CN102429873A - Desmethylvenlafaxine sustained-release pellet and preparation method thereof - Google Patents
Desmethylvenlafaxine sustained-release pellet and preparation method thereof Download PDFInfo
- Publication number
- CN102429873A CN102429873A CN2011103861530A CN201110386153A CN102429873A CN 102429873 A CN102429873 A CN 102429873A CN 2011103861530 A CN2011103861530 A CN 2011103861530A CN 201110386153 A CN201110386153 A CN 201110386153A CN 102429873 A CN102429873 A CN 102429873A
- Authority
- CN
- China
- Prior art keywords
- release
- add
- sustained
- micropill
- venlafaxine
- 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.)
- Pending
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention provides a desmethylvenlafaxine sustained-release pellet and a capsule or a tablet prepared from the obtained pellet. The pellet comprises a medicament-containing or blank pill core, a medicament layer and a sustained-release coating layer, wherein the sustained-release coating layer comprises a difficultly-water-soluble or water-insoluble polymer or an enteric polymer or a gastric-soluble polymer, and the pellet prepared by using a hydrophilic plasticizing agent is round and has high medicament release curve repeatability. The invention further discloses a method for preparing the pellet.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, specifically be meant slow-release micro-pill that changes the behavior of desmethylvenlafaxine drug release and preparation method thereof.
Background technology
Micropill is meant all kinds of pills of diameter less than 2.5mm, can be made into rapid release or slow-release micro-pill according to different needs.At present the emphasis of research is a slow-release micro-pill, and slow-release micro-pill is to be mixed and made into or to process earlier common ball core by medicine and blocker then to wrap release-controlled film again and form.Micropill can be suppressed in flakes, also can micropill be loaded on and process capsule in the capsule.Domestic and international many companies all produce this preparation now; Contac (Contac) slow releasing capsule like the production of Sino-U.S. SmithKline company; The aspirin sustained release capsule that pharmaceutical factory of China Medicine University produces, the import drugs diclofenac sodium extended release capsule (Olfen-100) of China's Ministry of Public Health approval in 1997 etc.Slow release, controlled release micro pill are a kind of novel forms that develops rapidly in the world; It is steady with blood drug level, toxic and side effects is little, take number of times few, can take together with liquid, characteristics such as relative low price receive numerous doctors and patient's welcome deeply; Market prospect is very good, will become a main trend slow, the controlled release preparation development.
Micropill has the advantage that many other oral formulations can't be compared:
1) can process sustained-release preparation through the controlled release micro pill coating;
2) big at the gastrointestinal tract distribution area, bioavailability is high, and zest is little;
3), receive digestive tract to carry the food rhythm and pace of moving things to influence little (close like pylorus etc.) because particle diameter is little;
4) controlled release micro pill can make blood drug level reach curative effect concentration rapidly, and keeps steady, long valid density, and the fluctuation of blood medicine is little;
5) good fluidity of micropill, size evenly are easy to handle (like coating, divided dose);
6) improve medicine stability, cover disagreeable taste;
7) compatibility of suitable compound preparation;
8) technology simply is fit to the big requirement of producing of industry.
Though slow-release micro-pill has above-mentioned advantage, in actual fabrication process, different pharmaceutical is prepared into slow-release micro-pill will faces a different technologies difficult problem.
Succinic acid desmethylvenlafaxine (Desvenlafaxine Succinate) chemistry 1-[2-(dimethylamino)-1-(4-hydroxy phenyl) ethyl] Hexalin by name has another name called the O-desmethylvenlafaxine, is the O-demethyl active metabolite of antidepressants venlafaxine.Launch such as slow-release micro-pill are not arranged at present as yet.
Summary of the invention
One of the object of the invention is to be to provide a kind of capsule or tablet that micropill that venlafaxine sustained-release micropill and application make is processed that go to add.This removes to add the venlafaxine sustained-release micropill and comprises pastille or celphere, medicine layer, sustained release coating layer.Prescription is formed as follows: medicine accounts for 2%～55% of prescription; Celphere accounts for 20～50% of prescription; The sustained release coating material accounts for prescription 10%～40%.Wherein, the sustained release coating material is insoluble in water or insoluble polymer or enteric polymer or gastric solubility polymer; Specifically, said slow-release material is Eudragit series plastics, cellulose acetate, ethyl cellulose, tacryl element, acrylic resin, cellulose acetate titanate esters, hydroxypropyl emthylcellulose titanate esters.
Further, described preparation slow release layer also includes plasticizer, and wherein, said plasticizer is a hydrophilic polymer, like the joint vector of polyethylene glycols or ripple Lip river pool nurse or saccharide and PEG.
