40-100%. In another embodiment, the purity is 50-100%. In another embodiment, the purity is 60-100%. In another embodiment, the purity is 70-100%. In another embodiment, the purity is 80-100%. In another embodiment, the purity is 90-100%. In a preferred embodiment, purity is more than 99%. In a more preferred embodiment, purity is more than 99.5%. In an embodiment, the solvated oxalate salt of Teneligliptin comprised in pharmaceutical composition is substantially pure.

[0070] In an embodiment, Teneligliptin 2.5 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0, comprised in pharmaceutical composition is 10-100% pure. In another embodiment, the purity level is 20-100%. In another embodiment, the purity is 30-100%. In another embodiment, the purity is 40-100%. In another embodiment, the purity is 50-100%. In another embodiment, the purity is 60-100%. In another embodiment, the purity is 70-100%. In another embodiment, the purity is 80-100%. In another embodiment, the purity is 90-100%. In a preferred embodiment, purity is more than 99%. In a more preferred embodiment, purity is more than 99.5%. In an embodiment, Teneligliptin 2.5 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0, comprised in pharmaceutical composition is substantially pure.

[0071] In an embodiment, Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0, comprised in pharmaceutical composition is 10-100% pure. In another embodiment, the purity level is 20-100%. In another embodiment, the purity is 30-100%. In another embodiment, the purity is 40-100%. In another embodiment, the purity is 50-100%. In another embodiment, the purity is 60-100%. In another embodiment, the purity is 70-100%. In another embodiment, the purity is 80-100%. In another embodiment, the purity is 90-100%. In a preferred embodiment, purity is more than 99%. In a more preferred embodiment, purity is more than 99.5%. In an embodiment, Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0, comprised in pharmaceutical composition is substantially pure.

[0072] Teneligliptin 2.5 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0 comprised in pharmaceutical compositions as described herein is in crystalline form.

[0073] Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0, comprised in pharmaceutical compositions as described herein is in crystalline form.

[0074] Teneligliptin 2.5 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0 comprised in pharmaceutical compositions as described herein is in amorphous form.

[0075] Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0, comprised in pharmaceutical compositions as described herein is in amorphous form.

[0076] In an embodiment of the present invention, there is provided pharmaceutical compositions as described herein, wherein Teneligliptin 2.5 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0 is characterized by X-ray powder diffraction pattern comprising reflections at 5.68°, 6.56°, 16.44°, 17.72°, 18.34°, 21.12°, 21.67°, 23.15°, 23.86°, 24.99° ± 2Θ and having an X-ray powder diffraction pattern as represented in FIG. 1.

[0077] In an embodiment of the present invention, there is provided pharmaceutical compositions as described herein, wherein Teneligliptin 2.5 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0 is characterized by differential scanning calorimetry (DSC) thermogram with an endotherm at 152.76°C and 169.68°C and represented by DSC curve in FIG. 2.

[0078] In an embodiment of the present invention, there is provided pharmaceutical compositions as described herein, wherein Teneligliptin 2.5 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0 is characterized by infra-red absorption (I R) peaks at 3452.22, 3011.77, 2540.88, 1721.37, 1650.04, 1207.43, 922.34, 708.96, 477.35cm ¹ and represented in FIG. 3.

[0079] In an embodiment of the present invention, there is provided pharmaceutical compositions as described herein, wherein Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0 is characterized by X-ray powder diffraction pattern comprising reflections at 5.69°, 6.57°, 16.43°, 17.71°, 21.66°, 23.15°, 23.86°, 24.99°± 2Θ and having an X-ray powder diffraction pattern as represented in FIG. 4.

[0080] In an embodiment of the present invention, there is provided pharmaceutical compositions as described herein, wherein Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0 is characterized by differential scanning calorimetry (DSC) thermogram with an endotherm at 177.34 °C and represented by DSC curve in FIG. 5A and at 171.6°C as represented in FIG. 5B.

[0081] In an embodiment of the present invention, there is provided pharmaceutical compositions as described herein, wherein Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0 is characterized by infra-red absorption (I R) peaks at 3464.93, 3011.34, 2537.55, 1911.30, 1720.10, 1651.64, 1456.82, 1363.34, 1209.29, 922.88, 709.74, 475.21 cm ^"1 and represented in FIG. 6.

[0082] In one embodiment, there is provided pharmaceutical compositions comprising Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0 and at least one or more pharmaceutically acceptable carriers, diluents and excipients. In one preferred embodiment, n is 1.0

[0083] In one particular embodiment, there are provided pharmaceutical compositions comprising Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, wherein the said salt exists in crystalline or amorphous form

[0084] In one embodiment, there are provided pharmaceutical compositions comprising Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, characterized by X-ray powder diffraction pattern comprising reflections at 5.69°, 6.57°, 16.43°, 17.71°, 21.66°, 23.15°, 23.86°, 24.99° ± 2Θ and having an X-ray powder diffraction pattern as represented in FIG. 4.

[0085] In yet another embodiment, there are provided pharmaceutical compositions comprising Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, which is substantially pure.

[0086] In an embodiment, the present invention provides pharmaceutical compositions comprising Teneligliptin 2.5 oxalate n. hydrate and Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0 and at least one or more pharmaceutically acceptable carriers, diluents and excipients. In on preferred aspect of this embodiment, n is 1.0. In preferred aspect of this embodiment, Teneligliptin 2.5 oxalate n. hydrate and Teneligliptin 3.0 oxalate n. hydrate are substantially pure.

[0087] In one embodiment, the present invention provides pharmaceutical compositions comprising oxalate salts of the compound of Formula (I) comprising

a. at least one stabilizer;

b at least one complexing agent;

c. at least one polymer

d at least one chelating agent; and

e combinations thereof. [0088] In a preferred embodiment, the pharmaceutical compositions further comprise at least one stabilizer which is pharmaceutically acceptable organic acid selected from group comprising of oxalic acid, citric acid, tartaric acid. In a more preferred embodiment, the stabilizer is oxalic acid.

[0089] In a preferred embodiment, the pharmaceutical compositions further comprise at least one complexing agent selected from the group consisting of alpha-cyclodextrin, beta-cyclodextrin, gamma cyclodextrin, methyl beta-cyclodextrin, hydroxypropyl-beta-cyclodextrin, their derivatives and combinations thereof.

[0090] . In a more preferred embodiment, the complexing agent is hydroxypropyl-beta-cyclodextrin.

[0091] In a preferred embodiment, the pharmaceutical compositions further comprise at least one polymer selected from the group comprising of gelatin, polyvinyl alcohol, copovidone, hydroxypropyl cellulose, ethyl cellulose, polyvinylpyrrolidone, hydroxyl propyl methyl cellulose, and combinations thereof. In a more preferred embodiment, the polymer is hydroxypropyl cellulose.

[0092] In an embodiment, the pharmaceutical compositions further comprise at least one chelating agent selected from the group consisting of EDTA, zinc sulfate, ferrous ascorbate, calcium carbonate, sodium chloride, potassium chloride, and combinations thereof. In a more preferred embodiment, the chelating agent is EDTA.

[0093] In an embodiment, the pharmaceutical compositions further comprise stabilizer and at least one polymer. The stabilizer is oxalic acid. The polymer is selected from the group comprising of gelatin, polyvinyl alcohol, copovidone, hydroxyl propyl cellulose, ethyl cellulose, polyvinylpyrrolidone, hydroxyl propyl methyl cellulose, and combinations thereof, preferably hydroxyl propyl celluose.

