CN107049977A - A kind of Carvedilol solid self-emulsifying sustained release tablets and preparation method thereof - Google Patents
A kind of Carvedilol solid self-emulsifying sustained release tablets and preparation method thereof Download PDFInfo
- Publication number
- CN107049977A CN107049977A CN201611149392.3A CN201611149392A CN107049977A CN 107049977 A CN107049977 A CN 107049977A CN 201611149392 A CN201611149392 A CN 201611149392A CN 107049977 A CN107049977 A CN 107049977A
- Authority
- CN
- China
- Prior art keywords
- emulsifying
- sustained release
- release tablets
- self
- carvedilol
- 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
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
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
-
- 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
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
-
- 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
- A61K9/2009—Inorganic compounds
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of preparation method of Carvedilol solid self-emulsifying sustained release tablets.Compound particle size is homogeneous first, the obvious hollow mesoporous silicon oxide of hollow structure, then using carry medicine hollow mesoporous silicon oxide as solid carrier, solidify liquid self-emulsifying, obtain Carvedilol solid self-emulsifying particle.Finally, Carvedilol solid self-emulsifying particle is well mixed with appropriate auxiliary material, wet granulation, tabletting obtains Carvedilol solid self-emulsifying sustained release tablets.This preparation method technique is simple, it is easy, with low cost to operate.Carvedilol solid self-emulsifying sustained release tablets produced by the present invention have obvious slow releasing function, have a extensive future.
Description
Technical field
The present invention relates to a kind of Carvedilol solid self-emulsifying sustained release tablets and preparation method thereof, belong to pharmaceutical technology field.
Background technology
Carvedilol (carvedilol, CAR) is a kind of new medicament for expanding vascellum, is clinically used for treating light moderate essential
Hypertension, ischemic heart disease and congestive heart failure.Carvedilol lipophilicity is strong, and dissolution rate is poor, and there is liver
First pass effect, it is low that these reasons result in Carvedilol bioavilability.In order to overcome these shortcomings, it is necessary to use preparation
Learn to do section and improve its bioavilability, such as Carvedilol cyclodextrin inclusion compound, Carvedilol physical dispersion body, Carvedilol are from micro-
Emulsification etc. preparation means.Therefore, develop can improve drug bioavailability method it is significant.
Hollow mesoporous silicon oxide is that, using hollow structure as core, porous silica layer is the dioxy of the nucleocapsid structure of shell
SiClx nano-particle.Meso-hole structure causes the hollow structure of inside to be connected with the external world, carries the hollow mesoporous silicon oxide of medicine and can lead to
Cross meso-hole structure and slowly discharge medicine, this effect makes it be had broad application prospects in medicament slow release field.And due to
There is hollow kernel, hollow mesoporous silicon oxide has bigger specific surface area and pore volume, therefore, in drug loading side
Face, hollow mesoporous silicon oxide has higher drugloading rate.
At present, the synthesis of hollow mesoporous silicon oxide has been achieved for very big progress, for preparing hollow structure, most often
It is exactly template and etching method.Template point soft template method and hard template method, but generally all there are problems that, such as
Soft template method, the size of hollow structure and the bad control of the thickness of shell, and for hard template method, remove the method phase of hollow template
To complicated, time-consuming, and template can not also be removed completely so that hollow structure is not obvious.Compared to the complexity of template, etching
Method is avoided using hollow template, still, and etching agent is bad to be removed and harmful to body.Therefore, develop and do not use hollow template
The method that hollow mesoporous silicon oxide is prepared with etching agent is significant.
Solid self-emulsifying is the solid pharmaceutical preparation for being mixed with liquid self-emulsifying microemulsion component and suitable solid carrier, liquid
Self-emulsifying microemulsion is usually liquid dosage form, is encapsulated in soft capsule or hard shell capsules, thus bring that production process is complicated, cost is higher,
The shortcomings of capsule leakage and single formulation may occur in long term storage, and solid self-emulsifying is to combine liquid self-emulsifying and solid
The two-fold advantage of body preparation, with stability increase, storage time extension, GI irritation reduce, it is convenient to take the features such as.
The content of the invention
The present invention for Carvedilol solubility it is low, poor bioavailability, and liver first-pass effect it is serious the problems such as, if
A kind of Carvedilol solid self-emulsifying sustained release tablets are counted, the invention provides to carry the hollow mesoporous silicon oxide of medicine as solid carrier
Carvedilol solid self-emulsifying sustained release tablets preparation method, specific preparation process is as follows：
(1) synthesis of solid carrier：Hollow mesoporous silicon oxide, 1：Mesoporous template cetyl trimethylammonium bromide is surpassed
Sound is dissolved in the aqueous solution of ethanol, adds ammoniacal liquor, and magnetic agitation is uniform；2：Tetraethyl orthosilicate is added into above-mentioned mixed solution
In to generate the mesoporous silicon oxide of containing mesopore template；3：Above-mentioned products therefrom is dissolved in deionized water, etched under high temperature,
Obtain the hollow mesoporous silicon oxide of containing mesopore template；4：Above-mentioned products therefrom is placed in flow back in hydrochloric acid/ethanol solution and gone
Except mesoporous template, filtration drying can obtain hollow mesoporous silicon oxide；
(2) liquid self-emulsifiable preparation is prepared：Oil phase, emulsifying agent, assistant for emulsifying agent are sequentially added, vortex oscillation is well mixed；
(3) sustained release tablets are prepared：To carry the hollow mesoporous silicon oxide of medicine as solid carrier, direct adsorptive liquid self-emulsifying,
Carvedilol solid self-emulsifying particle is formed, appropriate auxiliary material is added, prepares Carvedilol solid self-emulsifying sustained release tablets.
In step (1), the consumption of mesoporous template cetyl trimethylammonium bromide is in 0.7g~1.0g, preferably
0.9g；Ethanol: the ratio of deionized water is 180ml/300ml；The consumption of ammoniacal liquor is in 4ml~10ml, preferably 8ml；Magnetic agitation
One hour, it is well mixed, tetraethyl orthosilicate is added dropwise with 1ml/min speed.
In step (1), the consumption of deionized water is in 150~400ml, preferably 250ml；High temperature etching temperature is 60~90
DEG C, preferably 90 DEG C；The time 24h of etching~96h, preferably 72h；During removing template, ethanol consumption 120ml, hydrochloric acid consumption is
1.5ml, flows back twice, a 3h.
In step (1), the particle diameter of the hollow mesoporous silicon oxide of acquisition is 550nm~650nm, and average pore size is
3.02nm, hollow structure is obvious.
In step (2), selected oil phase is sad certain herbaceous plants with big flowers acid glycerol three ester, and emulsifying agent is Tween 80, and assistant for emulsifying agent is
PEG400, ratio is 3: 3: 4, and liquid self-emulsifying particle diameter is 100~200nm.
In step (3), liquid self emulsifying emulsions are adsorbed on the hollow mesoporous silicon oxide for carrying medicine, card dimension ground is formed
Lip river solid self-emulsifying particle, is then filler from microcrystalline cellulose, PVPP is disintegrant, polyvinylpyrrolidone
K30 is adhesive, and talcum powder is lubricant, and Carvedilol solid self-emulsifying sustained release tablets are made in wet granulation, tabletting.
The advantage of the invention is that：
(1) solubility of the Carvedilol in water is very low, and poor bioavailability has serious first pass effect.The present invention is adopted
Improve the shortcoming of Carvedilol with self-emulsifying microemulsion technology, improve the shortcoming of liquid self-emulsifying microemulsion, and hollow Jie with solid carrier
Hole silica has slow releasing function, is finally obtained the Carvedilol solid self-emusifying tablet with slow releasing function.
(2) preparation method of the invention is less demanding to instrument and equipment, and technical process is simple, can be amplified industrial metaplasia
Production, has a good application prospect.
