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

Novel crystalline state of roflumilast and preparation method thereof

A roflumilast, crystalline technology, used in the pharmaceutical field, can solve the problems of difficult removal, failure to meet drug quality standards, and affecting drug bioavailability.

Active Publication Date: 2012-01-11
大道隆达(北京)医药科技发展有限公司
View PDF5 Cites 9 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Yet the reproducibility experiment proves that the purity of the product prepared by this method is poor, especially some unknown impurities with less polarity are difficult to remove, the total amount of related substances (HPLC normalization method) is greater than 1%, and the largest single impurity exceeds 1%. 0.1%, can not meet the drug quality standards
In addition, the water solubility of the product obtained by crystallization with isopropanol is relatively poor, which delays the dissolution of its oral pharmaceutical preparation to a considerable extent, and then affects the bioavailability of the drug in the body. Often need to add PVP as solubilizer in preparation preparation process (see CN1635909A for details)

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
  • Novel crystalline state of roflumilast and preparation method thereof
  • Novel crystalline state of roflumilast and preparation method thereof
  • Novel crystalline state of roflumilast and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Suspend 5 grams of roflumilast crude product in 5 times the amount of ethyl acetate (w / v), heat to dissolve, add about 0.5 grams of activated carbon for decolorization, filter while hot, cool and crystallize, filter, and dry to constant weight. That is to say, the new crystalline state of roflumilast according to the present invention has a melting point of 161-162° C., the total amount of related substances detected by HPLC (normalization method) is less than 0.5%, and any largest single impurity does not exceed 0.1%.

Embodiment 2

[0026] Suspend 5 g of roflumilast crude product in 10 times the amount of anhydrous ether (w / v), heat to dissolve, add about 0.5 g of activated carbon for decolorization, filter while hot, freeze crystallization, filter, dry to constant weight, That is to say, the new crystalline state of roflumilast according to the present invention has a melting point of 162-163° C., and the total amount of related substances detected by HPLC (normalization method) is less than 0.4%, and any largest single impurity does not exceed 0.1%.

Embodiment 3

[0028] Suspend 5 grams of roflumilast crude product in 10 times the amount of acetone (w / v), heat to dissolve it, add about 0.5 grams of activated carbon for decolorization, filter while it is hot, cool and crystallize, filter, dry to constant weight, and obtain The new crystalline state of roflumilast according to the present invention has a melting point of 160-163° C., the total amount of related substances detected by HPLC (normalization method) is less than 0.4%, and any largest single impurity does not exceed 0.1%.

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

PropertyMeasurementUnit
melting pointaaaaaaaaaa
melting pointaaaaaaaaaa
melting pointaaaaaaaaaa
Login to View More

Abstract

The invention discloses a novel crystalline state of roflumilast and a preparation method thereof. The crystalline state is a stable high-purity roflumilast crystalline state form, and has the characteristics of easiness, convenience and practicability in operation and high adaptability to industrial mass production; particularly, the solubility of the product in a water-containing system is properly increased; and further, a medicinal preparation applying the crystalline state roflumilast prepared by the invention can still reach an effective dissolution rate under the condition of not adding PVP (Polyvinyl Pyrrolidone).

Description

technical field [0001] The invention relates to the technical field of pharmacy, describes a crystalline state of roflumilast, and is used as a PDE inhibitor for treating mild to moderate asthma, pulmonary hypertension and ophthalmic diseases. The invention also relates to the preparation method of the crystalline state and its application in oral preparations. technical background [0002] Roflumilast (Roflumilast) is a new type of PDE IV inhibitor. Existing clinical studies have proved that it is effective in the treatment of mild to moderate asthma, especially chronic obstructive pulmonary disease (COPD). An oral, once-daily, steroid-free asthma treatment. [0003] The chemical name of roflumilast is N-(3,5-dichloropyridin-4-yl)-3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzamide, and its chemical structure is : [0004] [0005] CN1046939C reports a general synthesis method of a series of PDE IV inhibitors including this compound, wherein the compound has a melting...

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): C07D213/75A61K31/44A61P11/06
Inventor 周华明葛永彪杨荣珍王家强郑艳萍
Owner 大道隆达(北京)医药科技发展有限公司
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