[0094] In a preferred embodiment, the pharmaceutical compositions further comprise at least one stabilizer, at least one polymer, and at least one complexing agent. In one embodiment, the stabilizer is oxalic acid. In another embodiment, the polymer is selected from the group comprising of gelatin, polyvinyl alcohol, copovidone, hydroxypropyl cellulose, ethyl cellulose, polyvinylpyrrolidone, hydroxyl propyl methyl cellulose, and combinations thereof, preferably hydroxypropyl cellulose. In an embodiment, the complexing agent is selected from the group comprising of beta-cyclodextrin, hydroxypropyl-beta-cyclodextrin, and combinations thereof, preferably hydroxypropyl beta cyclodextrin.

[0095] In a preferred embodiment, the pharmaceutical compositions of present invention further comprise at least one polymer and at least one chelating agent. In one embodiment, the polymer is selected from the group comprising of gelatin, polyvinyl alcohol, copovidone, hydroxypropyl cellulose, ethyl cellulose, polyvinylpyrrolidone, hydroxyl propyl methyl cellulose, and combinations thereof, preferably hydroxypropyl cellulose. In another embodiment, the chelating agent is selected from the group consisting of EDTA, zinc sulfate, ferrous ascorbate, calcium carbonate, sodium chloride, potassium chloride, and combinations thereof, preferably EDTA.

[0096] In an embodiment, the present invention provides a pharmaceutical compositions comprising (a) oxalate salt of compound (I) and solvate thereof selected from Teneligliptin 2.5 oxalate or Teneligliptin 3.0 oxalate and solvate thereof

(b) diluent is selected from mannitol or lactose

(c) binder is selected from hydroxypropy! cellulose or hypromellose

(d) Lubricant is selected from glyceryl dibehenate, or magnesium stearate

(e) disintegrant is selected from Low-Substituted Hydroxypropyl Cellulose, Crospovidone, Croscarmellose sodium

[0097] In an embodiment, the present invention provides a pharmaceutical compositions comprising

(a) oxalate salt of compound (I) and solvate thereof which is Teneligliptin 3.0 oxalate n. hydrate, wherein 1.0 to 4.0

(b) diluent is mannitol

(c) binder is hypromellose

(d) Lubricant is glyceryl dibehenate

(e) disintegrant is Low-Substituted Hydroxypropyl Cellulose

(f) stabilizing agent is selected from oxalic acid, beta-cyclodextrin, hydroxypropyl cellulose,

EDTA and combinations thereof.

[0098] In an embodiment, the present invention provides a pharmaceutical compositions comprising

(a) oxalate salt of compound (I) and solvate thereof is Teneligliptin 3.0 oxalate n. hydrate, wherein 1.0 to 4.0

(b) diluent is lactose

(c) binder is hypromellose

(d) Lubricant is glyceryl dibehenate

(e) disintegrant is Low-Substituted Hydroxypropyl Cellulose

(f) stabilizing agent is selected from oxalic acid, beta-cyclodextrin, hydroxypropyl cellulose, EDTA and combinations thereof.

[0099] In an embodiment of the present invention, there is provided pharmaceutical compositions comprising about 0.5 % to about 80.0 % by weight of oxalate salt of compound (I) and solvate thereof, about 10 % to about 95 % by weight of diluent, about 0.1% to about 10.0 % by weight of binder, about 0.1 % to about 20.0 % by weight of lubricant, about 0.1 % to about 30 % by weight of disintegrant and about 0.05 % to about 30 % by weight stabilizing agent.

[00100] In an embodiment of the present invention, there is provided pharmaceutical compositions comprising about 5 % to about 40.0 % by weight of oxalate salt of compound (I) and solvate thereof, about 15 % to about 95 % by weight of diluent, about 0.1% to about 10 % by weight of binder, about 0.1 % to about 20.0 % by weight of lubricant, about 0.1 % to about 30 % by weight of disintegrant and about 0.1 % to about 20 % by weight stabilizing agent. [00101] In an embodiment of the present invention, there is provided pharmaceutical compositions comprising about 5 % to about 40.0 % by weight of oxalate salt of compound (I) and solvate thereof, about 30 % to about 80 % by weight of diluent, about 0.1% to about 10 % by weight of binder, about 0.1 % to about 20.0 % by weight of lubricant, about 0.1 % to about 30 % by weight of disintegrant and about 0.1 % to about 20 % by weight stabilizing agent.

[00102] In an embodiment of the present invention, there is provided pharmaceutical compositions comprising about 5 % to about 15.0 % by weight of Teneligliptin 3.0 oxalate n. hydrate, about 30 % to about 80 % by weight of diluent, about 0.1% to about 10 % by weight of binder, about 1.0 % to about 15.0 % by weight of lubricant, about 1.0 % to about 20 % by weight of disintegrant and about 0.5 % to about 15 % by weight stabilizing agent. In one aspect of this embodiment, Teneligliptin 3.0 oxalate n. hydrate is crystalline Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0.

[00103] In an embodiment of the present invention, there is provided pharmaceutical compositions comprising about 0.5 % to about 10.0 % by weight of Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, about 5 % to about 40 % by weight of diluent, about 0.1% to about 10 % by weight of binder, about 0.5 % to about 5.0 % by weight of lubricant, about 0.5 % to about 10 % by weight of disintegrant and about 0.1 % to about 10 % by weight stabilizing agent and one or more anti-diabetic agent. In one aspect of this embodiment, Teneligliptin 3.0 oxalate n. hydrate is crystalline Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0.

[00104] In an embodiment, the present invention provides pharmaceutical compositions comprising substantially pure oxalate salt of compound of formula (I) and solvates thereof

[00105] In another embodiment, the present invention provides pharmaceutical compositions wherein purity of oxalate salt of compound of formula (I) is greater than 98.0 %.

[00106] In yet another embodiment, the present invention provides pharmaceutical compositions wherein purity of oxalate salt of compound of formula (I) is greater than 99.0 %.

[00107] In another embodiment, the present invention provides pharmaceutical compositions wherein purity of oxalate salt of compound of formula (I) is greater than 99.5 %.

[00108] In an embodiment, the present invention provides pharmaceutical compositions comprising substantially pure oxalate salt of compound of formula (I) and solvates thereof, wherein oxalate salt of compound of formula (I) is Teneligliptin 2.5 oxalate or Teneligliptin 3.0 oxalate and solvate thereof.

[00109] In an embodiment, the present invention also provides pharmaceutical compositions as described herein, further comprising at least one or more anti-diabetic agents selected from the group consisting of sulfonyl urea class of compounds and salts thereof, glitazone class of compounds and salts thereof, biguanide class of compounds and salts thereof, alpha-glucosidase inhibitor class of compounds and salts thereof, SG LT2 inhibitor class of compounds and salts thereof, and combinations thereof.

[00110] In an embodiment, the present invention provides pharmaceutical compositions comprising oxalate salt of compound of formula (I) and solvates thereof and at least one or more anti-diabetic agents selected from the group consisting of sulfonyl urea class of compounds and salts thereof, glitazone class of compounds and salts thereof, biguanide class of compounds and salts thereof, alpha- glucosidase inhibitor class of compounds and salts thereof, SGLT2 inhibitor class of compounds and salts thereof, and combinations thereof.

[00111] In one embodiment, said sulfonyl urea class of compounds used in pharmaceutical compositions of present invention comprises glimepiride, glipiride, tolbutamide, tolazamide, glibenclamide, gliclazide and the like. In preferred embodiment, sulfonyl urea compound is glimepiride.

