CN103211788A - Nifedipine film-controlled slow-release pellet capsule - Google Patents
Nifedipine film-controlled slow-release pellet capsule Download PDFInfo
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Abstract
The invention relates to a nifedipine film-controlled slow-release pellet capsule. A slow-release film of the nifedipine film-controlled slow-release pellet utilizes Eurdragit RL 30D as a film-formation material. A pellet core of the nifedipine film-controlled slow-release pellet contains croscarmellose sodium having high water expansibility. Excipients comprise microcrystalline cellulose and lactose as fillers and PEG 4000 as a solubilizer. The pellet core comprises 5 to 20wt% of croscarmellose sodium. The slow-release film comprises Eurdragit RL 30D, triethyl citrate as a plasticizer, and talcum powder as an antiplastering aid, wherein preferably, a ratio of Eurdragit RL 30D to triethyl citrate to talcum powder is 30: 3: 4 and a film weight increasing ratio is in a range of 21 to 35%. After absorbing water, the nifedipine film-controlled slow-release pellet obviously expands so that the slow-release film is stretched; the water-permeable micropore size is increased; and permeability is improved and the permeability reduction caused by film aging is counteracted. Therefore, the nifedipine film-controlled slow-release pellet keeps stable release performances in the period of validity.
Description
Technical field
The present invention relates to a kind of nifedipine film-controlled slow-release pellet capsule, specifically, relate to the nifedipine film-controlled slow-release pellet capsule that a kind of ball core contains cross-linking sodium carboxymethyl cellulose, belong to field of pharmaceutical preparations.
Background technology
Nifedipine is a calcium antagonist, and by the flow of calcium ions of selectivity antagonizing vessel smooth muscle, diastole Peripheral resistance blood vessel reduces Peripheral resistance, is used for the treatment of hypertension; Suppress myocardial contraction, reduce myocardial metabolism, reduce myocardial oxygen consumption, be used for the treatment of angina pectoris.
Nifedipine is almost insoluble in water, and Shang Shi ordinary preparation need be taken 2 times every day the earliest, and blood concentration fluctuation is big, and peak concentration is too high, and untoward reaction is serious.
Beyer Co., Ltd's nifedipine osmotic pump controlled release tablet (trade name: visit new with) that gone on the market, can accomplish that zero level discharges, release is even, the semipermeable membrane that shortcoming is to use macromolecular material to form is easily aging, drug residue is big, therefore must feed intake by 115% at least, just can guarantee to imitate the release in the end of term, make the osmotic pumps technology be difficult to be used widely.
Slow-release micro-pill is that medicine is made multiunit slow release medicine-releasing system, and it is oral generally to incapsulate the back, and after the capsule dissolves, slow-release micro-pill can be extensively, be evenly distributed in the gastrointestinal tract.Medicine increases at the distribution area on gastrointestinal surface, is guaranteeing that can also effectively reduce medicine when medicine evenly discharges stimulates gastrointestinal.The pellet particle diameter is less, and the transhipment unable to take food thing in gastrointestinal tract is carried the influence of the rhythm and pace of moving things, even when sphincter of pylorus is closed, still can pass through pylorus, so microgranule absorbs the influence that generally is not subjected to gastric emptying at gastrointestinal.What is more important, the drug release behavior of micropill system is a summation of forming each micropill drug release behavior of a dosage, error or the defective of indivedual micropills in preparation can not produce the drug release behavior of whole preparation and have a strong impact on, and therefore is being better than aspect the repeatability of release rule and the concordance by delaying of forming of a unit, controlled release tablet.
Nifedipine is suitable for making sustained-release pellet preparation, and the effective blood drug concentration longer duration, blood concentration fluctuation is little, side effect is little, individual variation is little, patient's compliance is good.
