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 polymorphic crystalline form of a compound of Formula I:
characterized by:
(i) a powder x-ray diffraction pattern comprising peaks at diffraction angles 2θ of 7.6°, 15.4°, and 18.8°±0.1; and
(ii) a Differential Scanning Calorimetry (DSC) endotherm in the range of about 150° C. to about 158° C.
2. A solid dosage form comprising the polymorphic crystalline form of a compound of Formula I of claim 1 .
3. The solid dosage form of claim 2 wherein the polymorphic crystalline form of a compound of Formula I is present from about 75% to about 99.99% of the total weight of tiacumicins.
4. The solid dosage form of claim 2 , wherein the polymorphic crystalline form of a compound of Formula I is present in about 90% of the total weight of tiacumicins.
5. A pharmaceutical composition comprising the solid dosage form of claim 2 .
6. The pharmaceutical composition of claim 5 further comprising a pharmaceutically acceptable excipient.
7. The polymorphic crystalline form of the compound of Formula I of claim 1 wherein the DSC endotherm is in the range of about 153° C. to about 156° C.
8. A polymorphic crystalline form of a compound of Formula I:
produced by crystallizing the polymorphic crystalline form from a mixture of ethyl acetate and the compound of formula I, wherein the polymorphic crystalline form has a powder x-ray diffraction pattern comprising peaks at diffraction angles 2θ of 7.6°, 15.4°, and 18.8°±0.1.
9. The polymorphic crystalline form of claim 8 , wherein the ethyl acetate is allowed to evaporate to crystallize the polymorphic crystalline form.
10. The polymorphic crystalline form of claim 8 , wherein the polymorphic crystalline form has a Differential Scanning Calorimetry (DSC) endotherm in the range of about 150° C. to about 158° C.
11. A solid dosage form comprising the polymorphic crystalline form of a compound of Formula I of claim 8 .
12. The solid dosage form of claim 11 wherein the polymorphic crystalline form of a compound of Formula I is present from about 75% to about 99.99% of the total weight of tiacumicins.
13. The solid dosage form of claim 12 , wherein the polymorphic crystalline form of a compound of Formula I is present in about 90% of the total weight of tiacumicins.
14. A pharmaceutical composition comprising the polymorphic crystalline form of claim 8 and a pharmaceutically acceptable excipient.