CN107011262B - A method of Sorafenib Tosylate polymorphic K particle is prepared based on supercritical anti-solvent technology - Google Patents
A method of Sorafenib Tosylate polymorphic K particle is prepared based on supercritical anti-solvent technology Download PDFInfo
- Publication number
- CN107011262B CN107011262B CN201710420640.1A CN201710420640A CN107011262B CN 107011262 B CN107011262 B CN 107011262B CN 201710420640 A CN201710420640 A CN 201710420640A CN 107011262 B CN107011262 B CN 107011262B
- Authority
- CN
- China
- Prior art keywords
- sorafenib tosylate
- polymorphic
- crystal form
- particle
- solvent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/54—Improvements relating to the production of bulk chemicals using solvents, e.g. supercritical solvents or ionic liquids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a kind of methods for preparing Sorafenib Tosylate polymorphic K particle based on supercritical anti-solvent technology.Method includes preparing Sorafenib Tosylate mixing crystal form solution: Sorafenib Tosylate polymorphic A and polymorph b being added in organic solvent by certain mass ratio, Sorafenib Tosylate mixing crystal form solution is obtained after ultrasonic treatment；Pre- thermal exhaust: setting crystallization apparatus temperature empties air in crystallization apparatus after preheating 30~50min, and then boosting is stablized to 8~14MPa；It is mixed with: by mixing crystal form solution and CO2It is passed through crystallization apparatus, continues to be passed through CO after reaction with 6~8L/min2, release after 0.5~1.5h collects Sorafenib Tosylate polymorphic K particle.Preparation method of the invention, easy to operate, mild condition, solvent usage amount is few, while realizing transformation of crystal and product crystal form micronized, and gained crystal form K diameter of particle is 1.325 μm, and narrow particle size distribution, improves the preparation feasibility and medication performance of crystal form K.
Description
Technical field
The invention belongs to drugs and supercritical technology field, and in particular to one kind prepares first based on supercritical anti-solvent technology
The method of benzene sulfonic acid Sorafenib polymorphic K particle.
Background technique
Sorafenib is that first substituted bisarylurea takes orally more kinases, multiple target point inhibitor, the entitled 4- { 4- [3- (4- of chemistry
Chloro- 3- trifluoromethyl-phenyl)-uride]-phenoxy group }-pyridine-2-carboxylic acids methylamine, Sorafenib is clinically used at present
Toluene fulfonate is developed jointly by German Bayer company and Onyx company, trade name Nexavar (Nexavar), and 2015 12
Treatment and first of the moon 20 by FDA approval for advanced renal cell carcinoma (RCC) are approved for advanced stage RCC treatment
Drug；Then, the CFDA approval Sorafenib on the 12nd of September in 2006 lists at home；FDA on November 16 ratifies Suo Lafei within 2007
Buddhist nun is used to not cutting off the liver cancer cells for the treatment of；In May, 2008, CFDA ratified its treatment for being used for advanced hepatocellular carcinoma (HCC).
WO2006034797 makes public for the first time Sorafenib Tosylate polymorphic I, polymorphic II, polymorphic III, and
Sorafenib tosilate methanol solvate compound and alcohol solvent compound.Odd pharmaceutical technology (Shijiazhuang) in Shi Yao group
Co., Ltd discloses polymorphic K and its preparation method of atent solvent crystallization is added after temperature control dissolution in polar solvent
(CN105439947A), this method solvent usage amount is big, and crystal form K yield is unsatisfactory.
Supercritical anti-solvent crystallization technique (supercritical anti-solvent, SAS) is reducing partial size, improves medicine
Have partial size small in object bioavilability compared with traditional granulation technique and the advantages such as particle diameter distribution is narrow, organic solvent residual is low.
Carbon dioxide is 31.1 DEG C, critical pressure 7.38MPa as most common fluid, its critical-temperature, and condition is relatively warm
With；And have many advantages, such as that environmentally protective, nontoxic, viscosity is low, diffusivity is good, and dissolubility is strong.It is super to face based on these characteristics
Boundary CO2Antisolvent crystallization technology is widely used in the preparation of drug microparticles.
