Macrolide polymorphs, compositions comprising such polymorphs, and methods of use and manufacture thereof
View Patent ↗The invention relates to novel forms of compounds displaying broad spectrum antibiotic activity, especially crystalline polymorphic forms and amorphous forms of such compounds, compositions comprising such crystalline polymorphic forms and amorphous forms of such compounds, processes for manufacture and use thereof. The compounds and compositions of the invention are useful in the pharmaceutical industry, for example, in the treatment or prevention of diseases or disorders associated with the use of antibiotics, chemotherapies, or antiviral therapies, including, but not limited to, colitis, for example, pseudo-membranous colitis; antibiotic associated diarrhea; and infections due to Clostridium difficile (“ C. difficile ”), Clostridium perfringens (“ C. perfringens ”), Staphylococcus species, for example, methicillin-resistant Staphylococcus , or Enterococcus including Vancomycin-resistant enterococci.
1. A pharmaceutical composition comprising a therapeutically effective amount of a polymorphic form of a compound of Formula I:
wherein the polymorphic form of a compound of Formula I is characterized by a powder x-ray diffraction pattern wherein said x-ray diffraction pattern comprises peaks at diffraction angles 2θ of 7.7°, 15.0°, and 18.8°±0.2 as said peaks are set forth in FIG. 1 .
2. The pharmaceutical composition of claim 1 , wherein the therapeutically effective amount of a polymorphic form of a compound of Formula I comprises about 0.001 mg to about 1000 mg.
3. The pharmaceutical composition of claim 1 , wherein the therapeutically effective amount of a polymorphic form of a compound of Formula I comprises about 0.01 mg to about 500 mg.
4. The pharmaceutical composition of claim 1 , wherein the therapeutically effective amount of a polymorphic form of a compound of Formula I comprises about 0.1 mg to about 100 mg.
5. The pharmaceutical composition of claim 1 , wherein the therapeutically effective amount of a polymorphic form of a compound of Formula I comprises about 0.5 mg to about 50 mg.
6. The pharmaceutical composition of claim 1 suitable for oral administration.
7. The pharmaceutical composition of claim 1 suitable for topical administration.
8. The pharmaceutical composition of claim 1 , wherein the polymorphic form of a compound of Formula I is a lyophilized powder.
9. The pharmaceutical composition of claim 8 , further comprising a pharmaceutically acceptable carrier.
10. The pharmaceutical composition of claim 1 , wherein the polymorphic form of the compound of Formula I is characterized by a DSC endotherm in the range of about 174° C. to about 186° C.
11. The pharmaceutical composition of claim 1 , wherein the polymorphic form of the compound of Formula I is characterized by:
(i) a powder x-ray diffraction pattern wherein said x-ray diffraction pattern comprises peaks at diffraction angles 2θ of 7.7°, 15.0°, and 18.8°±0.2 as said peaks are set forth in FIG. 1 ; and
(ii) a DSC endotherm in the range of about 174° C. to about 186° C.
12. The pharmaceutical composition of claim 1 , wherein the polymorphic form of the compound of Formula I is characterized by a powder X-ray diffraction pattern as set forth in FIG. 1 .
13. The pharmaceutical composition of claim 1 , wherein the polymorphic form of the compound of Formula I is present in the composition in about 75 wt. % to about 99.99 wt. %.
14. The pharmaceutical composition of claim 1 , wherein the polymorphic form of the compound of Formula I is present in the composition in at least about 85 wt. %.
15. The pharmaceutical composition of claim 1 , wherein the polymorphic form of the compound of Formula I is present in the composition in at least about 90 wt. %.
16. The pharmaceutical composition of claim 1 , wherein the polymorphic form of the compound of Formula I is present in the composition in at least about 95 wt. %.
17. The pharmaceutical composition of claim 1 , wherein the polymorphic form of the compound of Formula I is present in the composition in at least about 99 wt. %.