Patent DE-20122436-U1 (DE)
Title: New hydrate, anhydrous and solvate crystal forms of zolpidem hemitartrate, useful for treating insomnia in patients
IPC: A61K31/4184
Filed: 2001-04-24
Abstract: New hydrate, anhydrous and solvate crystal forms of zolpidem hemitartrate are disclosed. The following compounds are claimed: a zolpidem hemitartrate hydrate; a zolpidem hemitartrate monohydrate; a zolpidem hemitartrate dihydrate; a zolpidem hemitartrate trihydrate; a zolpidem hemitartrate tetrahydrate; a zolpidem hemitartrate solvate; a zolpidem hemitartrate anhydrous; an anhydrous zolpidem hemitartrate Form C; a zolpidem hemitartrate Form C, characterized by an X-ray powder diffraction pattern having peaks at about 7.3, 9.5, 17.8, and 23.8 +-0.2 degrees 2-theta; a zolpidem hemitartrate with not more than 1% water content; a zolpidem hemitartrate Form D monohydrate; a zolpidem hemitartrate Form D, characterized by a water content of 2.3-2.7wt.%; a zolpidem hemitartrate Form D hemiethanolate; a zolpidem hemitartrate Form D, characterized by an X-ray powder diffraction pattern having peaks at about 7.1, 9.5, 14.1, 19.6 and 24.5 +-0.2 degrees 2-theta; a zolpidem hemitartrate Form E dihydrate; a zolpidem hemitartrate Form E trihydrate; a zolpidem hemitartrate Form E tetrahydrate; a zolpidem hemitartrate Form E, characterized by a water content of 5.0-8.5wt.%; a zolpidem hemitartrate Form E, characterized by an X-ray powder diffraction pattern having peaks at about 5.2, 7.9, 10.4, 17.2, 18.0 and 18.8 +-0.2 degrees 2-theta; a zolpidem hemitartrate Form F methanolate; a zolpidem hemitartrate Form F, characterized by a methanol content of about 5.5wt.%; a zolpidem hemitartrate Form F, characterized by an X-ray powder diffraction pattern having peaks at about 7.6 and 18.0 +-0.2 degrees 2-theta; a zolpidem hemitartrate Form G solvate; a zolpidem hemitartrate Form G, characterized by an X-ray powder diffraction pattern having peaks at about 6.8 +-0.2 degrees 2-theta; a zolpidem hemitartrate Form H, characterized by an X-ray powder diffraction pattern having peaks at about 7.7, 17.4, 18.0 and 24.3 +-0.2 degrees 2-theta; a zolpidem hemitartrate Form L dihydrate; a zolpidem hemitartrate Form L, characterized by a water content of about 4.3wt.%; a zolpidem hemitartrate Form L, characterized by an X-ray powder diffraction pattern having peaks at about 6.8, 9.7, 17.3, 19.6, and 21.1 +-0.2 degrees 2-theta. Independent claims are also included for: (1) a method for synthesizing zolpidem hemitartrate, comprising: (a) forming a zolpidic acid halide from zolpidic acid; (b) reacting zolpidem acid halide with dimethyl amine, to form zolpidem base; (c) forming zolpidem hemitartrate salt from the zolpidem base; (2) a process for preparing zolpidem hemitartrate Form C comprising: (a) exposing zolpidem hemitartrate Form A to vapors of isopropyl alcohol; or (b) heating zolpidem hemitartrate to 70-150[deg]C to convert zolpidem hemitartrate to Form C; (3) a process for preparing zolpidem hemitartrate Form D comprising: (a) exposing zolpidem hemitartrate Form A to water vapor at a relative humidity from 60-100%; (b) exposing Form C to water vapor at a relative humidity of about 100%; (c) exposing zolpidem hemitartrate Form A or Form C to vapors of ethanol; (d) forming a slurry of zolpidem hemitartrate Form A in ethyl acetate, acetone, or isopropanol; (4) a process for preparing zolpidem hemitartrate Form C comprising forming a slurry of zolpidem hemitartrate Form A in isopropanol; (5) a process for preparing zolpidem hemitartrate Form D comprising granulating zolpidem hemitartrate Form A in butanol; (6) a process for preparing zolpidem hemitartrate Form E comprising: (a) exposing a solid form of zolpidem hemitartrate to water vapor at a relative humidity of about 100%; (b) forming a slurry of a solid form of zolpidem hemitartrate in water; or (c) granulating a solid form of zolpidem hemitartrate in water; (7) a process for preparing zolpidem hemitartrate Form F comprising exposing a solid form of zolpidem hemitartrate to vapors of methanol; (8) a process for preparing zolpidem hemitartrate Form G comprising: (a) exposing zolpidem hemitartrate Form A to vapors of ethyl acetate; (b) forming a slurry of zolpidem hemitartrate Form C in ethanol or methanol; or (c) granulating zolpidem hemitartrate Form C in ethanol or methanol; (9) a process for preparing zolpidem hemitartrate Form H comprising: (a) slurrying zolpidem hemitartrate Form A in ethanol or methanol; or (b) granulating zolpidem hemitartrate Form A in ethanol or methanol; (10) a process for preparing zolpidem hemitartrate Form L comprising: (a) dissolving zolpidem hemitartrate in a solvent mixture of methanol and water; (b) precipitating zolpidem hemitartrate from the solvent mixture; and (c) isolating zolpidem hemitartrate; (11) zolpidem hemitartrate having particles up to about 200 or 50 microns in size; (12) micronized zolpidem hemitartrate Form A having particles up to about 200 microns in size as measured by laser diffraction and an x-ray diffraction pattern having a peak at about 8.6+-0.2 degrees 2-theta. ACTIVITY : Somnogenic; hypnotic. MECHANISM OF ACTION : None given in the source material.