CN106606419A - Method for preparing indissolvable drug nanodispersion by applying micro-channel technology - Google Patents
Method for preparing indissolvable drug nanodispersion by applying micro-channel technology Download PDFInfo
- Publication number
- CN106606419A CN106606419A CN201510701342.0A CN201510701342A CN106606419A CN 106606419 A CN106606419 A CN 106606419A CN 201510701342 A CN201510701342 A CN 201510701342A CN 106606419 A CN106606419 A CN 106606419A
- Authority
- CN
- China
- Prior art keywords
- insoluble drug
- microchannel
- micro passage
- passage reaction
- nano
- 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.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
- A61J3/02—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of powders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a method for preparing an indissolvable drug nanodispersion by applying a micro-channel technology. The method comprises the steps of injecting an indissolvable drug solution and an auxiliary material aqueous solution into a micro-channel reactor for performing mixing to obtain suspension. The indissolvable drug nanodispersion is prepared by applying the micro-channel technology through optimization of process parameters; the average particle size is 30-80nm; the PDI value is 0.15-0.21; the particle size is small and the particle size distribution is relatively narrow; the preparation can be finished instantly; and the batch processing amount is not limited and can be increased on a large scale. After the nanodispersion is stored for two weeks at the room temperature, the average particle size is basically kept unchanged and good stability is displayed.
Description
Technical field
The present invention relates to pharmaceutical formulating art.Hardly possible is prepared more particularly, to a kind of using microchannel
The method of soluble drug Nanodispersion.
Background technology
According to statistics, the medicine that 70% is there are about at present has that water-soluble is poor, and this big class medicine is normal
Often it is difficult to reach the expected desired bioavailability for the treatment of after oral administration, therefore, largely limit
The application of such medicine.The dissolubility and bioavailability for improving insoluble drug is always study of pharmacy
Emphasis and focus.Although medicine can be improved by being prepared into the methods such as liposome, cyclodextrin clathrate
Dissolubility, but, still there are problems that low drug loading, complicated process of preparation,.
Research shows, for insoluble drug, process in leaching be restrict its bioavailability key because
Element.By Noyes-Whitney equation：
For dissolution velocity；
kDFor dissolution velocity Changshu；
A is surface area；
CsFor medicine saturation solubility；
CtFor drug level.
Understand, drug-eluting speed and drug particles specific surface area are proportional, and specific surface area can pass through
Reduce grain diameter to increase.Therefore, by reducing drug particles particle diameter, so as to improve insoluble drug
Dissolution velocity, and then the bioavailability of such medicine is increased.Particularly nano-dispersed
Body, overcoming conventional formulation needs first to dissolve the shortcoming of medicine, also, with drug loading it is big, can be direct
Oral the advantages of so that it is improving drug bioavailability, increases medicine stability and drug effect aspect is received
To increasing concern.Patent CN101322682A discloses a kind of based on high pressure homogenization method
The method for preparing Nano medication dispersion；Patent CN101106451A report one kind report it is a kind of quiet
The preparation method of arteries and veins Emulsion, gained particle size distribution is wider, between 100-500nm；United States Patent (USP)
2006/0280786 A1 adopts microemulsion method, and supercritical fluid method prepares submicron particle, and then obtains
Receive fine dispersion.By said method, medicine can be prepared and receive fine dispersion, meanwhile, medicine it is molten
Go out speed and also obtain certain raising.But, all be present complicated process of preparation in these methods, produce into
The shortcomings of this is high, more importantly, grain diameter prepared by these methods is big, skewness.In addition,
Because Nano medication granule has great specific surface area and higher surface energy, medicine prepared by said method
Composition granule is easily reunited in liquid phase medium, resulting Nanodispersion less stable.
Therefore, how with economy, efficiently method prepares that dispersive property is excellent, and nanometer stable in properties
Pharmaceutical dispersions become highly important study hotspot.
The content of the invention
It is an object of the present invention to provide one kind application microchannel prepares insoluble drug nanometer point
The method of a prose style free from parallelism.Contacted in micro passage reaction with the aqueous solution containing pharmaceutic adjuvant by drug solution,
The nano pulp for obtaining is carried out to be spray-dried prepared dry powder, dry powder to be met and can automatically form a nanometer medicine after water
Thing dispersion, so as to significantly improve drug-eluting speed and curative effect.
Further object is that provide a kind of insoluble drug of employing microchannel preparation receiving
Rice dispersion.
Research and analysis show that its internal micro structure causes microreactor equipment due to micro passage reaction
With great specific surface area, so it has fabulous mass transfer ability, it is possible to achieve the moment of material is equal
Even mixing, therefore its Determining Micromixing Characteristic Time is less than 0.1ms, is conducive to the quick formation of nucleus.With microchannel
Reactor is compared, and in traditional stirred-tank reactor, due to being unable to Quick uniform mixing, causes local mistake
Saturation is excessive, has a strong impact on nucleation process, causes nucleation uneven so that prepare granularity during granule
Skewness and batch reproducibility are poor.
