1. A crystalline form of grapiprant selected from the group consisting of Form X, Form X2, Form X3, Form F, Form K, Form L, Form M, and Form N, wherein the crystalline form is selected from the following group:
i. Form X, which exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta at about 6.5, about 10.1, about 14.9, about 15.3, about 19.7, about 20.3, about 21.3, about 22.7, about 23.1, and about 27.3;
ii. Form X, which exhibits a differential scanning calorimetry profile having endothermexotherm events at about 33-80\xb0 C. and at about 110-140\xb0 C.;
iii. Form X, which exhibits a thermogravimetric analysis showing a loss of mass of 12-13% when heated from about 24\xb0 to about 150\xb0 C.;
iv. Form X2, which exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta at about 10.2, about 14.9, about 16.8, about 18.3, about 21.8, about 22.7, about 23.9, about 24.3 about 25.9, and about 26.4;
v. Form X2, which exhibits a differential scanning calorimetry profile having endothermexotherm events at about 25-130\xb0 C., at about 130-150\xb0 C., and at about 150-190\xb0 C.;
vi. Form X2, which exhibits a thermogravimetric analysis showing a loss of mass of 14-15% when heated from about 25\xb0 to about 150\xb0 C.;
vii. Form X3, which exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta at about 13.6, about 21.0, about 24.5, and about 25.3;
viii. Form X3, which exhibits a differential scanning calorimetry profile having endothermexotherm events at about 75-115\xb0 C., at about 135-150\xb0 C., and at about 150-170\xb0 C.;
ix. Form X3, which exhibits a thermogravimetric analysis showing a loss of mass of 10-11% when heated from about 25\xb0 to about 135\xb0 C.;
x. Form F, which exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta at about 9.9, about 14.8, about 15.5, about 18.0, about 19.9, about 20.4, about 21.8, about 23.5, and about 27.7;
xi. Form F, which exhibits a differential scanning calorimetry profile having endothermexotherm events at about 122\xb0 C. and at about 143\xb0 C.;
xii. Form F, which exhibits a thermogravimetric analysis showing a loss of mass of about 20.5% when heated from about 25\xb0 to about 135\xb0 C.;
xiii. Form K, which exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta at about 11.3, about 15.9, about 16.6, about 18.2, about 19.0, about 21.7, about 21.9, about 25.7, and about 29.0;
xiv. Form K, which exhibits a differential scanning calorimetry profile having endothermexotherm events at about 48\xb0 C., about 95\xb0 C., and at about 155\xb0 C.;
xv. Form K, which exhibits a thermogravimetric analysis showing a loss of mass of about 8.7% when heated from about 25\xb0 to about 135\xb0 C.;
xvi. Form L, which exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta at about 6.8, about 11.1, about 13.8, about 16.7, about 20.7, about 23.2, about 25.0, about 26.0, and about 26.3;
xvii. Form L, which exhibits a differential scanning calorimetry profile having endothermexotherm events at about 106\xb0 C.;
xviii. Form L, which exhibits a thermogravimetric analysis showing a loss of mass of about 12.9% when heated from about 25\xb0 to about 135\xb0 C.;
xix. Form M, which exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta at about 6.2, about 6.5, about 13.0, about 18.9, about 19.5, about 27.4, about 37.9, about 38.0, and about 39.7;
xx. Form M, which exhibits a differential scanning calorimetry profile having endothermexotherm events at about 77\xb0 C., at about 99\xb0 C., and at about 138\xb0 C.;
xxi. Form M, which exhibits a thermogravimetric analysis showing a loss of mass of about 13.6% when heated from about 25\xb0 to about 135\xb0 C.;
xxii. Form N, which exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta at about 6.5, about 9.9, about 14.2, about 14.8, about 15.4, about 17.7, about 19.7, about 20.3, and about 23.4;
xxiii. Form N, which exhibits a differential scanning calorimetry profile having endothermexotherm events at about 121\xb0 C. and at about 157\xb0 C.; and
xxiv. Form N, which exhibits a thermogravimetric analysis showing a loss of mass of about 11% when heated from about 25\xb0 to about 135\xb0 C.
