CN106822020A - A kind of Ezetimibe tablet - Google Patents
A kind of Ezetimibe tablet Download PDFInfo
- Publication number
- CN106822020A CN106822020A CN201710092850.2A CN201710092850A CN106822020A CN 106822020 A CN106822020 A CN 106822020A CN 201710092850 A CN201710092850 A CN 201710092850A CN 106822020 A CN106822020 A CN 106822020A
- Authority
- CN
- China
- Prior art keywords
- ezetimibe
- pluronics
- tablet according
- polyethylene glycol
- fused solution
- 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
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Classifications
-
- 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
- A61K9/2853—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/397—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
-
- 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
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
Abstract
The invention belongs to pharmaceutical technology field, there is provided a kind of Ezetimibe tablet, it is prepared from by following methods, polyethylene glycol, PLURONICS F87 heating melting are made fused solution, Ezetimibe is added, is stirred to dissolve, then fused solution is coated and is prepared from after blank surface forms coatings；Described blank includes filler, disintegrant and lubricant.Compared with prior art, drug-eluting speed is fast, and stability is high for the present invention.
Description
Technical field
The invention belongs to pharmaceutical technology field, and in particular to a kind of Ezetimibe tablet.
Background technology
Entitled 1- (4- fluorophenyls) -3 (R)-[(the S)-hydroxypropyls of 3- (4- fluorophenyls) -3] -4 (S)-(4- of Ezetimibe chemistry
Hydroxyphenyl) -2- aza cyclo-butanones.White crystalline powder, it is readily soluble in ethanol, methyl alcohol and acetone, it is almost insoluble in water, according to folding
About 163 DEG C of wheat cloth fusing point, stablizes at room temperature.Clinic is mainly used in primary hypercholesterolemia, can individually or and HMG-CoA
Reductase inhibitor such as Statins is united and applied in treatment hypercholesterolemia, it is possible to decrease T-CHOL (TC), low-density lipoprotein
White cholesterol (LDL-C), apolipoprotein B (ApoB), or as the complementary therapy of other lipid-lowering therapies, can also be in other drops
For reducing TC the and LDL-C levels of HoFH patient when fat is failed to respond to any medical treatment.
Ezetimibe is water insoluble, and according to BCS genealogical classification judgment principles, Ezetimibe belongs to low-solubility, Thief zone
The BCS II class compounds of property.When the solid dosage forms of Ezetimibe is used by oral administration, the medicine must dissolve in ability in gastric juice
Curative effect is played by absorbing.The common preparation of the solid oral dosage form being made, such as tablet is usually because its rate of dissolution is limited
Its bioavilability, so as to have impact on the curative effect of medicine.Therefore how to improve compound dissolubility to expire by preparation technique
Sufficient dissolution rate and stability requirement, so as to ensure that the product effectively plays its therapeutic action, are finally reached and former triturate phase
Consistent quality, tool is of great significance and is worth.
Insoluble drug by reducing one of conventional method of increase solubility of granularity often formulation art, by reality
Test and show to reduce the granularity of Ezetimibe raw material by various modes to wish that improving dissolubility can not effectively make according to folding wheat
The dissolution rate of cloth is improved and reaches gratifying scope.So how to improve the solubility of preparation, increase bioavilability, turn into
A urgent demand in this research.
Patent CN103655481A uses ball milling solid dispersion technology, by Ezetimibe and pharmaceutically acceptable auxiliary material system
It is standby into solid orally ingestible.Although improve the dissolution rate of preparation, medicine and milling material are ground, milling material pole has
May be brought into medicine ball milling fine powder, unsafe factor is brought to patient medication.This is also that current ball grinding technique is generally acknowledged
Potential risk.
Patent CN103655453A is that Ezetimibe is suspended in appropriate solvent, is prepared into homogeneous Ezetimibe micro-
Meter level suspension solution；Again with suspension solution using spraying by the way of, pelletized using marumerization, by obtained particle preparation into
The medicinal minimum dose unit of Ezetimibe.Dissolution only 95% in 15min, not yet complete dissolution.
