Paeoniflorin crystallization process with controllable crystal form and granularity

A technology of azithromycin and particle size, which is applied in the crystallization process field of azithromycin, can solve the problems of inability to meet the polymorphic requirements of azithromycin, large fluctuations in particle size distribution, optimization of preparation methods, etc., to achieve stable preparation of crystal forms and good gloss , the effect of regular crystal appearance

Inactive Publication Date: 2011-05-18
NANJING TECH UNIV
View PDF4 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, the common preparation methods of azithromycin are mainly pure water extraction or cooling methods, which lack the control of the preparation process and the optimization of the preparation method, which leads to low stability of the crystal form, low purity, large particle size distribution fluctuations, and hygroscopicity. Strong, unable to meet the requirements of the pharmaceutical industry for polymorphic forms of azithromycin

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
  • Paeoniflorin crystallization process with controllable crystal form and granularity
  • Paeoniflorin crystallization process with controllable crystal form and granularity
  • Paeoniflorin crystallization process with controllable crystal form and granularity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Dissolve 20g of the amorphous azithromycin raw material in 170mL of absolute ethanol, adjust the pH value to 10.0, set the volume to 200mL, put it into a 1000mL three-neck flask, keep the constant temperature water bath at 40°C, and control the stirring speed at 500r·min -1 , add 2% sodium chloride of azithromycin quality. Then start to add pure water slowly, and the flow rate is controlled to be 20% azithromycin organic solution per hour. The initial volume is slightly turbid. After stopping the flow and adding crystal growth for 2 hours, continue to maintain the same flow rate and continue to add until 500mL is added. Pure water, suction filtration, vacuum, in the presence of desiccant anhydrous calcium chloride, and dried at 40°C for 4 hours. The finally obtained azithromycin crystal form has good stability (unit cell parameters are shown in Table 3), regular appearance, crystal form purity of 99%, main particle size of 40.3 μm, distribution width of 21.5 μm, and wat...

Embodiment 2

[0037] Dissolve 24g of amorphous azithromycin raw material in 170mL of ethylene glycol, adjust the pH value to 11.0, set the volume to 200mL and put it into a 1000mL three-neck flask, keep the constant temperature water bath at 20°C, and control the stirring speed at 300r·min -1 , add 2% sodium acetate by mass of azithromycin. Then start to add pure water slowly, and the flow rate is controlled at an initial volume of 15% azithromycin organic solution per hour, which is slightly turbid. After stopping the flow and adding crystal growth for 2 hours, continue to maintain the same flow rate and continue to feed until the flow is completed 500mL Purified water, filtered by suction, dried under vacuum at 40°C for 5 hours in the presence of desiccant silica gel. The final crystal form of azithromycin (see Table 3 for unit cell parameters) has a regular appearance, a crystal form purity of 99%, a main particle size of 72 μm, a distribution width of 44.2 μm, and a water content of 3.2...

Embodiment 3

[0039] Dissolve 30g of the amorphous azithromycin raw material in 170mL of tetrahydrofuran, adjust the pH value to 8.0, set the volume to 200mL, put it into a 1000mL three-neck flask, keep the constant temperature water bath at 30°C, and control the stirring speed at 500r·min -1 , add 2% sodium chloride by mass of azithromycin. Then start to add pure water slowly, and the flow rate is controlled at an initial volume of 15% azithromycin organic solution per hour, which is slightly turbid. After stopping the flow and adding crystal growth for 2 hours, continue to maintain the same flow rate and continue to feed until the flow is completed 500mL Pure water, suction filtration, vacuum, in the presence of desiccant anhydrous magnesium nitrate, and dried at 40°C for 8 hours. The final crystal form of azithromycin (see Table 3 for unit cell parameters) has a regular appearance, a crystal form purity of 99%, a main particle size of 32.4 μm, a distribution width of 20.2 μm, and a water...

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
particle sizeaaaaaaaaaa
widthaaaaaaaaaa
particle sizeaaaaaaaaaa
Login to view more

Abstract

The invention discloses an azithromycin crystallization process with controllable crystal form and grain size. In azithromycin organic solution with the pH value of between 7.0 and 11.0 and the initial concentration of between 80 and 200g.L<-1>, inorganic sodium salt and a solventing-out agent are added, the crystallization temperature is controlled to between 10 and 90 DEG C, the stirring speed is controlled to between 10 and 1,000r.min<-1>, the crystallization is performed by the synergy of elution and salting out, suction filtration is performed after complete crystallization, washing is repeatedly performed by the solventing-out agent, and then vacuum drying is performed. In the process, the aims of stable preparation of crystal form and controllable grain size of the azithromycin are achieved by regulating and controlling preparation conditions. The azithromycin prepared by the crystallization process has the advantages of good stability of crystal form, high purity (more than 99 percent), uniform grain size, good luster, weak hydroscopic property and the like.

Description

technical field [0001] The invention belongs to the technical field of crystallization, and in particular relates to a crystallization process of azithromycin. Background technique [0002] As the second-generation erythromycin product, azithromycin is the first semi-synthetic aza-15-membered ring macrolide antibiotic. Compared with erythromycin, azithromycin retains the advantages of erythromycin and has a further antibacterial spectrum. Expanded, the antibacterial effect on Chlamydia trachomatis is prominent and the tissue concentration is high. Azithromycin has always been a hot product in the international anti-infective drug market due to its advantages such as long half-life, less frequency of administration, short course of treatment, and low incidence of adverse reactions. The U.S. FDA Anti-Infection Advisory Committee recommends it as a drug for respiratory tract, genitourinary tract, skin and soft tissue infections caused by sensitive bacteria. Today, the incidenc...

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 Patents(China)
IPC IPC(8): C07H17/08
Inventor 应汉杰黄小权张磊熊健柏建新李振江
Owner NANJING TECH UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap