Amorphous and crystalline forms of rivastigmine hydrogentartrate - Patent EP1942100Rivastigmine hydrogentartrate in amorphous form or in a crystalline form characterized by an X-ray powder diffraction pattern exhibiting peaks at 2? values of 5.1, 14.7, 16.5, 17.6, 18.6, 20.4, 21.1° ± 0.2° (Form I), or 2? values of 9.5, 11.3, 13.2, 14.1, 15.5, 19.1 20.0° ± 0.2° (Form II), methods for its preparation and pharmaceutical compositions comprising the same.) concerns the synthesis of rivastigmine and its hydrogentartrate in optically pure form. The hydrogentartrate salt is crystallized from a mixture of ethanol and ethyl acetate by dissolving rivastigmine base and L-(+)-tartaric acid in ethanol at 60 to 70°C and gradually adding ethyl acetate. The resulting mixture is left to crystallize at 5°C. The product is said to have a melting point of 125 to 126°C. Alternatively, the free base and L-(+)-tartaric acid are dissolved in methanol, the clear solution is cooled to room temperature, gradually precipitated with acetone and left to crystallize at 5°C giving a product melting at 123 to 125°C. The polymorphic forms of rivastigmine hydrogentartrate of the present invention are particularly suitable for preparing medicaments. They can be used to improve the performance characteristics of pharmaceutical products. Furthermore, they enlarge the repertoire of materials that a formulation scientist has available for designing pharmaceutical dosage forms, such as dosage forms with a targeted release profile or other desired characteristics. In addition, the polymorphic forms of the present invention can easily be converted to an amorphous form. The skilled person now has the possibility to choose from different forms of rivastigmine hydrogentartrate with different physical properties.
