CN103211788B - Nifedipine film-controlled slow-release micro pill capsule - Google Patents
Nifedipine film-controlled slow-release micro pill capsule Download PDFInfo
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Abstract
The present invention relates to a kind of nifedipine film-controlled slow-release micro pill capsule, the sustained release clothing film of its micropill as filmogen, meets the Ac-Di-Sol that water contains high-expansion, the percentage for accounting for capsule core weight is 5~20% using Eurdragit RL 30D in capsule core；Excipient preferably microcrystalline cellulose, lactose are used as solubilizer as filler and PEG 4000.It is sustained clothing film and includes Eurdragit RL 30D, plasticizer triethyl citrate and antiplastering aid talcum powder, its ratio is preferably Eurdragit RL 30D: triethyl citrate: talcum powder=30: 3: 4, coating weight gain is preferably 21~35%.Due to can substantially be expanded after capsule core water suction, sustained release clothing film is caused to be stretched thinning, the aperture of permeable micropore becomes big, and permeability improves, and the permeability that compensate for film aging generation declines, and stable release performance can be remained before the deadline.
Description
Technical field
The present invention relates to a kind of nifedipine film-controlled slow-release micro pill capsule, it particularly relates to which a kind of capsule core is containing crosslinking
The nifedipine film-controlled slow-release micro pill capsule of sodium carboxymethylcellulose, belongs to field of pharmaceutical preparations.
Background technology
Nifedipine is calcium antagonist, passes through the flow of calcium ions of selective antagonizing vessel smooth muscle, diastole peripheral resistance
Blood vessel, reduces peripheral resistance, for treating hypertension；Suppress myocardial contraction, reduce myocardial metabolism, reduce myocardial oxygen consumption, use
In treatment angina pectoris.
Nifedipine is almost insoluble in water, and the ordinary preparation listed earliest need to take 2 times, blood concentration fluctuation daily
Greatly, Cmax is too high, and adverse reaction is serious.
Beyer Co., Ltd has listed nifedipine osmotic pump controlled release tablet (trade name：Nifedipine), Zero order release can be accomplished, released the drug
Uniformly, the easy aging of pellicle constituted using macromolecular material is had the disadvantage, medicament residue is big, it is therefore necessary at least thrown by 115%
Material, just can ensure that the drug release in the effect end of term so that osmotic pumps technology is difficult to be used widely.
Sustained release pellet is that medicine is made into multiunit slow-release system, general to load oral after capsule, capsule dissolving
Afterwards, sustained release pellet energy is extensive, be evenly distributed in intestines and stomach.Distribution area of the medicine on stomach and intestine surface increases, and is ensureing medicine
Thing can also effectively reduce stimulation of the medicine to intestines and stomach while uniformly release.Micropill preparation particle diameter is smaller, turning in intestines and stomach
Fortune is not influenceed by the food conveying rhythm and pace of moving things, when pyloric sphincter is closed, is remained to by pylorus, therefore particulate is in intestines and stomach
Absorption do not influenceed by gastric emptying typically.What is more important, the drug release behavior of micropill system is each of one dosage of composition
The summation of individual micropill drug release behavior, error or defect of indivedual micropills in preparation will not be produced to the drug release behavior of whole preparation
Have a strong impact on, therefore better than the slow, Dospan being made up of a unit in terms of the reappearance and uniformity of drug release rule.
Nifedipine is suitable to sustained-release pellet preparation is made, and effective blood drug concentration duration length, blood concentration fluctuation are small, pair
The small, individual difference of effect is small, patient compliance is good.
