Forms of afatinib dimaleate
The present disclosure is directed to a crystalline, hydrated form of afatinib dimaleate having about 2 to 3 molecules of water, designated as Form Z, a pharmaceutical composition comprising the form, its method of use for treating a patient, and process for its preparation.
1. A crystalline, hydrated form of afatinib dimaleate having about 2 to 3 molecules of water, designated as Form Z, wherein the Form Z comprises X-ray powder diffraction peaks, in terms of 2-theta, at about 11.1, about 10.7 and about 6.6.
2. Form Z according to claim 1 , wherein the Form Z further comprises one or more X-ray powder diffraction peaks, in terms of 2-theta, at about 5.3, about 5.8 and about 21.6.
3. Form Z according to claim 2 , wherein the Form Z further comprises one or more X-ray powder diffraction peaks, in terms of 2-theta, at about 25.4, about 10.3 and about 20.9.
4. Form Z according to claim 1 , wherein the Form Z comprises one or more X-ray powder diffraction peaks at d-spacing, in terms of Angstroms, at about 8.0, about 8.3 and about 13.4.
5. Form Z according to claim 4 , wherein Form Z further comprises one or more X-ray powder diffraction peaks at d-spacing, in terms of Angstroms, at about 16.8, about 15.2 and about 4.1.
6. Form Z according to claim 5 , wherein Form Z further comprises one or more X-ray powder diffraction peaks, at d-spacing, in terms of Angstroms, at about 3.5, about 8.6 and about 4.3.
7. Form Z according to claim 1 , wherein Form Z is characterized by an endothermic event at about 95.5° C., as measured by differential scanning calorimetry.
8. Form Z according to claim 1 , wherein Form Z is characterized by an endothermic event at about 128.3° C., as measured by differential scanning calorimetry.
9. A pharmaceutical composition comprising a pharmaceutically effective amount of Form Z according to claim 1 and pharmaceutically acceptable excipient.
10. A method of treating disease in a patient comprising administering a pharmaceutical composition according to claim 9 to the patient in need thereof.
11. A method of treating disease according to claim 10 , wherein the disease is lung cancer.
12. A method of making Form Z according to claim 1 , comprising exposing afatinib dimaleate to 2-butanol and water to yield Form Z.
13. A method of making Form Z according to claim 1 , comprising exposing a solution comprising afatinib free base and 2-butanol to an aqueous solution of maleic acid to yield Form Z.