Brief description of the drawings
Fig. 1 is hollow mesoporous silicon oxide scanning electron microscope diagram prepared by embodiment 1.
Fig. 2 is hollow mesoporous silicon oxide scanning electron microscope diagram prepared by embodiment 2.
Fig. 3 is the graph of pore diameter distribution of hollow mesoporous silicon oxide prepared by embodiment 2.
Fig. 4 is infared spectrum.(1) it is CAR, (2) are physical mixture, and (3) are CAR-HMS, and (4) are HMS.
Embodiment
Embodiment 1：The preparation of hollow mesoporous silicon oxide
(1) the accurate cetyl trimethylammonium bromide for weighing 0.9g, is dissolved in 180ml/300ml ethanol waters, magnetic
Power is stirred to being completely dissolved, and adds 8ml ammoniacal liquor, and magnetic agitation one hour is well mixed, and then adds tetraethyl orthosilicate, with
1ml/min speed is added dropwise, stirring reaction 6h, obtains white emulsion.Filtration washing is obtained containing cetyl trimethyl bromine
Change the mesoporous silicon oxide of ammonium.
(2) mesoporous silicon oxide for taking 0.5g above-mentioned is put into 150ml deionized waters, and 90 DEG C of high temperature etch 72h, cross diafiltration
Wash and obtain the hollow mesoporous silicon oxide containing cetyl trimethylammonium bromide, take the hollow mesoporous silicon oxide that 0.5g is above-mentioned
In acidity alcohol solution backflow 3h, cetyl trimethylammonium bromide is removed, twice, filtration washing obtains hollow mesoporous dioxy for backflow
SiClx.
Embodiment 2：The preparation of hollow mesoporous silicon oxide
The present embodiment is substantially the same manner as Example 1, the difference is that only：Cetyl trimethylammonium bromide consumption is
0.7g, ammonia volume is 4ml, stirring reaction 12h, takes 0.3g mesoporous silicon oxides to be put into 200ml deionized waters high temperature etching,
Temperature is 60 DEG C, and etch period is 48h.
Embodiment 3：The preparation of Carvedilol solid self-emulsifying particle
The liquid self-emulsifying that total amount is 100 microlitres is measured in 3: 3: 4 oil phase: emulsifying agent: the ratio of assistant for emulsifying agent, is vortexed
Shaken well, with the hollow mesoporous silicon oxide adsorptive liquid self-emulsifying for carrying medicine, obtains Carvedilol solid self-emulsifying particle.
Embodiment 4：The preparation of Carvedilol solid self-emulsifying sustained release tablets
It is filler from microcrystalline cellulose, PVPP is disintegrant, and PVP K30 is adhesive,
Talcum powder is lubricant, and Carvedilol solid self-emulsifying sustained release tablets are made in wet granulation, tabletting.
Carvedilol solid self-emulsifying sustained release tablets tablets in vitro is studied：Carvedilol solid self-emulsifying sustained release tablets 6 are taken, are used
Dissolution method (two methods of annex XC second of Chinese Pharmacopoeia 2010 edition) apparatus, according to drug release determination method (Chinese Pharmacopoeia
2010 editions two methods of annex XD first), using 900mlPH6.8 phosphate buffer solutions as solvent, 37 DEG C of temperature, rotating speed is 100r/
Min, is operated in accordance with the law, and solution 5ml is taken respectively in 2,4,6,8,12,24h, filtering, and adds equivalent isothermal phosphate-buffered in time
Solution, takes subsequent filtrate, and trap is determined at 241nm wavelength, calculates Accumulation dissolution.It is as shown in table 1 below, prepared by the method
Carvedilol solid self-emulsifying sustained release tablets have obvious slow releasing function.
