Particulates of a CRTH2 antagonist
View Patent ↗Provided herein are particulates of {4,6-bis(dimethylamino)-2-(4-(4-(trifluoromethyl)benzamido)benzyl)pyrimidin-5-yl}acetic acid in amorphous or crystalline forms, processes for their preparation, pharmaceutical compositions comprising them, and methods of their use for treating, preventing, or ameliorating one or more symptoms of a CRTH2-mediated disorder or disease.
1. Particulates of {4,6-bis(dimethylamino)-2-(4-(4-(trifluoromethyl)benzamido)-benzyl)pyrimidin-5-yl}acetic acid of Formula I:
in crystalline Form I; wherein the particulates have one or more characteristics, selected from the group consisting of:
(i) having an average particle size ranging from about 0.1 to about 150 μm;
(ii) having a uniformity coefficient ranging from about 1 to about 20;
(iii) having a tapped bulk density ranging from about 0.1 to about 1.0 g/mL;
(iv) containing no less than about 95% by weight of the acid of Formula I;
(v) having a residual organic solvent content of no greater than about 5% by weight;
(vi) having a residual methanol content of no greater than about 100,000 ppm;
(vii) containing no less than about 90% by weight of the particulates in Form I; and
wherein the particulates have a differential scanning calorimetric thermogram with an endotherm at a peak temperature of about 224° C. and an onset temperature of about 220° C.
2. The particulates of claim 1 , wherein the particulates have an X-ray powder diffraction pattern with one or more peaks expressed in two-theta at approximately 9.8, 13.1, 22.0, and 26.4°.
3. The particulates of claim 1 , wherein the particulates have an X-ray powder diffraction pattern with a peak expressed in two-theta at approximately 22.0±0.1°.
4. The particulates of claim 1 , wherein the crystal habit of the particulates is acicular.
5. The particulates of claim 1 , having an aqueous solubility of about 3 μg/mL at room temperature.
6. The particulates of claim 1 , wherein the particulates have a uniformity coefficient ranging from about 1 to about 20.
7. The particulates of claim 1 , wherein the particulates have a residual organic solvent content of no greater than about 5% by weight.
8. A pharmaceutical composition comprising the particulates of claim 1 , and a pharmaceutically acceptable carrier.
9. The pharmaceutical composition of claim 8 , wherein the composition is formulated for oral, nasal, bronchial, or topical administration.
10. The pharmaceutical composition of claim 8 , wherein the composition is formulated as a single dosage form.
11. 4,6-Bis(dimethylamino)-2-(4-(4-(trifluoromethyl)benzamido)-benzyl)pyrimidin-5-yl}acetic acid in crystalline Form I; wherein the crystalline form has an X-ray powder diffraction pattern with one or more peaks expressed in two-theta at approximately 9.8, 13.1, 22.0, and 26.4°; and wherein the particulates have a differential scanning calorimetric thermogram with an endotherm at a peak temperature of about 224° C. and an onset temperature of about 220° C.