Crystalline forms of a dimethylphenyl compound
The invention relates to crystalline free base forms of biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]methyl}-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl ester or a solvate thereof. This invention also relates to pharmaceutical compositions containing or prepared from such crystalline forms; processes and intermediates useful for preparing such crystalline forms; and methods of using such crystalline forms to, for example, treat a pulmonary disorder.
1. Form I of a crystalline free base of biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]methyl}-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl ester characterized by a powder x-ray diffraction pattern having diffraction peaks at 2θ values of about 17.7±0.3, 18.2±0.3, 21.7±0.3 and 23.2±0.3.
2. Form II of a crystalline free base of biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]methyl}-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl ester characterized by a powder x-ray diffraction pattern having diffraction peaks at 2θ values of about 20.7±0.3, 21.6±0.3, 22.5±0.3 and 23.2±0.3.
3. Form III of a crystalline free base of biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]methyl}-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl ester characterized by a powder x-ray diffraction pattern having diffraction peaks at 2θ values of about 15.5±0.3, 18.1±0.3, 19.2±0.3 and 21.8±0.3.
4. The crystalline free base form of claim 1 , wherein the crystalline free base form is characterized by a powder x-ray diffraction pattern in which the peak positions are substantially in accordance with the peak positions of the pattern shown in FIG. 1 .
5. The crystalline free base form of claim 2 , wherein the crystalline free base form is characterized by a powder x-ray diffraction pattern in which the peak positions are substantially in accordance with the peak positions of the pattern shown in FIG. 2 .
6. The crystalline free base form of claim 3 , wherein the crystalline free base form is characterized by a powder x-ray diffraction pattern in which the peak positions are substantially in accordance with the peak positions of the pattern shown in FIG. 3 .
7. The crystalline free base form of claim 1 , wherein the crystalline free base form is characterized by a differential scanning calorimetry trace which shows a maximum endothermic heat flow in the range of about 132° C. to about 138° C.
8. The crystalline free base form of claim 2 , wherein the crystalline free base form is characterized by a differential scanning calorimetry trace which shows a maximum endothermic heat flow in the range of about 142° C. to about 150° C.
9. The crystalline free base form of claim 3 , wherein the crystalline free base form is characterized by a differential scanning calorimetry trace which shows a maximum endothermic heat flow in the range of about 134° C. to about 140° C.
10. The crystalline free base form of claim 1 , wherein the crystalline free base form is characterized by a differential scanning calorimetry trace which is substantially in accordance with that shown in FIG. 4 .
11. The crystalline free base form of claim 2 , wherein the crystalline free base form is characterized by a differential scanning calorimetry trace which is substantially in accordance with that shown in FIG. 5 .
12. The crystalline free base form of claim 3 , wherein the crystalline free base form is characterized by a differential scanning calorimetry trace which is substantially in accordance with that shown in FIG. 6 .
13. The crystalline free base form of any one of claims 1 and 4 - 12 , wherein the crystalline free base form is micronized.