[00112] In an embodiment, said glitazone class of compounds used in pharmaceutical compositions of present invention comprises pioglitazone, rosiglitazone and the like. In preferred embodiment, glitazone compound is pioglitazone.

[00113] In another embodiment, said alpha-glucosidase inhibitor class of compounds used in pharmaceutical compositions of present invention comprises voglibose, acarbose, miglitol and the like. In preferred embodiment, alpha-glucosidase inhibitor is voglibose.

[00114] In an embodiment, said SG LT2 inhibitor class of compounds comprises remogliflozin, dapagliflozin, canagliflozin, empagliflozin, luseogliflozin and the like.

[00115] In an embodiment, said biguanide class of compounds comprises metformin, buformin, phenformin and the like. In a preferred embodiment, the member of the biguanides class of molecules is metformin or its pharmaceutically acceptable salt. In a preferred embodiment, member of biguanide class is metformin hydrochloride. In yet another embodiment, member of biguanide class is mixture of metformin and metformin hydrochloride.

[00116] In an embodiment, metformin part of pharmaceutical composition of present invention, is immediate release layer or extended release layer. In an embodiment, metformin part comprised in the pharmaceutical compositions is immediate release layer. In a preferred embodiment, metformin part comprised in the pharmaceutical compositions is extended release layer. In yet another embodiment, metformin comprised in the pharmaceutical compositions is a mixture of immediate and extended release layer of metformin.

[00117] In an embodiment, the pharmaceutical compositions as described herein further comprise at least one stabilizer, at least one complexing agent, at least one polymer, at least one chelating agent, and combinations thereof.

[00118] The pharmaceutical compositions of present invention comprising at least one stabilizer, at least one complexing agent, at least one polymer, at least one chelating agent or combinations thereof stabilize solvated oxalate salts of Teneligliptin and inhibit formation of compound of Formula (II) in said pharmaceutical compositions.

[00119] In an embodiment, there are provided pharmaceutical compositions comprising at least one stabilizer, at least one complexing agent, at least one polymer, at least one chelating agent, and combinations thereof function to stabilize Teneligliptin 2.5 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0.

[00120] In an embodiment, there are provided pharmaceutical compositions comprising at least one stabilizer, at least one complexing agent, at least one polymer, at least one chelating agent, and combinations thereof function to stabilize Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0.

[00121] In an embodiment, there are provided pharmaceutical compositions comprising at least one stabilizer, at least one complexing agent, at least one polymer, at least one chelating agent, and combinations thereof function to stabilize the mixture of Teneligliptin 2.5 oxalate n. hydrate and Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0.

[00122] In one embodiment, there is provided pharmaceutical compositions comprising Oxalate salt of compound of formula (I) and solvate thereof, wherein said oxalate salt is at least 99% pure and content of compound of formula (I I) is less than 1.0 %.

[00123] In one embodiment, there is provided pharmaceutical compositions comprising oxalate salt of compound of formula (I) and solvate thereof, wherein said oxalate salt is at least 99.5 % pure and content of compound of formula (II) is less than 0.5.0 %.

[00124] In one embodiment, there is provided pharmaceutical compositions comprising Oxalate salt of compound of formula (I) and solvate thereof, wherein said oxalate salt is at least 99.9 % pure and content of compound of formula (II) a is less than 0.1 %.

[00125] In one embodiment, there is provided pharmaceutical compositions comprising Teneligliptin 2.5 oxalate and solvate thereof, wherein said oxalate salt is at least 99% pure and content of compound of formula (I I) is less than 1.0 %.

[00126] In one embodiment, there is provided pharmaceutical compositions comprising Teneligliptin 2.5 oxalate and solvate thereof, wherein said oxalate salt is at least 99.5 % pure and content of compound of formula (II) is less than 0.5.0 %. In preferred embodiment, solvate is n. hydrate. In one more aspect of this embodiment, there is provided pharmaceutical compositions comprising Teneligliptin 2.5 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0.

[00127] In one embodiment, there is provided pharmaceutical compositions comprising Teneligliptin 2.5 oxalate and solvate thereof, wherein said oxalate salt is at least 99.9 % pure and content of impurity B is less than 0.1 %. In preferred embodiment, solvate is n. hydrate. In one more aspect of this embodiment, there is provided pharmaceutical compositions comprising Teneligliptin 2.5 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0.

[00128] In one embodiment, there is provided pharmaceutical compositions comprising Teneligliptin 3.0 oxalate and solvate thereof, wherein said oxalate salt is at least 99% pure and content of compound of formula (II) is less than 1.0 %. In preferred embodiment, solvate is n. hydrate. In one more aspect of this embodiment, there is provided pharmaceutical compositions comprising Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0.

[00129] In one embodiment, there is provided pharmaceutical compositions comprising Teneligliptin 3.0 oxalate and solvate thereof, wherein said oxalate salt is at least 99.5 % pure and content of impurity B is less than 0.5.0 %. In preferred embodiment, solvate is n. hydrate. In one more aspect of this embodiment, there is provided pharmaceutical compositions comprising Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0.

[00130] In one embodiment, there is provided pharmaceutical compositions comprising Teneligliptin 3.0 oxalate and solvate thereof, wherein said oxalate salt is at least 99.9 % pure and content of impurity B is less than 0.1 %. In preferred embodiment, solvate is n. hydrate. In one more aspect of this embodiment, there is provided pharmaceutical compositions comprising Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0.

[00131] In one embodiment, the present invention provides pharmaceutical compositions comprising Teneligliptin 3.0 oxalate n. hydrate, wherein said oxalate salt is at least 99% pure and content of compound of formula (II) is less than 1.0 %.

[00132] In one embodiment, the present invention provides pharmaceutical compositions comprising Teneligliptin 3.0 oxalate n. hydrate, wherein said oxalate salt is at least 99.5 % pure and content of compound of formula (II) is less than 0.5 %.

[00133] In one embodiment, the present invention provides pharmaceutical compositions comprising Teneligliptin 3.0 oxalate n. hydrate, wherein said oxalate salt is at least 99.9 % pure and content of compound of formula (II) is less than 0.1 %.

[00134] In one embodiment, the present invention provides pharmaceutical compositions comprising Teneligliptin 3.0 oxalate n. hydrate which is at least 99.0% pure, at least 99.5 % pure, at least 99.9 % pure, in crystalline form.

[00135] In an embodiment of the present invention, there are provided pharmaceutical compositions comprising Teneligliptin 3.0 oxalate n. hydrate wherein n is 1.0 to 4.0 preferably 1.0 and extended release metformin, wherein Teneligliptin to metformin w/w ratio is in the range of 1:10-1:50, preferably in the range of 1:10-1:40, particularly about 1:15 or 1:31.

[00136] In an embodiment of the present invention, there is provided pharmaceutical compositions comprising Teneligliptin 2.5 oxalate n. hydrate wherein n is 1.0 to 4.0 preferably 1.0 and extended release metformin, wherein Teneligliptin to metformin w/w ratio is in the range of 1:10-1:50, preferably in the range of 1:10-1:40, particularly about 1:15 or 1:31.

[00137] In an embodiment of the present invention, there is provided pharmaceutical compositions comprising a mixture of Teneligliptin 2.5 oxalate n. hydrate and Teneligliptin 3.0 oxalate n. hydrate wherein n is 1.0 to 4.0, preferably 1.0 and extended release metformin, wherein Teneligliptin to metformin w/w ratio is in the range of about 1:10-1:50, preferably in the range of about 1:10-1:40, particularly about 1:15 or 1:31.

