Nova Patents
EP3299359A1

Crystalline and amorphous forms of pitavastatin hemicalcium salt

Abstract

The present invention is directed to new crystalline forms of Pitavastatin hemicalcium salt, referred to hereinafter as polymorphic Forms A, B, C, D, E and F, as well as the amorphous form. Furthermore, the present invention is directed to processes for the preparation of these crystalline forms and the amorphous form and pharmaceutical compositions comprising these crystalline forms or the amorphous form.

EP3299359A1, drawing sheet 1
Sheet 1 of 8

Term

Term ended

Projected expiry passed 2 February 2024, 2.6 years ago.

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14 claims: 14 independent, 0 dependent

  1. 1
    A crystalline polymorph A of (3 R , 5 S )-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxy-6( E )-heptanoic acid hemicalcium salt which exhibits a characteristic X-ray powder diffraction pattern with characteristic peaks expressed in 2θ at 5.0 (s), 6.8 (s), 9.1 (s), 10.0 (w), 10.5 (m), 11.0 (m), 13.3 (vw), 13.7 (s), 14.0 (w), 14.7 (w), 15.9 (vw), 16.9 (w), 17.1 (vw), 18.4 (m), 19.1 (w), 20.8 (vs), 21.1 (m), 21.6 (m), 22.9 (m), 23.7 (m), 24.2 (s), 25.2 (w), 27.1 (m), 29.6 (vw), 30.2 (w), 34. 0 (w);wherein (vs) stands for very strong intensity;(s) stands for strong intensity;(m) stands for medium intensity;(w) stands for weak intensity;(vw) stands for very weak intensity.
  2. 2
    A crystalline polymorph A of (3 R , 5 S )-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxy-6( E )-heptanoic acid hemicalcium salt having an X-ray powder diffraction pattern substantially as depicted in Figure 1.
  3. 3
    A crystalline polymorph B of (3 R , 5 S )-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxy-6( E )-heptanoic acid hemicalcium salt which exhibits a characteristic X-ray powder diffraction pattern with characteristic peaks expressed in 2θ at 4.6 (w), 5.3 (vs), 6.2 (s), 7. 7 (s), 9.2 (m), 9.6 (m), 10.3 (w), 11.3 (m), 11.7 (w), 12. 6 (vw), 13.0 (w), 13.9 (m), 14.7 (vw), 14.9 (w), 15.6 (w), 16.3 (m), 17. 0 (vw), 17.4 (vw), 18.0 (w), 18.7 (m), 19.3 (m), 20.0 (s), 20.5 (w), 20. 8 (m), 21.2 (w, shoulder), 21.5 (m), 22.4 (m), 23.2 (s), 23.8 (m), 24.4 (vw), 25.2 (w, broad), 26.0 (w), 26.4 (vw), 27.0 (w), 27.9 (vw), 28.9 (w);wherein (vs) stands for very strong intensity;(s) stands for strong intensity;(m) stands for medium intensity;(w) stands for weak intensity;(vw) stands for very weak intensity.
  4. 4
    A crystalline polymorph B of (3 R , 5 S )-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxy-6( E )-heptanoic acid hemicalcium salt having an X-ray powder diffraction pattern substantially as depicted in Figure 2.
  5. 5
    A crystalline polymorph C of (3 R , 5 S )-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxy-6( E )-heptanoic acid hemicalcium salt which exhibits a characteristic X-ray powder diffraction pattern with characteristic peaks expressed in 2θ at 4.1 (m), 5.6 (s), 7.8 (m), 8.3 (m), 10.3 (m), 11.6 (w), 17.5 (w), 17.9 (w), 18.7 (m), 19.5 (s), 20.6 (m), 21.5 (vw), 21.9 (m), 23.1 (m), 24.0 (w), 24.8 (w);wherein (s) stands for strong intensity;(m) stands for medium intensity;(w) stands for weak intensity;(vw) stands for very weak intensity.
  6. 6
    A crystalline polymorph C of (3 R , 5 S )-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxy-6( E )-heptanoic acid hemicalcium salt having an X-ray powder diffraction pattern substantially as depicted in Figure 3.