Patent CN102292072A is disclosed with the method for drug microparticles coating carrier.Coating carrier can be in one-step method
Middle acquisition, the method needs the evaporation solvent from the solution droplets comprising API to obtain dry particulate, is then coated in carrier
On.But need special production equipment, industrialization is more difficult, and can not be quick and complete dissolution.
The lot of advantages such as there is solubility to improve for the micronizing of insoluble drug, dissolution rate quickening.But, direct micro mist
Chemical drug thing have the shortcomings that one it is common：Powder compounds are very easy to reunite, and usually prevent it from fully showing the excellent of micronizing
More property.Solid dispersions technique can improve the dissolution rate and bioavilability of Ezetimibe, but the preparation method is not made us
It is very satisfied because solid dispersions be long placed in easily it is aging, the Dissolution of Tablet of preparation improves a lot, but dispersion is too viscous
Thick, it is difficult to take out, industrialization is difficult.And need, using substantial amounts of carrier and some other pharmaceutic adjuvants, to cause the body of preparation
Product is excessive, is difficult to be received by patient.
The content of the invention
In view of prior art defect, inventor intends providing a kind of new Ezetimibe tablet, with high stability and quickly
The characteristics of dissolution.
Specifically, the present invention is realized by following technology：
The invention provides a kind of Ezetimibe tablet, it is prepared from by following methods：By polyethylene glycol, poloxamer
188 heating meltings are made fused solution, add Ezetimibe, are stirred to dissolve, and then fused solution is coated in blank surface shape
It is prepared from after into coatings；Described blank includes filler, disintegrant and lubricant.
Described Ezetimibe tablet, Ezetimibe is 1 with the weight ratio of polyethylene glycol:0.1-1, preferably 1:0.6.
Described Ezetimibe tablet, Ezetimibe is 1 with the weight ratio of PLURONICS F87:1-10, preferably 1:6.
Described Ezetimibe tablet, filler is selected from following one or more：Microcrystalline cellulose, lactose, mannitol,
Starch and dextrin；Described disintegrant is selected from following one or more：Sodium carboxymethyl starch, Ac-Di-Sol,
PVPP and low-substituted hydroxypropyl cellulose；Described lubricant is selected from following one or more：Magnesium stearate, tristearin
Furmaric acid sodium, talcum powder and silica.
Compared with prior art, drug-eluting speed is fast, and stability is high for the present invention.
Specific embodiment
Following examples further describe beneficial effects of the present invention, and embodiment is only used for the purpose of illustration, and this is not limited
The scope of invention, while those of ordinary skill in the art are also contained according to the obvious change made of the invention and modification
Within the scope of the invention.
Embodiment 1
Preparation technology：
Recipe quantity mannitol, low-substituted hydroxypropyl cellulose, magnesium stearate, are well mixed, and compressing tablet obtains blank.
After by Macrogol 4000,80 DEG C of heating meltings of PLURONICS F87, Ezetimibe is added to be stirred to dissolve, then
Fused solution is coated on blank and was both obtained.
Embodiment 2
Preparation technology：
Recipe quantity lactose, Ac-Di-Sol, magnesium stearate, are well mixed, and compressing tablet obtains blank.
After by Macrogol 6000,80 DEG C of heating meltings of PLURONICS F87, Ezetimibe is added to be stirred to dissolve, then
Fused solution is coated on blank and was both obtained.
Embodiment 3
Preparation technology：
Recipe quantity lactose, microcrystalline cellulose, PVPP, magnesium stearate, are well mixed, and compressing tablet obtains blank.
After by polyethylene glycol 1500,90 DEG C of heating meltings of PLURONICS F87, Ezetimibe is added to be stirred to dissolve, then
Fused solution is coated on blank and was both obtained.