The most frequently used implementation method of slow-release micro-pill is to adopt film controlling type, promptly wraps one deck extended release coatings film in the outside of ball core with the solution coating method, and the extended release coatings film contains filmogen, plasticizer, antiplastering aid etc.In one's early years coating solutions that adopt organic solvent to prepare the extended release coatings film more, because existing, pollutes and safety issue the organic solvent coating solution, in order to overcome the defective of organic solvent coating solution, the aqueous dispersion packaging technique is used widely, aqueous dispersion commonly used has Aquacoat, the crylic acid resin aqueous dispersion, polyvinyl acetate ester aqueous dispersion etc., polyvinyl acetate ester aqueous dispersion Kollicoat SR 30D for example, crylic acid resin aqueous dispersion Eurdragit RL 30D, Eurdragit RS 30D, Eurdragit NE 30D and Aquacoat Aquacoat and Surelease, yet we find: the nifedipine film controlling type sustained-release micro-pill capsules that adopts the preparation of aqueous dispersion coating, in a period of time that has just prepared, its release performance is good, yet after storing a period of time, its release performance begins to descend, storage time is long more, it is obvious more to descend, often in latter half effect duration of medicine regulation, release performance obviously descends.The analysis reason is because coating membrane causes compacting gradually owing to the aqueous dispersion microgranule continues to interosculate in the process of placing, and causes membrane permeability to descend, and makes release slack-off, and popular saying is for aging.
Summary of the invention
The problem that descends for the aging release that brings of film of the nifedipine film controlling type slow-release micro-pill that solves aqueous dispersion coating preparation, the invention provides a kind of film controlling type Nifedipine sustained-release pellet capsule that can remain stable release performance before the deadline, characteristics are to contain in the ball core of micropill has the cross-linking sodium carboxymethyl cellulose of meeting the water high-expansion, make sustained release coating film generation deformation by imbibition, thereby offset the aging of film.
Film controlling type delays controlled release micro pill aqueous dispersion build coating material commonly used at present, Eurdragit RL 30D for example, macromolecular material in the coating material itself is also water insoluble, but be dispersed in the water with particulate form, with make the aqueous dispersion coating solution after plasticizer, antiplastering aid etc. mixes, be sprayed on the micropill surface through spray gun, this operation is called as coating; When coating had just begun, these aqueous dispersions on micropill surface existed with a large amount of discontinuous particle shapes, and along with coating solution sprays into increase, these granules are in contact with one another, are out of shape, condense, and last partial fusion mutually forms a discontinuous film; Heat-treat then, after the water volatilization, polymer beads then is connected with each other, merges fully the formation coating membrane.Heat treatment is very big to the release performance influence of the film-controlled slow-release micropill of aqueous dispersion coating: the words that heat treatment is not enough, for example the time is too short or temperature is low excessively, the water that also contains trace in the coatings between the polymer beads, it can continue to evaporate in follow-up storage period, continue combination between the granule, film becomes and compacts more, and permeability decline causes discharging slack-off; For fear of this situation, usually adopt the method that increases heat treatment intensity to overcome, for example increase heat treatment time or improve heat treatment temperature, but this processing is easy to cause heat treatment excessive, causes film too dry and compact, and is qualified even the initial stage discharges, yet it is in follow-up storage period, the film meeting of compacting originally is slacken owing to the creep of suction and film forming macromolecular material from environment, and permeability rises, and causes discharging accelerating.Practice shows, for film controlling type Nifedipine sustained-release micropill, because drug release is fully by diffusion, thereby descend very responsive to the aging permeability that causes of film, accomplish that by Technology for Heating Processing just right to guarantee to remain before the deadline stable release performance be very difficult, in most cases heat treated temperature and time is not enough, and often the later stage discharges obviously slack-off.
At above-mentioned mechanism, the inventor is surprised to find that by research: if the nifedipine film controlling type slow-release micro-pill of aqueous dispersion coating adopts the ball core of the cross-linking sodium carboxymethyl cellulose that contains high-expansion, because cross-linking sodium carboxymethyl cellulose is water insoluble, but can absorb the water that is several times as much as weight own and expand, make the micropill volume become big, cause release membranes to be stretched, the thickness attenuation, it is big that the aperture of permeable micropore becomes, permeability improves, can compensate the heat treatment deficiency and cause the aging permeability that is produced of film to descend, thereby make middle and late stage rate of release substantially constant, latter stage is residual little.Can eliminate the excessive influence that causes film too to compact of heat treatment in addition, avoid the change of the lax release performance that brings of day caudacoria, thereby make interior drug releasing rate substantially constant of whole effect duration.Can improve the ageing resistace of the nifedipine film-controlled slow-release micropill of aqueous dispersion coating so greatly.Because the high-expansion of cross-linking sodium carboxymethyl cellulose in the ball core, expansive force is very big, with increasing standing time, expansion rate after the micropill suction is constant substantially, can irreversible plastic deformation take place the back so that release membranes is stretched, no matter how film changes (become loose or become and compact) all can be supportted the big similar degree that arrives, thereby the permeability that guarantees film is constant substantially.
