CN106176672A - The preparation method of famotidine medical resin microcapsule - Google Patents
The preparation method of famotidine medical resin microcapsule Download PDFInfo
- Publication number
- CN106176672A CN106176672A CN201610786067.1A CN201610786067A CN106176672A CN 106176672 A CN106176672 A CN 106176672A CN 201610786067 A CN201610786067 A CN 201610786067A CN 106176672 A CN106176672 A CN 106176672A
- Authority
- CN
- China
- Prior art keywords
- famotidine
- preparation
- microcapsule
- medical resin
- resin
- 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
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- 229920005989 resin Polymers 0.000 title claims abstract description 75
- 229960001596 famotidine Drugs 0.000 title claims abstract description 73
- XUFQPHANEAPEMJ-UHFFFAOYSA-N famotidine Chemical compound NC(N)=NC1=NC(CSCCC(N)=NS(N)(=O)=O)=CS1 XUFQPHANEAPEMJ-UHFFFAOYSA-N 0.000 title claims abstract description 73
- 239000003094 microcapsule Substances 0.000 title claims abstract description 70
- 238000002360 preparation method Methods 0.000 title claims abstract description 41
- 239000000463 material Substances 0.000 claims abstract description 42
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- 238000003756 stirring Methods 0.000 claims description 51
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- 238000001914 filtration Methods 0.000 claims description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 16
- 239000004606 Fillers/Extenders Substances 0.000 claims description 16
- 239000004014 plasticizer Substances 0.000 claims description 15
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- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 6
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- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 4
- 229920003149 Eudragit® E 100 Polymers 0.000 claims description 4
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 claims description 4
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 4
- NEDGUIRITORSKL-UHFFFAOYSA-N butyl 2-methylprop-2-enoate;2-(dimethylamino)ethyl 2-methylprop-2-enoate;methyl 2-methylprop-2-enoate Chemical compound COC(=O)C(C)=C.CCCCOC(=O)C(C)=C.CN(C)CCOC(=O)C(C)=C NEDGUIRITORSKL-UHFFFAOYSA-N 0.000 claims description 4
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- HVUMOYIDDBPOLL-UHFFFAOYSA-N 2-(3,4-Dihydroxyoxolan-2-yl)-2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)C1OCC(O)C1O HVUMOYIDDBPOLL-UHFFFAOYSA-N 0.000 claims description 3
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- IYFATESGLOUGBX-YVNJGZBMSA-N Sorbitan monopalmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O IYFATESGLOUGBX-YVNJGZBMSA-N 0.000 claims description 3
- NWGKJDSIEKMTRX-MDZDMXLPSA-N Sorbitan oleate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(O)C1OCC(O)C1O NWGKJDSIEKMTRX-MDZDMXLPSA-N 0.000 claims description 3
- 229920002472 Starch Polymers 0.000 claims description 3
- LWZFANDGMFTDAV-BURFUSLBSA-N [(2r)-2-[(2r,3r,4s)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O LWZFANDGMFTDAV-BURFUSLBSA-N 0.000 claims description 3
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- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims description 2
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
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Classifications
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- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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- A61K31/426—1,3-Thiazoles
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- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
- A61K9/5047—Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
Abstract
The preparation method of the open famotidine medical resin microcapsule of the present invention, comprises the following steps: 1) preparation of famotidine medical resin；2) preparation of pharmaceutical-impregnated resin；3) preparation of internal layer oil phase；4) preparation of outer layer oil phase；5) preparation of material；6) preparation of famotidine medical resin microcapsule.The famotidine microcapsule mouthfeel of the present invention is better than existing product, and easily by extensive patients, particularly child, old man and dysphagia person accepts.The capsule material of the present invention dissolves in the stomach less, thus reduces gastrointestinal stimulation.The famotidine dry suspension that this microcapsule is made, dissolution in vitro passed examination；Sedimentation volume ratio is 0.99, and redispersibility is good；The technical parameter used in the present invention is reliable and stable, operates favorable reproducibility, is suitable for commercial scale and produces；The present invention uses Sealing Arrangement to operate, and can control organic solvent volatilization greatly, have fewer environmental impacts.Gained microcapsule being carried out dissolvent residual investigation, result shows simultaneously, all meets new drug standard.
