FORM 2
THE PATENTS ACT 1970 (39 of 1970)
&
THE PATENTS RULE 2003
COMPLETE SPECIFICATION
(Section 10 and rule 13)
"PREMIX OF SAXAGLIPTIN"
Glenmark Generics Limited
an Indian Company, registered under the Indian company's Act 1957
having office at
Glenmark House,
HDO - Corporate Bldg,
Wing -A, B. D. Sawant Marg, Chakala,
Andheri (East), Mumbai - 400 099, INDIA
THE FOLLOWING SPECIFICATION DESCRIBES THE INVENTION

FIELD OF INVENTION
[0001] The present invention provides premix comprising saxagliptin or its pharmaceutically acceptable salts, more particularly to a premix wherein saxagliptin or its pharmaceuticaily acceptable salts, is in amorphous or partially crystalline form.
BACKGROUND OF THE INVENTION
[0002] Saxagliptin is an orally-active inhibitor of the DPP4 enzyme. Saxagliptin, chemically written as (lS,3S,5S)-2-[(2S)-2-amino-2-(3hydroxytricyclo[3.3.1.13,7]dec-l-yl)acetyl]-2-azabicyclo [3.1.0]hexane-3-carbonitrile, its hydrochloride and trifluoroacetic acid salts are disclosed in U.S. Pat. No. 6,395,767. Another U.S. Pat. No. 7420079 discloses Saxagliptin and its hydrochloride, trifluoroacetic acid and benzoate salts, as well as Saxagliptin monohydrate. Saxagliptin is marketed under the trade name ONGLYZA® by Bristol-Myers Squibb for the treatment of type 2 diabetes. U.S. Pat. No. 7943656 describes different crystalline polymorphs of Saxagliptin and its salts.
U.S. Pat. No. 7951400 describes that Saxagliptin undergoes intramolecular cyclization, leading to the formation of a degradant called as cyclic amidine (mainly cis-cyclic amidine (CA)), which is not therapeutically active and therefore, its formation is not desirable. The stress generated in regular pharmaceutical operations and/or the contact of saxagliptin to the commonly used pharmaceutical excipients triggers the cyclization, resulting into the formation of cyclic amidine. The preferred composition of patent 7951400 comprises (a) an inert tablet core (b) a inner seal coat (c) followed by a saxagliptin layer (d) and a final protective coat. Inner seal coat and outer protective coat of patent '400 avoids the direct contact of saxagliptin with excipients and outside humidity. However due to several coating layers, the compositions described in patent '400 are difficult to optimize and manufacture at commercial scale and are equally time consuming. However the inventors of the present invention have prepared the premix of saxagliptin or its pharmaceuticaily acceptable salts with pharmaceuticaily acceptable additives. The said premix of present invention can be readily incorporated into the pharmaceutical compositions such as tablets and capsules, if desired.

SUMMARY OF INVENTION
[0003] The present invention provides a premix comprising saxagliptin or its pharmaceutically acceptable salts and at least one pharmaceutically acceptable excipient.
[0004] In another aspect, the present invention provides a process for the preparation of a per-mix comprising saxagliptin or its pharmaceutically acceptable salts and at least one pharmaceutically acceptable excipient.
DETAILED DESCRIPTION OF INVENTION
[0005] As used herein, the term "premix" refers to a solid mixture comprising saxagliptin or its pharmaceutically acceptable salts in amorphous or partially crystalline form and at least one pharmaceutically acceptable excipient.
[0006] As used herein, the term "pharmaceutically acceptable salts" shall refer to the salts prepared from pharmaceutically acceptable non toxic bases or acids including inorganic or organic bases and inorganic or organic acids, however a premix of present invention may preferably contain saxagliptin HC1, in amorphous or partially crystalline form.
[0007] In one of the embodiments, the invention provides a premix comprising saxagliptin or its premix pharmaceutically acceptable salts and at least one pharmaceutically acceptable excipient. The premix produced in accordance with the present invention is characterized by X-ray diffraction pattern (XRD).
[0008] In one of the embodiment, the current invention provides a premix comprising saxagliptin or its pharmaceutically acceptable salts and at least one pharmaceutically acceptable excipient wherein the starting material for making the premix is saxagliptin free base.