The most frequently used implementation method of sustained release pellet is to use film controlling type, i.e., wrap one with solution coating method in the outside of capsule core
Layer sustained release clothing film, sustained release clothing film contains filmogen, plasticizer, antiplastering aid etc..It is many in one's early years that sustained release is prepared using organic solvent
The coating solution of clothing film, because organic solvent coating solution has pollution and safety issue, in order to overcome organic solvent coating solution
Defect, aqueous dispersion packaging technique is used widely, and conventional aqueous dispersion has Aquacoat, acrylic acid tree
Lipid aqueous dispersion, polyvinyl acetate ester aqueous dispersion etc., such as polyvinyl acetate ester aqueous dispersion Kollicoat SR 30D,
Crylic acid resin aqueous dispersion Eurdragit RL 30D, Eurdragit RS 30D, Eurdragit NE 30D and second
Base cellulose aqueous dispersions Aquacoat and Surelease, however we have found that：The nitre benzene of preparation is coated using aqueous dispersion
Flat film controlling type sustained-release micro-pill capsules, within a period of time just prepared, its release performance is good, but storage a period of time
Afterwards, its release performance is begun to decline, and storage time is longer, and decline is more obvious, often in term of validity latter half as defined in medicine, releases
Performance is put to be decreased obviously.Reason is analyzed, is because coating membrane is tied during placement because the continuation of aqueous dispersion particulate is mutual
Conjunction causes gradually to compact, and causes membrane permeability to decline, and makes release slack-off, and popular saying is aging.
The content of the invention
Under the release that film aging in order to solve nifedipine film controlling type sustained release pellet prepared by aqueous dispersion coating is brought
The problem of drop, the film controlling type nifedipine of stable release performance can be remained before the deadline the invention provides a kind of
Sustained-release micro-pill capsules, feature be micropill capsule core in contain with meet water high-expansion Ac-Di-Sol, lead to
Water swelling is crossed so that sustained release coating film is deformed upon, so as to counteract the aging of film.
Current film controlling type delays the conventional aqueous dispersion type coating material of controlled release micro pill, such as Eurdragit RL 30D, bag
Macromolecular material in clothing material is in itself and water insoluble, but is dispersed in water in particulate form, with plasticizer, antiplastering aid etc.
Aqueous dispersion coating solution is made after mixing, micropill surface is sprayed on through spray gun, this operation is referred to as being coated；When being coated firm start,
These aqueous dispersions on micropill surface exist with substantial amounts of discontinuous particle shape, increase as coating solution is sprayed into, these
Grain contacts with each other, deformed, condensing, last mutually partial fusion, forms a discontinuous film；Then it is heat-treated, water is waved
After hair, polymer beads are then connected with each other, fusion completely forms coating membrane.It is heat-treated the film-controlled slow-release being coated to aqueous dispersion micro-
The release performance influence of ball is very big：Not enough, such as time is too short or temperature is too low, polymer in coatings for heat treatment
Also contain micro water between particle, it may proceed to evaporate within follow-up storage period, continuing with film becomes between particle
Obtain and more compact, permeability, which declines, causes release slack-off；In order to avoid such case, generally using the side of increase heating strength
Method overcomes, for example, increase heat treatment time or improve heat treatment temperature, but this processing easily lead to it is heat treated
Head, causes film excessively to dry and compact, even if initial stage, release was qualified, but it is within follow-up storage period, the film compacted originally
It can become loose due to the water suction from environment and the creep of film-forming high molecular material, permeability rises, and causes release to accelerate.It is real
Trample and show, for film controlling type Nifedipine Sustained-release Beads, because insoluble drug release causes by diffusion, thus to film aging completely
Permeability decline very sensitive, accomplish just right to ensure to remain stable before the deadline by Technology for Heating Processing
Release performance is highly difficult, and the temperature and time being in most cases heat-treated is inadequate, and often later stage release is obvious becomes
Slowly.
For above-mentioned mechanism, the present inventor is surprised to find that by research：If the nifedipine film that aqueous dispersion is coated
Control type sustained release pellet uses the capsule core of the Ac-Di-Sol containing high-expansion, due to Ac-Di-Sol
It is water insoluble, but can absorb and be several times as much as the water of weight itself and expand so that micropill volume becomes big, causes release membranes to be stretched,
Thickness is thinning, and the aperture of permeable micropore becomes big, and permeability improves, can compensate heat treatment deficiency cause it is logical produced by film aging
Permeability declines, so that middle and later periods rate of release substantially constant, latter stage residual is small.It can additionally eliminate and be heat-treated excessive lead
The influence too compacted of film is caused, it is to avoid the day change of release performance that comes of caudacoria Relaxation Zone, so that medicine in the whole term of validity
Thing rate of release substantially constant.The anti-aging of the nifedipine film-controlled slow-release micropill that aqueous dispersion is coated can so be greatly improved
Performance.Due to the high-expansion of Ac-Di-Sol in capsule core, expansive force is very big, increases with standing time, and micropill is inhaled
Expansion rate after water is basically unchanged, and can make it that irreversible plastic deformation occurs after being stretched for release membranes, no matter how film becomes
Changing and (becoming loose or become and compact) can support and arrive similar degree greatly, so as to ensure that the permeability of film is basically unchanged.
