CN107041873A - The preparation method of rope fluorine cloth Wei coated tablet - Google Patents
The preparation method of rope fluorine cloth Wei coated tablet Download PDFInfo
- Publication number
- CN107041873A CN107041873A CN201710086054.8A CN201710086054A CN107041873A CN 107041873 A CN107041873 A CN 107041873A CN 201710086054 A CN201710086054 A CN 201710086054A CN 107041873 A CN107041873 A CN 107041873A
- Authority
- CN
- China
- Prior art keywords
- preparation
- cloth wei
- rope fluorine
- fluorine cloth
- coated tablet
- 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.)
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Classifications
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- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
- A61K9/2036—Silicones; Polysiloxanes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
Abstract
The present invention relates to field of pharmaceutical preparations, and in particular to a kind of rope fluorine cloth Wei coated tablet containing dimeticone auxiliary material.The tablet has good stability, and dissolution is not influenceed by temperature is coated.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, and in particular to a kind of preparation side of the rope fluorine cloth Wei coated tablet of Fast Stripping
Method.
Background technology
HCV (HCV) is to cause one of main pathogens of chronic hepatitis, mainly passes through blood born.According to generation
Boundary's health organization statistics, global HCV infection rate is about 3%, has about 1.8 hundred million people to infect HCV.HCV virus infection can cause
The necrosis of liver chronic inflammation and fibrosis, some patientss can develop into hepatic sclerosis even hepatocellular carcinoma.
The standard regimens of HCV infection are interferon-' alpha ' or Peg-IFN alpha-2b α joint Ribavirins, but this is controlled
The adverse drug reaction for the treatment of scheme is big, and unsatisfactory curative effect, its type of therapeutic gene 2 and 3 type HCV infection patients, and sustained virological should
It is 80% to answer (SVR), and there was only about 50% to the SVR of the type HCV infection person of gene 1.Rope fluorine cloth Wei is global first HCV specificity
The nucleosidic inhibitors of NS5B polymerases.Clinical test shows that rope fluorine cloth Wei and the full oral regimen of Ribavirin bigeminy can be used for controlling
The type of gene 2,3 type HCV infection are treated, 12 weeks SVR of medication are 78%.Rope fluorine cloth Wei combines Peg-IFN alpha-2b and Ribavirin
For the type of gene 1 and 4 type HCV infection, the SVR of medication 12 weeks is up to 90%.It takes simplicity to rope fluorine Bu Weiyin, and cure rate is high,
The low feature of adverse reaction rate, it has also become the heavy bomb drugs of hepatitis treatment.
CN104622836A is disclosed when preparing the coated tablet of the rope fluorine cloth Wei containing crystal formation 1, and the dissolution of medicine has
It is remarkably decreased.Reason is that tablet temperature is maintained at 46 ± 5 DEG C in conventional coating process, in the coated systems of the aqueous solution, brilliant
Type 1 easily forms hard plate-like solidification glue, causes disintegration of tablet slack-off, and drug-eluting speed is substantially reduced.To ensure medicine
Fast Stripping, CN104622836A uses the compound coating material containing ethyl cellulose and hydroxypropyl methylcellulose, to reduce bag
Clothing temperature is to 28 DEG C -38 DEG C.However, the non-large-scale commercial application of compound coating material, need to be particularly customized, cost is higher.
It is therefore an object of the present invention to provide it is a kind of can Fast Stripping, be adapted to industrialized production the rope fluorine cloth Wei of crystal formation 1
Coated tablet.
The content of the invention
The invention provides rope fluorine cloth Wei coated tablet of crystal formation 1 of a kind of Fast Stripping and preparation method thereof, it is adapted to industry
Change big production.
The rope fluorine cloth Wei coated tablet of crystal formation 1 of the present invention contains dimeticone auxiliary material.By substantial amounts of development test, this hair
It is bright it has surprisingly been found that using dimeticone the dissolution of the rope fluorine cloth Wei coated tablet of crystal formation 1 can be made not influenceed by temperature is coated.
Ripe commercialized conventional coating material can be used in the tablet of the present invention, is particularly suitable for industrialized production.
Present invention also offers a kind of preparation method of the rope fluorine cloth Wei coated tablet of crystal formation 1, comprise the following steps：
1) after rope fluorine cloth Wei, dimeticone and pharmaceutically acceptable auxiliary material being mixed, dry granulation；
2) tabletting after mixing obtained particle and pharmaceutically acceptable auxiliary material；
3) label is preheated in high-efficiency coating machine, and control sheet bed tempertaure is 40~55 DEG C, by coating solution even spraying to piece
Wicking surface is simultaneously fully dried, and obtains rope fluorine cloth Wei coated tablet.