[0009] In another embodiment, the current invention provides premix comprising saxagliptin or its pharmaceutically acceptable salts and at least one pharmaceutically acceptable excipient wherein the starting material for making the premix is saxagliptin monohydrate.
[0010] In a more preferred embodiment, the invention provides a premix comprising saxagliptin or its pharmaceutically acceptable salts and at least one pharmaceutically acceptable excipient wherein the starting material for making the premix is N-Boc saxagliptin.
[0011] These lists of pharmaceutically acceptable excipients are merely representative of those that can be used, and the lists are not intended to be exhaustive or limiting. For the purpose of this invention following pharmaceutically acceptable excipients polyvinylpyrrolidone (PVP), polyalkylene glycol such as polyethylene glycol, gelatin, polyvinyl alcohol (PVA), starch and derivatives thereof, cellulose derivatives, such as hydroxypropylmethyl cellulose (HPMC), hydroxypropyl cellulose, carboxymethyl cellulose, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, carboxyethyl cellulose, carboxymethylhydroxyethy! cellulose, acrylic acid polymers, polymethacrylates, or any other pharmaceutically acceptable polymer. Preferably for the purpose of the present invention polyvinyl pyrrolidone, polyvinyl alcohol or HPMC are preferred choices of polymers. Different viscosity grades of HPMC and polyvinyl pyrrolidone can also be used for the purpose of the present invention such 3cps, 5cps or 15 cps.
[0012] In one embodiment, the invention provides premix comprising saxagliptin or its premix pharmaceutically acceptable salts and at least one pharmaceutically acceptable excipient wherein the starting material for making the premix is saxagliptin free base and the ratio of drug to excipient may range from 1:0.1 to 1:10, preferably from 1:4 to 1:7, more preferably from 1:1 to 1:3.
[0013] The invention provides a premix comprising saxagliptin or its premix pharmaceutically acceptable salts and at least one pharmaceutically acceptable excipient wherein the starting material for making the premix is saxagliptin monohydrate and the ratio of drug to excipient may range from 1:0.1 to 1:10, preferably from 1:4 to 1:7, more preferably from 1:1 to 1:3.

[0014] In one of the preferred embodiment, the invention provides a premix comprising saxagliptin or its premix pharmaceutically acceptable salts and at least one pharmaceuticaily acceptable excipient wherein the starting material for making the premix is N- Boc saxagliptin and the ratio of starting material to excipient may range 1:0.1 to 1:10, preferably from 1:4 to 1:7, more preferably from 1:1 to 1:3.
[0015] The premix of present invention can also be prepared by using a saxagliptin in salt form as a starting material.
[0016] In yet another embodiment, a premix comprising saxagliptin HC1 and at least one pharmaceutically acceptable excipient wherein the starting material for making the premix is saxagliptin hydrochloride.
[0017] In yet another embodiment, the invention provides premix comprising saxagliptin HC1 and at least one pharmaceutically acceptable excipient wherein the starting material for making the premix is saxagliptin hydrochloride hemihydrate or saxagliptin hydrochloride monohydrate or saxagliptin hydrochloride dihydrate.
[0018] The lists of pharmaceutically acceptable excipients are merely representative of those that can be used, and the lists are not intended to be exhaustive or limiting. For the purpose of this invention following pharmaceutically acceptable excipients polyvinylpyrrolidone (PVP), polyalkylene glycol such as polyethylene glycol, gelatin, polyvinyl alcohol (PVA), Poloxamer, starch and derivatives thereof, cellulose derivatives, such as hydroxypropylmethyl. cellulose (HPMC), hydroxypropyl cellulose, carboxymethyl cellulose, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, carboxyethyl cellulose, carboxymethylhydroxyethyl cellulose, acrylic acid polymers, polymethacrylates, or any other pharmaceutically acceptable polymer. Preferably for the purpose of the present invention PVP, polyvinyl alcohol or HPMC are preferred choices of polymers. Different viscosity grades of HPMC and PVP can also be used for the purpose of the present invention.