Microchannel of the prior art is mainly used in heat exchange, organic synthesiss, separation process field,
And the method that current Nano medication preparation field is mainly adopted is for mechanical agitation, magnetic agitation, high-speed stirring
Mix, it is present, and local degree of supersaturation is excessive, and nucleation heterogeneity, crystal growth is uneven, and particle diameter is larger,
After dispersion easily reunite etc. shortcomings.There is presently no people and microchannel is expanded to into Nano medication system
Standby field, since it is desired that consider how to ensure that nucleation is homogeneous, crystal growth is uniform, products obtained therefrom particle diameter compared with
The a series of problem such as little.It is hydrophobic when granule is less than 100nm for Nano medication dispersion
Property colloid solution.The hydrophobic colloid solution appearance is transparent, there is obvious Tyndall phenomenon, and category thermodynamics are steady
Determine system, the long duration can be kept and will not be precipitated.So if the tune for passing through technological parameter
Become, overcome local degree of supersaturation excessive, nucleation heterogeneity, a series of problem such as crystal growth is uneven,
Microchannel is applied to prepare insoluble drug Nanodispersion, gained insoluble drug nanometer is prepared
Dispersion particle diameters are little, and narrow diameter distribution, good stability, dissolution rate are big, bioavailability is high.And because
Micro passage reaction equipment size is little, easy to operate, enlarge-effect is less, before wide development
Scape.
To reach above-mentioned first purpose, the present invention adopts following technical proposals：
A kind of method that application microchannel prepares insoluble drug Nanodispersion, methods described includes
To carry out being mixed to get suspension in insoluble drug solution and adjuvant aqueous solution injection micro passage reaction
Step.
Preferably, the insoluble drug solution is 1-5mL/min to injection rate in micro passage reaction；
The adjuvant aqueous solution to injection rate in micro passage reaction is 5-80mL/min.Choose this be preferably because
For, it is ensured that two streams can flow and can be completely filled with passage；If do not done this preferably, then
It cannot be guaranteed that two strands of materials are completely filled with passage.
It is highly preferred that the insoluble drug solution is 2-4 to injection rate in micro passage reaction
mL/min；The adjuvant aqueous solution to injection rate in micro passage reaction is 30-70mL/min.If not
Do this preferably, due to undercompounding in two strands of materials, cause local concentration excessive, have a strong impact on microcosmic
Mixing efficiency.
Preferably, the insoluble drug solution for injecting in micro passage reaction and the volume ratio of adjuvant aqueous solution
For 1:15-35.If both mixed proportion is not in this scope, adjuvant can not effective control medicine
Little particle grows.
Preferably, the concentration of the insoluble drug solution for injecting in micro passage reaction is 15-45mg/mL；
The concentration of the adjuvant aqueous solution in injection micro passage reaction is 2-20mg/mL.The concentration range can be true
Protect in product that medicine effective content will not be too low, and ensure that and efficiently controlled in the presence of adjuvant
The growth of small drug particles.
Preferably, the insoluble drug includes but is not limited to silibinin, resveratrol or fenofibrate
Deng.
Preferably, the adjuvant includes surfactant and cosurfactant；The cosurfactant
It is 1 with surfactant qualities ratio:20-200；The surfactant be Polyethylene Glycol, poloxamer,
In polyvinylpyrrolidone, hydroxypropyl methyl cellulose, Lactose, shitosan, Mannitol and cyclodextrin
One or more；The cosurfactant be potassium stearate, sodium stearate, sodium lauryl sulphate,
One or more in dodecylbenzene sodium sulfonate and Stepanol MG.Make this preferably main consideration table
The model of action of face activating agent and medicine, if do not done this preferably, surfactant can not hinder medicine brilliant
The growth of body, causes crystal growth uncontrollable.
Preferably, the solvent in the insoluble drug solution be methanol, ethanol, propanol, isopropanol,
One or more in acetone, DMF, dimethyl sulfoxide and N-Methyl pyrrolidone.
This preferably main consideration medicine dissolubility in a solvent and the impact in following spray-drying process are done,
If do not done this preferably, medicine can be caused to be completely dissolved with solvent, due to the temperature difference of local, very may be used
Medicine dissolubility in a solvent can be caused to change.
Preferably, the method that the application microchannel prepares slightly solubility Nano medication dispersion, including
Following steps：
1) insoluble drug solution and adjuvant aqueous solution are configured；
2) insoluble drug solution is mixed with adjuvant aqueous solution injection micro passage reaction, is obtained
Suspension；
3) suspension is carried out into spray drying treatment, obtains insoluble drug composite powder；
4) by step 3) in gained composite powder is soluble in water that Nano medication dispersion is obtained.