Summary of the invention
It is to be solved by this invention to ask in view of the disadvantage of above-mentioned existing Sorafenib Tosylate polymorphic K preparation method
Topic, which is to provide, a kind of utilizes supercritical CO2The method for preparing Sorafenib Tosylate polymorphic K particle.
Technical solution provided by the invention, including, Sorafenib Tosylate polymorphic A and polymorph b are pressed into certain matter
Amount ratio is added in organic solvent, and Sorafenib Tosylate mixing crystal form solution is obtained after ultrasonic treatment；Pre- thermal exhaust, setting
Crystallization apparatus temperature empties air in crystallization apparatus after preheating 30~50min, and then boosting is stablized to 8~14MPa；By toluene
Sulfonic acid Sorafenib mixing crystal form solution and CO2It is passed through crystallization apparatus, continues to be passed through CO after reaction with 6~8L/min2, 0.5
Sorafenib Tosylate polymorphic K particle is collected in release after~1.5h.
In order to further realize the object of the invention, it is preferable that the Sorafenib Tosylate polymorphic A and polymorph b
Mass ratio are as follows: 1: 10~0.1.
Preferably, the Sorafenib Tosylate mixed crystal solution concentration is 4~12mg/ml.
Preferably, the organic solvent is the mixture of dimethyl sulfoxide and ethyl alcohol, the volume of dimethyl sulfoxide and ethyl alcohol
Than being 1: 1~10.
Preferably, the pre- thermal exhaust, wherein the crystallization apparatus temperature that sets is 32~38 DEG C.
Preferably, the pre- thermal exhaust, wherein the ultrasonic treatment, be at 50~70Hz ultrasonic treatment 15~
20min。
Preferably, described to be mixed with, wherein the CO2It is passed through crystallization apparatus, being passed through flow velocity is 3~5L/min.
Sorafenib Tosylate polymorphic K of the present invention has X-ray powder diffraction as shown in Fig. 1
(XPRD) spectrogram.
Sorafenib Tosylate polymorphic K of the present invention has scanning electron microscope (SEM) figure as shown in Fig. 2,
The result shows that the flaky crystallization of crystal form K.
Sorafenib Tosylate polymorphic K of the present invention has size distribution as shown in Fig. 3, as a result table
Bright, compared with bulk pharmaceutical chemicals polymorphic A and polymorph b, the partial size of crystal form K is smaller, narrower particle size distribution.
Supercritical CO of the present invention2Its principle of anti-solvent technology is: dissolved with bulk pharmaceutical chemicals solution by nozzle by
Liquid pump is delivered in autoclave, and solution quickly forms tiny drop or droplet, solvent and supercritical CO in kettle2Between
Mass transfer enhancing, and dissolve in CO2In, cause solution to be rapidly achieved hypersaturated state, solute crystallization.Due to preparation
Process is in high pressure conditions, compared with conventional method, supercritical CO2Anti-solvent technology is easy to operate, is easier to that drug novel crystal forms are made, and
Product cut size is greatly reduced, and is conducive to the preparation feasibility and medication performance that improve crystal form K.
Compared with the existing technology, the present invention has the advantage that
1. it is simple that technical solution of the present invention prepares Sorafenib Tosylate polymorphic K, easy to operate, it is not necessary that inertia is added
Solvent, solvent usage amount is few, easy to industrialized production.
2. preparing Sorafenib Tosylate polymorphic K purity is high using technical solution of the present invention and yield being not less than
90%.
3. using the resulting crystal form K product cut size of technical solution of the present invention be significantly lower than original crystal form A and crystal form B, crystal form A
Diameter be 86.254 μm, crystal form B partial size be 56.983 μm, crystal form K partial size be 1.325 μm, improve crystal form K preparation feasibility and
Medication performance.
Detailed description of the invention
Fig. 1 is the XPRD figure of Sorafenib Tosylate crystal form A, crystal form B and 1 crystal form K of embodiment.