[0019] In one of the embodiments, a premix of the present invention comprises saxagliptin HCJ and at least one pharmaceutically acceptable excipient wherein the starting material for making the premix is saxagliptin hydrochloride and the ratio of drug to excipient may range from 1:0.1 to 1:10, preferably from 1:4 to 1:7, more preferably from 1:1 to 1:3.
[0020] In one embodiment, the invention provides a premix comprising saxagliptin HC1 and at least one pharmaceutically acceptable excipient wherein the starting material for making the premix is saxagliptin hydrochloride hemihydrate or saxagliptin hydrochloride monohydrate or saxagliptin hydrochloride dihydrate and the ratio of drug to excipient may range from 1:0.1 to 1:10, preferably from 1:4 to 1:7, more preferably from 1:1 to 1:3.
[0021] The premix obtained in the present invention can be amorphous or partially crystalline. The term 'amorphous' hereinafter means that the premix may contain 10% of crystalline saxagliptin in it. The term 'partially crystalline' hereinafter means that the premix may contain 50% of crystalline saxagliptin in it.
[0022] In another aspect, the present invention provides a process for the preparation of a premix comprising saxagliptin or its pharmaceutically acceptable salts and at least one pharmaceutically acceptable excipient wherein the starting material for making the premix is saxagliptin free base.
[0023] In one embodiment, the present invention provides a process for the preparation of a premix comprising saxagliptin or its pharmaceutically acceptable salts and at least one pharmaceutically acceptable excipient wherein the starting material for making the premix is saxagliptin free base and a pharmaceutically acceptable excipient is cellulosic polymer or polyvinyl alcohol.
[0024] In a preferred embodiment, the present invention provides a process for the preparation of a premix comprising saxagliptin or its pharmaceutically acceptable salts and at least one pharmaceutically acceptable excipient wherein the starting material for making the premix is

saxagliptin free base and a pharmaceutically acceptable excipient is hydroxy propyl methyl cellulose or polyvinyl alcohol.
[0025] In a more preferred embodiment, the present invention provides a process for the preparation of a premix comprising saxagliptin or its pharmaceutically acceptable salts and at least one pharmaceutically acceptable excipient wherein the starting material for making the premix is saxagliptin free base and a pharmaceutically acceptable excipient is hydroxy propyl methyl cellulose.
[0026] In another embodiment, the present invention provides a process for the preparation of a premix comprising saxagliptin or its pharmaceutically acceptable salts and at least one pharmaceutically acceptable excipient wherein the starting material for making the premix is saxagliptin monohydrate and a pharmaceutically acceptable excipient is cellulosic polymer or polyvinyl alcohol.
[0027] In a more preferred embodiment, the present invention provides a process for the preparation of a premix comprising saxagliptin or its pharmaceutically acceptable salts and at least one pharmaceutically acceptable excipient wherein the starting material for making the premix is saxagliptin monohydrate and a pharmaceutically acceptable excipient is hydroxy propyl methyl cellulose.
[0028] In present invention, when saxagliptin base or its monohydrate are used as a starting material for the premix of saxagliptin salts, it is essential for the starting material to react with the source of salt in reaction mixture. For the purpose of the present invention, preferred salt of saxagliptin is HC1. To obtain premix of saxagliptin HC1 using saxagliptin free base or monohydrate as a starting material, it is essential to react either of these starting material with 0.1N HC1 or any other source of chloride salt and it is further treated with any one of the pharmaceutically acceptable excipients to get the premix of saxagliptin HC1 salt.

[0029] In another more preferred embodiment, the present invention provides a process for the preparation of a premix comprising saxagliptin or its pharmaceutically acceptable salts and at least one pharmaceutically acceptable excipient wherein the starting material for making the premix is N-Boc saxagliptin and a pharmaceutically acceptable excipient is Polyvinylpyrrolidone.
[0030] In a further preferred embodiment, when a premix of saxagliptin HC1 is to be prepared using N-Boc saxagliptin as a saxagliptin material, it is essential for saxagliptin N-Boc to react with source of salt. In this case, N-Boc saxagliptin is treated with 10% methanolic HC1 solution or any other source of chloride salt which is further treated with at least one of the pharmaceutically acceptable excipients to obtain the premix of saxagliptin HC1.
[0031] In another embodiment, the present invention provides a process for the preparation of a premix comprising saxagliptin HC1 and at least one pharmaceutically acceptable excipient wherein the starting material for making the premix is saxagliptin HC1 and a pharmaceutically acceptable excipient is cellulosic polymer or polyvinyl alcohol.
[0032] In a preferred embodiment, the present invention provides a process for the preparation of a premix comprising saxagliptin HC1 and at least one pharmaceutically acceptable excipient wherein the starting material for making the premix is saxagliptin HC1 and a pharmaceutically acceptable excipient is hydroxy propyl methyl cellulose or polyvinyl alcohol.
[0033] In a more preferred embodiment, the present invention provides a process for the preparation of a premix comprising saxagliptin HC1 and at least one pharmaceutically acceptable excipient wherein the starting material for making the premix is saxagliptin HC1 and a pharmaceutically acceptable excipient is hydroxy propyl methyl cellulose.
[0034] In another embodiment, the present invention provides a process for the preparation of a premix comprising saxagliptin HC1 and at least one pharmaceutically acceptable excipient wherein the starting material for making the premix is saxagliptin hydrochloride hemihydrate or