Preferably, the condition of spray drying treatment be inlet temperature 120-160 DEG C, outlet temperature 60-80 DEG C,
Charging rate 10-40mL/min, compressed air pressure 0.5-0.7Mpa.Spray-drying process, predominantly goes
Except organic solvent and water, so as to obtain dry composite powder.If do not selected this preferably, powder can be caused
Humidity is too high, so as to glue wall, not easily collecting；If heightening spray drying temperature, being spray-dried air pressure,
Potential safety hazard is easily caused, and improves preparation cost.
To reach above-mentioned second purpose, the present invention adopts following technical proposals：
Prepared using the method for preparing insoluble drug Nanodispersion using microchannel as above
The medicament nano dispersion for obtaining, in the Nanodispersion particle diameter of medicine be 30-80nm, PDI values
For 0.15-0.21.
Existing microchannel is mainly used in heat transfer process, organic synthesiss process, and microchannel is applied to
Prodrug is prepared and not referred to.And the present invention is by the optimization to technological parameter, prior art (machine is overcome
Tool stirring, magnetic agitation etc.) it is uneven in the local concentration of prodrug preparation field presence, nucleation is uneven,
The uncontrollable shortcoming and defect of granule, is successfully applied to the preparation of slightly solubility Nano medication dispersion
Field, and achieve good Nano medication preparation effect.The applicant's research discovery, insoluble drug
Solution and adjuvant aqueous solution inject speed, concentration and the ratio of micro passage reaction and influence whether finally
The particle diameter distribution and result of extraction of Nano medication.Compared to preparing a nanometer medicine by the way of normal agitation
Composition granule, traditional alr mode time length, prepare particle diameter distribution heterogeneity and batch processed amount cannot be big
The raising of scale.The present invention is prepared by the improvement to charge ratio, inlet amount etc. using microchannel
Go out insoluble drug Nanodispersion, mean diameter in 30-80nm, grain diameter is little, particle diameter distribution compared with
It is narrow, PDI values be 0.15-0.21, and moment complete, batch processed amount is unrestricted, can be large-scale
Improve.After two weeks are placed under dispersions obtained room temperature, mean diameter is held essentially constant, and shows good
Stability.
Beneficial effects of the present invention are as follows：
The Nano medication granule application micro passage reaction of the present invention is prepared, micro passage reaction
Equipment has great specific surface area, with fabulous mass transfer ability, it is possible to achieve the moment of material is uniform
Mixing.Therefore its Determining Micromixing Characteristic Time is less than 0.1ms, is conducive to the quick formation of nucleus.By drug solution
With the aqueous solution containing stabilizer Jing after micro passage reaction mixes, you can obtain Nano medication slurry.If
Standby size is little, operation is simple, enlarge-effect is less.
Nano pulp is spray-dried, the dry powder that can be just readily transported and be stored.From slurry to
The whole preparation process of dry powder can be carried out continuously, it is easy to amplify and large-scale production.Spray powder meets meeting after water
Nanodispersion is automatically formed, grain diameter is little, particle diameter distribution is narrower.After two weeks are placed under room temperature, put down
Particle diameter is held essentially constant, and shows good stability.
The composition of the insoluble drug Nanodispersion of the present invention is fairly simple, and stabilizer is conventional medicinal
Adjuvant；Result of extraction is excellent compared with crude drug；Spray powder except redispersible into Nanodispersion in addition to,
Also can be widely used to Nano medication solid preparation, such as tablet, capsule and granule.
Description of the drawings
The specific embodiment of the present invention is described in further detail below in conjunction with the accompanying drawings.
Fig. 1 for embodiment 2 resveratrol nanoscale dispersoid in granule grain size distribution.
Fig. 2 is the resveratrol nanoscale dispersoid material object schematic diagram of embodiment 2.
Fig. 3 is the resveratrol nanoscale dispersoid of embodiment 3 and the stripping curve of resveratrol crude drug
Comparison diagram.
Fig. 4 is the silybin nanostructured dispersion of embodiment 5 and the stripping curve of silibinin crude drug
Comparison diagram.
Fig. 5 for embodiment 6 silybin nanostructured dispersion in granule grain size distribution.
Fig. 6 is the silybin nanostructured dispersion material object schematic diagram of embodiment 6.
Specific embodiment
In order to be illustrated more clearly that the present invention, the present invention is done into one with reference to preferred embodiments and drawings
The explanation of step.Similar part is indicated with identical reference in accompanying drawing.Those skilled in the art
It should be appreciated that following specifically described content is illustrative and be not restrictive, should not be limited with this
Protection scope of the present invention.
Embodiment 1
A：Weigh 300mg resveratrol crude drug to be dissolved in 20mL ethanol；
B：Weigh 750mg polyvinylpyrrolidones and be dissolved in 300mL water with 7.5mg sodium lauryl sulphates
In；
C：The raw material medicine solution prepared in step A and step B aqueous solution are injected in micro passage reaction,
It is 2mL/min, 30mL/min to adjust flow velocity, and in micro passage reaction outlet product is collected, and obtains white Herba chenopodii
Reed alcohol nano pulp；
D：Control spray dryer, inlet temperature is 125 DEG C, and outlet temperature is 60 DEG C, and charging rate is
15mL/min, compressed air pressure is 0.6MPa, and resveratrol nano pulp is spray-dried, and obtains white
Veratryl alcohol drug composite powder.
F：40mg resveratrol medicament composite granules are dissolved in 10mL water, you can clarified, thoroughly
Bright Nano medication dispersion.The mean diameter for determining granule in dispersion is 57nm, and PDI values are
0.204。
Comparative example 1
A：Weigh 300mg resveratrol crude drug to be dissolved in 20mL ethanol；
B：Weigh 750mg polyvinylpyrrolidones and be dissolved in 300mL water with 7.5mg sodium lauryl sulphates
In；
C：The raw material medicine solution prepared in step A and step B aqueous solution are added in beaker, regulation is stirred
It is 200r/min to mix speed, after stirring 12 hours, obtains resveratrol nano pulp；
D：Control spray dryer, inlet temperature is 125 DEG C, and outlet temperature is 60 DEG C, and charging rate is
15mL/min, compressed air pressure is 0.6MPa, and resveratrol nano pulp is spray-dried, and obtains white
Veratryl alcohol drug composite powder.
F：40mg resveratrol medicament composite granules are dissolved in 10mL water, Nano medication dispersion is obtained
Body, measure mean diameter is 150nm, and PDI values are 0.351.
Embodiment 2
A：Weigh 500mg resveratrol crude drug to be dissolved in 20mL acetone；
B：Weigh 500mg poloxamers to be dissolved in 200mL water with 30mg dodecylbenzene sodium sulfonate；
C：The raw material medicine solution prepared in step A and step B aqueous solution are injected in micro passage reaction,
It is 5mL/min, 75mL/min to adjust flow velocity, and in micro passage reaction outlet product is collected, and obtains white Herba chenopodii
Reed alcohol nano pulp；
D：Control spray dryer, inlet temperature is 140 DEG C, and outlet temperature is 85 DEG C, and charging rate is
35mL/min, compressed air pressure is 0.55MPa, and resveratrol nano pulp is spray-dried, and is obtained
Resveratrol medicament composite granule.
F：60mg resveratrol medicament composite granules are dissolved in 20mL water, you can clarified, thoroughly
Bright Nano medication dispersion.
Fig. 1 is the grain size distribution of granule in resveratrol nanoscale dispersoid manufactured in the present embodiment.From figure
In as can be seen that dispersion mean diameter be 31nm, PDI values be 0.201.
Fig. 2 is resveratrol nanoscale dispersoid manufactured in the present embodiment material object schematic diagram.Can see in logical figure
Go out, it is dispersions obtained for clarification, transparent Nano medication dispersion.
Comparative example 2
A：Weigh 500mg resveratrol crude drug to be dissolved in 20mL acetone；
B：Weigh 500mg poloxamers to be dissolved in 200mL water with 30mg dodecylbenzene sodium sulfonate；
C：The raw material medicine solution prepared in step A and step B aqueous solution are added in three-neck flask, is adjusted
Section mixing speed is 500r/min, after stirring 10 hours, obtains resveratrol nano pulp；
D：Control spray dryer, inlet temperature is 140 DEG C, and outlet temperature is 85 DEG C, and charging rate is
35mL/min, compressed air pressure is 0.55MPa, and resveratrol nano pulp is spray-dried, and is obtained
Resveratrol medicament composite granule.
F：60mg resveratrol medicament composite granules are dissolved in 20mL water, you can clarified, thoroughly
Bright Nano medication dispersion.The mean particle size determined in the dispersion is 130nm, and PDI values are
0.312。
Embodiment 3
A：Weigh 600mg resveratrol crude drug to be dissolved in 20mL glycerol；
B：Weigh 1000mg cyclodextrin to be dissolved in 400mL water with 5mg Stepanol MGs；
C：The raw material medicine solution prepared in step A and step B aqueous solution are injected in micro passage reaction,
It is 3mL/min, 60mL/min to adjust flow velocity, and in micro passage reaction outlet product is collected, and obtains white Herba chenopodii
Reed alcohol nano pulp；
D：Control spray dryer, inlet temperature is 132 DEG C, and outlet temperature is 70 DEG C, and charging rate is
25mL/min, compressed air pressure is 0.7MPa, and resveratrol nano pulp is spray-dried, and obtains white
Veratryl alcohol drug composite powder.
F：54mg resveratrol medicament composite granules are dissolved in 15mL water, you can clarified, thoroughly
Bright Nano medication dispersion.The mean diameter for determining granule in dispersion is 59nm, and PDI values are 0.186.
Its resveratrol composite powder is shown in Fig. 2 with the stripping curve comparison diagram of resveratrol crude drug, from figure
Can show that Nanodispersion dissolution rate is most fast, it is i.e. leachable complete in about 20min.