Preferably, step 1) described in pharmaceutically acceptable accessory package contain microcrystalline cellulose, mannitol, cross-linked carboxymethyl
Sodium cellulosate, colloidal silica, stearic a kind of or its combination.
Preferably, step 2) described in pharmaceutically acceptable accessory package contain Ac-Di-Sol, colloidal state dioxy
SiClx, one kind of magnesium stearate or its combination.
Preferably, present invention also offers a kind of preparation method of the rope fluorine cloth Wei coated tablet of crystal formation 1, including such as
Lower step：
1) by rope fluorine cloth Wei, dimeticone, microcrystalline cellulose, mannitol, Ac-Di-Sol, colloidal silica
After silicon, stearic acid mixing, dry granulation；
2) tabletting after mixing obtained particle and Ac-Di-Sol, colloidal silica, magnesium stearate；
3) label obtained by tabletting is preheated in high-efficiency coating machine, and control sheet bed tempertaure is 40~55 DEG C, and coating solution is uniform
It is sprayed to piece wicking surface and fully dries, obtains rope fluorine cloth Wei coated tablet.
Preferably, the dimeticone content is the 3-10%, more preferably 3-8% of piece weight.
Preferably, the content of rope fluorine cloth Wei crystal formation 6 is the 10-50%, more preferably 30-35% of piece weight.
Preferably, the preparation method also includes the pretreatment of rope fluorine cloth Wei raw material, i.e., by rope fluorine cloth Wei raw material micro mist
Reason, preferable particle size d (90)≤100um.Rope fluorine cloth Wei exists in the form of crystal formation 1.
Preferably, coating weight gain is 1.0%~5.0%.
Preferably, coating material contain polyethylene glycol (PEG), hydroxypropyl methylcellulose (HPMC) or polyvinyl alcohol (PVA) it
One or its combination, antiplastering aid, opacifier, plasticizer, color lake etc. can be also contained in coating.Preferably, coating material can optional business
The coating material of industry, such as Opadry film coating powder.Preferably, in granulation step, granulation squeeze pressure control 10~
20kg。
Preferably, in tableting step, piece weight scope control is within ± 5%.
Preferably, the solvent of coating includes the aqueous solution of organic solvent or organic solvent, and wherein organic solvent is selected from second
Alcohol or acetone, it is highly preferred that organic solvent is selected from ethanol.
The present invention also provides a kind of rope fluorine cloth Wei troche medical composition, and it includes core and Extra Section, and it is wrapped
Containing following composition by weight percentage：
Core：
Extra Section：
Ac-Di-Sol 1-5%
Colloidal silica 0.1-2%
Magnesium stearate 0.1-3%
Brief description of the drawings
Fig. 1 is the x-ray diffractogram of powder of the sample of crystal formation 1.
Embodiment
Below by way of specific embodiment, the invention will be further described, but these embodiments are not meant that to the present invention
Any limitation.
Embodiment 1
The same CN102858790A of preparation method of rope fluorine cloth Wei crystal formation 1.Crystal form samples to acquisition carry out powder x-ray diffraction
Analysis, its result is as shown in Figure 1.Analysis result shows the feature spectrogram and the rope fluorine cloth Wei of document report of prepared crystal form samples
The spectrogram of crystal formation 1 is consistent, with about 5.0,7.3,9.4,18.1 θ of XRPD 2 reflections.
Embodiment 2：
The dissolution rate of the rope fluorine cloth Wei piece of crystal formation 1 is obtained using following detection method in the present invention：
It is molten with pH6.8 phosphate-buffered by dissolution method (the second methods of C of two annex of Chinese Pharmacopoeia 2010 edition Ⅹ)
Liquid (takes 0.2mol/L potassium dihydrogen phosphate 250ml, plus 0.2mol/L sodium hydroxide solution 118ml, is diluted with water to
1000ml, shakes up, both) 900ml is dissolution medium, 75 turns per minute, medium temperature is 37.0 DEG C, is operated in accordance with the law, through 15 points
Zhong Shi, takes solution 10ml, filtration；Subsequent filtrate is taken to be configured to every milliliter of solution containing about the μ g of rope fluorine cloth Wei 20, it is molten as test sample
Liquid, according to AAS (two A of annex IV of Chinese Pharmacopoeia version in 2010), trap is determined at 260nm wavelength respectively；Separately
Take rope fluorine cloth Wei reference substance appropriate, it is accurately weighed, plus every 1ml is made containing about rope fluorine cloth Wei in the dissolving of pH6.8 phosphate buffer solutions
20 μ g solution, is used as reference substance solution.The stripping quantity of every is calculated by external standard method.
