WO2017032705A1

WO2017032705A1 - Crystalline form of omarigliptin

Info

Publication number: WO2017032705A1
Application number: PCT/EP2016/069687
Authority: WO
Inventors: Hannes Lengauer
Original assignee: Sandoz Ag
Priority date: 2015-08-25
Filing date: 2016-08-19
Publication date: 2017-03-02

Abstract

The present invention relates to a novel polymorph of omarigliptin, a process of preparing the same as well as a pharmaceutical composition comprising the same.

Description

Crystalline Form of Omarigliptin

Field of industrial applicability The present invention relates to a novel polymorph of omarigliptin, a process of preparing the same as well as a pharmaceutical composition comprising the same.

Background Omarigliptin is known under the IUPAC name "(2R,35^,,5R)-2-(2,5-difluoro- phenyl)-5-[2-(methylsulfonyl)-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]tetra- hydro-2H-pyran-3 amine" and can be represented by the following chemical structure according to Formula (A):

Formula (A)

Omarigliptin is reported to belong to the class of dipeptidyl peptidase-IV- inhibitors, also known as DPP-4-inhibitors or gliptins. While glucagon increases the blood glucose levels, DPP-4 inhibitors are able to reduce glucagon and, thus, also blood glucose levels. The mechanism of DPP-4 inhibitors is to increase the GLP- 1 and GIP levels, which inhibit glucagon release. In turn the inhibition of the glucagon release leads to the following: increase of insulin secretion, decrease of gastric emptying and decrease of blood glucose levels.

Omarigliptin is for example suitable for the treatment of type 2 diabetes, obesity and high blood pressure, in particular for the treatment of type 2 diabetes. The active pharmaceutical ingredient omarigliptin and its synthesis are described in WO 2010/056708 Al .

Further, WO 2013/003249 Al describes four polymorphic forms of omarigliptin. Form I is obtained by crystallization of raw (amorphous) omarigliptin in ethyl acetate. Form II is prepared by recrystallization of Form I in isopropyl acetate and heptane 1 : 1. Forms I and II are reported to be enantiotropically related and able to convert into each other depending on the temperature. Form I is considered to be the more stable form at temperatures above 13°C, whereas Form II seems to be more stable at temperatures below 13°C. In addition, Form I tends to be rather hygroscopic. Hygroscopic forms often show rather poor shelf-life and are more difficult to handle in a process for producing a pharmaceutical dosage form.

Further, Forms III and IV are obtained by dissolving Form I in methanol and tetrahydrofuran- water 1 : 1 , respectively followed by evaporating the solvents. Solvent evaporation is a technique only viable on a very small laboratory scale but certainly not on industrial scale. This is also confirmed by the fact that the applicant mentions that the characterization of Forms III and IV was limited to the amount of sample available. In addition, the preparation of Form III and Form IV requires the usage of toxic solvents such as methanol and tetrahydrofuran, respectively. Both solvents belong to ICH class 2 [see ICH harmonised tripartite guideline, Impurities: guideline for residual solvents Q3C(R5), current version 4 from February 4^th, 201 1] . Solvents belonging to this class should be limited in pharmaceutical products because of their inherent toxicity. Considering the fact that both forms are anhydrous, the mass loss visible in the TGA curves displayed in figure 12 and 15 of WO 2013/003249 Al can be mainly assigned to a residual organic solvent content which clearly exceeds the acceptable regulatory ICH limits for methanol (3000 ppm) and tetrahydrofuran (720 ppm). In order to lower the methanol content, Form III for example was heated to a temperature of 140°C; such harsh conditions cause at least some chemical degradation, though. Finally, both forms are reported to be metastable and convert into Forms I and II. All in all, the prior art forms disclosed in WO 2013/003249 Al show certain drawbacks which render their use rather challenging for pharmaceutical purposes. For example, the known polymorphic forms of omarigliptin do not seem to be adequately stable under pharmaceutically acceptable conditions and/or tend to convert into each other. Such a conversion of polymorphs often results in an unpredictable behaviour of the pharmaceutically active agent with regard to its in vivo and/or in vitro properties such as solubility, bioavailability and stability (shelf-life). In addition, some of the prior art forms are not producible in an industrial manner and do not show adequate purity with regard to residual organic solvents required by regulatory authorities.