Comparative example 3
A：Weigh 600mg resveratrol crude drug to be dissolved in 20mL glycerol；
B：Weigh 1000mg cyclodextrin to be dissolved in 400mL water with 5mg Stepanol MGs；
C：The raw material medicine solution prepared in step A and step B aqueous solution are added in three-neck flask, is adjusted
Section mixing speed is 1000r/min, after stirring 10 hours, obtains resveratrol nano pulp；
D：Control spray dryer, inlet temperature is 132 DEG C, and outlet temperature is 70 DEG C, and charging rate is
25mL/min, compressed air pressure is 0.7MPa, and resveratrol nano pulp is spray-dried, and obtains white
Veratryl alcohol drug composite powder.
F：54mg resveratrol medicament composite granules are dissolved in 15mL water, you can clarified, thoroughly
Bright Nano medication dispersion.The mean diameter for determining granule in dispersion is 113nm, and PDI values are
0.267。
Embodiment 4
A：Weigh 1000mg resveratrol crude drug to be dissolved in 50mL propanol；
B：Weigh 1000mg hydroxymethyl-propyl celluloses and be dissolved in 400mL with 50mg Potassium dodecylbenzenesulfonates
In water；
C：The raw material medicine solution prepared in step A and step B aqueous solution are injected in micro passage reaction,
It is 4mL/min, 80mL/min to adjust flow velocity, and in micro passage reaction outlet product is collected, and obtains white Herba chenopodii
Reed alcohol nano pulp；
D：Control spray dryer, inlet temperature is 155 DEG C, and outlet temperature is 60 DEG C, and charging rate is
30mL/min, compressed air pressure is 0.6MPa, and resveratrol nano pulp is spray-dried, and obtains white
Veratryl alcohol drug composite powder.
F：58mg resveratrol medicament composite granules are dissolved in 15mL water, you can clarified, thoroughly
Bright Nano medication dispersion.The mean diameter for determining granule in dispersion is 51nm, and PDI values are 0.182.
Embodiment 5
A：Weigh 400mg silibinin crude drug to be dissolved in 20mL ethanol；
B：Weigh 750mg polyvinylpyrrolidones and be dissolved in 100mL water with 30mg sodium lauryl sulphates
In；
C：The raw material medicine solution prepared in step A and step B aqueous solution are injected in micro passage reaction,
It is 2mL/min, 40mL/min to adjust flow velocity, and in micro passage reaction outlet product is collected, and obtains fine grinding
Ji guest's nano pulp；
D：Control spray dryer, inlet temperature is 145 DEG C, and outlet temperature is 70 DEG C, and charging rate is
35mL/min, compressed air pressure is 0.64MPa, and silybin nanostructured slurry is spray-dried, and is obtained
Silibinin drug composite powder.
F：50mg silibinin drug composite powders are dissolved in 10mL water, you can clarified, thoroughly
Bright Nano medication dispersion.The mean diameter for determining granule in dispersion is 75nm, and PDI values are 0.193.
The stripping curve comparison diagram of its silibinin composite powder and silibinin is shown in Fig. 4, can be with from figure
Show that Nanodispersion dissolution rate is most fast, it is i.e. leachable complete in about 20min.
Embodiment 6
A：Weigh 900mg silibinin crude drug to be dissolved in 30mL acetone；
B：Weigh 1500mg hydroxymethyl-propyl celluloses and be dissolved in 600mL with 50mg dodecylbenzene sodium sulfonate
In water；
C：The raw material medicine solution prepared in step A and step B aqueous solution are injected in micro passage reaction,
It is 4mL/min, 60mL/min to adjust flow velocity, and in micro passage reaction outlet product is collected, and obtains fine grinding
Ji guest's nano pulp；
D：Control spray dryer, inlet temperature is 136 DEG C, and outlet temperature is 63 DEG C, and charging rate is
13mL/min, compressed air pressure is 0.63MPa, and silybin nanostructured slurry is spray-dried, and is obtained
Silibinin drug composite powder.
F：70mg silibinin drug composite powders are dissolved in 7mL water, you can clarified, transparent
Nano medication dispersion.
Fig. 5 is the grain size distribution of granule in silybin nanostructured dispersion manufactured in the present embodiment.From figure
In as can be seen that dispersion mean diameter be 43nm, PDI values be 0.173.
Fig. 6 is silybin nanostructured dispersion material object schematic diagram manufactured in the present embodiment.Can see in logical figure
Go out, the dispersion is clarification, transparent Nano medication dispersion.
Embodiment 7
A：Weigh 1000mg silibinin crude drug to be dissolved in 30mL isopropanols；
B：Weigh 600mg Lactose to be dissolved in 300mL water with 90mg sodium stearates；
C：The raw material medicine solution prepared in step A and step B aqueous solution are injected in micro passage reaction,
It is 3mL/min, 45mL/min to adjust flow velocity, and in micro passage reaction outlet product is collected, and obtains fine grinding
Ji guest's nano pulp；
D：Control spray dryer, inlet temperature is 140 DEG C, and outlet temperature is 64 DEG C, and charging rate is
40mL/min, compressed air pressure is 0.67MPa, and silybin nanostructured slurry is spray-dried, and is obtained
Silibinin drug composite powder.