As preferably, nifedipine film-controlled slow-release pellet capsule of the present invention, the extended release coatings film of its micropill adopts Eurdragit RL 30D as filmogen, the cross-linking sodium carboxymethyl cellulose that contains high-expansion in the ball core of micropill, and the excipient used of other pharmaceutically acceptable slow-release micro-pill, described excipient preferably microcrystalline cellulose, lactose as filler and PEG 4000 as solubilizing agent; Wherein, to account for the percentage ratio of ball core weight be 5～20% to cross-linking sodium carboxymethyl cellulose in the ball core of micropill, the extended release coatings film of micropill comprises Eurdragit RL 30D, plasticizer triethyl citrate and antiplastering aid Pulvis Talci, its ratio is preferably Eurdragit RL30D: triethyl citrate: Pulvis Talci=30: 3: 4, the coating weightening finish is preferably 21～35%.
As one of preferred implementation of the present invention, the micropill of nifedipine film-controlled slow-release pellet capsule of the present invention prescription is as follows:
One, ball core prescription (1000 meters)
Two, extended release coatings film prescription
Preferred extended release coatings film coating weightening finish is 21～35%.
The present invention provides a kind of method of improving the nifedipine film-controlled slow-release pellet capsule ageing resistace of aqueous dispersion coating simultaneously, the extended release coatings film that it is characterized in that micropill adopts aqueous dispersion Eurdragit RL 30D as filmogen, the ball core contains cross-linking sodium carboxymethyl cellulose and slow-release micro-pill excipient commonly used, described excipient preferably microcrystalline cellulose, lactose as filler and PEG 4000 as solubilizing agent.Wherein the percentage ratio that cross-linking sodium carboxymethyl cellulose accounts for ball core weight in the ball core is 5～20%, the extended release coatings film comprises aqueous dispersion Eurdragit RL 30D, plasticizer triethyl citrate and antiplastering aid Pulvis Talci, weight ratio is Eurdragit RL 30D: triethyl citrate: Pulvis Talci=30: 3: 4, the coating weightening finish is 21～35%.Said method preferred is by 1000 capsules, and micropill adopts following prescription:
One, ball core prescription
Two, extended release coatings film prescription
The weightening finish of extended release coatings film coating is 21～35%.
The preparation method of film controlling type Nifedipine sustained-release micropill of the present invention can prepare according to the general technology of the slow controlled release micro pill of film controlling type in the prior art, comprises batch mixing, pill core, the slow clothing film of bag etc., and preferred employing is extruded spheronization and prepared the ball core.With the slow-release micro-pill that the makes common stomach dissolution type gelatine capsule of packing into, promptly obtain nifedipine film-controlled slow-release pellet capsule.
Film controlling type Nifedipine sustained-release pellet capsule of the present invention has following advantage:
1) antagonism extended release coatings film is aging: the extended release coatings film of forming with aqueous dispersion Eurdragit RL 30D+ triethyl citrate+Pulvis Talci can wear out, reason is that the aqueous dispersion microgranule is in conjunction with promoting film aging, cause membrane permeability to reduce, and contain ball core with the cross-linking sodium carboxymethyl cellulose of meeting the water high-expansion, can obviously expand after the suction, cause the extended release coatings film to be stretched, the thickness attenuation, it is big that the aperture of permeable micropore becomes, permeability improves, and has compensated the aging permeability that produces of film and has descended, thereby made middle and late stage rate of release substantially constant, latter stage is residual little, can remain stable release performance before the deadline.
2) supporting role: use the ball core of cross-linking sodium carboxymethyl cellulose, can obviously expand after the suction and play a supporting role, avoid in the gastrointestinal tract operation process in vivo being subjected to the gastrointestinal extruding and prominent the releasing of medicine that cause with water swelling.