Thus, it was an object of the present invention to overcome the drawbacks of the above-mentioned prior art forms and to provide omarigliptin which is present in a pure and/or stable form. Further, omarigliptin should be provided in a form that can be easily produced also on an industrial scale. Additionally, omarigliptin should be provided in a form which can be easily processed into a pharmaceutical dosage form, preferably by a dry process like direct compression.

In particular, a form of omarigliptin should be provided which on the one hand shows an advantageous low hygroscopicity and on the other hand usually does not convert into other polymorphic forms. Summary of the invention

The above objectives are unexpectedly achieved by the provision of a polymorphic form of omarigliptin which is designated omarigliptin Form V and a process for its preparation. Further, the invention provides pharmaceutical compositions comprising said omarigliptin Form V. Brief description of the drawings

Fig. 1 illustrates a representative X-ray powder diffraction (XRPD) pattern of omarigliptin Form V.

Fig. 2 illustrates a representative Fourier transform infrared (FTIR)- spectrum of omarigliptin Form V.

Fig. 3 illustrates a representative differential scanning calorimetry (DSC) curve of omarigliptin.

Fig. 4 illustrates representative gravimetric moisture sorption and desorption isotherms of omarigliptin Form I and Form V. Fig. 5 illustrates an overlay of the Raman spectra of omarigliptin Form V at the starting point (top) and the end point (bottom) of the gravimetric moisture sorption experiment

Detailed description of the invention

The term "polymorph" as used herein refers to a crystalline form having the same chemical composition but different spatial arrangements of the molecules, atoms and/or ions forming said crystal.

Further, a "polymorph" as referred to herein is considered to be a substantially pure polymorph. This means that the polymorphic form includes less than 10%, preferably less than 5%, more preferably less than 3%, in particular less than 1% by weight of any other physical forms of the compound. A polymorph can be characterized by its X-ray powder diffraction pattern. Such a diffraction pattern records the X-ray intensity as a function of 2-Theta angle. All the diffraction patterns are normally prepared as step-scans. The X-ray counts at each step are saved. Once finished, the data normally is smoothed with a weighted moving average. While the vertical axis records the X-ray intensity, the horizontal axis records angles in degrees 2-Theta. Low 2-Theta angles correspond to large d- spacings. As is known in the art, the peak positions (2-Theta) might show some inter- apparatus variabilities, which usually do not exceed ±0.2°. Further, it is also known in the art that relative peak intensities might show inter- apparatus variability as well as variability due to the degree of crystallinity, preferred orientation, preferred sample surface and other known factors. There are some alternatives to characterize a crystal, for example by using a group of three to six peaks at some positions in the XRPD pattern or by using the absence of a peak. In the present case the crystal form is characterized by peaks at positions being specific/characteristic for the polymorph. Thus, it is not necessary that these peaks show the highest relative intensity.

Thus, the subject of the present invention is a crystalline form of omarigliptin characterized by having an X-ray powder diffraction pattern comprising peaks at 2-Theta values of ( 18.5 + 0.1 , 18.9 + 0.1 , 21.0 + 0.1 , 22.1 + 0.1 and 24.9 + 0.1 )°, preferably of ( 18.5 + 0.2, 18.9 + 0.2, 21.0 + 0.2, 22.1 + 0.2 and 24.9 + 0.2)°, when measured at a temperature in the range of 20 to 30°C, for example at 25°C, with Cu-Kalpha_{1 >2} radiation having a wavelength of 0.15419 nm. This omarigliptin can be considered as the polymorphic Form V of omarigliptin.