saxagliptin hydrochloride monohydrate or saxagliptin hydrochloride dihydrate and a pharmaceutically acceptable excipient is cellulosic polymer or polyvinyl alcohol.
[0035] In a more preferred embodiment, the present invention provides a process for the preparation of a premix comprising saxagliptin HC1 and at least one pharmaceutically acceptable excipient wherein the starting material for making the premix is saxagliptin hydrochloride hemihydrate or saxagliptin hydrochloride monohydrate or saxagliptin hydrochloride dihydrate and a pharmaceutically acceptable excipient is hydroxy propyl methyl cellulose.
[0036] In one embodiment, the process of preparation of premix of saxagliptin or its pharmaceutically acceptable salts and at least one pharmaceutically acceptable excipient comprises
a) Providing a solution of starting material with at least one pharmaceutically acceptable excipient;
b) distillation of solvent or solvent mixtures; and
c) drying the product obtained.
[0037] The solution of saxagliptin or its pharmaceutically acceptable salts may be obtained by dissolving it in a suitable solvent, or such a solution may be obtained by directly from a reaction in which saxagliptin or its pharmaceutically acceptable salts is formed. In case of preparing solutions, any form of saxagliptin or its pharmaceutically acceptable salts such as the saxagliptin amorphous or crystalline or crystalline hydrates or crystalline solvates can be used.
[0038] The solution containing the pharmaceutically acceptable excipient and the starting material can be prepared by methods well known in the art. The pharmaceutical excipient can be added to the solution of starting material or viceversa. Two separate solution containing each of them can also be mixed together to get the reaction mixture. In any case, both the starting material and pharmaceutical excipient should be soluble is the solvent or solvent mixtures and should provide a clear solution.

[0039] Suitable solvents that may be used for providing a solution of starting material and one or more pharmaceutically acceptable excipients include but are not limited to, polar and non-polar solvents, and mixtures thereof. Non-limiting examples of Suitable solvents include, but are not limited to: polar solvents such as water, 0.1N HC1, methanolic HC1, methanol, ethanol, n-propanol, isopropanol, n-butanol, tetrahydrofuran, acetone, acetonitrile, non-polar solvents such as toluene, chloroform, n-hexane, ethyl acetate, dichloromethane, benzene, diethyl ether, and mixtures thereof. Generally, the more volatile solvents and solvents in which both the drug and excipients is completely soluble are preferred.
[0040] The temperature for dissolution of the starting material and one or more pharmaceutically acceptable excipient may range from about 0°C to about 80°C. Any temperature range can be used for to get a char solution of the starting material and any one of the pharmaceutically acceptable excipients provided at that temperature neither starting material nor any one of the pharmaceutically acceptable excipients gets degraded. Temperature of the reaction should also be such that the formed product should remain stable at that temperature. Such variations are all included herein without any limitation.
[0041] The solvent may be removed from the solution by techniques such as distillation under vacuum. The solvent may be distilled under reduced pressure. The distillation may be conducted at a temperature from about 30 to about 100° C, to dryness.
[0042] The solvent(s) may be also removed from the solution by techniques known in the art including but not limited to: rotational drying (such as with the Buchi Rotavapor), spray drying, or freeze-drying.
[0043] Drying can suitable be carried out by techniques known in the art including but not limited
to: a tray dryer or vacuum dryer. [0044] The premix of saxagliptin or its pharmaceutically Acceptable salts with one or more
pharmaceutically acceptable excipients are stable during storage. This property is important and