The Carvedilol solid self-emulsifying sustained release tablets Accumulation dissolution measurement result of table 1
Claims (7)
1. a kind of Carvedilol solid self-emulsifying sustained release tablets and preparation method thereof, it is characterised in that：This method comprises the following steps：
(1) synthesis of solid carrier：Hollow mesoporous silicon oxide, 1：Mesoporous template cetyl trimethylammonium bromide ultrasound is molten
Solution adds ammoniacal liquor in the aqueous solution of ethanol, and magnetic agitation is uniform；2：By tetraethyl orthosilicate add in above-mentioned mixed solution with
Generate the mesoporous silicon oxide of containing mesopore template；3：Above-mentioned products therefrom is dissolved in deionized water, etched under high temperature, is obtained
The hollow mesoporous silicon oxide of containing mesopore template；4：Above-mentioned products therefrom is placed in backflow in hydrochloric acid/ethanol solution and removed and is situated between
Hole template, filtration drying can obtain hollow mesoporous silicon oxide；
(2) liquid self-emulsifiable preparation is prepared：Oil phase, emulsifying agent, assistant for emulsifying agent are sequentially added, vortex oscillation is well mixed；
(3) sustained release tablets are prepared：To carry the hollow mesoporous silicon oxide of medicine as solid carrier, direct adsorptive liquid self-emulsifying is formed
Carvedilol solid self-emulsifying particle, adds appropriate auxiliary material, prepares Carvedilol solid self-emulsifying sustained release tablets.
2. a kind of Carvedilol solid self-emulsifying sustained release tablets and preparation method thereof according to claim 1, it is characterised in that：
In step (1), the consumption of mesoporous template cetyl trimethylammonium bromide is between 0.7g~1.0g, preferably 0.9g；Ethanol:
The ratio of deionized water is 180ml/300ml；The consumption of ammoniacal liquor is in 4ml~10ml, preferably 8ml；Magnetic agitation one hour, mixing
Uniformly, tetraethyl orthosilicate is added dropwise with 1ml/min speed.
3. a kind of Carvedilol solid self-emulsifying sustained release tablets and preparation method thereof according to claim 1, it is characterised in that：
In step (1), the consumption of deionized water is in 150~400ml, preferably 250ml；High temperature etching temperature is in 60~90 DEG C, preferably 90
℃；The time 24h of etching~96h, preferably 72h；During removing template, ethanol consumption 120ml, hydrochloric acid consumption is 1.5ml, backflow two
It is secondary, a 3h.
4. a kind of Carvedilol solid self-emulsifying sustained release tablets and preparation method thereof according to claim 1, it is characterised in that：
In step (1), the particle diameter of the hollow mesoporous silicon oxide of acquisition is 550nm~650nm, and average pore size is 3.02nm, hollow knot
Structure is obvious.
5. a kind of Carvedilol solid self-emulsifying sustained release tablets and preparation method thereof according to claim 1, it is characterised in that：
In step (2), selected oil phase is sad certain herbaceous plants with big flowers acid glycerol three ester, and emulsifying agent is Tween 80, and assistant for emulsifying agent is PEG400, and ratio is
3: 3: 4, liquid self-emulsifying particle diameter is 100~200nm.
6. a kind of Carvedilol solid self-emulsifying sustained release tablets and preparation method thereof according to claim 1, it is characterised in that：
In step (3), liquid self emulsifying emulsions are adsorbed on the hollow mesoporous silicon oxide for carrying medicine, Carvedilol solid are formed from breast
Change particle, be then filler from microcrystalline cellulose, PVPP is disintegrant, and PVP K30 is bonding
Agent, talcum powder is lubricant, and Carvedilol solid self-emulsifying sustained release tablets are made in wet granulation, tabletting.
