Polymorphs of fexofenadine base
OwnerBarnaba Krochmal, Dov Diller +3inventors
InventorsBarnaba Krochmal, Dov Diller, Ben-Zion Dolitzky, Judith Aronhime, Shlomit Wizel
Life of this patent
Estimating the term…
Abstract
The present invention provides novel crystal forms of fexofenadine base and processes for their preparation. The forms are useful for administration to humans and animals to alleviate symptoms caused by histamine. The present invention further provides pharmaceutical compositions of the new crystalline forms.
Claims58
Fexofenadine base Form I.
A fexofenadine base in a crystalline form characterized by a PXRD pattern with peaks at about 9.8, 11.6, 12.1, 13.5, 14.0, 18.0, 18.4 and 19.7±0.2 degrees two theta.
A fexofenadine base in a crystalline form having a differential scanning calorimetric thermogram with an endothermic peak at about 100° C. and an endothermic peak at about 143° C., and two exothermic peaks at about 155° C. and about 180° C.
A process for preparing fexofenadine base having at least one of characteristics of Form I comprising the steps of:
- a) preparing a solution of fexofenadine base in 1-propanol;
- b) admixing the solution with water, ice or a mixture thereof to precipitate fexofenadine base;
- and
- c) separating the precipitate.
Fexofenadine base Form II.
A fexofenadine base in a crystalline form having a PXRD pattern with peaks at about 7.4, 9.7, 11.7, 12.1, 13.8, 14.4, 18.0, 18.5 and 19.7±0.2 degrees two theta.
A fexofenadine base in a crystalline form having a differential scanning calorimetric thermogram with an endotherm at about 100° C., a maximum endotherm at about 223° C. and a minor endotherm at about 144° C., and two exotherms at about 146° C. and about 182° C.
A process for preparing fexofenadine base having at least one of characteristics of Form II comprising the steps of:
- a) preparing a solution of fexofenadine base in a mixture of water and 1-propanol, wherein fexofenadine base precipitates from the solution;
- and
- b) separating the fexofenadine base.
Fexofenadine base Form III.
A fexofenadine base in a crystalline form characterized by a PXRD diffraction pattern with peaks at about 4.4, 10.3, 11.3, 16.3, 19.8±0.2 degrees 2θ.
A fexofenadine base in a crystalline form characterized by a DSC thermogram with an endotherm followed by an exotherm at about 200° C., and an additional endotherm at about 226° C.
A process for preparing fexofenadine base having at least one of characteristics of Form III comprising the steps of:
- a) slurrying fexofenadine base in methanol;
- b) heating the slurry;
- and
- c) separating fexofenadine base Form III as a solid.
Fexofenadine base Form IV.
Fexofenadine base in a crystalline form characterized by a PXRD diffraction pattern with peaks at about 4.3, 8.7, 12.5, 13.1 and 13.6±0.2 degrees 2θ.
A process for preparing fexofenadine base having one of characteristics of Form IV comprising the steps of:
- a) preparing a solution of fexofenadine base in a mixture of a C1 to a C4 alcohol and water, with the proviso that the alcohol is not 1-propanol, wherein fexofenadine base precipitates from the solution;
- and
- b) separating the precipitate.
A process for preparing fexofenadine base having one of characteristics of Form IV comprising the steps of:
- a) preparing a solution of a sodium or a potassium salt of fexofenadine in a mixture of a C1 to a C4 alcohol and water, with the proviso that the alcohol is not 1-propanol;
- and
- b) acidifying the solution to precipitate fexofenadine base.
Fexofenadine base Form V.
A fexofenadine base in a crystalline form characterized by a PXRD diffraction pattern with peaks at about 17.2, 18.2, 18.8, 20.3±0.2 degrees 2θ.
A fexofenadine base in a crystalline form characterized by a DSC thermogram with an endotherm followed by an exotherm at about 200° C., and an additional endotherm at about 226° C.
A process for preparing fexofenadine base having at least one of characteristics of Form V comprising the steps of:
- a) slurrying fexofenadine base in methyl ethyl ketone;
- and
- b) separating fexofenadine base Form V as a solid.
Fexofenadine base Form VI.
A fexofenadine base in a crystalline form characterized by a PXRD pattern with peaks at about 3.9, 9.6, 11.8, 16.0 and 19.0±0.2 degrees 2θ.
A fexofenadine base in a crystalline form characterized by a DSC thermogram with endotherms at about 140° C. and about 229° C., and an exotherm at about 160° C.
A process for preparing fexofenadine base having at least one of characteristics of Form VI comprising the steps of:
- a) slurrying fexofenadine base in methanol under suitable condition;
- and
- b) separating fexofenadine base Form VI as a solid.
A Fexofenadine base Form VII.
A fexofenadine base in a crystalline form characterized by a PXRD pattern with peaks at about 3.9, 7.7, 10.6, 13.4, 14.5 and 19.2±0.2 degrees 2θ.
A fexofenadine base in a crystalline form characterized by a DSC thermogram with an endotherm at about 228° C.
A process for preparing fexofenadine base having at least one of characteristics of Form VII comprising carrying out an azeotropic distillation of fexofenadine base in toluene to remove water.
A pharmaceutical composition comprising an effective amount of fexofenadine selected from the group consisting of base Forms I, II, III, IV, V, VI and VII, and a pharmaceutically acceptable excipient.
Dependencies are inferred from the claim text.