F：80mg silibinin drug composite powders are dissolved in 10mL water, you can clarified, thoroughly
Bright Nano medication dispersion.The mean diameter for determining granule in dispersion is 68nm, and PDI values are 0.206.
Embodiment 8
A：Weigh 800mg silibinin crude drug to be dissolved in 30mL n-butyl alcohol；
B：Weigh 800mg Mannitol to be dissolved in 200mL water with 10mg potassium stearates；
C：The raw material medicine solution prepared in step A and step B aqueous solution are injected separately into into microchannel plate should
In device, it is 3mL/min, 60mL/min to adjust flow velocity, and in micro passage reaction outlet product is collected, and is obtained
To silybin nanostructured slurry；
D：Control spray dryer, inlet temperature is 155 DEG C, and outlet temperature is 65 DEG C, and charging rate is
25mL/min, compressed air pressure is 0.64MPa, and silybin nanostructured slurry is spray-dried, and is obtained
Silibinin drug composite powder.
F：100mg silibinin drug composite powders are dissolved in 25mL water, you can clarified, thoroughly
Bright Nano medication dispersion.The mean diameter for determining granule in dispersion is 74nm, and PDI values are 0.184.
Embodiment 9
A：Weigh 450mg fenofibrate crude drug to be dissolved in 30mL methanol；
B：Weigh 1400mg hydroxymethyl-propyl celluloses to be dissolved in 700mL water with 35mg sodium stearates；
C：The raw material medicine solution prepared in step A and step B aqueous solution are injected in micro passage reaction,
It is 3mL/min, 63mL/min to adjust flow velocity, and in micro passage reaction outlet product is collected, and obtains non-promise
Shellfish spy's nano pulp；
D：Control spray dryer, inlet temperature is 152 DEG C, and outlet temperature is 61 DEG C, and charging rate is
24mL/min, compressed air pressure is 0.64MPa, and fenofibrate nanometer slurry is spray-dried, and is obtained
Fenofibrate Drug composite granule.
F：150mg fenofibrate Drug composite granules are dissolved in 100mL water, you can clarified,
Transparent Nano medication dispersion.The mean diameter for determining granule in dispersion is 54nm, and PDI values are
0.204。
Embodiment 10
A：Weigh 1000mg fenofibrate crude drug to be dissolved in 25mL dimethyl sulfoxide；
B：Weigh 800mg polypropylene milling amine to be dissolved in 200mL water with 25mg dodecylbenzene sodium sulfonate；
C：The raw material medicine solution prepared in step A and step B aqueous solution are injected in micro passage reaction,
It is 4mL/min, 72mL/min to adjust flow velocity, and in micro passage reaction outlet product is collected, and obtains non-promise
Shellfish spy's nano pulp；
D：Control spray dryer, inlet temperature is 147 DEG C, and outlet temperature is 64 DEG C, and charging rate is
35mL/min, compressed air pressure is 0.67MPa, and fenofibrate nanometer slurry is spray-dried, and is obtained
Fenofibrate Drug composite granule.
F：200mg fenofibrate Drug composite granules are dissolved in 100mL water, you can clarified,
Transparent Nano medication dispersion.The mean diameter for determining granule in dispersion is 49nm, and PDI values are
0.184。
Embodiment 11
A：Weigh 300mg fenofibrate crude drug to be dissolved in 10mL PEG400s；
B：Weigh 800mg Macrogol 4000s to be dissolved in 100mL water with 35mg sodium lauryl sulphates；
C：The raw material medicine solution prepared in step A and step B aqueous solution are injected in micro passage reaction,
It is 5mL/min, 75mL/min to adjust flow velocity, and in micro passage reaction outlet product is collected, and obtains non-promise
Shellfish spy's nano pulp；
D：Control spray dryer, inlet temperature is 140 DEG C, and outlet temperature is 75 DEG C, and charging rate is
20mL/min, compressed air pressure is 0.7MPa, and fenofibrate nanometer slurry is spray-dried, and obtains non-
Nobert drug composite powder.
F：50mg fenofibrate Drug composite granules are dissolved in 10mL water, you can clarified, thoroughly
Bright Nano medication dispersion.The mean diameter for determining granule in dispersion is 72nm, and PDI values are 0.194.
Embodiment 12
A：Weigh 300mg fenofibrate crude drug to be dissolved in 10mL ethanol；
B：Weigh 1200mg Macrogol 4000s and be dissolved in 300mL water with 50mg sodium lauryl sulphates
In；
C：The raw material medicine solution prepared in step A and step B aqueous solution are injected in micro passage reaction,
It is 3mL/min, 72mL/min to adjust flow velocity, and in micro passage reaction outlet product is collected, and obtains non-promise
Shellfish spy's nano pulp；
D：Control spray dryer, inlet temperature is 149 DEG C, and outlet temperature is 63 DEG C, and charging rate is
13mL/min, compressed air pressure is 0.54MPa, and fenofibrate nanometer slurry is spray-dried, and is obtained
Fenofibrate Drug composite granule.