Wherein, the above-mentioned pill core that contains also contains hydrophilic framework material or osmotic pumps penetrating agent.
In the above-mentioned preparation, specifically, the component of celphere can be microcrystalline Cellulose, starch, sucrose, lactose, glucose, dextrin, phosphate, acetate, aminoacid, sodium chloride, potassium chloride, mannitol, sorbitol; Above material can use separately also and can be used.
Medicine layer is made up of the mixture of medicine and adjuvant, and adjuvant can comprise hydrophilic framework material, for example hypromellose; Or the hydroxypropyl clathrate of the Benexate Hydrochloride of the solid dispersion of medicine or medicine or medicine is formed.The operable carrier of the solid dispersion of medicine comprises Polyethylene Glycol, Bo Luoshamu, polyvidone, carbamide, Eudragit resin, ethyl cellulose, acrylic resin.
Further, slow release layer is made up of slow-release material, plasticizer and porogen.Plasticizer also can be selected from and comprise triethyl citrate, Methyl Benzene-o-dicarboxylate, dibutyl sebacate, diethyl phthalate, dibutyl phthalate; Porogen is selected from hydroxypropyl emthylcellulose, hydroxypropyl cellulose, Polyethylene Glycol, polyvidone, micropowder sodium chloride.
Further, remove to add the venlafaxine sustained-release micropill, can add filler and fluidizer is pressed into tablet; Wherein, said filler is the water-insoluble material, like ethyl cellulose, chitosan; And enteric solubility, like HPMCP (phthalic acid hydroxypropyl cellulose), crylic acid resin or can be used as the mixture that the polymer of floating tablets is formed; And said fluidizer is the water-insoluble material.
In addition, the invention discloses a kind of said method for preparing of venlafaxine sustained-release micropill of going to add, remove first venlafaxine raw material and sieve, subsequent use; Get polyvidone and add 80% dissolve with ethanol, subsequent use as binding agent; And slow-release material and/or plasticizer used dissolve with ethanol, subsequent use as sustained release coating liquid;
Get blank or contain pill core, put in the coating pan or in the centrifugal coating granulator, spray into binding agent, add desmethylvenlafaxine medicated powder, process micropill;
Spray into sustained release coating liquid, with micropill bag release membranes, coating finishes after drying and makes timing slow-releasing micrpill.
Further, said method for preparing also comprises the method that is made into tablet or capsule.At this
In bright, desmethylvenlafaxine is preferably the succinic acid venlafaxine.
The inventor finds through experiment accident ground, adopts the micropill rounding of method for preparing, and is good to the drug release control force, drug release curve favorable reproducibility.
The specific embodiment
Below further describe the present invention through embodiment, should be noted that these embodiment provide as the purpose of illustration, do not constitute limitation of the scope of the invention.
Embodiment 1 desmethylvenlafaxine slow-release micro-pill and tablet (1000 preparation units)
Prescription of preparation and preparation method thereof is:
Prescription
Micropill:
Tablet:
Eudragit?L100 24g
Microcrystalline Cellulose 12g
Magnesium stearate 2g
Method for preparing:
Remove first venlafaxine raw material and cross 80 mesh sieves, subsequent use.Get polyvidone and add 80% alcohol dissolving, subsequent use as binding agent; Ethyl cellulose, triethyl citrate, Polyethylene Glycol add ethanol or acetone solution, and be subsequent use as sustained release coating liquid;
Get celphere, put in the coating pan or in the centrifugal coating granulator, spraying into polyvidone ethanol liquid is binding agent, add desmethylvenlafaxine medicated powder, process micropill.Spray into sustained release coating liquid, with micropill bag release membranes, coating finishes after drying 1 hour.In 40 ℃ of dryings 12 hours, obtain slow-release micro-pill again.
To remove to add the venlafaxine sustained-release micropill incapsulates and promptly gets the desmethylvenlafaxine slow releasing capsule.
Or above-mentioned micropill added the mixture of tablet formulation (removing magnesium stearate) material, and adds an amount of water or ethanol and process granule, drying, the adding magnesium stearate is pressed into sizeable tablet.
Adopt two appendix XD first methods of Chinese Pharmacopoeia version in 2010 to measure the release degree of said preparation, record this preparation and discharged fully in about 24 hours.