Description
Technical field
The present invention relates to industry medicament, oral liquid, be specifically related to the preparation side of famotidine medical resin microcapsule
Method.
Background technology
Powder, dry suspension, (carefully) granule, the solid preparation such as Orodispersible tablets is because unit volume is less or can be
In oral cavity, rapid disintegrate becomes little granule, is particularly well-suited to old man, child or other are because of the poor patient of function of deglutition.But for
There is the technological means such as bad mouthfeel medicine need of coating such as bitterness and prepare microcapsule to cover bitterness, make patient acceptant.?
When using microgranule coating means to cover bitter taste of drug, must not make the declined bioavailability of oral administration of medicine, this will make coating prepare
Microcapsule does not only discharge during oral, and discharges the most rapidly.And medicine preferable for water solublity, microcapsule needs
Add disintegrating agent to accelerate the release of medicine.Additionally when in oral formulations, the particle diameter of insoluble granule is more than 200 microns, oral cavity
Middle meeting has grittiness, and the mean diameter being therefore desirable to the medicine after controlling coating or drug containing microgranule is not more than 200 microns.
After coating to be controlled, the mean diameter of microcapsule is at 200 microns or less, and disintegrating agent adds in prescription after needing to pulverize, but disintegrate
Agent can make medicine absorb the release having delayed medicine in disintegrating agent in a large number because specific surface area is greatly increased after pulverizing.
Famotidine is another the H2 receptor antagonists occurred after cimetidine and ranitidine, its action intensity ratio
Big 30-100 times of cimetidine, big 6-10 times than ranitidine.Healthy People and Peptic Ulcers famotidine 20mg
Basal secretion and the gastric acid and the pepsinia increase that cause because giving various stimulation there is inhibitory action.Intravenous 20mg energy
Suppress basal secretion and because pentagastrin etc. stimulates caused secretion；Oral 20mg is to gastric acid and pepsin in 7 hours nights
The suppression of secretory volume, respectively 91.8% and 71.8%.Famotidine relatively cimetidine action time and ranitidine are about
30%, oral 20mg can maintain more than 12 hours to the inhibitory action of gastric acid output.Famotidine is to losing blood and giving histamine
Caused rat stomach is hemorrhage inhibited, and the double blinding comparative test of upper gastrointestinal hemorrhage also demonstrates that famotidine has hemostasis effect
Really.Intravenous 20mg every day 2 times, hemostatic efficiency reaches 91%, after intravenously administrable hemostasis, oral 20mg every day 2 times, can preferably tie up
Hold haemostatic effect.Famotidine does not change gastric emptying rate, does not disturb pancreatic function, to cardiovascular system and renal function also without
Harmful effect.
Summary of the invention
Goal of the invention: first technical problem to be solved by this invention there is provided famotidine medical resin microcapsule
Preparation method, this preparation method overcomes the technological deficiency that prior art exists, and such as fluid bed, to there is the response rate low, Electrostatic Absorption etc.
Problem.
Technical scheme: in order to solve above-mentioned technical problem, the invention provides the preparation of famotidine medical resin microcapsule
Method, comprises the following steps:
1) preparation of famotidine medical resin: famotidine medicine adds slow-release material, stirring, sucking filtration, cleans, dries
Famotidine medical resin is obtained after Gan；
2) preparation of pharmaceutical-impregnated resin: by famotidine medical resin and extender and initial core mix and blend, shape
Become pharmaceutical-impregnated resin；
3) preparation of internal layer oil phase: capsule material is dissolved in solvent, and add pharmaceutical-impregnated resin and plasticizer, stirring,
Make both dispersed, form suspension, as internal layer oil phase；
4) preparation of outer layer oil phase: liquid paraffin and emulsifying agent are placed in reactor, forms outer layer oil phase；
5) preparation of material: internal layer oil phase is slowly added in the outer layer oil phase of stirring, and necessarily reacting temperature
Being stirred after solvent steams completely under degree, the vacuum of distillation and rotating speed, reaction end obtains material；
6) preparation of famotidine medical resin microcapsule: material is released, the most i.e. obtains by petroleum ether filtering and washing
Famotidine medical resin microcapsule.