Specific embodiment
The Nifedipine sustained-release pellet capsule of embodiment 1 common ball core
One, prescription
1, ball core prescription (1000)
2, extended release coatings film coating fluid prescription
3, No. 0 stomach dissolution type gelatine capsule shell is 1000
Two, preparation technology:
1, ball core preparation technology:
(1) nifedipine is crossed 80 mesh sieves;
(2) take by weighing nifedipine, microcrystalline Cellulose PH101, lactose, the PEG 4000 of recipe quantity, put mix homogeneously in the wet granulator;
(3) 2% sodium carboxymethyl cellulose 10% alcoholic solution system soft material;
(4) put on the extruder and extrude, mesh size is 1.0mm, and extruded velocity is 20～30rpm;
(5) round as a ball, round as a ball speed is 900～1000rpm, dries in the fluid bed;
(6) sieve, get the ball core between 16～30 orders.
2, extended release coatings film coating solution preparation technology:
The triethyl citrate that takes by weighing recipe quantity is put in the water of recipe quantity, stirs, and adds the Pulvis Talci of recipe quantity again, stirs and shears evenly, adds Eurdragit RL 30 D at last and mixes evenly, promptly.
3, coating (extended release coatings film):
The ball core is placed the fluid bed coating, the weightening finish of control clothing film, the coating weightening finish is 14.7%.
4, heat treatment:
With the micropill of wrapping extended release coatings in fluid bed, heat treatment under 40 ℃/2h condition.
5, filled capsules:
Coated micropill is filled promptly on capsule filling machine.
Three, release, assay and result
The operation of release lucifuge.Get this product, according to drug release determination method (two appendix XD first methods of Chinese Pharmacopoeia version in 2005), adopt dissolution method first subtraction unit (two appendix X of Chinese Pharmacopoeia version in 2005 C), 1000ml is a solvent with hydrochloric acid solution (9 → 1000), rotating speed is that per minute 100 changes, operation in accordance with the law, got solution 10ml respectively at 2,4,8 hours, and in process container, replenish above-mentioned hydrochloric acid solution 10ml immediately, filter, get subsequent filtrate respectively,, measure trap at the wavelength place of 237nm according to spectrophotography (2005 editions two appendix IVA of Chinese Pharmacopoeia).Precision takes by weighing through 1 hour the about 37.5mg of nifedipine reference substance of 105 ℃ of dryings in addition, puts in the 25ml measuring bottle, adds anhydrous alcohol solution and is diluted to scale, shakes up; Precision is measured 2ml, puts in the 100ml measuring bottle, adds above-mentioned hydrochloric acid solution dilution and makes the solution that contains 30 μ g among every 1ml, and product solution is measured trap with method in contrast.Calculate every burst size respectively at different time.Every burst size at 2,4 and 8 hours of this product should be respectively more than 30%～55%, 50%～70% and 70% of labelled amount, all should be up to specification.
Assay is got 10 of this product, and inclining content, and content decided in accurate title, porphyrize, precision take by weighing fine powder an amount of (being equivalent to nifedipine 30mg approximately), put in the mortar, add chloroform 2ml, grind, quantitatively be transferred in the 100ml measuring bottle with the dehydrated alcohol gradation, add dehydrated alcohol and be diluted to scale, shake up, filter, precision is measured subsequent filtrate 5ml, puts in the 50ml measuring bottle, adds dehydrated alcohol and is diluted to scale, shake up, as need testing solution; It is an amount of that precision takes by weighing the nifedipine reference substance in addition, add anhydrous alcohol solution and the solution that contains nifedipine 30 μ g among every 1ml is approximately made in dilution, product solution is measured trap according to spectrophotography (two appendix IV of Chinese Pharmacopoeia version in 2005 A) at the wavelength place of 333nm in contrast, calculate, promptly.Result such as table 1:
Table 1 embodiment 1 discharges the result
The result shows that embodiment 1 ball core does not contain the Nifedipine sustained-release pellet capsule of intumescent material, and initial release is good, and along with increase standing time, film is constantly aging, and rate of release is slack-off, residual obvious increase.
