Polymorphs of an epothilone analog
View Patent ↗There are provided in accordance with the present invention two crystalline polymorphs, designated Form A and Form B, respectively, as well as mixtures thereof, of an epothilone analog represented by the formula Also provided are methods of forming the novel polymorphs, therapeutic methods utilizing them and pharmaceutical dosage forms containing them.
1. A pharmaceutical composition comprising: an effective amount of a crystalline polymorph of an epothilone analog represented by the formula
wherein said crystalline polymorph is Form A; and one or more non-solubilizing pharmaceutically-acceptable carriers, excipients or diluents thereof.
2. The pharmaceutical composition according to claim 1 wherein said Form A is characterized by: unit cell parameters approximately equal to the following:
Cell dimensions a =14.152(6) Å
b=30.72(2) Å
c=6.212(3) Å
Space group P2 1 2 1 2 1
Molecules/unit cell 4.
3. The pharmaceutical. composition according to claim 1 wherein said Form A is characterized by a melting point with decomposition in the range of about 182° C. to about 185° C.
4. The pharmaceutical composition according to claim 1 wherein said Form A is characterized by: a powder x-ray diffraction substantially as shown in FIG. 1 .
5. The pharmaceutical composition according to claim 1 wherein said Form A is characterized by characteristic peaks in the powder x-ray diffraction pattern at values of two theta (CuKα λ=1.5406 Å at 22° C.): 5.69, 6.76, 8.38, 11.43, 12.74, 13.62, 14.35, 15.09, 15.66, 16.43, 17.16, 17.66, 18.31, 19.03, 19.54, 20.57, 21.06, 21.29, 22.31, 23.02, 23.66, 24.18, 14.98, 25.50, 26.23, 26.23, 26.46, 27.59, 28.89, 29.58, 30.32, 31.08 and 31.52.
6. The pharmaceutical composition according to claim 1 wherein said crystalline polymorph is substantially free of Form B.
7. The pharmaceutical composition according to claim 1 wherein said crystalline polymorph has a purity of at least 99.4%.
8. A crystalline polymorph of an epothilone analog represented by the formula
comprising Form A, wherein said crystalline polymorph is substantially free of Form B.
9. A crystalline polymorph of an epothilone analog represented by the formula
comprising Form A, wherein said crystalline polymorph has a purity of at least 99.4%.