Wherein, above-mentioned steps 1) in slow-release material be cation exchange resin and methylcellulose, ethyl cellulose,
One or more in acrylic resin and hydroxypropyl methylcellulose.
Wherein, above-mentioned steps 2) in extender be polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, polyvidone, hydroxypropyl
One or more in ylmethyl cellulose, hydroxypropyl cellulose, methylcellulose or starch.
Wherein, above-mentioned steps 2) in initial core be macromolecular material or particulate material.As kayexalate,
Polystyrene carboxylic acid sodium.
Wherein, above-mentioned steps 3) in capsule material be Eudragit E 100, acrylic resin RS100, acrylic resin
One or more in RL100, acrylic resin L100, ethyl cellulose or aqueous dispersion.Predominantly water-insoluble high score
Sub-material, capsule material consumption is about the 20% of capsule core material (medical resin) weight.
Wherein, medicine is played load effect by initial core, is combined with covalent bond or other chemical reaction modes with medicine, rises
To increasing the effect such as medicine stability, taste masking, there is high stability.Capsule material is mainly sustained-release polymer material, not with medicine
Directly contact, plays secondary packet to medicine and wraps up in effect, occurs swelling to make medicine slowly discharge in release medium.Shared by initial core
Ratio much larger than capsule material.
Wherein, above-mentioned steps 3) in plasticizer be in triethyl citrate, Polyethylene Glycol, triacetyl glycerine and glycerol
One or more.When the water-insoluble macromolecule in capsule material is more crisp, when being difficult to film forming, it is frequently necessary to increase plasticizer.Increase
Mould consumption is capsule material weight about the 20% of agent.
Wherein, above-mentioned steps 3) in the consumption of plasticizer is initial core weight 0～35%.
Above-mentioned steps 3) in the volumetric concentration of solvent of capsule material be 0.5-0.6%.
Above-mentioned steps 3) in solvent be in water, methanol, ethanol, propanol, isopropanol, acetone, chloroform, dichloromethane
Plant or several.
Wherein, above-mentioned steps 4) in emulsifying agent be span 20, span 40, sorbester p18, sorbester p17, tween20, tween
40, one or more in tween 60, tween 80.
Wherein, above-mentioned steps 5) in reaction temperature be 40-60 DEG C, reactor rotating speed is 200-300r/min, distillation
Vacuum is 0.04-0.1MPa.
Wherein, the mean diameter of above-mentioned famotidine medical resin microcapsule is 100-180 micron.
The famotidine medical resin microcapsule that above-mentioned preparation method prepares.In this famotidine medical resin microcapsule
Extender, because little with medicament contact area, so medicine is nearly free from adsorption, can guarantee that medicine discharges rapidly.This
Invention famotidine microcapsule mouthfeel is better than existing product, and easily by extensive patients, particularly child, old man and dysphagia person connects
It is subject to.This famotidine medical resin microcapsule does not discharge medicine in the chance i.e. 15-300 second at water initial stage, when water permeates through microcapsule membrane
After dilatancy core, described dilatancy core is that extender covers nuclei originis and formed in the heart, and microcapsule expands and makes capsular rupture,
Drug microparticles is rapidly dispersed in dissolution medium, accelerates the release of medicine.This mean diameter with microcapsule may diminish to 200
Below Wei meter.The specific surface area of microcapsule is very big, and water solublity capsule material just can make microcapsule cyst membrane reach enough by the biggest amount
Thickness with hinder medicine release, the very conference of capsule material consumption reduce medicament contg, make the preparation dose of patient be greatly increased,
So capsule material water-insoluble to be used macromolecular material.
Above-mentioned famotidine medical resin microcapsule is preparing tasteless tablet, tasteless granule, tasteless dry suspension or glue
Application in wafer dosage form.
Wherein, said medicine is not limited only to famotidine, and this famotidine can also be other soluble drug, it is possible to
With local bitterness or other are such as medicine of bad mouthfeel such as sour, puckery, the numbest etc..
