Crystal form of azilsartan medoxomil and preparation method of crystal form

A technology of azilsartan medoxomil and its crystal form, which is applied in the field of the crystal form of azilsartan medoxomil and its preparation, and can solve problems such as low solubility, high melting point, and unsuitable formulations

Active Publication Date: 2016-09-21
SOLIPHARMA
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] The known crystal form J2 mentioned in the patent document WO2012 / 090043A1 has low solubility in water, which affects the dissolution of the drug, thereby affecting the bioavailability, and the melting point is too high, so it is not suitable for the preparation obtained by the hot-melt extrusion method, and The crystalline form has small particles, which is not conducive to the compressibility of the tablet; the known crystalline form J4 mentioned is a hydrate, which has a low dehydration temperature and poor thermal stability

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
  • Crystal form of azilsartan medoxomil and preparation method of crystal form
  • Crystal form of azilsartan medoxomil and preparation method of crystal form
  • Crystal form of azilsartan medoxomil and preparation method of crystal form

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0248] The known crystal form J2 of azilsartan medoxomil can be prepared according to the method described in Example 1 of patent document WO2012 / 090043A1.

[0249] Specifically, the preparation method of known crystal form J2 of azilsartan medoxomil is as follows: at 15-20°C, dissolve 0.5g of known crystal form I of azilsartan medoxomil in 50mL of methanol, and volatilize the solution after filtering to obtain Form J2 is known.

[0250] The XRPD pattern of the known crystal form J2 is shown in Figure 37 .

[0251] See DSC diagram Figure 38 , showing a melting point of 170 °C.

[0252] See TGA diagram Figure 39 , showing as anhydrous substance, the decomposition temperature is 229°C.

[0253] PLM diagram see Figure 40 , showing extremely small particles.

Embodiment 2

[0255]The known crystal form J4 of azilsartan medoxomil can be prepared according to the method described in Example 4 of the patent document WO2012 / 090043A1.

[0256] Specifically, the preparation method of the known crystal form J4 of azilsartan medoxomil is as follows: 0.5 g of azilsartan medoxomil crystal form I is dissolved in acetone (7.5 mL) and ethyl acetate (7.5 mL) at 40-50° C. ) in the mixed solution, lower the temperature to 0-5°C and stir, and filter to obtain the known crystal form J4.

[0257] The XRPD pattern of the known crystal form J4 is shown in Figure 41 .

[0258] See DSC diagram Figure 42 , showing that it transformed at 146°C after desolvation to form anhydrous known crystal form J2 with a melting point of about 170°C.

[0259] See TGA diagram Figure 43 , showing that there is a 6.4% weight loss at 95°C, which is about 2 water molecules, which is a dihydrate, and the decomposition temperature is 222°C.

Embodiment 3

[0261] Weigh 100mg of known crystal form J2 and add it to a 30mL single-necked flask, then add 10mL of acetone, spin dry quickly, and obtain a foamy solid amorphous.

[0262] The XRPD pattern of the amorphous substance is shown in Figure 4 , no XRPD diffraction peak, it is amorphous.

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
decomposition temperatureaaaaaaaaaa
decomposition temperatureaaaaaaaaaa
melting pointaaaaaaaaaa
Login to view more

Abstract

The invention relates to a crystal form of azilsartan medoxomil and a preparation method of the crystal form, in particular to multiple novel crystal forms of a compound 1-[[2'-(2,5-dihydro-5-oxo-1,2,4-oxadiazole-3-base)[1,1'-biphenyl]-4-base]methyl]-2-ethoxy-1H-benzimidazole-7-carboxylic acid(5-methyl-2-oxo-1,3-dioxole-4-yl)methyl ester and a preparation method of the novel crystal forms. Compared with the prior art, water solubility of the novel crystal forms is high, the melting point is low, therefore, compared with an existing crystal form, good dissolubility and bioavailability are achieved, and a pharmaceutic preparation can be obtained more conveniently through a hot-melt extrusion method.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical crystals. Specifically, it relates to a crystal form of azilsartan medoxomil and a preparation method thereof. Background technique [0002] Azilsartan medoxomil is a novel angiotensin II receptor blocker developed by Japan's Takeda Pharmaceutical Company, which was approved by the U.S. FDA in February 2011 under the trade name Edabi. The drug is also a prodrug of the new angiotensin II receptor blocker azilsartan, which is used for the treatment of hypertension and related complications. The drug is taken orally and can be used alone or in combination with other antihypertensive drugs for the treatment of hypertension and related complications. In the phase III clinical trial of once-daily administration of 20-80 mg azilsartan medoxomil, its safety and efficacy were confirmed, and in the comparative experiments with losartan and olmesartan medoxomil, it had higher hypotensive effect. T...

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): C07D413/14A61K31/4245A61P9/12
CPCC07B2200/13C07D413/14
Inventor 沈涛盛晓霞盛晓红
Owner SOLIPHARMA
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