Preferably, the nifedipine film-controlled slow-release micro pill capsule of the present invention, the sustained release clothing film of its micropill is used
Eurdragit RL 30D are as filmogen, the Ac-Di-Sol containing high-expansion in the capsule core of micropill, with
And the excipient of other pharmaceutically acceptable sustained release pellets, the excipient preferably microcrystalline cellulose, lactose are used as filling
Agent and PEG 4000 are used as solubilizer；Wherein, Ac-Di-Sol accounts for the percentage of capsule core weight in the capsule core of micropill
For 5~20%, the sustained release clothing film of micropill includes Eurdragit RL 30D, plasticizer triethyl citrate and antiplastering aid talcum
Powder, its ratio is preferably Eurdragit RL30D: triethyl citrate: talcum powder=30: 3: 4, coating weight gain is preferably 21~
35%.
As one of the preferred embodiment of the present invention, at the micropill of nifedipine film-controlled slow-release micro pill capsule of the invention
Side is as follows：
First, capsule core prescription (1000 meters)
2nd, it is sustained clothing film prescription
It is preferred that sustained release clothing film coating weightening is 21~35%.
Invention also provides a kind of nifedipine film-controlled slow-release micro pill capsule for improving aqueous dispersion coating is anti-aging
The method of performance, it is characterized in that the sustained release clothing film of micropill is used as filmogen, ball using aqueous dispersion Eurdragit RL 30D
Core contains Ac-Di-Sol and the conventional excipient of sustained release pellet, the excipient preferably microcrystalline cellulose, lactose
Solubilizer is used as filler and PEG 4000.Wherein Ac-Di-Sol accounts for the percentage of capsule core weight in capsule core
For 5~20%, sustained release clothing film includes aqueous dispersion Eurdragit RL 30D, plasticizer triethyl citrate and antiplastering aid talcum
Powder, weight ratio is Eurdragit RL 30D: triethyl citrate: talcum powder=30: 3: 4, coating weight gain is 21~35%.On
The preferred of method is stated, is that based on 1000 capsules, micropill uses following prescription：
First, capsule core prescription
2nd, it is sustained clothing film prescription
It is 21~35% to be sustained clothing film coating weightening.
The preparation method of film controlling type Nifedipine Sustained-release Beads of the present invention, can be according to film controlling type in the prior art
Delay the general technology of controlled release micro pill to prepare, including the slow clothing film of batch mixing, pill core, bag etc., it is preferred to use extrusion spheronization method
Prepare capsule core.The sustained release pellet made is loaded into common stomach dissolution type gelatine capsule, that is, obtains nifedipine film-controlled slow-release micropill glue
Capsule.
Film controlling type Nifedipine Sustained-release Beads capsule of the present invention has the following advantages：
1) aging of confrontation sustained release clothing film：With aqueous dispersion Eurdragit RL 30D+ triethyl citrates+talcum powder group
Into sustained release clothing film can aging, reason be aqueous dispersion particulate combine promote film aging, cause membrane permeability to reduce, and containing tool
There is the capsule core for the Ac-Di-Sol for meeting water high-expansion, can substantially be expanded after water suction, cause sustained release clothing film to be stretched,
Thickness is thinning, and the aperture of permeable micropore becomes big, and permeability improves, and the permeability that compensate for film aging generation declines, so that
Middle and later periods rate of release substantially constant, latter stage residual is small, and stable release performance can be remained before the deadline.
2) supporting role：, can be obvious after water suction using the capsule core of the Ac-Di-Sol with water swelling
Expansion is played a supporting role, and medicine is dashed forward caused by can avoiding the extruding by intestines and stomach in intestines and stomach operation process in vivo
Release.