[00138] In a particular embodiment of the present invention, there is provided pharmaceutical compositions comprising Teneligliptin 2.5 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0 and extended release metformin and at least one or more pharmaceutically acceptable carriers, diluents and excipients.

[00139] In a particular embodiment of the present invention, there is provided pharmaceutical compositions comprising Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0 and extended release metformin and at least one or more pharmaceutically acceptable carriers, diluents and excipients.

[00140] In a particular embodiment of the present invention, there is provided pharmaceutical compositions comprising a mixture of Teneligliptin 2.5 oxalate n. hydrate and Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0 and extended release metformin and at least one or more pharmaceutically acceptable carriers, diluents and excipients.

[00141]The present invention provides pharmaceutical compositions as described herein for use in prophylactic treatment of glucose metabolism in a patient.

[00142]The present invention provides pharmaceutical compositions as described herein for use in curative treatment of glucose metabolism in a patient.

[00143]The present invention provides a method of prophylactic curative treatment of a patient with glucose metabolism disorder comprising administering a physiologically relevant amount of pharmaceutical compositions as described herein.

[00144] The present invention provides a method of curative treatment of a patient with glucose metabolism disorder comprising administering a physiologically relevant amount of pharmaceutical compositions as described herein.

[00145] In an embodiment of the present invention, there is provided pharmaceutical compositions as described herein comprising granules of n. hydrate oxalate salts of Teneligliptin, wherein n is 1.0 to 4.0, preferably 1.0. In a particular embodiment, there is provided pharmaceutical compositions as described herein comprising granules of Teneligliptin 2.5 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0. In a particular embodiment, there is provided pharmaceutical compositions as described herein comprising granules of Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0.

[00146] In one embodiment, the present invention provides process for preparing pharmaceutical composition of oxalate salt of compound of formula (I) wherein said process steps comprises of:

(a) Sifting oxalate salt of compound of formula (I) with pharmaceutically acceptable excipients or one or more anti-diabetic agents or mixture thereof;

(b) Granulating sifted material of step (a) with binder solution;

(c) Drying and sifting granulate obtained in step (b);

(d) lubricating sifted granulate of step (c) with suitable lubricant to obtain blend;

(e) compressing lubricated blend of step (d) to form tablet or filling blend of step (d) into capsules

(f) optionally compressing lubricated blend of step (d) with blend of one or more antidiabetic agents to form tablet or filling blend mixture into capsules Step (a) of above process involves sifting of oxalate salt of compound of formula (I) and solvate thereof with suitable excipients. In one embodiment, oxalate salt of compound of formula (I) and solvate thereof is Teneligliptin 2.5 oxalate or Teneligliptin 3.0 oxalate and solvate thereof. In one preferred embodiment, the solvate is n. hydrate. In one preferred embodiment, oxalate salt of compound of formula (I) and solvate thereof is Teneligliptin 2.5 oxalate n. hydrate or Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0.

[00147] In one embodiment, the present invention provides a process for preparing pharmaceutical composition comprising oxalate salt of compound of formula (I) and solvate thereof, wherein said process steps comprises of:

(a) sifting pharmaceutically acceptable excipients

(b) preparing binder solution comprising oxalate salt of compound of formula (I) and solvate thereof;

(c) granulating sifted pharmaceutically acceptable excipients of step (a) with binder solution of step (b);

(d) Drying and sifting granulate obtained in step (c);

(e) lubricating sifted granulate of step (c) with sifted pharmaceutically acceptable excipients to obtain blend;

(f) compressing lubricated blend of step (d) to form tablet or filling blend of step (d) into capsules

(g) optionally compressing lubricated blend of step (d) with blend of one or more anti- diabetic agents to form tablet or filling blend mixture into capsules. [00148] In one embodiment, the present invention provide process for preparing pharmaceutical composition comprising oxalate salt of compound of formula (I) and solvate thereof, wherein said process steps comprises of:

(a) obtaining solution of oxalate salt of compound of formula (I) and solvate thereof with stabilizer or complexing agent

(b) spray drying the solution obtained in step (a)

(c) sifting the spray dried mixture obtained in step (b)

(d) lubricating sifted granulate of step (c) with sifted pharmaceutically acceptable excipients;

(e) compressing lubricated blend of step (d) to form tablet or filling blend of step (d) into capsules.

[00149] In one embodiment, the present invention provide process for preparing pharmaceutical composition comprising oxalate salt of compound of formula (I) and solvate thereof, wherein said process steps comprises of:

(a) Sifting Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0 with pharmaceutically acceptable excipients or one or more anti-diabetic agents or mixture thereof;

(b) Granulating sifted material of step (a) with binder solution;

(c) Drying and sifting granulate obtained in step (b);

(d) lubricating sifted granulate of step (c) with suitable lubricant to obtain blend;

(e) compressing lubricated blend of step (d) to form tablet or filling blend of step (d) into capsules;

(f) optionally compressing lubricated blend of step (d) with blend of one or more anti-diabetic agents to form tablet or filling blend mixture into capsules.

[00150] In one embodiment, the present invention provide, a process for preparing pharmaceutical composition comprising Teneligliptin 3.0 oxalate n. hydrate, wherein said process steps comprises of:

(a) sifting pharmaceutically acceptable excipients;

(b) preparing binder solution comprising Teneligliptin 3.0 oxalate n. hydrate;

(c) granulating sifted pharmaceutically acceptable excipients of step (a) with binder solution of step (b);

(d) Drying and sifting granulate obtained in step (c);

(e) lubricating sifted granulate of step (c) with sifted pharmaceutically acceptable excipients to obtain blend;

(f) compressing lubricated blend of step (d) to form tablet or filling blend of step (d) into capsules; and

(g) optionally compressing lubricated blend of step (d) with blend of one or more anti-diabetic agents to form tablet or filling blend mixture into capsules. [00151] In one embodiment, the present invention provide, a process for preparing pharmaceutical composition comprising Teneligliptin 3.0 oxalate n. hydrate, wherein said process steps comprises of:

(a) obtaining solution of Teneligliptin 3.0 oxalate n. hydrate with stabilizer or complexing agent;

(b) spray drying the solution obtained in step (a) ;

(c) sifting the spray dried mixture obtained in step (b);

(d) lubricating sifted granulate of step (c) with sifted pharmaceutically acceptable excipients; and

(e) compressing lubricated blend of step (d) to form tablet or filling blend of step (d) into capsules.

[00152] In an embodiment, granules of oxalate salt of compound (I) and solvate thereof, as contemplated by this invention can be made of oxalate salt of compound (I) and solvate thereof in association with suitable diluents, lubricant, binder, fluidizing agent, disintegrant, soiubilizing agent and like.

[00153] In an embodiment, granules of Teneligliptin 2.5 oxalate and solvate thereof, as contemplated by this invention can be made Teneligliptin 2.5 oxalate and solvate thereof in association with suitable diluents, lubricant, binder, fluidizing agent, disintegrant, soiubilizing agent and like.

[00154] In an embodiment, granules of Teneligliptin 3.0 oxalate and solvate thereof, as contemplated by this invention can be made of Teneligliptin 3.0 oxalate and solvate thereof in association with suitable diluents, lubricant, binder, fluidizing agent, disintegrant, solubi!izing agent and like.

[00155] In an embodiment, granules of Teneligliptin 2.5 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0, as contemplated by this invention can be made of Teneligliptin 2.5 oxalate n. hydrate in association with suitable diluents, lubricant, binder, fluidizing agent, disintegrant, soiubilszing agent and like.