Above-mentioned Eudragit E 100, acrylic resin RS100, acrylic resin RL100, acrylic resin L100 and
Ethyl cellulose is commercially available prod.
Reactor equipment used in the present invention refers to set reactor structure function and configuration adnexa according to reaction condition
The combined reaction container of meter.All can complete pre-set with higher automaticity from the charging-reaction-discharging started
Reactions steps, the temperature in course of reaction, pressure, mechanics are controlled the important parameter such as (stirring etc.) and carry out strict regulation and control.
Its structure is typically made up of kettle, actuating device, agitating device, heater, sealing device.
Forming O/O type emulsification system in equipment, capsule material, plasticizer etc. are dissolved in internal layer oil phase, and initial core is in stirring
Being uniformly distributed therein under state, outer layer oil phase comprises emulsifying agent, and under stirring, internal layer oil phase is slowly added to outer oil
Phase, in whipping process, dissolves the organic solvent volatilization of slow release capsule material in internal layer oil phase, outer layer solvent can not be dissolved, therefore its
Separate out to medical resin, gradually form the microcapsule membrane of even compact.
The present invention is with the solvent solution of kayexalate for initial core, in a kettle. to famotidine medicine tree
Fat is coated, and does distillation condensed fluid with dehydrated alcohol, makes solvent gradually be distilled off by stirring, forms microcapsule.This
Microcapsule has the core of a water swelling, uses water after water soluble drug is coated in expansile core further
Insoluble material is made.Microcapsule does not discharge medicine in chance water initial stage (15-300 second), when water penetrates into expansion through microcapsule membrane
Property core after, core expand make microcapsule membrane rupture, drug microparticles is rapidly dispersed in dissolution medium, accelerate medicine dissolution, with
Add in extender compared with type (extender directly mixes with medicine) microcapsule, there is in the microcapsule of expanding core extender because and medicine
Thing contact area is little, so medicine is nearly free from adsorption, can guarantee that medicine discharges rapidly.The average particle of this microcapsule
Footpath can be less than 200 microns, and as preferably, general range is at 100-180 micron.
In order to be better understood by the essence of the present invention, with part of test results, advantages of the present invention is described below.
Micromorphology is observed.Use optical microscope inspection dilatancy core to meet state before and after water, and microcapsule meets water
After state.The dilatancy core of preparation is about 100 microns, is essentially all simple grain, and microgranule does not occur serious gathering
Collection.Illustrate that present invention process and equipment meet the requirements.After dilatancy core meets water, extender expands substantially.The microcapsule of preparation is put down
All particle diameter is less than 200 microns, illustrates that microcapsule ruptures fully after meeting water.
The microcapsule that the present invention is directly mixed with compared with extender and medicine, involved microcapsules medicine thing contacts with disintegrating agent
Area greatly reduces, and disintegrating agent is the most weak to the toner cartridge effect of medicine, and this microcapsule does not discharge in chance water initial stage (15-300 second)
Medicine.Microcapsule swelling fracture subsequently, makes drug microparticles be rapidly dispersed in dissolution medium, accelerates the release of medicine.Above-mentioned averagely
Particle diameter can reach less than 200 microns, is avoided that oral cavity has grittiness when taking.
Beneficial effect: the invention have the advantages that the famotidine microcapsule mouthfeel of the present invention is better than existing product, easily quilt
Extensive patients, particularly child, old man and dysphagia person accept.The capsule material of the present invention dissolves in the stomach less, thus reduces
Gastrointestinal stimulation.But medicine is hydrochlorate, it is easy to absorption under one's belt, the capsule heart (medical resin) covers parcel uniformly.This microcapsule system
The famotidine dry suspension become, dissolution in vitro passed examination；Sedimentation volume ratio is 0.99, and redispersibility is good；The present invention
The technical parameter of middle employing is reliable and stable, operates favorable reproducibility, is suitable for commercial scale and produces；The present invention uses Sealing Arrangement to grasp
Make, organic solvent volatilization can be controlled greatly, have fewer environmental impacts.Gained microcapsule is carried out dissolvent residual investigation, knot simultaneously
Fruit display, all meets new drug standard.