Fig. 2 is the SEM figure of Sorafenib Tosylate crystal form A, crystal form B and 2 crystal form K of embodiment.
Fig. 3 is the particle size distribution figure of Sorafenib Tosylate crystal form A, crystal form B and 2 crystal form K of embodiment.
Specific embodiment
In order to make the foregoing objectives, features and advantages of the present invention clearer and more comprehensible, right combined with specific embodiments below
A specific embodiment of the invention is described in detail.
In the following description, numerous specific details are set forth in order to facilitate a full understanding of the present invention, but the present invention can be with
Implemented using other than the one described here other way, those skilled in the art can be without prejudice to intension of the present invention
In the case of do similar popularization, therefore the present invention is not limited by the specific embodiments disclosed below.
The completion process of laboratory stage setting of the present invention are as follows:
1, Sorafenib Tosylate mixing crystal form solution is prepared, it is more than weighing Sorafenib Tosylate by certain mass
Crystal form A and polymorph b, 50~70Hz ultrasound, 5~10min is dissolved in two kinds of in the mixed solvents at room temperature.
2, it checks the air-tightness of entire experimental system, opens low temperature thermostat bath, start CO2The heating control of storage tank and crystallization kettle
Device processed, set temperature preheating.
3, after the completion of preheating, CO is opened2CO at the top of steel gas cylinder and crystallization kettle2Intake valve, CO2Cool down through low temperature thermostat bath,
Air accumulator, CO are entered by air pressure pump compression simultaneously2Enter crystallization kettle from kettle top after preheating in air accumulator, opens simultaneously
CO2Air outlet valve adjusts reset valve, with bottle pressure except 8~15min of air in kettle.
4, CO is closed2Air outlet valve sets CO2Pressure in storage tank and crystallization kettle, CO2Enter crystallization kettle, pressure in kettle through nozzle
Constantly it is increased to preset pressure.
5, after pressure and temperature is stablized, liquid pump is opened, by the Sorafenib Tosylate mixed crystal solution prepared in 1 to set
Flow velocity be delivered in crystallization kettle through nozzle.Solution sample introduction finishes, and stops liquid pump, maintains pressure 30min~90min in kettle, into
One step excludes residual organic solvent in crystallization kettle.CO2 intake valve is closed, decompression is down to atmospheric pressure to pressure, is taken out in crystallization kettle
Sample carries out next step detection and cleans whole system.
Embodiment 1
Accurate weighing Sorafenib Tosylate crystal form A and each 100mg of crystal form B respectively, ultrasound 15min is complete under 70Hz
It is dissolved in 20mL mixed solvent (dimethyl sulfoxide: ethyl alcohol volume=1: 4 (V/V))；It checks super-critical crystallization device air-tightness, opens
Low temperature thermostat bath starts CO2The heating controller of storage tank and crystallization kettle sets 35 DEG C of preheating 40min of crystallization temperature；Preheating is completed
Afterwards, CO is opened2CO at the top of steel gas cylinder and crystallization kettle2Intake valve, CO2Enter crystallization kettle from kettle top, opens simultaneously CO2Air outlet valve,
Reset valve is adjusted, with bottle pressure except air 15 minutes in kettle；Close CO2Air outlet valve boosts to the crystallization pressure 12MPa of setting；
After temperature and pressure is stablized, CO2It is passed through crystallization kettle with 3L/min rate, liquid pump is by prepared mixed crystal solution with 0.6mL/
Min sprays into crystallization kettle by nozzle, opens CO2Air outlet valve and reset valve, maintain crystallization kettle in pressure in 12MPa；To solution into
Stop liquid pump after sample, maintains CO2Flow keeps pressure 40min in 5L/min, removes residual solvent；Close CO2Intake valve,
Start to be depressured, pressure is reduced to zero in kettle to be crystallized, opens crystallization kettle and collects sample.