[00156] In an embodiment, granules of Teneligliptin 3.0 oxalate n. hydrate, as contemplated by this invention can be made of Teneligliptin 3.0 oxalate n. hydrate in association with suitable diluents, lubricant, binder, fluidizing agent, disintegrant, solubiiizing agent and like.

[00157] Suitable binder include, but are not limited to, hydroxypropylcellulose, polyvinyl alcohol, povidone, copovidone, ethyl cellulose, hypromellose and like.

[00158] Suitable diluents include, but are not limited to, mannito!, sorbitol, xyiitol, starch, lactose, cellulose, calcium dihydrogen phosphate and like.

[00159] Suitable lubricants include but are not limited to glyceryl dibehenate, sodium or calcium stearyl fumarate, magnesium stearate, stearic acid, glyceryl palmitostearate.

[00160] Granules of oxalate salt of compound of formula (I) and solvate thereof can be prepared by mixing oxalate salt of compound of formula (I) and pharmaceutically acceptable excipients; adding a binder solution to the mixture of compound of formula (I) and pharmaceutically acceptable excipients and drying the wet mixture of oxalate salt of compound of formula (I) and pharmaceutically acceptable excipients followed by sieving to form granules.

[00161] Alternatively, granules of oxalate salt of compound of formula (I) and solvate thereof can be prepared after mixing oxalate salt of compound of formula (I) and pharmaceutically acceptable excipients, a binder solution can be sprayed on the mixture in a fluidized bed-processor followed by drying of the wet granules and subsequent optional sieving. As another alternative, flakes of oxalate salt of compound of formula (I) can be prepared by dry mixing oxalate salt of compound of formula (I) and pharmaceutically acceptable excipients to form a blend; roll-compacting the blend one or more times to form flakes followed by granulating and sieving the flakes. The oxalate salt of compound of formula (I) granules or flakes can be lubricated with any of the lubricants mentioned above. This mixture can then be punched in a tableting machine or can be filled into capsules by a capsule-filling machine. Optionally, a coating can be applied to the tablet. The coating solution or suspension contains excipients like hypromellose, polyethylene glycol, colorant such as red or yellow iron oxide, titanium dioxide and talc. These tablets can be alternatively, filled into capsules of suitable size. The capsule volume can be suitably selected, ranging from 0.13- 1.37 ml to accommodate the oxalate salt of compound of formula (I) containing lubricated blend or tablets. In one aspect of present embodiment, oxalate salt of compound of formula (I) used for preparing Teneligliptin containing granules is Teneligliptin 3.0 oxalate or solvate thereof. In first aspect of this embodiment, Teneligliptin 3.0 oxalate or solvate is in crystalline form.

[00162] In an alternative, a direct compression process for producing Teneligliptin tablets is also contemplated by the invention. The tablets are prepared by mixing Teneligliptin with one or more pharmaceutically acceptable excipients to prepare a blend for direct compression; compressing the blend of to form a tablet; optionally a coating can be applied to the tablet, as described above.

[00163] In an embodiment of the present invention, there is provided pharmaceutical compositions comprising oxalate salt of compound of formula (I) and solvate thereof and metformin or its pharmaceutically acceptable salt thereof as described herein, wherein the content of metformin or its pharmaceutically acceptable salt thereof can be suitably selected so as to deliver a dose of metformin in the range of 1 -2000 mg, preferably 250-1000 mg, more preferably 500-1000 mg, still more preferably 500 mg or 1000 mg. Such a pharmaceutical composition contains Teneligliptin and metformin in separate portions. For example, a multi-layered composition containing Teneligliptin and metformin in separate layers of a bi- or tri-!ayered tablet; a composition containing metformin in the core and Teneligliptin in the coating and other similar variants thereof.

[00164] In an embodiment of the present invention, there is provided pharmaceutical compositions comprising oxalate salts of Teneligliptin and solvates thereof and at least one or more anti-diabetic agents selected from the group consisting of sulfonyl urea class of compounds and salts thereof, glitazone class of compounds and salts thereof, biguanide class of compounds and salts thereof, alpha- glucosidase inhibitor class of compounds and salts thereof, SGLT2 inhibitor class of compounds and salts thereof, and combinations thereof as described herein, wherein weight concentration of oxalate salts of Teneligliptin and solvates thereof is in the range of 0.5 to 10.0 %, preferably 0.5 to 8.0 %. in a preferred embodiment, anti-diabetic agent is metformin and salts thereof. In a more preferred embodiment, the anti-diabetic agent is extended release metformin. In an embodiment, the dose amount of extended release metformin in said pharmaceutical formulation is 500mg. In another embodiment, the dose amount of extended release metformin in said pharmaceutical formulation is lOOOmg.

[00165] In an embodiment of the present invention, there is provided pharmaceutical compositions comprising oxalate salts of Teneligliptin and solvates thereof, preferably Teneligliptin 3.0 oxalate n. hydrate and metformin or its pharmaceutically acceptable salt thereof, preferably extended release metformin as described herein, wherein Teneligliptin to metformin w/w ratio in said composition is in the range of 1:10-1:50. In an embodiment, the w/w ratio is about 1:15. In another embodiment, the w/w ratio is about 1:31. In an embodiment, the dosage amount of Teneligliptin is in the range of about 5-50%, preferably 20-40%, more preferably 25-35%. In an embodiment, the dosage amount of metformin is in the range of 100-2000mg, preferably 500-lOOOmg, more preferably SOOmg or lOOOmg.

[00166] In one embodiment the present invention provides method for treating, preventing, or slowing the progression of a metabolic disorder by administering to a patient in need thereof a pharmaceutical composition comprising oxalate salt of compound of formula (I) and at least one other anti-diabetic agent, wherein the metabolic disorder is selected from the group consisting of type 1 diabetes meilitus, type 2 diabetes meilitus, impaired glucose tolerance (IGT), impaired fasting blood glucose (I PG), hyperglycemia, postprandial hyperglycemia, overweight, obesity, insulin resistance and metabolic syndrome in a patient in need thereof.

[00167] In one embodiment, the present invention provides a method of treating type 2 diabetes meilitus by administering to a patient in need thereof a pharmaceutical composition comprising oxalate salt of compound of formula (I) and at least one other anti-diabetic agent or pharmaceutically acceptable salts thereof.

[00168] In one embodiment the present invention provides method for improving giycemic control in a patient treated with monotherapy of an antidiabetic drug by administering to a patient in need thereof a pharmaceutical composition comprising oxalate salt of compound of formula (I) and at least one other anti-diabetic agent or pharmaceutically acceptable salts thereof.

[00169] In one embodiment the present invention provides method for improving giycemic control and/or for reducing of fasting plasma glucose, of postprandial plasma glucose and/or of glycosylated hemoglobin HbAlc in a patient by administering to a patient in need thereof a pharmaceutical composition comprising oxalate salt of compound of formula (I) and at least one other anti-diabetic agent or pharmaceutically acceptable salts thereof. [00170] In one embodiment the present invention provides method for treating, preventing, or slowing the progression of a condition or disorder selected from the group consisting of complications of diabetes meiiitus in a patient by administering to a patient in need thereof a pharmaceutical composition comprising oxalate salt of compound of formula (I) and at least one other anti-diabetic agent or pharmaceutically acceptable salts thereof. Complications of diabetes meiiitus according to the present invention include cataracts and micro- and macrovascular diseases, such as nephropathy, retinopathy, neuropathy, learning and memory impairment, neurodegenerative or cognitive disorders, cardio- or cerebrovascular diseases, tissue ischaemia, diabetic foot or ulcers, arteriosclerosis, hypertension, endothelial dysfunction, myocardial infarction, acute coronary syndrome, unstable angina pectoris, stable angina pectoris, stroke, peripheral arterial occlusive disease, cardiomyopathy, heart failure, heart rhythm disorders and vascular restenosis and the likes

[00171] In one embodiment the present invention provides method for treating, preventing, or slowing the progression of degeneration of pancreatic beta cells and/or the decline of the functionality of pancreatic beta cells and/or for improving and/or restoring the functionality of pancreatic beta ceils and/or restoring the functionality of pancreatic insulin secretion in a patient by administering to a patient in need thereof a pharmaceutical composition comprising oxalate salt of compound of formula (I) and at least one other anti-diabetic agent or pharmaceutically acceptable salts thereof.