Accompanying drawing explanation
The In-vitro release curves figure of the dry suspension of the medical resin microcapsule of Fig. 1 experimental example of the present invention；
Fig. 2 is famotidine resin microcapsule scanning electron microscopic picture of the present invention.
Detailed description of the invention
Embodiment 1
1) precision weighs 40g famotidine medicine as in reactor, adds 4L distilled water, in the mixing speed of 500rpm
Lower stirring, after medicine dissolution, adds 80g cation exchange resin, and the drug level stirred to solution no longer reduces, and takes out
Filter, and clean filter cake for several times with distilled water, drying famotidine medical resin.
2) in beaker, add 2L distilled water, be heated to 60 DEG C, under stirring, add 400g plasticizer P EG4000,
After it dissolves, add famotidine medical resin 100g, add extender polyvinylpolypyrrolidone 20g and initial core polyphenyl second
Alkene sodium sulfonate 30g, stirs 1 hour sucking filtration under the conditions of 60 DEG C and i.e. obtains pharmaceutical-impregnated resin.
3) adding 2.4g acrylic resin RS 100 and 2.4g acrylic resin RL 100 in 960ml acetone, stirring makes
Be completely dissolved, add 32g pharmaceutical-impregnated resin and 16ml plasticizer P EG400, stir 1h, make both dispersed, formed mixed
Suspension, as internal layer oil phase.
4) 2880ml liquid paraffin and 120ml sorbester p17 are joined in reactor, as outer layer oil phase after stirring.
5) internal layer oil phase is slowly added in the outer layer oil phase of stirring in reactor, reacts under the conditions of 40 DEG C,
Reactor rotating speed is 200r/min, and the vacuum of distillation is 0.06MPa, and stirring is after acetone steams completely, and reaction end obtains
Material.
6) being released by material, the famotidine medical resin the most i.e. obtaining the present invention by petroleum ether filtering and washing is micro-
Capsule.
Embodiment 2
1) precision weighs 40g famotidine medicine as in reactor, adds 4L distilled water, under 500rpm mixing speed
Stirring, after medicine dissolution, adds 80g methylcellulose, and the drug level stirred to solution no longer reduces, sucking filtration, and uses
Distilled water cleans filter cake for several times, drying famotidine medical resin.
2) in beaker, add 2L distilled water, be heated to 60 DEG C, under stirring, add 400g plasticizer P EG6000,
After it dissolves, add famotidine medical resin 100g, add extender hydroxypropyl methyl cellulose 30g and initial core
Kayexalate 40g, stirs 1 hour sucking filtration under the conditions of 60 DEG C and i.e. obtains pharmaceutical-impregnated resin.
3) adding 4.8g acrylic resin RS 100 in 1000ml ethanol, stirring is allowed to be completely dissolved, and adds 36g dipping
Medical resin and 16ml plasticizer triacetyl glycerine, stir 30 minutes, make both dispersed, forms suspension, as interior
Layer oil phase.
4) 3000ml liquid paraffin and 120ml span 20 are joined in reactor, as outer layer oil phase after stirring.
5) internal layer oil phase is slowly added in the outer layer oil phase of stirring in reactor.React under the conditions of 50 DEG C,
Reactor rotating speed is 280r/min, and the vacuum of distillation is 0.04MPa, and stirring is after ethanol steams completely, and reaction end obtains
Material.
6) material is released, the most i.e. obtain famotidine medical resin microcapsule of the present invention by petroleum ether filtering and washing.
Embodiment 3
1) precision weighs 20g famotidine medicine as in reactor, adds 4L distilled water, under 500rpm mixing speed
Stirring, after medicine dissolution, adds 100g hydroxypropyl methylcellulose, and the drug level stirred to solution no longer reduces, sucking filtration,
And clean filter cake for several times with distilled water, drying famotidine medical resin.