X-ray powder diffraction (XPRD) detection, radiation are carried out to the Sorafenib Tosylate crystal that embodiment 1 obtains
Source is copper target, and XPRD map is as shown in Fig. 1, the results showed that the crystallite be crystal form K, 2 angles θ be 4.34,11.01,13.13,
14.70, there is at 16.59,17.79,19.33,20.39,20.75,21.43,22.81 characteristic diffraction peak.
Embodiment 2
Accurate weighing Sorafenib Tosylate crystal form A and each 100mg of crystal form B respectively, ultrasound 20min is complete under 70Hz
It is dissolved in 20ml mixed solvent (dimethyl sulfoxide: ethyl alcohol volume=1: 9 (V/V))；It checks super-critical crystallization device air-tightness, opens
Low temperature thermostat bath starts CO2The heating controller of storage tank and crystallization kettle sets 37 DEG C of preheating 40min of crystallization temperature；Preheating is completed
Afterwards, CO is opened2CO at the top of steel gas cylinder and crystallization kettle2Intake valve, CO2Enter crystallization kettle from kettle top, opens simultaneously CO2Air outlet valve,
Reset valve is adjusted, with bottle pressure except air 15 minutes in kettle；Close CO2Air outlet valve boosts to the crystallization pressure 10MPa of setting；
After temperature and pressure is stablized, CO2It is passed through crystallization kettle with 3L/min rate, liquid pump is by prepared mixed crystal solution with 0.6mL/
Min sprays into crystallization kettle by nozzle, opens CO2Air outlet valve and reset valve, maintain crystallization kettle in pressure in 10MPa；To solution into
Stop liquid pump after sample, maintains CO2Flow keeps pressure 40min in 5L/min, removes residual solvent；Close CO2Intake valve,
Start to be depressured, pressure is reduced to zero in kettle to be crystallized, opens crystallization kettle and collects sample.
Electronic Speculum (SEM) characterization is scanned to the Sorafenib Tosylate crystal that embodiment 2 obtains, as a result such as attached drawing 2
It is shown, the results showed that crystal form K is flake.Malvern granularity is used to the Sorafenib Tosylate crystal that embodiment 2 obtains
Analyzer is analyzed, and as a result as shown in Fig. 3, partial size D (50) is shown as 1.865 μm, and partial size more former crystal form A and crystal form B is aobvious
Writing reduces, and is conducive to the preparation feasibility and medication performance that improve crystal form K.
Embodiment 3
Accurate weighing Sorafenib Tosylate crystal form A 140mg, crystal form B 60mg respectively, the ultrasound 20min under 70Hz
It is completely dissolved in 20mL mixed solvent (dimethyl sulfoxide: ethyl alcohol volume=1: 9 (V/V))；Check super-critical crystallization device air-tightness,
Low temperature thermostat bath is opened, CO is started2The heating controller of storage tank and crystallization kettle sets 33 DEG C of preheating 40min of crystallization temperature；Preheating
After the completion, CO is opened2CO at the top of steel gas cylinder and crystallization kettle2Intake valve, CO2Enter crystallization kettle from kettle top, opens simultaneously CO2Out
Air valve adjusts reset valve, with bottle pressure except air 15 minutes in kettle；Close CO2Air outlet valve boosts to the crystallization pressure of setting
10MPa；After temperature and pressure is stablized, CO2Be passed through crystallization kettle with 3L/min rate, liquid pump by prepared mixed crystal solution with
0.8mL/min sprays into crystallization kettle by nozzle, opens CO2Air outlet valve and reset valve, maintain crystallization kettle in pressure in 10MPa；To
Stop liquid pump after solution sample introduction, maintains CO2Flow keeps pressure 40min in 5L/min, removes residual solvent；Close CO2
Intake valve starts to be depressured, and pressure is reduced to zero in kettle to be crystallized, opens crystallization kettle and collects sample.
Fig. 2 and Fig. 3 shows the Sorafenib Tosylate polymorphic K particle prepared based on supercritical anti-solvent technology
Partial size is greatly reduced.Compared with original polymorphic K preparation method, supercritical anti-solvent technology of the present invention can be further realized
The process of transformation of crystal and micronized significantly simplifies production process, and easy to operate, mild condition, solvent usage amount is few, especially
The partial size of crystal form K is greatly reduced, so that Sorafenib Tosylate crystal form K, in preparation, feasibility increases, and reducing partial size can
It is water-soluble to improve drug, which has a good application prospect in terms of studying drug novel crystal forms and reducing.