Embodiment 2 desmethylvenlafaxine slow-release micro-pill and tablet (1000 preparation units)
Prescription
Micropill:
Tablet:
Method for preparing:
Remove first venlafaxine raw material and cross 80 mesh sieves, subsequent use.Get polyvidone and add 80% dissolve with ethanol, subsequent use as binding agent; Hydroxypropyl methylcellulose E50, triethyl citrate, Polyethylene Glycol add ethanol or acetone solution, and be subsequent use as sustained release coating liquid;
Get celphere, put in the coating pan or in the centrifugal coating granulator, spraying into polyvidone ethanol liquid is binding agent, add desmethylvenlafaxine medicated powder, process micropill.Spray into sustained release coating liquid, with micropill bag release membranes, coating finishes after drying 1 hour.In 40 ℃ of dryings 12 hours, obtain slow-release micro-pill again.
To remove to add the venlafaxine sustained-release micropill incapsulates and promptly gets the desmethylvenlafaxine slow releasing capsule.
Or above-mentioned micropill added the mixture of tablet formulation material, be pressed into sizeable tablet.
Adopt two appendix XD first methods of Chinese Pharmacopoeia version in 2010 to measure the release degree of said preparation, record this preparation and discharged fully in about 24 hours.
Embodiment 3 desmethylvenlafaxine slow-release micro-pill and tablet (1000 preparation units)
Prescription
The ball core:
Desmethylvenlafaxine 20g
Cane sugar powder 20g
Polyvidone 5g
Micropill:
The ball core
Tablet:
Microcrystalline Cellulose 12g
Ethyl cellulose 10g
Magnesium stearate 2g
Method for preparing:
Remove first venlafaxine raw material and cross 80 mesh sieves, subsequent use.Get the principal agent of ball core recipe quantity, and polyvidone is added 80% dissolve with ethanol, subsequent use as binding agent; Prepare the ball core with adding binding agent behind principal agent and the cane sugar powder mix homogeneously;
Hydroxypropyl methylcellulose E50, triethyl citrate, propylene glycol are added ethanol or acetone solution, subsequent use as sustained release coating liquid; Get and contain pill core, put in the coating pan or in the centrifugal coating granulator, spraying into polyvidone ethanol liquid is binding agent, add desmethylvenlafaxine medicated powder, process micropill.Spray into sustained release coating liquid, with micropill bag release membranes, coating finishes after drying 1 hour.In 40 ℃ of dryings 12 hours, obtain slow-release micro-pill again.
To remove to add the venlafaxine sustained-release micropill incapsulates and promptly gets the desmethylvenlafaxine slow releasing capsule.
Or above-mentioned micropill added the mixture of tablet formulation material, be pressed into sizeable tablet.
Adopt two appendix XD first methods of Chinese Pharmacopoeia version in 2010 to measure the release degree of said preparation, record this preparation and discharged fully in about 24 hours.
Embodiment 4 desmethylvenlafaxine slow-release micro-pill and tablet (1000 preparation units)
Prescription
The ball core:
Micropill:
Contain pill core
Tablet:
Method for preparing:
Remove first venlafaxine raw material and cross 80 mesh sieves, subsequent use.Get the principal agent of ball core recipe quantity, and polyvidone is added 80% dissolve with ethanol, subsequent use as binding agent; Prepare the ball core with adding binding agent behind principal agent, sodium chloride and the cane sugar powder mix homogeneously;
Ethyl methylcellulose, triethyl citrate, propylene glycol are added ethanol or acetone solution, subsequent use as sustained release coating liquid; Get and contain pill core, put in the coating pan or in the centrifugal coating granulator, spraying into polyvidone ethanol liquid is binding agent, add desmethylvenlafaxine medicated powder, process micropill.Spray into sustained release coating liquid, with micropill bag release membranes, coating finishes after drying 1 hour.In 40 ℃ of dryings 12 hours, obtain slow-release micro-pill again.
To remove to add the venlafaxine sustained-release micropill incapsulates and promptly gets the desmethylvenlafaxine slow releasing capsule.
Or above-mentioned micropill added the mixture of tablet formulation material, be pressed into sizeable tablet.
Adopt two appendix XD first methods of Chinese Pharmacopoeia version in 2010 to measure the release degree of said preparation, record this preparation and discharged fully in about 24 hours.
In addition, it should be noted that above-mentioned micropill all can be used as the preparation administration, the micropill of can also packing into, the drug release curve is with to be prepared into tablet similar, and each time point fluctuates and does not exceed 2%.
Each embodiment desmethylvenlafaxine cumulative release degree of table 1
What need explanation is that above embodiment is just to illustrating the present invention.Under the prerequisite that does not depart from spirit of the present invention and essence, those skilled in the art can design multiple alternative of the present invention and improvement project, and it all should be understood to be within protection scope of the present invention.