Specific embodiment
The Nifedipine Sustained-release Beads capsule of the common capsule core of embodiment 1
First, prescription
1st, capsule core prescription (1000)
2nd, it is sustained clothing film coating liquid prescription
3rd, No. 0 stomach dissolution type gelatine capsule shell 1000
2nd, preparation technology：
1st, capsule core preparation technology：
(1) nifedipine is crossed into 80 mesh sieves；
(2) nifedipine of recipe quantity, microcrystalline cellulose PH101, lactose, PEG 4000 are weighed, is put in wet granulator
It is well mixed；
The ethanol solution softwood of (3) 2% sodium carboxymethylcellulose 10%；
(4) put and extruded on extruder, mesh size is 1.0mm, extruded velocity is 20~30rpm；
(5) round as a ball, round as a ball speed is drying in 900~1000rpm, fluid bed；
(6) sieve, take the capsule core between 16~30 mesh.
2nd, it is sustained clothing film coating liquid preparing process：
The triethyl citrate for weighing recipe quantity is put in the water of recipe quantity, is stirred, and adds the talcum powder of recipe quantity,
Stirring shearing is uniform, is eventually adding the D of Eurdragit RL 30 and mixes uniformly, produces.
3rd, it is coated (sustained release clothing film)：
Capsule core is placed in fluid bed and is coated, control clothing film weightening, coating weight gain is 14.7%.
4th, it is heat-treated：
By the micropill for wrapping extended release coatings in fluid bed, it is heat-treated under the conditions of 40 DEG C/2h.
5th, capsule is filled：
Coating micro-pill is produced in filling on capsule filling machine.
3rd, release, assay and result
Release lucifuge is operated.This product is taken, according to drug release determination method (two annex XD first of China's coastal port
Method), using the subtraction unit of dissolution method first (two annex X C of China's coastal port), with hydrochloric acid solution (9 →
1000) 1000ml is solvent, and rotating speed is 100 turns per minute, is operated in accordance with the law, 2, takes solution 10ml respectively within 4,8 hours, and immediately
Above-mentioned hydrochloric acid solution 10ml is supplemented in process container, filters, subsequent filtrate is taken respectively, according to AAS (Chinese Pharmacopoeia 2005
Two annex IVA of version), trap is determined at 237nm wavelength.Another precision is weighed through 105 DEG C of dry 1 hour nifedipines
Reference substance about 37.5mg, puts in 25ml measuring bottles, plus anhydrous alcohol solution and is diluted to scale, shakes up；Precision measures 2ml, puts
In 100ml measuring bottles, add state hydrochloric acid solution dilution be made in every 1ml contain 30 μ g solution, as reference substance solution, be measured in the same method
Trap.Every burst size in different time is calculated respectively.This product every is 2, the burst size of 4 and 8 hours should be respectively mark
30%~55%, 50%~70% and more than the 70% of the amount of showing, all should meet regulation.
Assay takes this product 10, pours out content, and accurately weighed content is finely ground, and it is appropriate (about that precision weighs fine powder
Equivalent to nifedipine 30mg), put in mortar, chlorination imitates 2ml, grind, 100ml measuring bottles are quantitatively transferred to by several times with absolute ethyl alcohol
In, plus absolute ethyl alcohol is diluted to scale, shakes up, and filters, precision measures subsequent filtrate 5ml, put in 50ml measuring bottles, plus absolute ethyl alcohol is dilute
Release to scale, shake up, be used as need testing solution；It is appropriate that another precision weighs nifedipine reference substance, plus anhydrous alcohol solution and dilute
Release and solution in every 1ml containing about the μ g of nifedipine 30 is made, as reference substance solution, according to AAS (Chinese Pharmacopoeia 2005
Year two annex IV A of version) trap is determined at 333nm wavelength, calculate, produce.As a result such as table 1：
The releasing result of 1 embodiment of table 1
As a result show, the capsule core of embodiment 1 is free of the Nifedipine Sustained-release Beads capsule of intumescent material, initial release is good,
As standing time increases, the continuous aging of film, rate of release is slack-off, residual substantially increase.