Claims (5)
1. a kind of method for preparing Sorafenib Tosylate polymorphic K particle based on supercritical anti-solvent technology, the toluene
X-ray powder diffraction (XPRD) map of sulfonic acid Sorafenib polymorphic K, which is shown, has following 2 θ value diffraction maximum: 4.34 °,
11.01 °, 13.13 °, 14.70 °, 16.59 °, 17.79 °, 19.33 °, 20.39 °, 20.75 °, 21.43 °, 22.81 °, feature
It is, the preparation method includes the following steps:
Prepare Sorafenib Tosylate mixing crystal form solution: by Sorafenib Tosylate polymorphic A and polymorph b by certain
Mass ratio is added in organic solvent, Sorafenib Tosylate mixing crystal form solution is obtained after ultrasonic treatment, described is organic
Solvent is the mixture of dimethyl sulfoxide and ethyl alcohol, and the volume ratio of dimethyl sulfoxide and ethyl alcohol is 1: 1~10；
Pre- thermal exhaust: setting crystallization apparatus temperature empties air in crystallization apparatus after preheating 30~50min, and then boosting is stablized
To 8~14MPa, described sets crystallization apparatus temperature as 32~38 DEG C；
It is mixed with: by Sorafenib Tosylate mixing crystal form solution and CO2Be passed through crystallization apparatus, after reaction with 6~
8L/min continues to be passed through CO2, release after 0.5~1.5h collects Sorafenib Tosylate polymorphic K particle；
The XPRD figure of the Sorafenib Tosylate polymorphic A, polymorph b are substantially as shown in Fig. 1.
2. the side of Sorafenib Tosylate polymorphic K particle is prepared based on supercritical anti-solvent technology as described in claim 1
Method, it is characterised in that: the mass ratio of the Sorafenib Tosylate polymorphic A and polymorph b are as follows: 1: 10~0.1.
3. the side of Sorafenib Tosylate polymorphic K particle is prepared based on supercritical anti-solvent technology as described in claim 1
Method, it is characterised in that: the Sorafenib Tosylate mixed crystal solution concentration is 4~12mg/mL.
4. the side of Sorafenib Tosylate polymorphic K particle is prepared based on supercritical anti-solvent technology as described in claim 1
Method, it is characterised in that: the ultrasonic treatment is 15~20min of ultrasonic treatment at 50~70Hz.
5. the side of Sorafenib Tosylate polymorphic K particle is prepared based on supercritical anti-solvent technology as described in claim 1
Method, it is characterised in that: described to be mixed with, wherein the CO2It is passed through crystallization apparatus, being passed through flow velocity is 3~5L/min.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710420640.1A CN107011262B (en) | 2017-06-01 | 2017-06-01 | A method of Sorafenib Tosylate polymorphic K particle is prepared based on supercritical anti-solvent technology |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710420640.1A CN107011262B (en) | 2017-06-01 | 2017-06-01 | A method of Sorafenib Tosylate polymorphic K particle is prepared based on supercritical anti-solvent technology |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107011262A CN107011262A (en) | 2017-08-04 |
| CN107011262B true CN107011262B (en) | 2019-10-29 |
Family
ID=59452147
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710420640.1A Active CN107011262B (en) | 2017-06-01 | 2017-06-01 | A method of Sorafenib Tosylate polymorphic K particle is prepared based on supercritical anti-solvent technology |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107011262B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104159574A (en) * | 2012-01-13 | 2014-11-19 | X喷雾微粒公司 | A method for producing stable, amorphous hybrid nanoparticles comprising at least one protein kinase inhibitor and at least one polymeric stabilizing and matrix- forming component |
| CN105439947A (en) * | 2014-12-01 | 2016-03-30 | 石药集团中奇制药技术（石家庄）有限公司 | Novel crystal form of sorafenib tosylate and preparation method for novel crystal form |