2) in beaker, add 2L distilled water, be heated to 60 DEG C, under stirring, add 200g PEG4000, treat that it is molten
Xie Hou, adds famotidine medical resin 80g, adds extender cross-linking sodium carboxymethyl cellulose 30g and initial core polyphenyl
Vinyl sulfonic acid sodium 40g, stirs 1 hour sucking filtration under the conditions of 60 DEG C and i.e. obtains pharmaceutical-impregnated resin.
3) adding 4.8g acrylic resin RL 100 in 960ml acetone, stirring is allowed to be completely dissolved, and adds 40g dipping
Medical resin and 16ml triethyl citrate plasticizer, stir 50 minutes, make both dispersed, forms suspension, as interior
Layer oil phase.
4) 3200ml liquid paraffin and 100ml span 40 are joined in reactor, as outer layer oil phase after stirring.
5) internal layer oil phase is slowly added in the outer layer oil phase of stirring in reactor.React under the conditions of 60 DEG C,
Reactor rotating speed is 300r/min, and the vacuum of distillation is 0.1MPa, and stirring is after acetone steams completely, and reaction end obtains thing
Material.
6) material is released, the most i.e. obtain famotidine medical resin microcapsule of the present invention by petroleum ether filtering and washing.
Embodiment 4
1) precision weighs 50g famotidine medicine as in reactor, adds 4L distilled water, under 500rpm mixing speed
Stirring, after medicine dissolution, adds 50g acrylic resin and cation exchange resin, stirs the drug level to solution not
Reduce again, sucking filtration, and clean filter cake for several times with distilled water, drying famotidine medical resin.
2) in beaker, add 2L distilled water, be heated to 60 DEG C, under stirring, add 100g PEG6000, treat that it is molten
Xie Hou, adds famotidine medical resin 90g, adds extender methylcellulose or starch 25g and initial core polyphenyl second
Alkene sodium sulfonate 25g, stirs 1 hour sucking filtration under the conditions of 60 DEG C and i.e. obtains pharmaceutical-impregnated resin.
3) adding 2.2g Eudragit E 100 and 2.8g acrylic resin L 100 in 960ml dichloromethane, stirring makes
Be completely dissolved, add 35g pharmaceutical-impregnated resin and 10ml triacetyl glycerine plasticizer, stir 20 minutes, make both uniform
Dispersion, forms suspension, as internal layer oil phase.
4) 2880ml liquid paraffin and 150ml sorbester p18 are joined in reactor, as outer layer oil phase after stirring.
5) internal layer oil phase is slowly added in the outer layer oil phase of stirring in reactor.React under the conditions of 50 DEG C,
Reactor rotating speed is 240r/min, and the vacuum of distillation is about 0.05MPa, and stirring, after dichloromethane steams completely, is reacted
Terminate to obtain material.
6) material is released, the most i.e. obtain famotidine medical resin microcapsule of the present invention by petroleum ether filtering and washing.
Embodiment 5
1) precision weighs 30g famotidine medicine as in reactor, adds 4L distilled water, under 500rpm mixing speed
Stirring, after medicine dissolution, adds 80g ethyl cellulose, and the drug level stirred to solution no longer reduces, sucking filtration, and uses
Distilled water cleans filter cake for several times, drying famotidine medical resin.
2) in beaker, add 2L distilled water, be heated to 60 DEG C, under stirring, add 150g PEG6000, treat that it is molten
Xie Hou, adds famotidine medical resin 90g, add extender polyvinylpolypyrrolidone and cross-linking sodium carboxymethyl cellulose 50g and
Initial core kayexalate 60g, stirs 1 hour sucking filtration under the conditions of 60 DEG C and i.e. obtains pharmaceutical-impregnated resin.
3) adding 2g acrylic resin RS 100 and 3g ethyl cellulose in 960ml isopropanol and acetone, stirring is allowed to
It is completely dissolved, adds 36g pharmaceutical-impregnated resin and 20ml triethyl citrate, Polyethylene Glycol plasticizer, stir 40 minutes, make two
Person is dispersed, forms suspension, as internal layer oil phase.
4) 3160ml liquid paraffin and 128ml tween20 are joined in reactor, as outer oil after stirring
Phase.