  7. 7
    A crystalline polymorph D of (3 R , 5 S )-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxy-6( E )-heptanoic acid hemicalcium salt which exhibits a characteristic X-ray powder diffraction pattern with characteristic peaks expressed in 2θ at 5.0 (m), 6.5 (m), 6.8 (s), 8.7 (m), 10.0 (m), 10.2 (m), 10.8 (m), 13.1 (w), 13.5 (m), 14.3 (s), 15.3 (vw), 16.1 (m), 16.8 (w), 18.2 (w), 18.5 (m), 19.0 (w), 19.9 (m), 20.5 (m), 21.0 (vs), 21.7 (s), 22.3 (w), 23.4 (m), 24.0 (m), 25.6 (w), 26.2 (m);wherein (vs) stands for very strong intensity;(s) stands for strong intensity;(m) stands for medium intensity;(w) stands for weak intensity;(vw) stands for very weak intensity.
  8. 8
    A crystalline polymorph D of (3 R , 5 S )-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxy-6( E )-heptanoic acid hemicalcium salt having an X-ray powder diffraction pattern substantially as depicted in Figure 4.
  9. 9
    A crystalline polymorph E of (3 R , 5 S )-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxy-6( E )-heptanoic acid hemicalcium salt which exhibits a characteristic X-ray powder diffraction pattern with characteristic peaks expressed in 2θ at 4.4 (vw), 5.0 (s), 6.6 (s), 6.8 (s), 8.9 (s), 10.0 (m), 10.3 (s), 10.8 (m), 13.3 (s), 13.6 (m), 14.0 (s), 15.2 (vw), 15.9 (w), 16.4 (w), 16.9 (vw), 17.8 (vw), 18.3 (m), 18.9 (w), 20.2 (vs), 20.4 (m), 20.7 (m), 20.9 (m), 21.1 (vs), 21. 6 (m), 21.7 (m), 22.3 (m), 23.5 (m), 23.8 (m), 24.1 (w), 24.7 (vw), 25.4 (vw), 26.6 (m), 30.2 (w), 34.0 (vw);wherein (vs) stands for very strong intensity;(s) stands for strong intensity;(m) stands for medium intensity;(w) stands for weak intensity;(vw) stands for very weak intensity.
  10. 10
    A crystalline polymorph E of (3 R , 5 S )-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxy-6( E )-heptanoic acid hemicalcium salt having an X-ray powder diffraction pattern substantially as depicted in Figure 5.
  11. 11
    A crystalline polymorph F of (3 R , 5 S )-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxy-6( E )-heptanoic acid hemicalcium salt which exhibits a characteristic X-ray powder diffraction pattern with characteristic peaks expressed in 2θ at 5.1 (m), 5.6 (w), 7.0 (s), 8.8 (m), 9.6 (s), 10.2 (w), 10.9 (m), 11.3 (w), 11.9 (m), 12.5 (m), 13.0 (s), 13.7 (m), 14.4 (s), 14.7 (m), 15.3 (vw), 15.5 (w), 16.8 (m), 17.6 (w), 18.3 (m), 19.3 (m), 19.7 (m), 20.6 (m), 21.2 (vs), 21.8 (s), 22. 8 (s), 23.1 (w), 23.8 (w, shoulder), 24.1 (s), 24.8 (s), 25.7 (m), 26.2 (vw), 26.6 (m), 26.9 (w), 28.4 (w), 29.5 (w), 29.8 (vw), 30.9 (m);wherein (vs) stands for very strong intensity;(s) stands for strong intensity;(m) stands for medium intensity;(w) stands for weak intensity;(vw) stands for very weak intensity.
  12. 12
    A crystalline polymorph F of (3 R , 5 S )-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxy-6( E )-heptanoic acid hemicalcium salt having an X-ray powder diffraction pattern substantially as depicted in Figure 6.
  13. 13
    The amorphous form of (3 R , 5 S )-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxy-6( E )-heptanoic acid hemicalcium salt.
  14. 14
    The amorphous form of (3 R , 5 S )-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxy-6( E )-heptanoic acid hemicalcium salt having an X-ray powder diffraction pattern substantially as depicted in Figure 7.
Independent claims14