2. A pharmaceutical composition, the composition comprising at least one crystalline form of grapiprant of claim 1 and at least one pharmaceutically acceptable excipient, wherein the crystalline form of grapiprant is selected from the group consisting of Form X, Form X2, Form X3, Form F, Form K, Form L, Form M, and Form N, wherein the crystalline form is selected from the following group:
i. Form X, which exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta at about 6.5, about 10.1, about 14.9, about 15.3, about 19.7, about 20.3, about 21.3, about 22.7, about 23.1, and about 27.3;
ii. Form X, which exhibits a differential scanning calorimetry profile having endothermexotherm events at about 33-80\xb0 C. and at about 110-140\xb0 C.;
iii. Form X, which exhibits a thermogravimetric analysis showing a loss of mass of 12-13% when heated from about 24\xb0 to about 150\xb0 C.;
iv. Form X2, which exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta at about 10.2, about 14.9, about 16.8, about 18.3, about 21.8, about 22.7, about 23.9, about 24.3 about 25.9, and about 26.4;
v. Form X2, which exhibits a differential scanning calorimetry profile having endothermexotherm events at about 25-130\xb0 C., at about 130-150\xb0 C., and at about 150-190\xb0 C.;
vi. Form X2, which exhibits a thermogravimetric analysis showing a loss of mass of 14-15% when heated from about 25\xb0 to about 150\xb0 C.;
vii. Form X3, which exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta at about 13.6, about 21.0, about 24.5, and about 25.3;
viii. Form X3, which exhibits a differential scanning calorimetry profile having endothermexotherm events at about 75-115\xb0 C., at about 135-150\xb0 C., and at about 150-170\xb0 C.;
ix. Form X3, which exhibits a thermogravimetric analysis showing a loss of mass of 10-11% when heated from about 25\xb0 to about 135\xb0 C.;
x. Form F, which exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta at about 9.9, about 14.8, about 15.5, about 18.0, about 19.9, about 20.4, about 21.8, about 23.5, and about 27.7;
xi. Form F, which exhibits a differential scanning calorimetry profile having endothermexotherm events at about 122\xb0 C. and at about 143\xb0 C.;
xii. Form F, which exhibits a thermogravimetric analysis showing a loss of mass of about 20.5% when heated from about 25\xb0 to about 135\xb0 C.;
xiii. Form K, which exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta at about 11.3, about 15.9, about 16.6, about 18.2, about 19.0, about 21.7, about 21.9, about 25.7, and about 29.0;
xiv. Form K, which exhibits a differential scanning calorimetry profile having endothermexotherm events at about 48\xb0 C., about 95\xb0 C., and at about 155\xb0 C.;
xv. Form K, which exhibits a thermogravimetric analysis showing a loss of mass of about 8.7% when heated from about 25\xb0 to about 135\xb0 C.;
xvi. Form L, which exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta at about 6.8, about 11.1, about 13.8, about 16.7, about 20.7, about 23.2, about 25.0, about 26.0, and about 26.3;
xvii. Form L, which exhibits a differential scanning calorimetry profile having endothermexotherm events at about 106\xb0 C.;
xviii. Form L, which exhibits a thermogravimetric analysis showing a loss of mass of about 12.9% when heated from about 25\xb0 to about 135\xb0 C.;
xix. Form M, which exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta at about 6.2, about 6.5, about 13.0, about 18.9, about 19.5, about 27.4, about 37.9, about 38.0, and about 39.7;
xx. Form M, which exhibits a differential scanning calorimetry profile having endothermexotherm events at about 77\xb0 C., at about 99\xb0 C., and at about 138\xb0 C.;
xxi. Form M, which exhibits a thermogravimetric analysis showing a loss of mass of about 13.6% when heated from about 25\xb0 to about 135\xb0 C.;
xxii. Form N, which exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta at about 6.5, about 9.9, about 14.2, about 14.8, about 15.4, about 17.7, about 19.7, about 20.3, and about 23.4;
xxiii. Form N, which exhibits a differential scanning calorimetry profile having endothermexotherm events at about 121\xb0 C. and at about 157\xb0 C.; and
xxiv. Form N, which exhibits a thermogravimetric analysis showing a loss of mass of about 11% when heated from about 25\xb0 to about 135\xb0 C.
3. A process for preparing a substantially pure crystalline Form A of grapiprant, the process comprising:
i. contacting grapiprant at ambient temperature with a solvent comprising dichloromethane and acetone to form a saturated or a near saturated solution; and
ii. forming crystals of the substantially pure crystalline Form A of grapiprant,
wherein the crystalline Form A exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta at about 9.9, about 13.5, about 14.3, about 16.1, about 17.7, about 21.8, about 24.14, and about 25.8;
a differential scanning calorimetry profile having showed an endothermexotherm at about 155-170\xb0 C.; and
a thermogravimetric analysis showing a loss of mass of 0.5-0.6% when heated from about 30\xb0 to about 150\xb0 C.
4. The process of claim 3, wherein the solvent comprises a volume-to-volume ratio from 1:1 to 1:3 of dichloromethaneacetone.