4th, expansion rate is determined
Assay method：Added into 100ml measuring bottles and be preheated to 37 DEG C of distillation appropriate amount of water, be dipped in 37 DEG C of water-baths and with steaming
Distilled water constant volume is to standby after scale；3 500ml beakers are taken, the distilled water that 300ml is preheated to 37 DEG C is separately added into, is immersed in 37
It is standby in DEG C water-bath；Capsule 10 to be measured is taken, capsule shells is removed, micropill in capsule is poured out, put in above-mentioned 100ml measuring bottles, it is fast
Distilled water in the pipette, extract measuring bottle that speed is 0.01ml with minimum scale value is until liquid level is fallen after rise to measuring bottle scale, then accurately
The volume of water in pipette is read, the average external volume of micropill in every capsule is calculated, is designated as V0.30 capsules to be measured are taken, are divided into 3
Group, every group 10, removes capsule shells, micropill in capsule is poured out, put in above-mentioned 3 500ml beakers and soak respectively, exist respectively
2h, 4h, 8h respectively take out 1 group, filtration, and the water of micropill surface residual is blotted with filter paper, and that has been put again that constant volume crosses is above-mentioned
In 100ml measuring bottle, rapidly with distilled water in above-mentioned pipette, extract measuring bottle until liquid level is fallen after rise to measuring bottle scale, then accurately
The volume of water in pipette is read, the average external volume of micropill in every capsule is calculated, is designated as VT.When each sampling is calculated as follows
Between the expansion rate put, the results are shown in Table 2.
Computing formula：Expansion rate (%)=(VT-V0)/V0× 100%
Expansion rate result after the placement for a long time of the room temperature of table 2
Test result indicate that, capsule core be free of high-expansion material Nifedipine Sustained-release Beads capsule, micropill expansion rate compared with
It is small, and as room temperature is placed for a long time, expansion rate reduces therewith, does not offset the effect of sustained release clothing film aging.
Nifedipine Sustained-release Beads capsule of the embodiment 2 containing 5% Ac-Di-Sol
First, prescription
1st, capsule core prescription (1000)
2nd, it is sustained clothing film coating liquid prescription：Be the same as Example 1.
3rd, No. 0 stomach dissolution type gelatine capsule shell 1000.
2nd, preparation technology：
1st, capsule core preparation technology：
(1) nifedipine is crossed into 60 mesh sieves；
(2) nifedipine of recipe quantity, microcrystalline cellulose PH101, lactose, PEG 4000, cross-linked carboxymethyl fiber are weighed
Plain sodium, puts in wet granulator and is well mixed；
(3) with the ethanol solution softwood of 2% sodium carboxymethylcellulose 10%；
(4) put and extruded on extruder, mesh size is 1.0mm, extruded velocity is 20~30rpm；
(5) round as a ball, round as a ball speed is drying in 900~1000rpm, fluid bed；
(6) sieve, take the capsule core between 16~30 mesh.
2nd, it is sustained clothing film coating liquid preparing process：
Be the same as Example 1.
3rd, it is coated (sustained release clothing film)：
Capsule core is placed in fluid bed and is coated, control clothing film weightening, coating weight gain is 20.6%.
4th, it is heat-treated：Be the same as Example 1.
5th, capsule is filled：Be the same as Example 1.
3rd, release, assay and result
Assay method：Be the same as Example 1, the results are shown in Table 3：
The releasing result of 3 embodiment of table 2
As a result show, at the beginning of Nifedipine Sustained-release Beads capsule of the capsule core containing Ac-Di-Sol 5% of embodiment 2
Beginning release performance is good, as standing time increases, and still very well, end point release remains equal very little to releasing effect.
4th, swelling rate test
Experimental method：Be the same as Example 1, the results are shown in Table 4：
Expansion rate result after the placement for a long time of the room temperature of table 4
Test result indicate that, the Nifedipine Sustained-release Beads of capsule core Ac-Di-Sol containing intumescent material 5%
Capsule, micropill expansion rate is larger, under room temperature is placed for a long time, and expansion rate keeps constant, counteracts the aging of sustained release clothing film.
Nifedipine Sustained-release Beads capsule of the embodiment 3 containing 10% Ac-Di-Sol
First, prescription
1st, capsule core prescription (1000)
2nd, it is sustained clothing film coating liquid prescription：Be the same as Example 1.