EXAMPLES

[00172] The following examples are presented to provide what is believed to be the most useful and readily understood description of procedures and conceptual aspects of this invention. The examples provided below are merely illustrative of the invention and are not intended to limit the same to disclosed embodiments. Variations and changes obvious to one skilled in the art are intended to be within the scope and nature of the invention.

Example 1 Pharmaceutical compositions comprising Teneligliptin 3.0 oxalate n. hydrate

[00173] The tables below disclose exemplary compositions comprising Teneligliptin 3.0 oxalate n. hydrate, preferably monohydrate.

[00174] Table 1 provides a formulation comprising oxalic acid as stabilizer to prevent degradation of Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0. Table 1: Formulation Comprising Oxalic Acid as a Stabilizer

[00175] Manufacturing process:

1. Sifting: Co-sift Teneligliptin Oxalate, L-HPC and mannitol through #060 mesh sieve;

2. Preparation of binder: Add and dissolve under stirring Oxalic Acid and Hydroxypropul Cellulose in purified water;

3. Granulation: Granulate the materials of step 1 with binder solution of step 2 with suitable process parameters in FBP. After completion of granulation, dry the wet mass till desired LoD is achieved;

4. Sift the sized granules through #030 mesh sieve. Mill the left over using 1.0 mm screen and sift through #030 mesh sieve;

5. Co-sift L-Hydroxypropyl Cellulose and Glyceryl dibehenate through #040 mesh sieve;

6. Lubrication: Lubricate the granules of step 4 with sifted excipients of step 5 using suitable blender;

7. Compression: Compress the lubricated blend with suitable tooling and process parameters;

8. Coating: Coat the compressed tablets using aqueous dispersion of opadry yellow; and

9. Pack the film coated tablets in blister pack.

[00176] Table 2 provides a formulation comprising oxalic acid, polymer and complexing agent to prevent degradation of Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0.

Table 2

[00177] Manufacturing process:

1. Sifting: Co-sift L-HPC and mannitol through #060 mesh sieve;

2. Preparation of binder: Add and dissolve under stirring Oxalic Acid, β Cyclodextrin and Hydroxypropyl Cellulose in purified water;

3. Granulation: Granulate the materials of step 1 with binder solution of step 2 with suitable process parameters in FBP. After completion of granulation, dry the wet mass till desired LoD is achieved;

4. Sift the sized granules through #030 mesh sieve. Mill the left over using 1.0 mm screen and sift through #030 mesh sieve;

5. Co-sift L-Hydroxypropyl Cellulose and Glyceryl dibehenate through #040 mesh sieve;

6. Lubrication: Lubricate the granules of step 4 with sifted excipients of step 5 using suitable blender;

7. Compression: Compress the lubricated blend with suitable tooling and process parameters;

8. Coating: Coat the compressed tablets using aqueous dispersion of opadry yellow; and

9. Pack the film coated tablets in blister pack.

[00178] Table 3 provides a formulation comprising complexing agent to prevent degradation of Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0.

Table 3

[00179] Manufacturing process:

1. Solution Preparation: Add and dissolve Mannitol, β Cyclodextrin and Teneligliptin Oxalate in purified water under stirring;

2. Spray dry the solution of the step 1;

3. Sift the spray died material through #030 mesh sieve;

4. Co-sift Mannitol, L-Hydroxypropyl Cellulose and Glyceryl dibehenate through #040 mesh sieve;

5. Lubrication: Lubricate the granules of step 3 with sifted excipients of step 4 using suitable blender;

6. Compression: Compress the lubricated blend with suitable tooling and process parameters;

7. Coating: Coat the compressed tablets using aqueous dispersion of opadry yellow; and

8. Pack the film coated tablets in blister pack.

[00180] Table 4 provides a formulation comprising a polymer to prevent degradation of Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0.

Table 4

[00181] Manufacturing process:

1. Sifting: Sift L-HPC and mannitol through #060 mesh sieve;

2. Preparation of binder: Add and dissolve under stirring Hydroxypropyl Cellulose in purified water;

3. Granulation: Granulate the materials of step 1 with binder solution of step 2 with suitable process parameters in FBP. After completion of granulation, dry the wet mass till desired LoD is achieved;

4. Sift the sized granules through #030 mesh sieve. Mill the left over using 1.0 mm screen and sift through #030 mesh sieve;

5. Co-sift Mannitol, L-Hydroxypropyl Cellulose and Glyceryl dibehenate through #040 mesh sieve;

6. Lubrication: Lubricate the granules of step 4 with sifted excipients of step 5 using suitable blender;

7. Compression: Compress the lubricated blend with suitable tooling and process parameters;

8. Coating: Coat the compressed tablets using aqueous dispersion of opadry yellow; and

9. Pack the film coated tablets in blister pack.

[00182] Table 5 provides a formulation comprising a polymer to prevent degradation of Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0.

Table 5

[00183] Manufacturing process:

1. Solution Preparation: Add and dissolve Mannitol, Oxalic Acid and Teneligliptin Oxalate in purified water under stirring;

2. Spray dry the solution of the step 1;

3. Sift the spray died material through #030 mesh sieve;

4. Co-sift Mannitol, L-Hydroxypropyl Cellulose and Glyceryl dibehenate through #040 mesh sieve;

5. Lubrication: Lubricate the granules of step 3 with sifted excipients of step 4 using suitable blender;

6. Compression: Compress the lubricated blend with suitable tooling and process parameters;

7. Coating: Coat the compressed tablets using aqueous dispersion of opadry yellow; and

8. Pack the film coated tablets in blister pack.

[00184] Table 6 provides a formulation comprising a polymer and chelating agent to prevent degradation of Teneligliptin 3.0 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0. Table 6

[00185] Manufacturing process:

1. Sifting: Co-sift L-HPC and mannitol through #060 mesh sieve;

2. Preparation of binder: Add and dissolve under stirring Oxalic Acid, EDTA and Hydroxypropyl Cellulose in purified water;

3. Granulation: Granulate the materials of step 1 with binder solution of step 2 with suitable

process parameters in FBP. After completion of granulation, dry the wet mass till desired LoD is achieved;

4. Sift the sized granules through #030 mesh sieve. Mill the left over using 1.0 mm screen and sift through #030 mesh sieve;

5. Co-sift L-Hydroxypropyl Cellulose and Glyceryl dibehenate through #040 mesh sieve;

6. Lubrication: Lubricate the granules of step 4 with sifted excipients of step 5 using suitable

blender;

7. Compression: Compress the lubricated blend with suitable tooling and process parameters;

8. Coating: Coat the compressed tablets using aqueous dispersion of opadry yellow; and

9. Pack the film coated tablets in blister pack.

[00186] It is to be appreciated by a person skilled in the art that the exemplary formulations disclosed herein can be modified by a person skilled in art without straying from the intended teachings of the invention. Furthermore, it is to be appreciated by a person skilled in the relevant art that similar formulations comprising Teneligliptin 2.5 oxalate n. hydrate, wherein n is 1.0 to 4.0, preferably 1.0 are contemplated within this disclosure and well within the expertise of a person skilled in the art to arrive at, including any modifications.