advantageous for the desired use of saxagliptin or its pharmaceutically acceptable salts in pharmaceutical product formulations.
[0045] The premix compositions of this invention as described in the different embodiments above are useful in the preparation of pharmaceutical compositions for the delivery of saxagliptin or its pharmaceutically acceptable salts. A pharmaceutical composition contains one or more pharmaceutically acceptable excipients that are non-toxic to the mammal intended to be treated when the composition is administered in an amount effective to treat the mammal.
[0046] The pharmaceutical compositions may be in the form of encapsulated free flowing powders or granules; compressed solid dosage forms such as tablets like chewable or dispersible or mouth dissolving or liquid dosage forms such as solutions, syrup, suspensions or emulsions.
[0047] The pharmaceutical compositions of the present invention may contain one or more other commonly used excipients to make up the final composition mass so that it becomes easier for the patient and supplier to handle.
[0048] The tabletting powder contains number of inert materials known as excipients. They may be classified according to the role they play in the tablet. The primary composition includes fillers, binders or diluents, lubricants, disintegrants, acidifying agents and glidants. Other excipients which give physical characteristics to the finished tablet are coloring agents, and flavors in the case of chewable tablets. Typically, excipients are added to a formulation to impart good flow and compression characteristics to the material being comprised.
[0049] One or more fillers or diluents can be selected. Examples of pharmaceutically acceptable fillers or diluents include, but are not limited to, sucrose, and lactose, in particular lactose monohydrate, mannitol, sorbitol, microcrystalline cellulose, powdered cellulose. Different grades of lactose or microcrystalline cellulose can be used. In case of a water soluble active ingredient, like the one described in this invention, more preferably water insoluble fillers, such as starch, microcrystalline cellulose, dibasic calcium phosphate dihydrate, and anhydrous dibasic calcium

phosphate, preferably microcrystalline cellulose, can be used in addition or instead of the water soluble fillers. In preferred embodiment combination of water soluble and water insoluble fillers are used.
[0050] Disintegrants are often included to ensure that the tablet has an acceptable rate of disintegration. One or more disintegrants can be selected. Examples of pharmaceutically acceptable disintegrants include, but are not limited to, starches; clays; celluloses; alginates; gums; cross-linked polymers, e.g., crospovidone, cross-linked Ca-CMC and Na-CMC, Sodium starch glycoalte. Disintegrants are included to ensure that the tablet has an acceptable rate of disintegration.
[0051] Another commonly used class of excipients in tablets is binders. Binders are agents, which impart cohesive qualities to the powdered material. The compositions described herein also can comprise binders, examples of pharmaceutically acceptable binders include, but are not limited to, povidones (e.g., PVP K-30, PVP K-60, and PVP K-90), cellulose derivatives (e.g., methylcellulose and sodium carboxymethylcellulose), gelatin, polyethylene glycol, polymethacrylates, ethyl cellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, pregelatinized starch and sodium alginate, wherein HPMC is particularly preferred.
[0052] Lubricants are typically added to prevent the tabletting materials from sticking to punches, minimize friction during tablet compression, and allow for removal of the compressed tablet from the die. Examples of pharmaceutically acceptable lubricants include, but are not limited to, magnesium stearate, calcium stearate, canola oil, glyceryl palmitostearate, hydrogenated vegetable oil, magnesium oxide, mineral oil, poloxamer, polyethylene glycol, polyvinyl alcohol, sodium benzoate, sodium lauryl sulfate, sodium stearyl fumarate, stearic acid, talc, hydrogenated vegetable oil, zinc stearate and the like.

[0053] Acidifying agents are typically added to the composition to lower the pH of composition and may act as a stabilizer. Examples of pharmaceutically acceptable lubricants include, but are not
j
limited to, ascorbic acid, tartaric acid, malic acid, cysteine HCl, citric acid.
EXAMPLES
[0054] The following examples describe compositions of the present invention containing Saxagliptin or its pharmaceutically acceptable salts, but they are not to be interpreted as limiting the scope of the claims
Example 1:
Preparation of pre mix of saxagliptin HCl with PVP as an excipient.
7.5g of N-Boc saxagliptin was loaded at room temperature in 250 ml 4 neck round bottom flask (RBF) equipped with overhead stirrer, thermo pocket and guard tube N2 gas inlet. 40ml of 10% methanolic HCl was added in RBF and solution was mixed for l0 min at room temperature. The reaction mass was heated for 3-4hrs at 50°C. TLC was done after 4 hours. TLC was matched for the absence of starting material. Reaction mixture was allowed to cool at room temperature.
To above reaction mixture, 1.6 gm of polyvinyl pyrrolidone (PVP) was added at room temprature and stirred for 10-15 mins till a clear solution was obtained. Solvent was distilled out under vacuum at 45°C and it was stripped off 3 times by 50ml of dichloromethane. The obtained solid was dried under vacuum at 50°C for 4 hours. 3.3gm of solid was obtained. Water content (by K.F) of solid obtained was less than 5.5%, preferably it was 4.4%. XRD as shown in Fig.l
Example 2:
Preparation pre mix of saxagliptin base form with Methocel E5LV
Saxagliptin monohydrate and HPMC (Methocel E5LV) (1:4) were dissolved in solvent mixture of IPA and MDC (1:1). Resulting solution was loaded in rota vapour and distillation of solvents

