Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Process for preparing zolpidem hemitartrate and tartrate polymorphs

A technology of hemi-tartrate and tartaric acid, applied in organic chemistry, nervous system diseases, drug combination, etc., can solve the problems of difficult processing of polymorphs and increased production costs

Inactive Publication Date: 2008-10-01
MALLINCKRODT INC
View PDF1 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Additional chemical process steps and solvent recovery steps are required in the process, which increase production costs
Also, some polymorphs are difficult to process due to their physical properties

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Process for preparing zolpidem hemitartrate and tartrate polymorphs
  • Process for preparing zolpidem hemitartrate and tartrate polymorphs
  • Process for preparing zolpidem hemitartrate and tartrate polymorphs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Example 1. Selective preparation of polymorph E

[0028]Zolpidem free base (5 g) was dissolved in methanol (36 mL) to give a first solution. L-(+)-tartaric acid (1.2 g) was dissolved in methanol (12 mL) to produce a second solution. The first solution and the second solution were mixed in a flask to obtain a feed solution, which was stirred at 65° C. for 30 minutes. Water (50 mL) was added to the sample solution. The sample solution was distilled until 50 mL of distillate was distilled from the sample solution. Distillation resulted in a sample solution containing less than 30% residual methanol. The remaining sample solution was cooled to ambient temperature with stirring until a solid product precipitated from the sample solution. The solution was then rotary evaporated to dryness at a pressure of 100 mb and a temperature of 40°C to obtain a dry powder. The dry powder was removed from the flask by adding 100 mL of water. Scrape the flask to remove as much powder...

Embodiment 2

[0030] Example 2. Selective preparation of polymorph E

[0031] Zolpidem free base (5 g) was dissolved in methanol (36 mL) to give a first solution. L-(+)-tartaric acid (1.2 g) was dissolved in methanol (12 mL) to produce a second solution. The first solution and the second solution were combined to produce a sample solution, which was stirred at 65°C for 30 minutes. The sample solution was distilled at 75°C until the effluent distilled from the sample solution was 15 mL. Water (25 mL) was then added to the sample solution and further distilled until the vapor temperature reached 94°C. At this point, approximately 30 mL was distilled again such that the final volume of distillate collected was 45 mL. The remaining sample solution was cooled to ambient temperature with stirring until a solid product precipitated from the sample solution. The zolpidem hemitartrate suspension was filtered through a vacuum funnel and the powder collected in the filter. Save the filtrate for l...

Embodiment 3

[0034] Example 3. Selective preparation of polymorph H

[0035] Zolpidem base (1 g) and L-(+)-tartaric acid (0.24 g) were dissolved in ethanol (10 mL). The solution was stirred at 60°C until all solids had dissolved. The solution was cooled to ambient temperature and a solid precipitated and crystallized. The suspension was filtered and the solid was dried under vacuum for 4 hours to give 1.0 g of powder (yield 81%). An isolated powder was prepared for pXRD analysis, which indicated that the solid contained polymorph H.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

A method for preparing a polymorph of a hemitartrate salt of a compound having the structure as follow comprises dissolving a free base form of the compound in a liquid medium comprising an alcohol and a tartrate derivative to form a solution comprising the compound, the alcohol, and the tartrate derivative; heating the solution to a temperature sufficient to dissolve the compound and the tartrate derivative; and cooling the solution to a temperature sufficient to precipitate the hemitartrate salt of the compound.

Description

field of invention [0001] The present invention relates to the preparation of various polymorphic forms of pharmaceutical compounds, and more particularly, the present invention relates to processes for the preparation of selected polymorphic forms of zolpidem hemitartrate and tartrate. Background of the invention [0002] Benzodiazepine Hypnotics and sleep aids including triazolam (Halcion ), alprazolam (Xanax ) and diazepam (Valium ) and many more. known benzodiazepines Members of the class have anxiolytic, sedative, hypnotic, anticonvulsant and muscle relaxant properties. Listed as Ambien Stilnox and Stilnoct Zolpidem hemitartrate is a non-benzodiazepine class of drugs, which are part of the imidazopyridine class, but zolpidem hemitartrate has been found to interact with benzodiazepines Similar pharmacological effects. [0003] Zolpidem hemitartrate is known to exist in several polymorphic forms, of which the A, B, C, D, E, F, G and H crystalline form...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07D471/04
CPCC07D471/04A61P25/20
Inventor 布赖恩·K·程
Owner MALLINCKRODT INC
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com