Example 2: Process for combination of Teneligliptin 3.0 oxalate and Metformin HCI

[00187] Metformin part (For 500 mg dose): Metformin Hydrochloride is milled using multimill. Co-sifted milled Metformin Hydrochloride and Carboxymethyl Cellulose sodium through #40 mesh s.s. sieve. Guar Gum sifted through #100 mesh s.s. sieve. Sifted Metformin Hydrochloride, Carboxymethyl Cellulose and Guar Gum granulated in rapid mixer granulator for 20 minutes. Binder solution prepared by adding Methylparaben and Propylparaben in purified water under stirring. Granulated mixture of Metformin Hydrochloride, Carboxymethyl Cellulose and Guar Gum granulated with binder solution in Fluidized Bed Dryer. Wet granulated mass obtained is dried to obtain granules. Granules obtained sifted through 16 # sieve using vibratory sifter. Over-sized granules collected and milled using multimill. Milled granules collected and sifted through #16 sieves using vibratory sifter. Co-sifted Hydroxypropylmethyl Cellulose, Pregelatinised starch, Polyethylene Oxide and Hydrogenated Castor Oil through sieve # 40 and Magnesium Stearate through sieve # 40 using vibratory sifter. Lubrication pre-mix prepared by mixing fine granules and Co-sifted Hydroxypropylmethyl Cellulose, Pregelatinised starch, Polyethylene Oxide and Hydrogenated Castor Oil. Milled granules lubricated with lubrication pre-mix in blender to obtain metformin HCI blend.

[00188] Metformin part (For 1000 mg dosage form): Metformin Hydrochloride is milled using multimill and sift through #40 mesh s.s. sieve. Sift Carboxymethyl Cellulose sodium through #40 mesh s.s. sieve. Guar Gum sifted through #100 mesh s.s. sieve. Sifted Metformin Hydrochloride and Carboxymethyl Cellulose granulated in rapid mixer granulator for 20 minutes. Binder solution prepared by adding Methylparaben and Propylparaben in purified water under stirring. Granulated mixture of Metformin Hydrochloride, Carboxymethyl Cellulose with purified water using suitable process parameter. Wet granulated mass obtained is semi-dried and sifted throughl6 # sieve. Semi-dried granules dried in Fluidized bed dryer. Sift the dried granules through sieve #16 using vibratory sifter. Over-sized granules collected and milled using multimill. Milled granules collected and sifted through #16 sieves using vibratory sifter. Co-sifted Hydroxypropyl methyl cellulose and Maize Starch through sieve # 40 using vibratory sifter and Magnesium Stearate through sieve # 60. Milled granules lubricated with Co-sifted Hydroxypropyl methyl cellulose and Maize Starch and sifted Magnesium Stearate in suitable blender.

Example 3

Stability of Teneligliptin 3.0 oxalate n. hydrate in formulations

[00189] Table 7 below depicts the stability profile of the formulation of Table 1 at 1 month and 2 month. Table 7

[00190] As seen from Table 7 above, it can be appreciated that even after 2 months of storage at 40°C ± 2°C & 75 % RH ± 5 % RH, the levels of impurity B (an undesired by-product of the formulation resulting in loss of oxalate) are below the permissible levels of l%w/w. Similar results were also observed for formulations depicted in Tables 2 to 6. It is to be appreciated that the enhanced stability of each of the formulations in Tables 1 to 6 are due to the particular presence of oxalic acid, a polymer, a complexing agent, a chelating agent, or combinations thereof. The advantageous and unexpected stability of the formulation afforded by the presence of any of oxalic acid, a polymer, a complexing agent, a chelating agent, or combinations thereof can be further appreciated in view of formulations as given below which are devoid of any of oxalic acid, a polymer, a complexing agent, a chelating agent, or combinations thereof, and consequently show elevated levels of impurity B, which are beyond permissible limits.

[00191] Table 8 depicts a formulation which shows impermissible levels of impurity B.

Table 8

[00192] Table 9 depicts the stability profile of the formulation of Table 8. Table 9

[00193] Table 10 depicts a formulation which shows impermissible levels of impurity B. Table 10

[00194] Table 11 depicts the stability profile of the formulation of Table 10.

Table 10

[00195] Table 12 depicts a formulation which shows impermissible levels of impurity B. Table 12

[00196] Table 13a depicts the stability profile of the formulation of Table 12. Table 13a

[00197] Table 13b depicts the stability profile of the formulation of Table 12. Table 13b

Example 4

Formulations comprising Teneligliptin 3.0 oxalate n. hydrate and Glimepiride

[00198] Table 14a depicts a formulation comprising Teneligliptin 3.0 oxalate n. hydrate and Glimepiride.

Table 14a

[00199] Table 14b depicts a formulation comprising Teneligliptin 3.0 oxalate n. hydrate and Glimepiride (monolayer strategy 2).

Table 14b

[00200] Brief strategy of manufacturing process for formulation of Table 14a-b.

1. Sifting: Co-sift Teneligliptin Oxalate, Glimepiride and L-HPC and mannitol through #060 mesh sieve;

2. Preparation of binder: Add and dissolve under stirring Oxalic Acid and Hydroxypropul Cellulose in purified water;

3. Granulation: Granulate the materials of step 1 with binder solution of step 2. After completion of granulation, dry the wet mass;

4. Sift the sized granules through #030 mesh sieve. Mill the left over using 1.0 mm screen and sift through #030 mesh sieve;

5. Co-sift L-Hydroxypropyl Cellulose and Glyceryl dibehenate through #040 mesh sieve;

6. Lubrication: Lubricate the granules of step 4 with sifted excipients of step 5 using suitable blender;

7. Compression: Compress the lubricated blend with suitable tooling and process parameters;

8. Coating: Coat the compressed tablets using aqueous dispersion of opadry yellow; and

9. Pack the film coated tablets in blister pack. [00201] Table 14c depicts a formulation comprising Teneligliptin 3.0 oxalate n. hydrate and Glimepiride.

Table 14c

[00202] Table 14d depicts a formulation comprising Teneligliptin 3.0 oxalate n. hydrate and Glimepiride (bilayer strategy 2).

Table 14d

[00203] Brief strategy of manufacturing process for formulation of Table 14c-d

Teneligliptin part:

1. Sifting: Co-sift Teneligliptin Oxalate, and L-H PC and mannitol through #060 mesh sieve;

2. Preparation of binder: Add and dissolve under stirring Oxalic Acid and Hydroxypropul Cellulose in purified water;

3. Granulation: Granulate the materials of step 1 with binder solution of step 2. After completion of granulation, dry the wet mass;

4. Sift the sized granules through #030 mesh sieve. Mill the left over using 1.0 mm screen and sift through #030 mesh sieve;

5. Co-sift L-Hydroxypropyl Cellulose and Glyceryl dibehenate through #040 mesh sieve; and 6. Lubrication: Lubricate the granules of step 4 with sifted excipients of step 5 using suitable blender.