was carried out, till all the solvents got evaporated. Product thus obtained was collected and milled. This Milled sample was sent for XRD. XRD as shown in Fig.2
Example 3:
Premix of Example 1 was mixed with commonly used excipients and then compressed into the tablets as given below.

Ingredient Qty/Tab (in mg)
Saxagliptin HC1 premix equivalent to saxagliptin 5
Lactose Monohydrate 73.7
Microcrystalline Cellulose 110.00
Croscarmellose Sodium 6.75
Povidone 6.75
Purifeid Water qs
Croscarmellose Sodium 4.50
Microcrystalline cellulose 20.00
Talc 1.00
Magnesium stearate 2.30
Core tablet weight 230.00
Opadry ® II-Complete Film Coating System' 7.00
Coated tablet weight 237.00
Example 4:
Premix of Example \ was mixed with commonly used excipients and filled into the capsules as given below

Ingredient Qty/Tab (in mg)
Saxagliptin HC1 premix equivalent to saxagliptin 5
Lactose Monohydrate 71.16
Microcrystalline Cellulose 110.00
Croscarmellose Sodium 6.75
Magnesium stearate 2.30
Total 195.00

Claims:
1. A Premix comprising saxagliptin or pharmaceutically acceptable salts thereof and at least one pharmaceutically acceptable excipient.
2. The premix of claim 1 wherein, saxagliptin or its pharmaceutically acceptable salts is in amorphous or partially crystalline form.
3. The premix of claim 1 wherein, the pharmaceutically acceptable salt is hydrochloride salt.
4. The premix of claim 1 wherein, the pharmaceutically acceptable excipient is selected from polyvinylpyrrolidone (PVP), polyalkylene glycol such as polyethylene glycol, gelatin, polyvinyl alcohol (PVA), Poloxamer, starch and derivatives thereof, cellulose derivatives, such as hydroxypropylmethyl cellulose (HPMC), hydroxypropyl cellulose, carboxymethyl cellulose, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, carboxyethyl cellulose, carboxymethylhydroxyethyl cellulose, acrylic acid polymers, polymethacrylates, or any other pharmaceutically acceptable polymer.
5. The premix of claim 4 wherein, the pharmaceutically acceptable excipient is selected from different grades of PVP, polyvinyl alcohol or HPMC.
6. A process of preparation of premix of saxagliptin or pharmaceutically acceptable salts thereof and at least one pharmaceutically acceptable excipient comprising

a) providing a solution of starting material with at least one pharmaceutically acceptable excipient;
b) distillation of solvent or solvent mixtures; and
c) drying the product obtained.

7. A process of preparation of premix of saxagliptin or pharmaceutically acceptable salts thereof and at least one pharmaceutically acceptable excipient according to claim 6, wherein the starting material is selected from the group of saxagliptin free base, saxagliptin monohydrate, N-Boc saxagliptin or saxagliptin salts.
8. A process of preparation of premix of saxagliptin or pharmaceutically acceptable salts thereof and at least one pharmaceutically acceptable excipient according to claim 7, wherein the starting material is saxagliptin hydrochloride, saxagliptin hydrochloride hemihydrate, saxagliptin hydrochloride monohydrate or saxagliptin hydrochloride dihydrate.

9. A process of preparation of premix of saxagliptin or pharmaceutically acceptable salts thereof and at least one pharmaceutically acceptable excipient according to claim 6 wherein, ratio of the starting material ranges from 1:0.1 to 1:10, preferably from 1:4 to 1:7, more preferably from 1:1 to 1:3.