Crystalline forms of 3-[5-(2-fluorophenyl)-[1,2,4] oxadiazol-3-yl]-benzoic acid
View Patent ↗The present invention relates to crystalline forms of 3-[5-(2-fluorophenyl)-[1,2,4]oxadiazol-3-yl]-benzoic acid, pharmaceutical compositions and dosage forms comprising the crystalline forms, methods of making the crystalline forms and methods for their use for the treatment, prevention or management of diseases ameliorated by modulation of premature translation termination or nonsense-mediated mRNA decay.
1. A solid pharmaceutical composition comprising a crystal form of the compound of formula (I):
which has an X-ray powder diffraction pattern comprising at least three peak positions (°2θ±0.2) when measured using Cu Kα radiation, selected from the group consisting of 4.96, 6.39, 10.10, 11.54, 12.62, 12.81, 13.92, 14.16, 14.55, 14.88, 15.07, 15.58, 16.27, 16.61, 18.74, 18.94, 19.28, 19.94, 20.27, 20.74, 20.97, 21.22, 21.93, 22.58, 22.80, 23.00, 23.79, 24.14, 24.46, 25.44, 25.64, 26.07, 26.34, 26.74, 27.06, 27.79, 28.42, 29.09 and 30.48.
2. The pharmaceutical composition of claim 1 further comprising one or more carriers, excipients or diluents.
3. The pharmaceutical composition of claim 2 suitable for oral administration, wherein the pharmaceutical composition is a single unit solid dosage form.
4. The pharmaceutical composition of claim 1 , wherein the crystal form has the following unit cell parameters when measured at 150 K: a=24.220 Å; b=3.74640 Å; c=27.4678 Å; a=90°; β=92.9938°; γ=90°; V=2489.38(17) Å 3 ; Z=8; calculated density (d calc , g cm −3 ) is 1.517 g cm −3 ; and the space group is P2 1 /n (no. 14).
5. The pharmaceutical composition of claim 1 , wherein the crystal form has an X-ray powder diffraction pattern comprising at least one peak position (°2θ±0.2) when measured using Cu Kα radiation, selected from the group consisting of 10.10, 11.54, 14.55, 14.88 and 15.07.
6. The pharmaceutical composition of claim 5 , wherein the crystal form has a differential scanning calorimetry thermogram which has an endothermic event with a peak temperature at 244° C.
7. The pharmaceutical composition of claim 5 , wherein the crystal form has a thermogravimetric analysis thermogram which has a mass loss of less than 1% of the total mass of the sample upon heating from 33° C. to 205° C.
8. The pharmaceutical composition of claim 5 , wherein the crystal form is non-hygroscopic.
9. The pharmaceutical composition of claim 1 , wherein the crystal form is characterized by 13 C CP/MAS solid-state NMR signals at the following positions: 172.6, 167.0, 131.3, 128.4 and 117.1 ppm, when externally referenced to glycine at 176.5 ppm.
10. The pharmaceutical composition of claim 1 , wherein the crystal form is characterized by a 13 C CP/MAS solid-state NMR spectrum as shown in FIG. 4 .
11. The pharmaceutical composition of claim 1 , wherein the crystal form is pure and has an X-ray powder diffraction pattern comprising peak positions (°2θ±0.2) when measured using Cu Kα radiation, of 10.10, 11.54, 14.55, 14.88 and 15.07.