Process of making regadenoson and novel polymorphs thereof
Novel processes for making the N-pyrrazole substituted 2-adenosine derivative regadenoson and a novel polymorph thereof. The novel polymorph of regadenoson designated form H and drug substances and pharmaceutical compositions including the novel polymorph H are disclosed.
1. A polymorphic form of regadenoson characterized by
(a) a powder X-ray diffraction (XRPD) spectrum comprising peaks at the following angles: 6.16, 10.31, 10.72 and 25.52±0.2 (°2θ), and further comprising one or more peaks selected from the group consisting of 12.38, 16.37, 21.57, 22.59, 26.28, and 27.76±0.2 (°2θ), measured with a Cu-Kα irradiation;
(b) a differential scanning calorimetry (DSC) peak in the range of 265-280° C. measured with a heating rate of 10° C./min; and
(c) the absence of an exothermic DSC peak in the range of about 30° C. up to the polymorphic form melting point as measured with a heating rate of 10° C./min.
2. A regadenoson drug substance comprising about 5% by weight or more of the polymorphic form of regadenoson according to claim 1 .
3. A regadenoson drug substance comprising about 50% by weight or more of the polymorphic form of regadenoson according to claim 1 .
4. A regadenoson drug substance comprising about 95% by weight or more of the polymorphic form of regadenoson according to claim 1 .
5. A pharmaceutical composition comprising the polymorphic form of regadenoson according to claim 1 .
6. The polymorphic form of regadenoson according to claim 1 characterized by a powder X-ray diffractogram comprising peaks at 6.16, 10.31, 10.72, 12.38, 16.37, 21.57, 22.59, 25.52, 26.28, and 27.76±0.2 (°2θ), measured with a Cu-Kα irradiation.
7. A regadenoson drug substance comprising about 5% by weight or more of the polymorphic form of regadenoson according to claim 6 .
8. A regadenoson drug substance comprising about 50% by weight or more of the polymorphic form of regadenoson according to claim 6 .
9. A regadenoson drug substance comprising about 95% by weight or more of the polymorphic form of regadenoson according to claim 6 .
10. A pharmaceutical composition comprising the polymorphic form of regadenoson according to claim 6 .