In a preferred embodiment of the invention omarigliptin Form V can comprise at least one further peak in the X-ray powder diffraction pattern at 2-Theta values of (10.3 + 0.1 , 14.6 + 0.1 , 16.2 + 0.1 and/or 16.6 + 0.1)°, preferably of ( 10.3 + 0.2, 14.6 + 0.2, 16.2 + 0.2 and/or 16.6 + 0.2)°, when measured at a temperature in the range of 20 to 30°C, e.g. at 25°C, with Cu-Kalpha_1>2 radiation having a wavelength of 0.15419 nm. Preferably omarigliptin Form V comprises two out of the four above-mentioned peaks, more preferably three out of four and most preferably four out of four.

In a further preferred embodiment omarigliptin Form V can comprise peaks in the X-ray powder diffraction pattern at 2-Theta values of ( 10.3 + 0.1 , 14.6 + 0.1 , 16.2 + 0.1 , 16.6 + 0.1 , 18.5 + 0.1 , 18.9 + 0.1 , 21.0 + 0.1 , 22.1 + 0.1 , 24.0 + 0.1 , 24.9 + 0.1 and 25.9 + 0.1)°, preferably of ( 10.3 + 0.2, 14.6 + 0.2, 16.2 + 0.2, 16.6 + 0.2, 18.5 + 0.2, 18.9 + 0.2, 21.0 + 0.2, 22.1 + 0.2, 24.0 + 0.2, 24.9 + 0.2 and 25.9 + 0.2)°, when measured at a temperature in the range of 20 to 30°C, e.g. at 25°C, with Cu-Kalpha_{1 >2} radiation having a wavelength of 0.15419 nm.

In an alternatively preferred embodiment omarigliptin can be characterized by an X-ray powder diffraction pattern as depicted in Figure 1. The complete listing of peaks shown in Figure 1 and the corresponding relative intensities of the peaks are reported in the following table 1 :

Position Relative Intensity

[± 0.1, preferably ± 0.2° 2-Theta] [ ]

25.4 15

25.9 25

26.8 12

28.9 10

29.5 8

30.4 16

33.2 4

35.0 2

38.2 6

38.9 5

Table XRPD peak list and relative intensities of omarigliptin Form V

In a further preferred embodiment of the invention omarigliptin Form V is characterized by having a Fourier transform infrared (FTIR) spectrum comprising peaks at wavenumbers of (1608 + 2) cnT¹, (1498 + 2) cnT¹, (1369 + 2) cnT¹, (1273 + 2) cnT¹ and (1172 + 2) cnT¹, when measured at a temperature in the range of 20 to 30°C, e.g. at 25°C with a diamond ATR cell. In contrast to Form I of WO 2013/003249 Al, the Fourier transform infrared spectrum of Form V of the present invention preferably shows no peaks at wavenumbers of (3033 + 2) cnT¹, (2893 + 2) cnT¹ and (1734 + 2) cnT¹, when measured at a temperature in the range of 20 to 30°C, e.g. at 25°C with a diamond ATR cell.

The complete listing of peaks shown in Figure 2 is reported in the following table 2:

Table 2: FTIR peak list of omarigliptin Form V

In another embodiment of the invention omarigliptin Form V is characterized by having a Raman spectrum comprising characteristic peaks at wavenumbers of (1275 + 2) cnT¹, (1244 + 2) cnT¹, (597 + 2) cnT¹, (401 + 2) cm^-1, when measured at a temperature in the range of 20 to 30°C, e.g. at 25°C and a wavelength of 785 nm.

The complete listing of peaks of omarigliptin Form V measured at the starting point of the gravimetric moisture sorption experiment shown in Figure 5 is reported in the following table 3:

Wavenumbers Wavenumbers

[± 2 cm^-1] [± 2 cm^-1]

1261 564

1244 552

1191 506

1172 468

1150 453

1107 441

1085 416

1071 401

1059 388

994 378

973 333

964 320

942 298

926 262

874 245

Table 3: Raman peak list of omarigliptin Form V

In a further embodiment of the invention omarigliptin Form V is characterized by having a differential scanning calorimetry (DSC) curve comprising an endotherm with an onset temperature of 168 + 1°C, when measured at a heating rate of 10 K/min.

It was unexpectedly found that omarigliptin Form V is present in a stable form, i.e. it does not convert into other polymorphic forms in the temperature range of 5 to 40°C. This range is considered to be very sensible since active pharmaceutical agents as well as dosage forms are usually stored at these temperatures.

