Crystalline antifungal polymorph
The crystalline polymorph Form I of (−)-4-[4-[4-[4-[[(2R-cis)-5-(2,4-difluorophenyl)tetrahydro-5-(1H-1,2,4-triazol-1-ylmethyl)furan-3-yl]methoxy]phenyl]-1-piperazinyl]phenyl-2,4-dihydro-2-[(S)-1-ethyl-2(S)-hydroxylpropyl]-3H-1,2,4-triazol-3-one represented by the formula I pharmaceutical compositions containing such a polymorph and methods of using such a polymorph to treat fungal infections in mammals are disclosed.
1. A crystalline polymorph Form I of the compound represented by the formula I
and characterized by at least one of the following properties:
a melting point range of about 164 to about 165° C. wherein the melting point range is determined using USP Class Ia procedure;
a specific rotation equal to [a] 25 D =−29.4° wherein the specific rotation is determined using a concentration of 10 mg/ml in methanol;
an X-ray powder diffraction pattern substantially similar to that presented in FIG. 1 ;
a differential scanning calorimetry thermogram substantially similar to that presented in FIG. 7 ; or
the proton NMR spectrum substantially similar to that presented in FIG. 10 .
2. A pharmaceutical composition comprising an anti-fungally effective amount of the crystalline polymorph form I of claim 1 and a pharmaceutically acceptable carrier.
3. A method of treating and/or preventing fungal infections in a mammal which comprises administering to said mammal an anti-fungally effective amount of the crystalline polymorph form I of claim 1 .
4. A crystalline polymorph Form III of the compound represented by the formula I
and characterized by an X-ray powder diffraction pattern displaying d spacing peaks at 28.69, 14.45, 10.59, 7.27, 6.59, 4.14, 3.58, and 3.53 +/−0.04.
5. The crystalline polymorph Form III of claim 4 further characterized by an X-ray powder diffraction pattern substantially similar to that presented in FIG. 3 .
6. A pharmaceutical composition comprising an anti-fungally effective amount of the crystalline polymorph Form III of claim 4 and a pharmaceutically acceptable carrier.
7. A method of treating and/or preventing fungal infections in a mammal which comprises administering to said mammal an anti-fungally effective amount of the crystalline polymorph Form III of claim 4 .