Claims (10)
1. one kind is removed to add the venlafaxine sustained-release micropill, comprises pastille or celphere, medicine layer, sustained release coating layer.
2. according to claim 1ly remove to add the venlafaxine sustained-release micropill, prescription calculates according to mass ratio, and form as follows: medicine accounts for 2%～55% of prescription; Celphere accounts for 20～50% of prescription; The sustained release coating material accounts for prescription 10%～40%.
3. according to claim 2ly remove to add the venlafaxine sustained-release micropill, wherein slow-release material is insoluble in water or insoluble polymer or enteric polymer or gastric solubility polymer.
4. according to claim 3ly remove to add the venlafaxine sustained-release micropill, described preparation slow release layer also includes hydrophilic plasticizer.
5. according to claim 4ly remove to add the venlafaxine sustained-release micropill, said plasticizer is a swelling polymer.
6. each describedly removes to add the venlafaxine sustained-release micropill according to claim 1-5, and it contains pill core and contains hydrophilic framework material or osmotic pumps penetrating agent.
7. according to claim 6ly remove to add the venlafaxine sustained-release micropill, said slow-release material is Eudragit series plastics, cellulose acetate, ethyl cellulose, tacryl element, acrylic resin, cellulose acetate titanate esters, hydroxypropyl emthylcellulose titanate esters; Plasticizer is selected from triethyl citrate, Methyl Benzene-o-dicarboxylate, dibutyl sebacate, diethyl phthalate, dibutyl phthalate.
8. according to claim 7ly remove to add the venlafaxine sustained-release micropill, can add filler and fluidizer is pressed into tablet.
9. according to claim 8ly remove to add the venlafaxine sustained-release micropill, the said filler mixture that to be the water-insoluble material rent with enteric solubility or gastric solubility polymer, and said fluidizer is the water-insoluble material.
10. go to add the said method for preparing of venlafaxine sustained-release micropill according to claim 1-9 is described, remove first venlafaxine raw material and sieve, subsequent use; Get polyvidone and add 80% dissolve with ethanol, subsequent use as binding agent; And slow-release material and/or plasticizer used dissolve with ethanol, subsequent use as sustained release coating liquid;
Get blank or contain pill core, put in the coating pan or in the centrifugal coating granulator, spray into binding agent, add desmethylvenlafaxine medicated powder, process micropill;
Spray into sustained release coating liquid, with micropill bag release membranes, coating finishes after drying and makes timing slow-releasing micrpill;
And, above-mentionedly go to add the said method for preparing of venlafaxine sustained-release micropill, also can comprise micropill mixed with filler and fluidizer and adopt the step that is pressed into tablet behind dry method or the wet granulation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011103861530A CN102429873A (en) | 2011-11-29 | 2011-11-29 | Desmethylvenlafaxine sustained-release pellet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011103861530A CN102429873A (en) | 2011-11-29 | 2011-11-29 | Desmethylvenlafaxine sustained-release pellet and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102429873A true CN102429873A (en) | 2012-05-02 |
Family
ID=45978463
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011103861530A Pending CN102429873A (en) | 2011-11-29 | 2011-11-29 | Desmethylvenlafaxine sustained-release pellet and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102429873A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103893153A (en) * | 2014-04-17 | 2014-07-02 | 石家庄市华新药业有限责任公司 | Venlafaxine hydrochloride sustained-release capsule and preparation method of venlafaxine hydrochloride sustained-release capsule |
| CN104839195A (en) * | 2015-05-08 | 2015-08-19 | 青岛海纳生物科技有限公司 | Pesticide sustained release granule containing thiamethoxam and preparation method thereof |
| CN107519147A (en) * | 2016-06-21 | 2017-12-29 | 广州医药研究总院有限公司 | Desmethylvenlafaxine slow-release pill and preparation method thereof |
| CN110314152A (en) * | 2018-11-27 | 2019-10-11 | 西安圣雪沙药物开发有限公司 | A kind of ibuprofen slow-release micro pill capsule and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101987091A (en) * | 2009-08-07 | 2011-03-23 | 北京天衡药物研究院 | Venlafaxine hydrochloride sustained-release pellet capsules |
| CN102085197A (en) * | 2010-12-14 | 2011-06-08 | 北京万生药业有限责任公司 | Venlafaxine slow-release preparation and preparation method thereof |