Surprisingly, Form V is even stable at accelerated stress conditions such as atmospheres having a temperature of about 40°C and a relative humidity of about 75%. Further, omarigliptin Form V exhibits an excellent low hygroscopicity, which is for example advantageously smaller than the hygroscopicity of omarigliptin Form I.

Additionally, omarigliptin Form V is easy to process in the further processing of a dosage form.

Further, omarigliptin Form V is easily available from synthesis without the need of a time-consuming and cost-intensive purification step. For example, Form V is obtained from a solvent comprising w-propanol, an ICH class 3 solvent with a less strict residual solvent limit compared to ICH class 2 solvents such as methanol or tetrahydrofuran .

Therefore, a further subject of the present invention is a process for preparing a crystalline form of omarigliptin according to the present invention comprising the steps of i) providing a solution comprising omarigliptin and a solvent containing at least 50 volume percent w-propanol;

ii) precipitating omarigliptin from the solution of step i);

iii) optionally separating at least a part of omarigliptin Form V from its mother- liquor;

iv) optionally washing isolated omarigliptin Form V obtained in step iii);

v) optionally drying isolated omarigliptin Form V obtained in step iii) or iv). In a preferred embodiment omarigliptin Fom V as obtained in step ii) is subsequently subjected to steps iii), iv) and v).

Omarigliptin can for example be prepared as described in WO 2013/003249.

In step i) omarigliptin is dissolved, preferably completely dissolved, in a solvent comprising at least 50 volume percent w-propanol. In a preferred embodiment the solvent comprises at least 70 volume percent w-propanol, more preferably at least 80 volume percent w-propanol, even more preferably at least 90 volume percent n- propanol, in particular 95 to 100 volume percent w-propanol.

As known in the art, volume percent is an expression of a solution's concentration and can be calculated according to the following equation: volume of solute

volume percent =— : — -—— * 100

volume of solution

In the present invention the solute is preferably w-propanol.

Apart from w-propanol, the solvent can contain one or more further organic solvent(s), wherein these further organic solvents are preferably solvents comprising 1 to 4 carbon atoms. Solvents comprising 1 to 4 carbon atoms are for example dichlorormethane, methanol, ethanol, acetone, isopropanol, methylethyl ketone, w-butanol, isobutanol, sec-butanol, iert-butanol, ethyl acetate and isopropyl acetate. Preferred are ethanol, isopropanol and isopropyl acetate. Most preferably, the solvent is substantially free of water. In a preferred embodiment the water content of the solvent is less than 2 wt.%, preferably less than 1 wt.%, more preferably less than 0.5 wt.%.

In step i) omarigliptin is dissolved in a solvent comprising at least 50 volume percent w-propanol, preferably under heating, preferably from 20°C to the boiling point of the applied solvent or solvent mixture. It is further preferred that step i) is conducted under a mechanical agitation such as stirring.

Step ii) comprises the precipitation of omarigliptin, in particular of omarigliptin Form V, from the solution of step i). This step can preferably include filtering the solution of step i) and then preferably cooling the solution from step i) to a temperature of 0°C to 27°C, preferably 5°C to 25°C, in particular 10°C to 23°C. Further, it is preferred that step ii) is conducted under a mechanical agitation such as stirring. In a preferred embodiment stirring can be carried out for 1 to 96 hours, preferably 5 to 90 hours, in particular 10 to 80 hours. Seed crystals of omarigliptin Form V may be added to promote crystallization. Seeding may also be employed to control growth of Form V or to control the particle size distribution of the crystalline product.

The separation of omarigliptin Form V from its mother liquor in step iii) can preferably be carried out by collecting the precipitate from step ii) by any conventional method such as filtration or centrifugation, most preferably by filtration. The term "mother liquor" as used herein refers to the solution remaining after crystallization of a solid. Further, the precipitate, omarigliptin Form V, can preferably be washed, preferably with w-propanol. Subsequently, omarigliptin Form V can preferably be dried. Drying can preferably be carried out under reduced pressure of 1 to 500 mbar, in particular 3 to 45 mbar. Further, drying can preferably be carried out at a temperature of 20°C to 40°C, preferably at 23°C. In a more preferred embodiment drying is carried at 23°C under reduced pressure.