5) internal layer oil phase is slowly added in the outer layer oil phase of stirring in reactor.React under the conditions of 45 DEG C,
Reactor rotating speed is 260r/min, and the vacuum of distillation is 0.08MPa, and stirring, after isopropanol and acetone steam completely, is reacted
Terminate to obtain material.The ethanol that simultaneously may be used without-10 DEG C does condensed fluid.Compare and do condensed fluid with water, the speed that acetone steams
Greatly speed up.
6) material is released, the most i.e. obtain famotidine medical resin microcapsule of the present invention by petroleum ether filtering and washing.
Experimental example: the performance parameter experiment of famotidine medical resin microcapsule
1, prepared famotidine medical resin microcapsule carrying out particle size determination, display particle size range is 110-180 micron.
Due to less than 200 microns, it is possible to ensure oral without grittiness.
2, We conducted dissolvent residual experiment simultaneously, show solvent and the petroleum ether of all employings in embodiment 1～5
Solvent residual amount meansigma methods be about 0.0015% and 0.0011%, be far smaller than national standard limited amount 0.01%.
3, the famotidine medical resin microcapsule of preparation is made dry suspension, dissolution in vitro passed examination by us；Heavy
Fall volume ratio is 0.99, and redispersibility is good.
4, the release in vitro examination of the famotidine medical resin microcapsule that embodiment 1 prepares is investigated by dissolution rate
Test.The 900ml 0.15mol/l NaCl using degassed process is release medium: rotating speed 50r/min, temperature 37 DEG C.According to
The 2015 editions annex Ⅹ C paddle method operations of state's pharmacopeia, sample 5ml, filter through 0.45 μm microporous filter membrane, discard just filtrate, take subsequent filtrate
Standby, add synthermal in time, the respective media of same volume, subsequent filtrate is measured at 266nm absorbance, according to standard curve
Calculate different time sample liquid concentration, investigate the Cumulative release amount of 12 hours and the relation of time.
Experimental result is as shown in fig. 1.Result shows, famotidine slow-release dry suspension prepared in embodiment 1
Vitro release 12 hours is 75%-85%, it is thus possible to make medicine slowly discharge into internal.
The above is only the preferred embodiment of the present invention, it should be pointed out that: those skilled in the art are come
Saying, under the premise without departing from the principles of the invention, it is also possible to make some improvements and modifications, these improvements and modifications also should be regarded as
Protection scope of the present invention.
Claims (10)
1. the preparation method of famotidine medical resin microcapsule, it is characterised in that comprise the following steps:
1) preparation of famotidine medical resin: famotidine medicine is added slow-release material, stirring, sucking filtration, clean, dry after
Obtain famotidine medical resin；
2) preparation of pharmaceutical-impregnated resin: by famotidine medical resin and extender and initial core mix and blend, form leaching
Stain medical resin；
3) preparation of internal layer oil phase: capsule material is dissolved in solvent, and add pharmaceutical-impregnated resin and plasticizer, stirring, make two
Person is dispersed, forms suspension, as internal layer oil phase；
4) preparation of outer layer oil phase: liquid paraffin and emulsifying agent are placed in reactor, forms outer layer oil phase；
5) preparation of material: internal layer oil phase is slowly added in the outer layer oil phase of stirring, and in certain reaction temperature, steaming
Being stirred under the vacuum evaporated and rotating speed after solvent steams completely, reaction end obtains material；
6) preparation of famotidine medical resin microcapsule: material is released, the most i.e. obtains method not by petroleum ether filtering and washing
For fourth medical resin microcapsule.
The preparation method of famotidine medical resin microcapsule the most according to claim 1, it is characterised in that described step 1)
In slow-release material be cation exchange resin and methylcellulose, ethyl cellulose, acrylic resin and hydroxypropyl are fine
One or more in dimension element.
The preparation method of famotidine medical resin microcapsule the most according to claim 1, it is characterised in that described step 2)
In extender be polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, polyvidone, hydroxypropyl methyl cellulose, hydroxy propyl cellulose
One or more in element, methylcellulose or starch.
The preparation method of famotidine medical resin microcapsule the most according to claim 1, it is characterised in that described step 2)
In initial core be macromolecular material or particulate material.