Glimepiride part:

1. Sifting: Co-sift Glimepiride, and L-HPC and mannitol through #060 mesh sieve. Sift ferric oxide yellow through #0100 mesh sieve;

2. Preparation of binder: Add and dissolve under stirring tween 80 and Hydroxypropul Cellulose in purified water;

3. Granulation: Granulate the materials of step 1 with binder solution of step 2. After completion of granulation, dry the wet mass;

4. Sift the sized granules through #030 mesh sieve. Mill the left over using 1.0 mm screen and sift through #030 mesh sieve;

5. Co-sift L-Hydroxypropyl Cellulose and magnesium stearate through #040 mesh sieve; and

6. Lubrication: Lubricate the granules of step 4 with sifted excipients of step 5 using suitable blender.

Compression, coating, packing: Compress both lubricated blends of Teneligliptin part and Glimepiride part with suitable tooling using a bilayer compression machine. Coat the compressed tablets using aqueous dispersion of opadry yellow. Pack the film coated tablets in blister pack.

Example 5

Formulations comprising Teneligliptin 3.0 oxalate n. hydrate and Pioglitazone

[00204] Table 15a depicts a formulation comprising Teneligliptin 3.0 oxalate n. hydrate and Pioglitazone (monolayer strategy 1).

Table 15a

[00205] Table 15b depicts a formulation comprising Teneligliptin 3.0 oxalate n. hydrate and Pioglitazone.

Table 15b

[00206] Brief strategy of manufacturing process for formulation of Table 15a-b

1. Sifting: Co-sift Teneligliptin Oxalate, Pioglitazone and L-HPC and mannitol through #060 mesh sieve;

2. Preparation of binder: Add and dissolve under stirring Oxalic Acid and Hydroxypropul Cellulose in purified water;

3. Granulation: Granulate the materials of step 1 with binder solution of step 2. After completion of granulation, dry the wet mass;

4. Sift the sized granules through #030 mesh sieve. Mill the left over using 1.0 mm screen and sift through #030 mesh sieve;

5. Co-sift L-Hydroxypropyl Cellulose and Glyceryl dibehenate through #040 mesh sieve;

6. Lubrication: Lubricate the granules of step 4 with sifted excipients of step 5 using suitable blender; 7. Compression: Compress the lubricated blend with suitable tooling and process parameters;

8. Coating: Coat the compressed tablets using aqueous dispersion of opadry yellow; and

9. Pack the film coated tablets in blister pack.

[00207] Table 15c depicts a formulation comprising Teneligliptin 3.0 oxalate n. hydrate and Pioglitazone (bilayer strategy 1).

Table 15c

[00208] Table 15d depicts a formulation comprising Teneligliptin 3.0 oxalate n. hydrate and Pioglitazone.

Table 15d

[00209] Brief strategy of manufacturing process for formulation of Table 15c-d

Teneligliptin part:

1. Sifting: Co-sift Teneligliptin Oxalate, and L-H PC and mannitol through #060 mesh sieve;

2. Preparation of binder: Add and dissolve under stirring Oxalic Acid and Hydroxypropul Cellulose in purified water;

3. Granulation: Granulate the materials of step 1 with binder solution of step 2. After completion of granulation, dry the wet mass; 4. Sift the sized granules through #030 mesh sieve. Mill the left over using 1.0 mm screen and sift through #030 mesh sieve;

5. Co-sift L-Hydroxypropyl Cellulose and Glyceryl dibehenate through #040 mesh sieve; and

6. Lubrication: Lubricate the granules of step 4 with sifted excipients of step 5 using suitable blender.

Pioglitazone part

1. Sifting: Co-sift Pioglitazone, and L-HPC and mannitol through #060 mesh sieve. Sift ferric oxide yellow through #0100 mesh sieve;

2. Preparation of binder: Add and dissolve under stirring Hydroxypropyl Cellulose in purified water;

3. Granulation: Granulate the materials of step 1 with binder solution of step 2. After completion of granulation, dry the wet mass;

4. Sift the sized granules through #030 mesh sieve. Mill the left over using 1.0 mm screen and sift through #030 mesh sieve;

5. Co-sift L-Hydroxypropyl Cellulose and magnesium stearate through #040 mesh sieve; and

6. Lubrication: Lubricate the granules of step 4 with sifted excipients of step 5 using suitable blender.

Compression, coating, packing: Compress both lubricated blends of Teneligliptin part and Pioglitazone part with suitable tooling using a bilayer compression machine. Coat the compressed tablets using aqueous dispersion of opadry yellow.

Example 6

Formulations comprising Teneligliptin 3.0 oxalate n. hydrate and Voglibose

[00210] Table 16a depicts a formulation comprising Teneligliptin 3.0 oxalate n. hydrate and Voglibose.

Table 16a

[00211] Table 16b depicts a formulation comprising Teneligliptin 3.0 oxalate n. hydrate and Voglibose.

Table 16b

[00212] Brief strategy of manufacturing process of formulation of Table 16a-b

1. Sifting: Co-sift Teneligliptin Oxalate, Voglibose and L-HPC and mannitol through #060 mesh sieve;

2. Preparation of binder: Add and dissolve under stirring Oxalic Acid and Hydroxypropyl Cellulose in purified water;

3. Granulation: Granulate the materials of step 1 with binder solution of step 2. After completion of granulation, dry the wet mass;

4. Sift the sized granules through #030 mesh sieve. Mill the left over using 1.0 mm screen and sift through #030 mesh sieve;

5. Co-sift L-Hydroxypropyl Cellulose and Glyceryl dibehenate through #040 mesh sieve; 6. Lubrication: Lubricate the granules of step 4 with sifted excipients of step 5 using suitable blender;

7. Compression: Compress the lubricated blend with suitable tooling and process parameters;

8. Coating: Coat the compressed tablets using aqueous dispersion of opadry yellow; and

9. Pack the film coated tablets in blister pack.

0213] Table 16c depicts a formulation comprising Teneligliptin 3.0 oxalate n. hydrate and Voglibose.

Table 16c

[00214] Table 16d depicts a formulation comprising Teneligliptin 3.0 oxalate n. hydrate and Voglibose.

Table 16d

[00215] Brief strategy of manufacturing process of formulation of Table 16c-d:

Teneligliptin part:

1. Sifting: Co-sift Teneligliptin Oxalate, and L-H PC and mannitol through #060 mesh sieve; 2. Preparation of binder: Add and dissolve under stirring Oxalic Acid and Hydroxypropyl Cellulose in purified water

3. Granulation: Granulate the materials of step 1 with binder solution of step 2. After completion of granulation, dry the wet mass;

4. Sift the sized granules through #030 mesh sieve. Mill the left over using 1.0 mm screen and sift through #030 mesh sieve;

5. Co-sift L-Hydroxypropyl Cellulose and Glyceryl dibehenate through #040 mesh sieve; and

6. Lubrication: Lubricate the granules of step 4 with sifted excipients of step 5 using suitable blender.

Voglibose part

1. Sifting: Co-sift Voglibose, and L-HPC and mannitol through #060 mesh sieve. Sift ferric oxide yellow through #0100 mesh sieve;

2. Add and dissolve under stirring Hydroxypropyl Cellulose in purified water;

3. Granulate the materials of step 1 with binder solution of step 2. After completion of granulation, dry the wet mass;

4. Sift the sized granules through #030 mesh sieve. Mill the left over using 1.0 mm screen and sift through #030 mesh sieve;

5. Co-sift L-Hydroxypropyl Cellulose and magnesium stearate through #040 mesh sieve; and

6. Lubrication: Lubricate the granules of step 4 with sifted excipients of step 5 using suitable blender.

[00216] Although the invention herein has been described with reference to particular embodiments, it is to be understood that these embodiments and examples are merely illustrative of the principles and application of the present invention. It is therefore to be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present invention disclosed herein.