A further subject of the invention is a crystalline form of omarigliptin obtainable or obtained by the process of the present invention. A further subject of the invention is a crystalline form of omarigliptin according to the invention for use as a medicament, in particular in the treatment of type 2 diabetes, obesity and high blood pressure, even more particularly for the treatment of type 2 diabetes. The invention also relates to a pharmaceutical composition comprising a) a crystalline form of omarigliptin according to the present invention and b) at least one pharmaceutically acceptable excipient.

The pharmaceutical composition may be formulated with one or more pharmaceutically acceptable excipients and optionally other active pharmaceutical ingredients. Pharmaceutically acceptable excipients relate to substances known for example from the European Pharmacopeia (Ph. Eur.) such as diluents, binders, disintegrants, lubricants, preservatives and coating material. The present pharmaceutical composition can be prepared by the methods known to a person skilled in the art. It is further preferred that the pharmaceutical composition is processed into an oral dosage form. The oral dosage form, preferably a tablet or a capsule, more preferably a tablet, can preferably be coated, preferably film coated.

One particular embodiment of the invention refers to a film coated tablet comprising a tablet core containing omarigliptin Form V, mannitol, microcrystalline cellulose, magnesium stearate and croscarmellose sodium and a film coating comprising a commercially available Opadry^® film coating mixture. Preferably, the tablet core contains about 10 to 20% omarigliptin Form V, 50 to 70% mannitol, 10 to 30% microcrystalline cellulose, 1 to 5% magnesium stearate and 1 to 5% croscarmellose sodium. Preferably, the tablet core comprises about 10 to 30 mg, such as about 12.5 or 25 mg, of omarigliptin Form V.

The pharmaceutical compositions described herein can be prepared by wet or dry processing methods. In certain embodiments the pharmaceutical compositions are prepared by wet processing methods, such as, but not limited to, wet granulation methods. Suitable wet granulation methods comprise high-shear granulation or fluid-bed granulation. In another embodiment the pharmaceutical compositions are prepared by dry processing methods, such as, but not limited to, direct compression or dry granulation methods. An example of dry granulation is roller compaction. The pharmaceutical compositions obtained by dry or wet processing methods may be compressed into tablets, encapsulated or metered into sachets.

The following non-limiting examples are illustrative for the disclosure. Experimental part Analytical Methods XRPD:

X-ray powder diffraction (XRPD) was performed with a PANalytical X'Pert PRO diffractometer equipped with a theta/theta coupled goniometer in transmission geometry, Cu-Kalpha_{1 2} radiation (wavelength 0.15419 nm) with a focusing mirror and a solid state PIXcel detector. The pattern was recorded at a tube voltage of 45 kV and a tube current of 40 mA, applying a step size of 0.013° 2-Theta with 40 s per step (255 channels) in the angular range of 2° to 40° 2-Theta at ambient conditions. A typical precision of the 2-Theta values is in the range of about + 0.2° 2-Theta. Thus, for example the diffraction peak of omarigliptin Form V that appears at 22.1° 2-Theta can appear between 21.9 and 22.3° 2-Theta on most X-ray diffractometers under standard conditions. In an alternative embodiment the precision of the 2-Theta values is in the range of about ± 0.1° 2-Theta.