| CN106491536A (en) * | 2016-10-20 | 2017-03-15 | 中国药科大学 | One kind utilizes supercritical CO2Prepare the method and system of Gefitinib ultrafine dust |
-
2017
- 2017-06-01 CN CN201710420640.1A patent/CN107011262B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104159574A (en) * | 2012-01-13 | 2014-11-19 | X喷雾微粒公司 | A method for producing stable, amorphous hybrid nanoparticles comprising at least one protein kinase inhibitor and at least one polymeric stabilizing and matrix- forming component |
| CN105439947A (en) * | 2014-12-01 | 2016-03-30 | 石药集团中奇制药技术（石家庄）有限公司 | Novel crystal form of sorafenib tosylate and preparation method for novel crystal form |
| CN106491536A (en) * | 2016-10-20 | 2017-03-15 | 中国药科大学 | One kind utilizes supercritical CO2Prepare the method and system of Gefitinib ultrafine dust |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107011262A (en) | 2017-08-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Zhang et al. | Micronization of atorvastatin calcium by antisolvent precipitation process | |
| CN105461647B (en) | Valsartan sand library is than solid-state form of bent trisodium salt composite and its preparation method and application | |
| TWI711626B (en) | New specific crystal form of dapagliflozin and preparation method thereof | |
| Kalogiannis et al. | Production of amoxicillin microparticles by supercritical antisolvent precipitation | |
| Uchida et al. | Production of theophylline nanoparticles using rapid expansion of supercritical solutions with a solid cosolvent (RESS-SC) technique | |
| JP2004528899A5 (en) | ||
| JP2006517465A (en) | Particle formation method | |
| CN107011262B (en) | A method of Sorafenib Tosylate polymorphic K particle is prepared based on supercritical anti-solvent technology | |
| Liu et al. | Development of nimesulide amorphous solid dispersions via supercritical anti-solvent process for dissolution enhancement | |
| CN106008529A (en) | Ibrutinib solvate and preparation method thereof | |
| Guo et al. | Enabling the drug combination of celecoxib through a spherical co-agglomeration strategy with controllable and stable drug content and good powder properties | |
| CN104586770A (en) | Hot-melt extrusion preparation of pazopanib hydrochloride and preparation method of hot-melt extrusion preparation | |
| CN112500385B (en) | Method for preparing diosmetin derivative ultrafine particles | |
| CN106512737B (en) | Particle controllable method for preparing and device based on the continuous anti-solvent film dialysis process of ultrasonic wave added | |
| Kudryashova et al. | Micronization of levofloxacin by supercritical antisolvent precipitation | |
| CN1612780A (en) | Method for the production of particles | |
| CN113941317B (en) | SiO (silicon dioxide) 2 Preparation and application of @ Uio-66 solid-phase extraction column | |
| CN106083958B (en) | Tylonolide cyclohexane solvent compound and preparation method | |
| CN105696066A (en) | Method for preparing eutectic by sheeting process | |
| CN110002498A (en) | A kind of porous nano V2O5Preparation method | |
| CN106966941B (en) | The method that overcritical compression Anti-solvent Precipitation prepares ezetimibe ultrafine dust | |
| JP7481259B2 (en) | Spray drying process with continuous adjustment of the spray solution | |
| CN106008629B (en) | Tylonolide 1,4- dioxane solvent compound and preparation method | |
| Tenorio et al. | Supercritical antisolvent process applied to the pharmaceutical industry | |
| Calvignac et al. | The impinging jets technology: A contacting device using a SAS process type |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20211108 Address after: 214181 Qian Zhou Jie Dao Fu Zhou Cun, Huishan District, Wuxi City, Jiangsu Province Patentee after: Wuxi Hecheng Textile Co.,Ltd. Address before: No. 639 Jiangning longmian Road District of Nanjing City, Jiangsu province 211198 Patentee before: CHINA PHARMACEUTICAL University |
|
| TR01 | Transfer of patent right |