The preparation method of famotidine medical resin microcapsule the most according to claim 1, it is characterised in that described step 3)
In capsule material be Eudragit E 100, acrylic resin RS100, acrylic resin RL100, acrylic resin L100, ethyl
One or more in cellulose or aqueous dispersion.
The preparation method of famotidine medical resin microcapsule the most according to claim 1, it is characterised in that described step 3)
In plasticizer be one or more in triethyl citrate, Polyethylene Glycol, triacetyl glycerine and glycerol.
The preparation method of famotidine medical resin microcapsule the most according to claim 1, it is characterised in that described step 3)
In the consumption of plasticizer is initial core weight 0 ~ 35%.
The preparation method of famotidine medical resin microcapsule the most according to claim 1, it is characterised in that described step 4)
In emulsifying agent be in span 20, span 40, sorbester p18, sorbester p17, tween20, tween 40, tween 60, tween 80
One or more.
The preparation method of famotidine medical resin microcapsule the most according to claim 1, it is characterised in that described step 5)
In reaction temperature be 40-60 DEG C, reactor rotating speed is 200-300r/min, and the vacuum of distillation is 0.04-0.1 MPa.
The preparation method of famotidine medical resin microcapsule the most according to claim 1, it is characterised in that described method is not
Mean diameter for fourth medical resin microcapsule is 100-180 micron.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110327295A (en) * | 2019-08-05 | 2019-10-15 | 五邑大学 | A kind of formula and preparation method thereof of ranitidine hydrochloride slow-release suspension |
| CN114903850A (en) * | 2022-05-07 | 2022-08-16 | 江苏大学 | Famotidine hydrochloride sustained-release suspension preparation and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1729964A (en) * | 2005-08-11 | 2006-02-08 | 沈阳药科大学 | Flavor hidden microcapsule with expanding core and method for preparing the same |
| US20060204587A1 (en) * | 1999-12-20 | 2006-09-14 | Karl Kolter | Use of film coating as taste-masking coating of oral dosage forms |
| CN102973533A (en) * | 2012-11-12 | 2013-03-20 | 中国药科大学 | Preparation method of famotidine gastric-floating-type pellet tablets |
| CN105496967A (en) * | 2015-12-22 | 2016-04-20 | 江苏苏南药业实业有限公司 | Ranitidine hydrochloride releasing-controlling dry suspension and preparing method thereof |
-
2016
- 2016-08-30 CN CN201610786067.1A patent/CN106176672B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060204587A1 (en) * | 1999-12-20 | 2006-09-14 | Karl Kolter | Use of film coating as taste-masking coating of oral dosage forms |
| CN1729964A (en) * | 2005-08-11 | 2006-02-08 | 沈阳药科大学 | Flavor hidden microcapsule with expanding core and method for preparing the same |
| CN102973533A (en) * | 2012-11-12 | 2013-03-20 | 中国药科大学 | Preparation method of famotidine gastric-floating-type pellet tablets |
| CN105496967A (en) * | 2015-12-22 | 2016-04-20 | 江苏苏南药业实业有限公司 | Ranitidine hydrochloride releasing-controlling dry suspension and preparing method thereof |
Non-Patent Citations (4)
| Title |
|---|
| 《药学服务指南丛书》组委会: "《药学服务指南 处方药使用手册》", 30 April 2005, 群言出版社 * |
| 孟胜男等: "《药剂学》", 30 September 2011, 上海科学技术出版社 * |
| 江涛等: ""法莫替丁-甲壳胺缓释微囊释药机理的研究"", 《中国海洋药物》 * |
| 许真玉等: ""离子交换树脂控释混悬剂的研究进展"", 《沈阳药科大学学报》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110327295A (en) * | 2019-08-05 | 2019-10-15 | 五邑大学 | A kind of formula and preparation method thereof of ranitidine hydrochloride slow-release suspension |
| CN114903850A (en) * | 2022-05-07 | 2022-08-16 | 江苏大学 | Famotidine hydrochloride sustained-release suspension preparation and preparation method thereof |
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