Embodiment 3：
Rope fluorine cloth Wei granularity：D90=80 μm.
Preparation process：
1) pelletize：By the supplementary material rope fluorine cloth Wei of core recipe quantity, dimeticone, microcrystalline cellulose, mannitol, friendship
Join sodium carboxymethylcellulose, colloidal silica, magnesium stearate to be well mixed, dry granulation, whole grain；
2) it is total mixed：By obtained particle and Extra Section auxiliary material Ac-Di-Sol, colloidal silica, tristearin
Sour magnesium is always mixed；
3) tabletting：Adjustment sheet weight, main frame pressure, tabletting obtains plain piece.
4) it is coated：Plain piece is added in coating pan and is coated, about 45 DEG C of control sheet bed tempertaure.
Dissolution rate testing result shows that 15 minutes dissolution rates of coating tablet made from the above method are 96%.
Embodiment 4：
Rope fluorine cloth Wei granularity：D90=60 μm.
About 55 DEG C of control sheet bed tempertaure, the preparation method of other conditions be the same as Example 2 prepares rope fluorine cloth Wei tablet.
Dissolution rate testing result shows that 15 minutes dissolution rates of coating tablet made from the above method are 99%.
Embodiment 5：
The sample of embodiment 3 and 4 is detected, sample size is above 99% after 40 DEG C accelerate 6 months by HPLC, is shown
Good stability is shown.
Comparative example 1：
Rope fluorine cloth Wei granularity：D90=80 μm.
Preparation process：
1) pelletize：By supplementary material rope fluorine cloth Wei, microcrystalline cellulose, mannitol, the cross-linked carboxymethyl of core recipe quantity
Sodium cellulosate, colloidal silica, magnesium stearate are well mixed, dry granulation, whole grain；
2) it is total mixed：By obtained particle and Extra Section auxiliary material Ac-Di-Sol, colloidal silica, tristearin
Sour magnesium, diformazan silicon, it is total mixed；
3) tabletting：Adjustment sheet weight, main frame pressure, tabletting obtains plain piece.
4) it is coated：Plain piece is added in coating pan and is coated, about 45 DEG C of control sheet bed tempertaure.
Dissolution rate testing result shows that 15 minutes dissolution rates of coating tablet made from the above method are less than 90%.Therefore two
First silicone oil must be added in granulation, and just being added in tabletting can have a negative impact to tablet dissolution.
Comparative example 2：
Rope fluorine cloth Wei granularity：D90=80 μm.
The preparation method of be the same as Example 3 prepares rope fluorine cloth Wei tablet.
Dissolution rate testing result shows that 15 minutes dissolution rates of plain piece made from the above method and coating tablet are respectively 99%
With 87%.Therefore, when dimeticone auxiliary material is not used, the dissolution rate of coating tablet is substantially reduced, and causes active component quick
Dissolution.
Claims (10)
1. a kind of preparation method of the coated tablet of rope fluorine cloth Wei crystal formation 1, comprises the following steps：
1) after rope fluorine cloth Wei crystal formation 1, dimeticone and pharmaceutically acceptable auxiliary material being mixed, dry granulation；
2) tabletting after mixing obtained particle and pharmaceutically acceptable auxiliary material；
3) label is preheated in high-efficiency coating machine, and control sheet bed tempertaure is 40~55 DEG C, by coating solution even spraying to label table
Face is simultaneously fully dried, and obtains rope fluorine cloth Wei coated tablet.
2. preparation method according to claim 1, it is characterised in that the dimeticone content is the 3-10% of piece weight.
3. preparation method according to claim 1, it is characterised in that the dimeticone content is the 3-8% of piece weight.
4. preparation method according to claim 1, it is characterised in that step 1) described in pharmaceutically acceptable accessory package
Containing microcrystalline cellulose, mannitol, Ac-Di-Sol, colloidal silica, stearic a kind of or its combination.