3rd, No. 0 stomach dissolution type gelatine capsule shell 1000.
2nd, preparation technology：
1st, capsule core preparation technology：Be the same as Example 2.
2nd, it is sustained clothing film coating liquid preparing process：Be the same as Example 1.
3rd, it is coated (sustained release clothing film)：
Capsule core is placed in fluid bed and is coated, control clothing film weightening, coating weight gain is 23.5%, 28.4%.
4th, it is heat-treated：Be the same as Example 1.
5th, capsule is filled：Be the same as Example 1.
3rd, release, assay and result
Assay method：Be the same as Example 1, the results are shown in Table 5：
The releasing result of 5 embodiment of table 3
As a result show, Nifedipine Sustained-release Beads capsule initial release of the capsule core containing Ac-Di-Sol 10%
Can be good, as standing time increases, still very well, end point discharges the equal very little of residual to releasing effect.
4th, expansion rate is tested
Experimental method：Be the same as Example 1, the results are shown in Table 6：
Expansion rate result after the placement for a long time of the room temperature of table 6
Test result indicate that, Nifedipine Sustained-release Beads capsule of the capsule core containing Ac-Di-Sol 10%, micropill
Expansion rate is larger, under room temperature is placed for a long time, and expansion rate keeps constant, counteracts the aging of sustained release clothing film.
Nifedipine Sustained-release Beads capsule of the embodiment 4 containing 15% Ac-Di-Sol
First, prescription
1. capsule core prescription (1000)
2. it is sustained clothing film coating liquid prescription：Be the same as Example 1.
No. 3.0 stomach dissolution type gelatine capsule shells 1000.
2nd, preparation technology
1st, capsule core preparation technology：Be the same as Example 2.
2nd, it is sustained clothing film coating liquid preparing process：Be the same as Example 1.
3rd, it is coated (sustained release clothing film)：
Capsule core is placed in fluid bed and is coated, control clothing film weightening, coating weight gain is 32.3%.
4th, it is heat-treated：Be the same as Example 1.
5th, capsule is filled：Be the same as Example 1.
3rd, release, assay and result
Assay method：Be the same as Example 1, the results are shown in Table 7：
The releasing result of 7 embodiment of table 4
As a result show, Nifedipine Sustained-release Beads capsule initial release of the capsule core containing Ac-Di-Sol 15%
Can be good, as standing time increases, still very well, end point discharges the equal very little of residual to releasing effect.
4th, expansion rate is tested
Experimental method：Be the same as Example 1, the results are shown in Table 8：
Expansion rate after the placement for a long time of the room temperature of table 8
As a result show, Nifedipine Sustained-release Beads capsule of the capsule core containing Ac-Di-Sol 15%, micropill expansion
Rate is larger, under room temperature is placed for a long time, and expansion rate keeps constant, counteracts the aging of sustained release clothing film.
Nifedipine Sustained-release Beads capsule of the embodiment 5 containing 20% Ac-Di-Sol
First, prescription
1. capsule core prescription (1000)
2. it is sustained clothing film coating liquid prescription：Be the same as Example 1
No. 3.0 stomach dissolution type gelatine capsule shells 1000.
2nd, preparation technology
1st, capsule core preparation technology：Be the same as Example 2.
2nd, it is sustained clothing film coating liquid preparing process：Be the same as Example 1.
3rd, it is coated (sustained release clothing film)：
Capsule core is placed in fluid bed and is coated, control clothing film weightening, coating weight gain is 35.2%.
4th, it is heat-treated：Be the same as Example 1.
5th, capsule is filled：Be the same as Example 1.
3rd, release, assay and result
Assay method：Be the same as Example 1, the results are shown in Table 9：
The releasing result of 9 embodiment of table 5
As a result show, Nifedipine Sustained-release Beads capsule initial release of the capsule core containing Ac-Di-Sol 20%
Can be good, as standing time increases, still very well, end point discharges the equal very little of residual to releasing effect.
4th, expansion rate is tested
Experimental method：Be the same as Example 1, the results are shown in Table 10：
Expansion rate after the placement for a long time of the room temperature of table 10
As a result show, Nifedipine Sustained-release Beads capsule of the capsule core containing Ac-Di-Sol 20%, micropill expansion
Rate is larger, under room temperature is placed for a long time, and expansion rate keeps constant, counteracts the aging of sustained release clothing film.