5. The process of claim 4, wherein the solvent comprises 0 wt. % to 0.5 wt. % water.
6. A process for preparing a substantially pure crystalline Form X of grapiprant, the process comprising:
i. contacting grapiprant at 35\xb0 C. with a solvent comprising dichloromethaneacetone in a 1:0.5 to 1:5 volume-to-volume ratio to form a suspension; and
ii. forming crystals of the substantially pure crystalline Form X of grapiprant,
wherein the crystalline Form X, which exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta at about 6.5, about 10.1, about 14.9, about 15.3, about 19.7, about 20.3, about 21.3, about 22.7, about 23.1, and about 27.3;
a differential scanning calorimetry profile having endothermexotherm events at about 33-80\xb0 C. and at about 110-140\xb0 C.; and
a thermogravimetric analysis showing a loss of mass of 12-13% when heated from about 24\xb0 C. to about 150\xb0 C.
7. The process of claim 6, wherein the solvent comprises a volume-to-volume ratio from 1:1 to 2:1.
8. The process of claim 6, further comprising converting Form X to Form A by slurry in dichloromethaneacetone with a volume-to-volume ratio of 1:1,
wherein Form A exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta at about 9.9, about 13.5, about 14.3, about 16.1, about 17.7, about 21.8, about 24.14, and about 25.8;
a differential scanning calorimetry profile having showed an endothermexotherm at about 155-170\xb0 C.; and
a thermogravimetric analysis showing a loss of mass of 0.5-0.6% when heated from about 30\xb0 to about 150\xb0 C.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A device for separating solids from liquids comprising a generally cylindrical enclosure, the generally cylindrical enclosure having an axis, and a first substantially cylindrical screen member within said generally cylindrical enclosure, said substantially cylindrical screen member also having an axis, said axis being coexistent or substantially parallel to the axis of said cylindrical enclosure, said substantially cylindrical screen member comprising a convex screen and a concave screen, said convex screen and said concave screen being connected in sealed relationship and defining a space between them whereby, when said substantially cylindrical screen member is contacted with liquid containing solids, at least some solids will be retained on said screen member and said liquid will pass through said convex and concave screens to said space.
2. The device of claim 1 wherein said substantially cylindrical screen member has a substantially linear opening, said substantially linear opening being substantially parallel to its axis, whereby said substantially linear opening facilitates contact of said liquid containing solids with said convex screen.
3. The device of claim 1 wherein said cylindrical enclosure has at least one inlet for contacting said liquid containing solids with said concave screen and said convex screen of said substantially cylindrical screen.
4. The device of claim 1 wherein said concave and said convex screens are wedge wire screens.
5. The device of claim 3 wherein said screen member has an outlet for liquid.
6. The device of claim 1 including a central, substantially cylindrical, screen.
7. The device of claim 1 including a second substantially cylindrical screen member comprising convex and concave screens, said second screen member being situated within said substantially cylindrical enclosure.
8. The device of claim 7 wherein said second substantially cylindrical screen member is substantially concentrically within said first substantially cylindrical screen member.
9. A solidsliquid separator comprising a first generally cylindrical screen having a screen surface facing outwardly, a second generally cylindrical screen of a diameter smaller than that of said first screen and having a screen surface facing inwardly, said second screen being situated substantially concentrically within said first screen, said first and second screens being connected in sealed relation to form a generally C-shaped profile and a space between said first and said second screens for collecting liquid filtrate.
10. A separator of claim 9 wherein said first and second screens are wedge wire screens.
11. A separator of claim 9 including a second separator of claim 9 within the C-shaped profile of said separator of claim 9.
12. A separator of claim 11 wherein said first and second separators comprise wedge wire screens.
13. A high volume separator comprising a plurality of devices of claim 1.
14. A high volume separator comprising a plurality of separators of claim 9.
15. The separator of claim 9 including a substantially cylindrical wedge wire screen within and substantially concentric to said generally C-shaped profile.
16. A substantially cylindrical device for separating solids and liquids comprising (a) a substantially cylindrical convex wedge wire screen and (b) a substantially cylindrical concave wedge wire screen, said substantially cylindrical concave wedge wire screen being fixed and sealed substantially concentrically within and apart from said substantially cylindrical convex wedge wire screen, whereby said convex and concave screens form an interior space.
17. The substantially cylindrical device of claim 16 having a C-shaped cross section.
18. A device for screening solids from liquids comprising at least one device of claim 16 enclosed and sealed within an enclosure having an inlet for liquid containing solids, said inlet providing access for said liquid to the convex surface of said convex wedge wire screen and also the to concave surface of said concave wedge wire screen.
19. The device of claim 18 in the form of a candle filter.
20. The device of claim 1 oriented in the form of a candle filter, having an opening at the top of said defined space, said device being substantially enclosed within a vessel having means for collecting and draining solids at the bottom thereof.