-
2011
- 2011-11-29 CN CN2011103861530A patent/CN102429873A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101987091A (en) * | 2009-08-07 | 2011-03-23 | 北京天衡药物研究院 | Venlafaxine hydrochloride sustained-release pellet capsules |
| CN102085197A (en) * | 2010-12-14 | 2011-06-08 | 北京万生药业有限责任公司 | Venlafaxine slow-release preparation and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 周建平等: "《药剂学》", 31 March 2007, 东南大学出版社 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103893153A (en) * | 2014-04-17 | 2014-07-02 | 石家庄市华新药业有限责任公司 | Venlafaxine hydrochloride sustained-release capsule and preparation method of venlafaxine hydrochloride sustained-release capsule |
| CN103893153B (en) * | 2014-04-17 | 2016-04-13 | 石家庄市华新药业有限责任公司 | A kind of venlafaxine hydrochloride slow-release capsule and preparation method thereof |
| CN104839195A (en) * | 2015-05-08 | 2015-08-19 | 青岛海纳生物科技有限公司 | Pesticide sustained release granule containing thiamethoxam and preparation method thereof |
| CN104839195B (en) * | 2015-05-08 | 2017-08-29 | 青岛海纳生物科技有限公司 | A kind of pesticide slow-release particle containing Diacloden and preparation method thereof |
| CN107519147A (en) * | 2016-06-21 | 2017-12-29 | 广州医药研究总院有限公司 | Desmethylvenlafaxine slow-release pill and preparation method thereof |
| CN110314152A (en) * | 2018-11-27 | 2019-10-11 | 西安圣雪沙药物开发有限公司 | A kind of ibuprofen slow-release micro pill capsule and preparation method thereof |
| CN110314152B (en) * | 2018-11-27 | 2021-03-26 | 西安圣雪沙药物开发有限公司 | Ibuprofen sustained-release pellet capsule and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5705319B2 (en) | Gastric juice-resistant pharmaceutical or nutritional supplement containing one or more alginic acid salts | |
| CN101977593B (en) | Drug delivery systems comprising weakly basic drugs and organic acids | |
| CN1174745C (en) | Use of coating as taste masking agent for oral preparation | |
| CN101987091B (en) | Venlafaxine hydrochloride sustained-release pellet capsules | |
| JP6929407B2 (en) | Abuse-resistant pharmaceutical composition | |
| CN104922086A (en) | Preparation method of proton pump inhibitor enteric-coated tablet | |
| CN101190179A (en) | Enteric medicinal composition for treating diabetes and preparation method thereof | |
| US20170049724A1 (en) | Extended-release dosage form | |
| JP2015506337A (en) | New formulation | |
| CN1161112C (en) | Pharmaceutical capsule compositions containing loratadine and pseudoephedrine | |
| CN105456223B (en) | Mesalazine sustained release pellet and preparation method thereof and Mesalazine spansule | |
| CN102429873A (en) | Desmethylvenlafaxine sustained-release pellet and preparation method thereof | |
| EP1839649A1 (en) | Coated formulations for tolterodine | |
| CN104906160B (en) | A kind of enteric coated preparations of erigeron breviscapus extract | |
| CN102579398A (en) | Enteric microcapsule with function of balancing bad taste of medicament and preparation method of enteric microcapsule | |
| CN103845323B (en) | Mycophenolic Acid and its salt enteric coated preparations and preparation method | |
| CN104758937A (en) | Metoprolol sustained-release pellet preparation | |
| CN102755302A (en) | Delayed release preparation containing safe and reliable plasticizer and preparation method thereof | |
| US8252312B1 (en) | Oral solid composition comprising a lipid absorption inhibitor | |
| CN1506044A (en) | Slow-releasing prepn containing volatile oil and its prepn process | |
| CN102579366A (en) | Method for preparing Etofibrate sustained-release pellet | |
| CN106420649A (en) | Acetaminophen press-coated controlled release tablet based on polyelectrolyte self-assembled film and preparation method of acetaminophen press-coated controlled release tablet | |
| CN102579358B (en) | A kind of drug sustained-release pellet and preparation method thereof | |
| CN104114157A (en) | Oral formulation comprising lansoprazole and the preparation method thereof | |
| CN102600108A (en) | Flurbiprofen sustained release capsules and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C53 | Correction of patent of invention or patent application | ||
| CB02 | Change of applicant information |
Address after: 100083 A building, block 15, Tiangong building, No. 30, Haidian District, Beijing, Xueyuan Road Applicant after: Beijing Kexin Bicheng Medicine Science & Technology Developing Co., Ltd. Address before: 100190, room 1410, satellite building, No. 63, Zhichun Road, Beijing, Haidian District Applicant before: Beijing Kexin Bicheng Medicine Science & Technology Developing Co., Ltd. |
|
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20120502 |