F：90mg fenofibrate Drug composite granules are dissolved in 25mL water, you can clarified, thoroughly
Bright Nano medication dispersion.The mean diameter for determining granule in dispersion is 65nm, and PDI values are 0.156.
Obviously, the above embodiment of the present invention is only intended to clearly illustrate example of the present invention, and
It is not the restriction to embodiments of the present invention, for those of ordinary skill in the field,
Can also make other changes in different forms on the basis of described above, here cannot be to all
Embodiment be exhaustive, it is every to belong to the obvious change that technical scheme is extended out
Change or change the row still in protection scope of the present invention.
Claims (10)
1. a kind of method that application microchannel prepares insoluble drug Nanodispersion, it is characterised in that：
Methods described includes being mixed insoluble drug solution with adjuvant aqueous solution injection micro passage reaction
The step of obtaining suspension.
2. one kind according to claim 1 prepares insoluble drug nano-dispersed using microchannel
The method of body, it is characterised in that：The insoluble drug solution is to injection rate in micro passage reaction
1-5mL/min；The adjuvant aqueous solution to injection rate in micro passage reaction is 5-80mL/min.
3. one kind according to claim 1 prepares insoluble drug nano-dispersed using microchannel
The method of body, it is characterised in that：Preferably, the insoluble drug solution is noted into micro passage reaction
Enter speed for 2-4mL/min；The adjuvant aqueous solution to injection rate in micro passage reaction is 30-70
mL/min。
4. one kind according to claim 1 prepares insoluble drug nano-dispersed using microchannel
The method of body, it is characterised in that：Insoluble drug solution in injection micro passage reaction is water-soluble with adjuvant
The volume ratio of liquid is 1:15-35.
5. one kind according to claim 1 prepares insoluble drug nano-dispersed using microchannel
The method of body, it is characterised in that：The concentration of insoluble drug solution in injection micro passage reaction is
15-45mg/mL；The concentration of the adjuvant aqueous solution in injection micro passage reaction is 2-20mg/mL.
6. one kind according to claim 1 prepares insoluble drug nano-dispersed using microchannel
The method of body, it is characterised in that：The adjuvant includes surfactant and cosurfactant；It is described to help
Surfactant is 1 with surfactant qualities ratio:20-200；The surfactant be Polyethylene Glycol,
Poloxamer, polyvinylpyrrolidone, polyethylene oxide, polyacrylamide, hydroxypropyl methyl fiber
One or more in element, Lactose, shitosan, Mannitol and cyclodextrin；The cosurfactant is
Potassium stearate, sodium stearate, Oleic acid are received, sodium lauryl sulphate, dodecylbenzene sodium sulfonate and 12
One or more in alkylsurfuric acid magnesium.
7. one kind according to claim 1 prepares insoluble drug nano-dispersed using microchannel
The method of body, it is characterised in that：Solvent in the insoluble drug solution be methanol, ethanol, propanol,
Isopropanol, glycerol, n-butyl alcohol, acetone, tetrahydrofuran, DMF, dimethyl are sub-
One or more in sulfone and N-Methyl pyrrolidone.
8. one kind according to claim 1 prepares insoluble drug nano-dispersed using microchannel
The method of body, it is characterised in that comprise the steps：
1) insoluble drug solution and adjuvant aqueous solution are configured；
2) insoluble drug solution is mixed with adjuvant aqueous solution injection micro passage reaction, is obtained
Suspension；
3) suspension is carried out into spray drying treatment, obtains insoluble drug composite powder；
4) by step 3) in gained composite powder is soluble in water that Nano medication dispersion is obtained.
9. one kind according to claim 8 prepares insoluble drug nano-dispersed using microchannel
The method of body, it is characterised in that：The condition of spray drying treatment is inlet temperature 120-160 DEG C, and outlet is warm
60-80 DEG C of degree, charging rate 10-40mL/min, compressed air pressure 0.5-0.7Mpa.