FTIR:

Fourier transform infrared spectroscopy (FTIR) was performed on an MKII Golden Gate™ Single Reflection Diamond ATR (attenuated total reflection) cell with a Bruker Tensor 27 FTIR spectrometer with 4 cnT¹ resolution at ambient conditions. To record a spectrum a spatula tip of a sample was applied to the surface of the diamond in powder form. Then the sample was pressed onto the diamond with a sapphire anvil and the spectrum was recorded. A spectrum of the clean diamond was used as background spectrum. A typical precision of the wavenumber values is in the range of about + 2 cm^-1. Thus, for example the infrared peak of Form V that appears at 1498 cnT¹ can appear between 1496 and 1500 cnT¹ on most infrared spectrometers under standard conditions. Raman:

Raman spectra were recorded with a Kaiser Optical Systems RXN1 Raman spectrometer applying a 785 nm Invictus NIR laser with 400 mW and a PhAT Probe with 6 mm aperture beam diameter and a maximum focal length of 250 mm. To record a spectrum a powdered sample was spread in an aluminium cup which was placed under the laser beam. A typical precision of the wavenumber values is in the range of about + 2 cm^"1. Thus, for example the Raman peak of Form V that appears at 1628 cnT¹ can appear between 1626 and 1630 cnT¹ on most Raman spectrometers under standard conditions.

DSC:

Differential scanning calorimetry (DSC) was performed on a Mettler Toledo Polymer DSC R instrument. About 1 mg of the sample was heated in 40 μΐ_^ aluminium pans with pierced aluminium lids from room temperature to 250°C at a rate of 10 K/min. Nitrogen (purge rate 50 mL/min) was used as purge gas.

Gravimetric Moisture Sorption:

Moisture sorption isotherms were recorded with an SPSx-Ιμ moisture sorption analyzer (proUmid, Ulm). The measurement cycle was started at ambient relative humidity (r.h.) of 35% and first decreased to 3% r.h. and 0% r.h.. Then r.h. was increased from 0% to 10% in 5% steps, from 10 to 90% in 10% steps and from 90 to 95% in a 5% step. Then r.h. was decreased from 95% to 90% in a 5% step and from 90% to 0% in 10% steps. Finally, r.h. was increased from 0% to 10% in a 10% step and to ambient relative humidity of 35% in one step. The time per step was set to a minimum of 2 hours and a maximum of 5 hours. If an equilibrium condition with a constant mass of + 0.01% within 1 hour was reached before the maximum time for all examined samples, the sequential humidity step was applied before the maximum time of 5 hours. If no equilibrium was achieved, the consecutive humidity step was applied after the maximum time of 5 hours. The temperature was 25 + 0.1 °C. Examples:

Example 1: Preparation of omarigliptin Form V Omarigliptin Form I ( 1 g) was added to w-propanol (40 mL). After heating to 97 °C the omarigliptin was dissolved and the solution was filtered. The filtrate was cooled to 23 °C (ambient temperature) and stored at this temperature for three days. The precipitate was collected via filtration and dried under vacuum at 35 mbar at 23°C to yield omarigliptin Form V (0.75 g).

XRPD: as depicted in Figure 1

FTIR: as depicted in Figure 2

DSC: as depicted in Figure 3

Raman: as depicted in Figure 5 (top spectrum)

As can be seen from Figure 4 omarigliptin Form V shows a mass increase of only about 1.9%, whereas Form I shows a mass increase of about 5.2% in the first sorption cycle from 0 to 95% relative humidity. Therefore, Form V is significantly less hygroscopic compared to Form I.

Figure 5 shows an overlay of the Raman- spectra of Form V before (top) and after (bottom) the gravimetric moisture sorption experiment. As can be seen the spectra at the start and the end point are more or less identical proving that omarigliptin Form V is stable and does not convert into other forms even during the processes of water adsorption and desorption.

Example 1A: Preparation of omarigliptin Form V (solvent mixtures)

Omarigliptin Form I (0.2 g) was dissolved in different solvent mixtures (8 mL each) under reflux, respectively. The solutions were cooled to 23°C (ambient temperature) and stored at this temperature for 16 hours. The corresponding precipitates were collected via filtration and dried under vacuum at 35 mbar at 23 °C to yield omarigliptin Form V.

Table 4: Composition of solvents mixture Example 2: Stress tests with omarigliptin Form V

Omarigliptin Form V (prepared according to the procedure disclosed in example 1 herein) was stressed at accelerated stress conditions at a temperature of 40°C and 75% relative humidity, either alone or in binary mixtures with common pharmaceutically acceptable excipients at a 1 : 1 ratio. The stressed samples were stored open at said conditions and investigated by XRPD after certain points in time. The stress tests show that omarigliptin Form V is stable under accelerated stress conditions even in the presence of excipients. The results are summarized in the table 4.