Embodiment 4
Preparation technology：
Recipe quantity mannitol, low-substituted hydroxypropyl cellulose, magnesium stearate, are well mixed, and compressing tablet obtains blank.
After by 80 DEG C of heating meltings of Macrogol 4000, Ezetimibe is added to be stirred to dissolve, then by fused solution in sky
It is coated in white tiles and both obtained.
Embodiment 5
Preparation technology：
Recipe quantity mannitol, low-substituted hydroxypropyl cellulose, magnesium stearate, are well mixed, and compressing tablet obtains blank.
After by 80 DEG C of heating meltings of PLURONICS F87, Ezetimibe is added to be stirred to dissolve, then by fused solution in sky
It is coated in white tiles and both obtained.
Comparative example 1
Preparation technology：
Macrogol 4000,80 DEG C of heating meltings of copolyvidone, are subsequently adding recipe quantity Ezetimibe, are stirred to dissolve,
Then this fused solution is pelletized on the mixed powder of mannitol and sodium carboxymethyl starch, 20 mesh sieve whole grains add recipe quantity stearic acid
Magnesium, closes uniform, and compressing tablet is formed.
Comparative example 2
Preparation technology：
PVP K-30 and Ezetimibe are dissolved in 95% ethanol.Lactose is placed in wet granulator,
With PVP K-30 and the ethanol solution of Ezetimibe 95% granulation 60S.Obtained particle is together with PVPP
It is placed in mixer and mixes 30 minutes, add magnesium stearate to remix 3 minutes, compressing tablet determines dissolution.
Comparative example 3
Preparation technology：
Ezetimibe air-flow crushing, D90=9.6 μm, lactose then with recipe quantity, sodium carboxymethyl starch mixing are equal
It is even, recipe quantity magnesium stearate is added, it is well mixed, compressing tablet is formed.
Comparative example 4
Preparation technology：
1g polyvinylpyrrolidones k30 is dissolved in pure water, the 5% polyvinylpyrrolidone k30 aqueous solution is obtained；Will be according to folding
Mai Bu, lactose, lauryl sodium sulfate, after being sufficiently mixed, add the 5% polyvinylpyrrolidone k30 aqueous solution to be well mixed, system
Grain 1 minute, 60 DEG C of dryings, dry particle crosses 20 eye mesh screen whole grains.Particle ball milling 10 minutes in ball mill, ball milling powder crosses 50 mesh
Sieve；Microcrystalline cellulose and Ac-Di-Sol are added in ball milling powder, are sufficiently mixed.5% is added in mixed powder
The polyvinylpyrrolidone k30 aqueous solution, is well mixed, and pelletizes 1 minute, and 60 DEG C of dryings, dry particle crosses 20 eye mesh screen whole grains.Will
The particle for obtaining mixes 20 minutes with Ac-Di-Sol, then 5 minutes, compressing tablet are well mixed with magnesium stearate.
Checking embodiment
Dissolution determination：Determined according to Chinese Pharmacopoeia version in 2010 two annex are lower, paddle method, rotating speed be with 50 revs/min,
Dissolution medium contains in the acetate buffer of 0.45% lauryl sodium sulfate for 900ml, with UV detectors under 234nm
Detection, 15min dissolutions limit is 80%.
Each embodiment dissolution determination result
As seen from the table, embodiment of the present invention 1-3 dissolutions are rapid, and dissolution is substantially unchanged after acceleration；4,5 five points of embodiment
Clock dissolution rate is slightly worse.The preparation method of comparative example 1 is different from the present invention, although all using melting, but dissolution rate is relative to this
Invention also has gap.Comparative example 2, are provided without the technology of the present invention, therefore dissolution is unhappy；Comparative example 3, at raw material micronizing
Reason, dissolution is more of the invention slow；Comparative example 4, and using disclosed ball grinding technique, dissolution is more of the invention slow.