5. preparation method according to claim 1, it is characterised in that step 2) described in pharmaceutically acceptable accessory package
Containing Ac-Di-Sol, colloidal silica, one kind of magnesium stearate or its combination.
6. preparation method according to claim 1, it is characterised in that the preparation method also includes rope fluorine cloth Wei raw material
Pretreatment, i.e., by the processing of rope fluorine cloth Wei raw material micro mist, particle diameter d (90)≤100um.
7. preparation method according to claim 1, it is characterised in that the content of rope fluorine cloth Wei crystal formation 1 is the 10- of piece weight
50%.
8. preparation method according to claim 1, it is characterised in that coating weight gain 1.0%~5.0%.
9. a kind of rope fluorine cloth Wei coated tablet according to prepared by claim any one of 1-8.
10. the rope fluorine cloth Wei coated tablet described in a kind of claim 9 is preparing the application for the treatment of hepatitis medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710086054.8A CN107041873B (en) | 2017-02-17 | 2017-02-17 | Preparation method of sofosbuvir coated tablet |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710086054.8A CN107041873B (en) | 2017-02-17 | 2017-02-17 | Preparation method of sofosbuvir coated tablet |
Publications (2)
| Publication Number | Publication Date |
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| CN107041873A true CN107041873A (en) | 2017-08-15 |
| CN107041873B CN107041873B (en) | 2020-02-28 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201710086054.8A Active CN107041873B (en) | 2017-02-17 | 2017-02-17 | Preparation method of sofosbuvir coated tablet |
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|---|---|---|---|---|
| US20140212491A1 (en) * | 2013-01-31 | 2014-07-31 | Gilead Pharmasset Llc | Combination formulation of two antiviral compounds |
| CN104039319A (en) * | 2011-11-29 | 2014-09-10 | 吉利德法莫赛特有限责任公司 | Compositions and methods for treating hepatitis c virus |
| CN104622836A (en) * | 2014-12-23 | 2015-05-20 | 浙江华海药业股份有限公司 | Sofosbuvircoated tablet and preparation method thereof |
| CN104840964A (en) * | 2015-05-07 | 2015-08-19 | 南京正大天晴制药有限公司 | Stable sofosbuvir drug combination and preparation method thereof |
| WO2015132321A1 (en) * | 2014-03-05 | 2015-09-11 | Galenicum Health S.L. | Stable pharmaceutical compositions of sofosbuvir |
| CN104906062A (en) * | 2015-06-30 | 2015-09-16 | 浙江天顺生物科技有限公司 | Sofosbuvir tablet and preparation method thereof |
| CN105380922A (en) * | 2015-12-18 | 2016-03-09 | 北京华禧联合科技发展有限公司 | Sofosbuvir film-coated tablets and preparation method thereof |
| WO2016178876A2 (en) * | 2015-05-01 | 2016-11-10 | Cocrystal Pharma, Inc. | Nucleoside analogs for treatment of the flaviviridae family of viruses and cancer |
-
2017
- 2017-02-17 CN CN201710086054.8A patent/CN107041873B/en active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104039319A (en) * | 2011-11-29 | 2014-09-10 | 吉利德法莫赛特有限责任公司 | Compositions and methods for treating hepatitis c virus |
| US20140212491A1 (en) * | 2013-01-31 | 2014-07-31 | Gilead Pharmasset Llc | Combination formulation of two antiviral compounds |
| WO2015132321A1 (en) * | 2014-03-05 | 2015-09-11 | Galenicum Health S.L. | Stable pharmaceutical compositions of sofosbuvir |
| CN104622836A (en) * | 2014-12-23 | 2015-05-20 | 浙江华海药业股份有限公司 | Sofosbuvircoated tablet and preparation method thereof |
| WO2016178876A2 (en) * | 2015-05-01 | 2016-11-10 | Cocrystal Pharma, Inc. | Nucleoside analogs for treatment of the flaviviridae family of viruses and cancer |
| CN104840964A (en) * | 2015-05-07 | 2015-08-19 | 南京正大天晴制药有限公司 | Stable sofosbuvir drug combination and preparation method thereof |
| CN104906062A (en) * | 2015-06-30 | 2015-09-16 | 浙江天顺生物科技有限公司 | Sofosbuvir tablet and preparation method thereof |
| CN105380922A (en) * | 2015-12-18 | 2016-03-09 | 北京华禧联合科技发展有限公司 | Sofosbuvir film-coated tablets and preparation method thereof |
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| CN107041873B (en) | 2020-02-28 |
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