Claims (4)
1. a kind of nifedipine film-controlled slow-release micro pill capsule for remaining stable release performance before the deadline, it is characterized in that
The sustained release clothing film of micropill is using Eurdragit RL 30D as filmogen, and capsule core contains Ac-Di-Sol and its
The excipient of his pharmaceutically acceptable sustained release pellet, the excipient of other pharmaceutically acceptable sustained release pellets is
Ac-Di-Sol accounts for capsule core weight in filler microcrystalline cellulose, lactose and solubilizer PEG 4000, the capsule core of micropill
The percentage of amount is 5~20%, and the sustained release clothing film of micropill includes Eurdragit RL 30D, plasticizer triethyl citrate and resisted
Stick talcum powder, the composition weight ratio of the sustained release clothing film of micropill is Eurdragit RL 30D: triethyl citrate: talcum powder=
30: 3: 4, coating weight gain is 21~35%.
2. nifedipine film-controlled slow-release micro pill capsule as claimed in claim 1, it is characterized in that based on 1000 capsules, it is described micro-
Ball has following prescription：
Capsule core prescription：
It is sustained clothing film prescription：
It is 21~35% to be sustained clothing film coating weightening.
3. a kind of improve the method for the nifedipine film-controlled slow-release micro pill capsule ageing resistace that aqueous dispersion is coated, it is characterized in that
The sustained release clothing film of micropill is using Eurdragit RL 30D as filmogen, and the capsule core of micropill contains cross-linked carboxymethyl cellulose
The excipient of sodium and other pharmaceutically acceptable sustained release pellets, the tax of other pharmaceutically acceptable sustained release pellets
Shape agent is filler microcrystalline cellulose, lactose and solubilizer PEG 4000, and Ac-Di-Sol is accounted in the capsule core of micropill
The percentage of capsule core weight is 5~20%, and the sustained release clothing film of micropill includes Eurdragit RL 30D, plasticizer lemon triethylenetetraminehexaacetic acid
Ester and antiplastering aid talcum powder and weight ratio are Eurdragit RL 30D: triethyl citrate: talcum powder=30: 3: 4, it is coated and increases
Weight is 21~35%.
4. method as claimed in claim 3, it is characterized in that based on 1000 capsules, the micropill uses following prescription：
Capsule core prescription：
It is sustained clothing film prescription：
It is 21~35% to be sustained clothing film coating weightening.
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| CN201210014371.6A CN103211788B (en) | 2012-01-18 | 2012-01-18 | Nifedipine film-controlled slow-release micro pill capsule |
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| CN201210014371.6A CN103211788B (en) | 2012-01-18 | 2012-01-18 | Nifedipine film-controlled slow-release micro pill capsule |
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| CN103211788B true CN103211788B (en) | 2017-07-18 |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1600296A (en) * | 2003-09-22 | 2005-03-30 | 北京德众万全药物技术开发有限公司 | Method for preparing tiny pellets of difficult soluble drugs and formulation containing the pellets |
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| ATE413165T1 (en) * | 2004-09-27 | 2008-11-15 | Sigmoid Pharma Ltd | MICROCAPSULES WITH A METHYLXANTHINE AND A CORTICOSTEROID |
| US8865213B2 (en) * | 2009-12-30 | 2014-10-21 | Usv Limited | Modified release pharmaceutical compositions |
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2012
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1600296A (en) * | 2003-09-22 | 2005-03-30 | 北京德众万全药物技术开发有限公司 | Method for preparing tiny pellets of difficult soluble drugs and formulation containing the pellets |
Non-Patent Citations (2)
| Title |
|---|
| 流化床包衣法制备硝苯地平缓释微丸;王立，等;《中国药学杂志》;20090831;第44卷(第15期);第1159-1163页 * |
| 硝苯地平缓释微丸的制备;刘彦生，等;《中国新药杂志》;20091231;第18卷(第4期);第356-359页 * |
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| Publication number | Publication date |
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| CN103211788A (en) | 2013-07-24 |
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