Claims (6)
1. a kind of Ezetimibe tablet, it is characterised in that be prepared from by following methods：Polyethylene glycol, PLURONICS F87 are added
Heat fusing is made fused solution, adds Ezetimibe, is stirred to dissolve, and is then coated fused solution and forms coating on blank surface
It is prepared from after layer；Described blank includes filler, disintegrant and lubricant.
2. Ezetimibe tablet according to claim 1, it is characterised in that Ezetimibe is with the weight ratio of polyethylene glycol
1:0.1-1。
3. Ezetimibe tablet according to claim 1, it is characterised in that Ezetimibe is with the weight ratio of polyethylene glycol
1:0.6。
4. Ezetimibe tablet according to claim 1, it is characterised in that the weight of Ezetimibe and PLURONICS F87
Than being 1:1-10.
5. Ezetimibe tablet according to claim 1, it is characterised in that the weight of Ezetimibe and PLURONICS F87
Than being 1:6.
6. Ezetimibe tablet according to claim 1, it is characterised in that filler is selected from following one or more：
Microcrystalline cellulose, lactose, mannitol, starch and dextrin；Described disintegrant is selected from following one or more：CMS
Sodium, Ac-Di-Sol, PVPP and low-substituted hydroxypropyl cellulose；Described lubricant is selected from following one
Plant or various：Magnesium stearate, sodium stearyl fumarate, talcum powder and silica.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710092850.2A CN106822020A (en) | 2017-02-21 | 2017-02-21 | A kind of Ezetimibe tablet |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710092850.2A CN106822020A (en) | 2017-02-21 | 2017-02-21 | A kind of Ezetimibe tablet |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106822020A true CN106822020A (en) | 2017-06-13 |
Family
ID=59133856
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710092850.2A Pending CN106822020A (en) | 2017-02-21 | 2017-02-21 | A kind of Ezetimibe tablet |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106822020A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111803458A (en) * | 2020-08-10 | 2020-10-23 | 北京福元医药股份有限公司 | Ezetimibe pharmaceutical preparation |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101375834A (en) * | 2007-09-02 | 2009-03-04 | 杨喜鸿 | Solid dispersion of Ailamode and preparation method thereof and medicament application |
| CN102362863A (en) * | 2011-11-21 | 2012-02-29 | 山东新时代药业有限公司 | Orlistat-containing preparation and preparation method thereof |
| CN103655453A (en) * | 2013-12-27 | 2014-03-26 | 华润赛科药业有限责任公司 | Preparation method of ezetimibe medicine composition |
| CN104666260A (en) * | 2015-02-03 | 2015-06-03 | 山东新时代药业有限公司 | Ezetimibe tablet |
| CN104825407A (en) * | 2015-04-20 | 2015-08-12 | 山东新时代药业有限公司 | Ezetimibe tablet |
-
2017
- 2017-02-21 CN CN201710092850.2A patent/CN106822020A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101375834A (en) * | 2007-09-02 | 2009-03-04 | 杨喜鸿 | Solid dispersion of Ailamode and preparation method thereof and medicament application |
| CN102362863A (en) * | 2011-11-21 | 2012-02-29 | 山东新时代药业有限公司 | Orlistat-containing preparation and preparation method thereof |
| CN103655453A (en) * | 2013-12-27 | 2014-03-26 | 华润赛科药业有限责任公司 | Preparation method of ezetimibe medicine composition |
| CN104666260A (en) * | 2015-02-03 | 2015-06-03 | 山东新时代药业有限公司 | Ezetimibe tablet |
| CN104825407A (en) * | 2015-04-20 | 2015-08-12 | 山东新时代药业有限公司 | Ezetimibe tablet |
Non-Patent Citations (1)
| Title |
|---|
| 刘晓杰 等: "依折麦布固体分散体的制备及其体外溶出", 《沈阳药科大学学报》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111803458A (en) * | 2020-08-10 | 2020-10-23 | 北京福元医药股份有限公司 | Ezetimibe pharmaceutical preparation |
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| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170613 |
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| RJ01 | Rejection of invention patent application after publication |