Ibrutinib solid forms and production process therefor
AssigneePerrigo Api Ltd.
InventorsItai ADIN, Sonia KERIVONOS, Yevgeny ROZENBLAT, Alex WEISMAN, Ana FERNADEZ CASARES, Gloria TEN FIGAS, Revital BEN-DANIEL
Life of this patent
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Abstract
Provided are ibrutinib polymorphs, e.g., crystalline ibrutinib Forms III, IV, V, VI, VII, VIII and Form IX and processes for producing these crystalline forms, stable amorphous ibrutinib and processes for preparing stable amorphous ibrutinib, pharmaceutical compositions comprising these forms and methods of using these crystalline and amorphous forms.
Claims31
1-89. (canceled)
Crystalline ibrutinib Form VII characterized by an X-ray powder diffraction pattern exhibiting strong diffraction peaks at 6.5, 13.0, 17.7, 18.3, 20.0, 21.0, 21.5, and 23.9±0.2 degrees 2θ.
A process for preparing crystalline ibrutinib polymorph VII, the process comprising:
- dissolving or slurrying ibrutinib in anisole or in a mixture of anisole with another solvent or anti-solvent;
- optionally heating;
- optionally adding an anti-solvent;
- optionally cooling;
- optionally seeding with crystalline ibrutinib Form VII;
- and
- isolating the solid and, optionally, drying the solid.
A pharmaceutical composition comprising crystalline ibrutinib Form VII and one or more pharmaceutically acceptable additives or excipients.
A method for treating mantle cell lymphoma and chronic lymphoid leukemia comprising administering to a subject in need a therapeutically effective dose of ibrutinib Form VII.
A process for preparing ibrutinib Form VII, comprising:
- dissolving ibrutinib in a first solvent;
- exposing the solution to the vapors of a second solvent for a period of at least one day to produce crystals;
- isolating the crystals;
- and
- optionally drying the crystals to afford dry ibrutinib Form VII.
A process for preparing amorphous ibrutinib, comprising
- dissolving ibrutinib in a solvent, optionally with heating;
- and
- distilling out the solvent, optionally under reduced pressure.
A process for preparing amorphous ibrutinib, comprising:
- dissolving ibrutinib in a first solvent, optionally with heating;
- optionally adding a second solvent;
- inserting the mixture into a spray-dryer and spray-drying;
- and
- isolating the formed solid and, optionally, drying the solid.
A process for preparing amorphous ibrutinib, comprising:
- dissolving ibrutinib in a solvent or mixture of solvents, optionally with heating;
- loading the solution onto a chromatographic column,
- eluting the ibrutinib from the column,
- optionally concentrating the eluting solution,
- spray drying the solution to give amorphous ibrutinib and
- optionally drying the amorphous product.
A process for preparing amorphous ibrutinib, comprising:
- dissolving ibrutinib in a solvent or mixture of solvents, optionally with heating;
- mixing the solution with silica,
- filtering the silica out
- eluting the ibrutinib from the silica,
- optionally concentrating the eluting solution,
- spray drying the solution to give amorphous ibrutinib and
- optionally drying the amorphous product.
Amorphous ibrutinib obtained by spray drying, which is characterized by being slightly hygroscopic.
A process for preparing amorphous ibrutinib, comprising:
- dissolving ibrutinib in a solvent or solvent mixture, optionally with heating;
- optionally filtering the solution;
- freezing the mixture;
- and
- freeze-drying the mixture;
A pharmaceutical composition comprising amorphous ibrutinib and at least one pharmaceutically acceptable excipient.
A method for treating mantle cell lymphoma and chronic lymphoid leukemia comprising administering to a subject in need a therapeutically effective dose of amorphous ibrutinib.
Dependencies are inferred from the claim text.