7. a kind of Carvedilol solid self-emulsifying sustained release tablets and preparation method thereof according to claim 1, it is characterised in that：
In step (3), the Carvedilol solid self-emulsifying sustained release tablets of acquisition have obvious slow releasing function.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611149392.3A CN107049977A (en) | 2016-12-08 | 2016-12-08 | A kind of Carvedilol solid self-emulsifying sustained release tablets and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611149392.3A CN107049977A (en) | 2016-12-08 | 2016-12-08 | A kind of Carvedilol solid self-emulsifying sustained release tablets and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107049977A true CN107049977A (en) | 2017-08-18 |
Family
ID=59619330
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201611149392.3A Pending CN107049977A (en) | 2016-12-08 | 2016-12-08 | A kind of Carvedilol solid self-emulsifying sustained release tablets and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107049977A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1823743A (en) * | 2005-12-26 | 2006-08-30 | 沈阳药科大学 | Self emulsified osmotic pump controlled release administration system of liposoluble medicine and its preparation technology |
| CN104524587A (en) * | 2014-12-03 | 2015-04-22 | 上海交通大学 | Antibacterial drug system and preparation method thereof |
-
2016
- 2016-12-08 CN CN201611149392.3A patent/CN107049977A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1823743A (en) * | 2005-12-26 | 2006-08-30 | 沈阳药科大学 | Self emulsified osmotic pump controlled release administration system of liposoluble medicine and its preparation technology |
| CN104524587A (en) * | 2014-12-03 | 2015-04-22 | 上海交通大学 | Antibacterial drug system and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6799612B2 (en) | Palbociclib pharmaceutical formulation and its preparation method | |
| CN102920654B (en) | Valsartan spray-dried nanosuspension and preparation method of valsartan spray-dried nanosuspension | |
| CN106389374A (en) | Pharmaceutical composition containing LCZ696 and preparation method of pharmaceutical composition | |
| CN102861106B (en) | Preparation method of compound paracetamol and amantadine pellets | |
| CN104447933B (en) | A kind of synthetic method of pharmaceutical grade Deslanoside | |
| CN107049977A (en) | A kind of Carvedilol solid self-emulsifying sustained release tablets and preparation method thereof | |
| CN103585122A (en) | Tablet containing everolimus, and preparation method thereof | |
| CN101780046B (en) | Itraconazole composite powder and preparation method thereof | |
| CN103804310A (en) | Method for preparing high-purity 7-chloro-5-phenyl-benzodiazepine-2-one | |
| CN106692057A (en) | Ibuprofen cubic liquid crystal precursor solution, cubic liquid crystal nanoparticles and preparation method of cubic liquid crystal nanoparticles | |
| CN104644599B (en) | Isosorbide mononitrate micro-porous osmotic pump controlled release preparation and preparation method thereof | |
| CN103936808A (en) | Isonicotinamide eutectic crystal of 17beta estradiol, and preparation method and application thereof | |
| CN108498455A (en) | A kind of water-soluble medicament nano crystalline substance of oiliness and preparation method thereof | |
| CN102274204B (en) | Omeprazole enteric-coated capsule and preparation method theroef | |
| CN103271902B (en) | A kind of insoluble medicine solid dispersoid and preparation method thereof | |
| CN104606139A (en) | Preparation and application of drug powder | |
| CN106361727A (en) | Bilobalide-PVA nanoparticle and preparation method thereof | |
| CN102274274B (en) | Self-microemulsifiable kudzu root flavone oral micro-pill composition and preparation method thereof | |
| CN104162167A (en) | Tamibarotene cyclodextrin or cyclodextrin derivative clathrate and preparation method thereof | |
| CN108324686A (en) | A kind of ellagic acid is from micro emulsion and preparation method thereof | |
| CN105566294B (en) | A kind of dextrorotation Iprazole sodium compound and its pharmaceutical composition | |
| CN107441047A (en) | A kind of preparation method of the dendrobine liposome based on Active loading mode | |
| CN103169691A (en) | Dronedarone or powder of salt thereof and pharmaceutical composition prepared therefrom | |
| CN102343100B (en) | Method for quickly preparing rutin inclusion compound | |
| CN106924206A (en) | A kind of net oral solid formulations of Yi Gelie and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20170818 |
|
| WD01 | Invention patent application deemed withdrawn after publication |