10. prepare insoluble drug using the application microchannel as described in claim 1-9 is arbitrary to receive
The medicament nano dispersion that the method for rice dispersion is prepared, it is characterised in that：The Nanodispersion
The mean diameter of middle medicine is 30-80nm, and PDI values are 0.15-0.21.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510701342.0A CN106606419B (en) | 2015-10-26 | 2015-10-26 | A method of insoluble drug Nanodispersion is prepared using microchannel |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510701342.0A CN106606419B (en) | 2015-10-26 | 2015-10-26 | A method of insoluble drug Nanodispersion is prepared using microchannel |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106606419A true CN106606419A (en) | 2017-05-03 |
| CN106606419B CN106606419B (en) | 2019-10-18 |
Family
ID=58613619
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510701342.0A Active CN106606419B (en) | 2015-10-26 | 2015-10-26 | A method of insoluble drug Nanodispersion is prepared using microchannel |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106606419B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101375825A (en) * | 2008-10-10 | 2009-03-04 | 北京工业大学 | Equipment for preparing micronizing medicament |
| WO2009107046A1 (en) * | 2008-02-25 | 2009-09-03 | Philips Intellectual Property & Standards Gmbh | Preparation of nanoparticles from metal salts or metal oxides |
| CN101780047A (en) * | 2009-01-16 | 2010-07-21 | 北京化工大学 | Nano-micro structure silibinin drug composite powder and preparation method thereof |
| CN103768012A (en) * | 2013-12-24 | 2014-05-07 | 浙江凯胜科技有限公司 | Method for preparing curcumin lipid nano-particle suspension or nano-particles |
-
2015
- 2015-10-26 CN CN201510701342.0A patent/CN106606419B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009107046A1 (en) * | 2008-02-25 | 2009-09-03 | Philips Intellectual Property & Standards Gmbh | Preparation of nanoparticles from metal salts or metal oxides |
| CN101375825A (en) * | 2008-10-10 | 2009-03-04 | 北京工业大学 | Equipment for preparing micronizing medicament |
| CN101780047A (en) * | 2009-01-16 | 2010-07-21 | 北京化工大学 | Nano-micro structure silibinin drug composite powder and preparation method thereof |
| CN103768012A (en) * | 2013-12-24 | 2014-05-07 | 浙江凯胜科技有限公司 | Method for preparing curcumin lipid nano-particle suspension or nano-particles |
Non-Patent Citations (3)
| Title |
|---|
| WEN-ZHEN ZHU 等: "Liquid antisolvent preparation of amorphous cefuroxime axetil nanoparticles in a tube-in-tube microchannel reactor", 《INTERNATIONAL JOURNAL OF PHARMACEUTICS》 * |
| 张乾霞 等: "T型微通道反应器内丙酸倍氯米松纳米颗粒的制备研究", 《第六届全国化学工程与生物化工年会论文集》 * |
| 张乾霞 等: "微通道反应器内纳米头孢呋辛酯制备工艺优化", 《北京化工大学学报( 自然科学版)》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106606419B (en) | 2019-10-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102188372B (en) | Medicinal transparent nano dispersant and preparation method thereof | |
| CN101361713B (en) | Curcumin nano crystallization preparation and preparation method thereof | |
| Kankala et al. | Supercritical fluid (SCF)-assisted fabrication of carrier-free drugs: an eco-friendly welcome to active pharmaceutical ingredients (APIs) | |
| EP1942873A2 (en) | Method and device for producing very fine particles and coating such particles | |
| CN102824356A (en) | Baicalin nano crystal suspension, nano crystal dry powder and methods for preparing baicalin nano crystal suspension and nano crystal dry powder | |
| CN108658817A (en) | A kind of preparation method of Florfenicol nanocrystal | |
| CN107320460A (en) | A kind of nilotinib oral administration nanometer preparation and preparation method thereof | |
| CN105456228A (en) | Loaded aprepitant nanocrystal lipid microcapsule and preparation method thereof | |
| CN104902873A (en) | Oral and/or buccal composition in the form of a thin film of a weakly soluble active ingredient, method of preparing same and use of same | |
| CN104887633B (en) | A kind of razaxaban tablet and preparation method thereof | |
| CN101829331A (en) | Three-dimensionally ordered macroporous silicon dioxide medicament administration system suitable for slightly soluble medicament | |
| CN101780047B (en) | Nano-micro structure silibinin drug composite powder and preparation method thereof | |
| CN106606419A (en) | Method for preparing indissolvable drug nanodispersion by applying micro-channel technology | |
| CN107095844A (en) | A kind of Pharmaceutical composition for being used to prepare slightly soluble oral medicine preparation | |
| CN107468650A (en) | A kind of Irbesartan self-emulsifying soft capsule and preparation method thereof | |
| CN103908431A (en) | Entecavir compound nano-preparation and preparation method thereof | |
| CN101780046A (en) | Itraconazole composite powder and preparation method thereof | |
| CN106668027A (en) | Obeticholic acid pharmaceutical composition and preparation method thereof | |
| CN106265548A (en) | A kind of preparation method of carbamazepine dispersible tablet | |
| CN105307642A (en) | Nanoparticulate formulation comprising a TRPA1 antagonist | |
| CN102274274B (en) | Self-microemulsifiable kudzu root flavone oral micro-pill composition and preparation method thereof | |
| CN107875126A (en) | A kind of carbamazepine solid dispersions and its preparation | |
| CN105412022B (en) | A kind of ginkolide B fast release micropill and preparation method thereof | |
| CN103585131A (en) | Preparation method for ivermectin sustained-release gelatin microcapsule | |
| CN103006556A (en) | Scutellarin nanosuspension and preparation method thereof |
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 |