Table 5: Summary of stress test results performed with omarigliptin Form V Omarigliptin Form V was also stored in a closed glass vial at a temperature in the range of 2 to 8°C for 3 months. XRPD confirmed that Form V was still present. Example 3: Film coated tablets comprising omarigliptin Form V

Table 7: Tablet core comprising 25 mg omarigliptin Form V The above tablets are manufactured by blending omarigliptin Form V, mannitol, microcrystalline cellulose and croscarmellose sodium, lubricating with magnesium stearate followed by compression and subsequent film coating with an Opadry^® ready to use film coating mixture such as Opadry^® Yellow 20A92710, Opadry^® Blue 20A99172 or Opadry^® White 20A18334.

Claims

Claims:

1. Crystalline form of omarigliptin characterized by having an X-ray powder diffraction pattern comprising peaks at 2-Theta values of (18.5 + 0.2)°, (18.9 + 0.2)°, (21.0 + 0.2)°, (22.1 + 0.2)° and (24.9 + 0.2)° when measured with Cu- Kalpha_1>2 radiation having a wavelength of 0.15419 nm.

2. The crystalline form according to claim 1, characterized by having an X-ray powder diffraction pattern comprising at least one further peak at 2-Theta values of (10.3 + 0.2)°, (14.6 + 0.2)°, (16.2 + 0.2)° and (16.6 + 0.2)° when measured with Cu-Kalpha_{1 2} radiation having a wavelength of 0.15419 nm.

3. The crystalline form according to claim 1 or 2, characterized by having an X- ray powder diffraction pattern comprising peaks at 2-Theta values of (10.3 + 0.2)°, (14.6 + 0.2)°, (16.2 + 0.2)°, (16.6 + 0.2)°, (18.5 + 0.2)°, (18.9 + 0.2)°, (21.0 + 0.2)°, (22.1 + 0.2)°, (24.0 + 0.2)°, (24.9 + 0.2)° and (25.9 + 0.2)° when measured with Cu-Kalpha_1>2 radiation having a wavelength of 0.15419 nm.

4. The crystalline form according to any one of the preceding claims characterized by having a Fourier transform infrared spectrum comprising characteristic peaks at wavenumbers of (1608 + 2) cm^-1, (1498 + 2) cm^-1, (1369 + 2) cm^"1, (1273 + 2) cm^"1 and (1 172 + 2) cm^"1.

5. The crystalline form according to any one of the preceding claims characterized by having a Raman spectrum comprising characteristic peaks at wavenumbers of (1275 + 2) cm^"1, (1244 + 2) cm^"1, (597 + 2) cm^"1 and (401 + 2) cm^"1 when measured at a wavelength of 785nm.

6. The crystalline form according to any one of the preceding claims characterized by having a differential scanning calorimetry curve comprising an endotherm with an onset temperature of (168 + 1)°C, when measured at a heating rate of 10 K/min.

7. Process for preparing a crystalline form of omarigliptin according to any one of claims 1 to 6 comprising the steps of i) providing a solution comprising omarigliptin and a solvent containing at least 50 volume percent w-propanol;

ii) precipitating omarigliptin from the solution of step i).

8. Process according to claim 7, wherein the solution of step i) is obtained by heating omarigliptin in a solvent comprising at least 50 volume percent n- propanol.

9. Process according to claim 7 or 8, wherein the solvent contains at least 95 volume percent w-propanol.

10. Pharmaceutical composition comprising a) a crystalline form of omarigliptin according to any one of claims 1 to 6 and b) at least one pharmaceutically acceptable excipient.

1 1. The crystalline form according to any one of claims 1 to 6 or the pharmaceutical composition according to claim 10 for use as a medicament.

12. The crystalline form according to any one of claims 1 to 6 or the pharmaceutical composition according to claim 10 for use in the treatment of type 2 diabetes.

13. A crystalline form of omarigliptin obtainable by the process according to claim 7.