Browse Prior Art Database

Crystalline forms of 1 ethylsulfonyl 3 4 7H pyrrolo 2 3 d pyrimidin 4 yl 1H pyrazol 1 yl azetidin 3 yl acetonitrile baricitinib

IP.com Disclosure Number: IPCOM000244270D
Publication Date: 2015-Nov-27
Document File: 9 page(s) / 255K

Publishing Venue

The IP.com Prior Art Database

Related People

Balazs Volk: AUTHOR [+2]

Abstract

Crystalline forms of baricitinib were found and are described hereinbelow 1 Ethylsulfonyl 3 4 7H pyrrolo 2 3 d pyrimidin 4 yl 1H pyrazol 1 yl azetidin 3 yl acetonitrile baricitinib of the following formula is in Phase III development as a potential treatment for rheumatoid arthritis It is in Phase II development as a potential treatment for psoriasis and diabetic nephropathy The names of the crystalline forms of baricitinib were given based on their appearance temperature As follows the polymorph observed at room temperature has been denoted as the crystalline form of baricitnib at room temperature while the polymorph obtained at high temperature as the crystalline form of baricitinib at high temperature

This text was extracted from a Microsoft Word document.
At least one non-text object (such as an image or picture) has been suppressed.
This is the abbreviated version, containing approximately 19% of the total text.

Crystalline forms of {1-(ethylsulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile (baricitinib)

Éva Sipos, János L. Héder, Gyula Simig, Tamás Nagy, Katalin Kátai-Fadgyas, Zoltán Varga, Balázs Volk

Egis Pharmacetuticals Plc., Directorate of Drug Substance Development and Directorate of Finished Product Development, P.O. Box 100, H-1475 Budapest, Hungary

Abstract

Crystalline forms of baricitinib were found and are described hereinbelow. {1-(Ethylsulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile (baricitinib) of the following formula

is in Phase III development as a potential treatment for rheumatoid arthritis. It is in Phase II development as a potential treatment for psoriasis and diabetic nephropathy. The names of the crystalline forms of baricitinib were given based on their appearance temperature. As follows, the polymorph observed at room temperature has been denoted as the crystalline form of baricitnib at room temperature, while the polymorph obtained at high temperature asthe crystalline form of baricitinib at high temperature.

Solid state characterization of crystalline forms of baricitnib

X-ray powder diffraction

The crystalline form of baricitinib at room temperature can be characterized by the following characteristic X-ray powder diffraction peaks: 2θ (±0.2° 2θ): 12.47; 15.40; 16.67; 19.06; 25.52. More particularly this crystalline form of baricitinib at room temperature can be characterized by the following characteristic X-ray powder diffraction peaks: 2θ (±0.2° 2θ): 4.15; 12.47; 13.98; 14.58; 15.40; 16.28; 16.67; 19.06; 25.18; 25.52. Most particularly this crystalline form of baricitinib at room temperature can be characterized by the following characteristic X-ray powder diffraction peaks: 2θ (±0.2° 2θ): 4.15; 12.47; 12.68; 13.19; 13.98; 14.58; 14.97; 15.10; 15.40; 15.69; 16.28; 16.67; 16.88; 17.41; 19.06; 19.24; 19.61; 19.88; 20.38; 20.71; 21.94; 22.06; 22.44; 22.61; 24.15; 25.18; 25.52; 26.07; 26.28; 26.57; 27.47; 28.44; 29.18; 29.41; 29.82; 30.05; 30.32; 30.77. The XRPD pattern of the crystalline form of baricitinib at room temperature is depicted in Figure 1.

Figure 1: The XRPD pattern of the crystalline form of baricitinib at room temperature (in transmission mode).

Thermoanalytical study

Figure 2 shows the TGA thermogram of the crystalline form of baricitinib at room temperature. In the thermogram, a substantial weight loss can not be seen up to approximately 210 ºC. Above 210 °C, an intensive thermal degradation occurs accompanying the melting process. This result confirms that the crystalline form of baricitinib at room temperature is a hydrate- and solvent-free crystalline form with thermal stability up to 210 °C.

The DSC thermogram of the crystalline form of baricitinib at room temperature is plotted in Figure 3. In the thermogram, a sharp endothermic peak can be seen between 200 and 220 °C. The onset temperature...