Four, expansion rate is measured
Assay method: it is an amount of to add the distilled water be preheated to 37 ℃ in the 100ml measuring bottle, is dipped in 37 ℃ of water-baths and standby behind the scale with the distilled water standardize solution; Get 3 500ml beakers, add 300ml respectively and be preheated to 37 ℃ distilled water, be immersed in 37 ℃ of water-baths standby; Get 10 of capsules to be measured, remove capsule shells, micropill in the capsule is inclined to, put in the above-mentioned 100ml measuring bottle, be that distilled water falls after rise to the measuring bottle scale until liquid level in the pipette, extract measuring bottle of 0.01ml rapidly with minimum scale value, accurately read the volume of water in the pipet then, calculate the average external volume of micropill in every capsules, be designated as V
0Get 30 capsules to be measured, be divided into 3 groups, every group 10, remove capsule shells, micropill in the capsule is inclined to, put respectively in above-mentioned 3 500ml beakers and soak, respectively take out 1 group at 2h, 4h, 8h respectively, filter, blot the remaining water in micropill surface, it is put again in the measuring bottle of the above-mentioned 100ml that standardize solution crosses with filter paper, fall after rise to the measuring bottle scale until liquid level with distilled water in the above-mentioned pipette, extract measuring bottle rapidly, accurately read the volume of water in the pipet then, calculate the average external volume of micropill in every capsules, be designated as V
TBe calculated as follows the expansion rate of each sampling time point, the results are shown in Table 2.
Computing formula: expansion rate (%)=(V
T-V
0)/V
0* 100%
Expansion rate result after the long-term placement of table 2 room temperature
Experimental result shows that the ball core does not contain the Nifedipine sustained-release pellet capsule of high-expansion material, and the micropill expansion rate is less, and along with room temperature is placed for a long time, expansion rate reduces thereupon, does not offset the aged effect of extended release coatings film.
Embodiment 2 contains the Nifedipine sustained-release pellet capsule of 5% cross-linking sodium carboxymethyl cellulose
One, prescription
1, ball core prescription (1000)
2, extended release coatings film coating fluid prescription: with embodiment 1.
3, No. 0 stomach dissolution type gelatine capsule shell is 1000.
Two, preparation technology:
1, ball core preparation technology:
(1) nifedipine is crossed 60 mesh sieves;
(2) take by weighing nifedipine, microcrystalline Cellulose PH101, lactose, PEG 4000, the cross-linking sodium carboxymethyl cellulose of recipe quantity, put mix homogeneously in the wet granulator;
(3) with 2% sodium carboxymethyl cellulose, 10% alcoholic solution system soft material;
(4) put on the extruder and extrude, mesh size is 1.0mm, and extruded velocity is 20～30rpm;
(5) round as a ball, round as a ball speed is 900～1000rpm, dries in the fluid bed;
(6) sieve, get the ball core between 16～30 orders.
2, extended release coatings film coating solution preparation technology:
With embodiment 1.
3, coating (extended release coatings film):
The ball core is placed the fluid bed coating, the weightening finish of control clothing film, the coating weightening finish is 20.6%.
4, heat treatment: with embodiment 1.
5, filled capsules: with embodiment 1.
Three, release, assay and result
Assay method:, the results are shown in Table 3 with embodiment 1:
Table 3 embodiment 2 discharges the result
The result shows, the ball core of embodiment 2 contains that the Nifedipine sustained-release pellet capsule initial release performance of cross-linking sodium carboxymethyl cellulose 5% is all good, and along with increase standing time, releasing effect is still fine, and the end point discharges residual all very little.
Four, swelling rate test
Experimental technique:, the results are shown in Table 4 with embodiment 1:
Expansion rate result after the long-term placement of table 4 room temperature
Experimental result shows that the ball core contains the Nifedipine sustained-release pellet capsule of intumescent material cross-linking sodium carboxymethyl cellulose 5%, and the micropill expansion rate is bigger, and room temperature is long-term places down, and expansion rate remains unchanged, and has offset the aging of extended release coatings film.
Embodiment 3 contains the Nifedipine sustained-release pellet capsule of 10% cross-linking sodium carboxymethyl cellulose
One, prescription
1, ball core prescription (1000)
2, extended release coatings film coating fluid prescription: with embodiment 1.
3, No. 0 stomach dissolution type gelatine capsule shell is 1000.
Two, preparation technology:
1, ball core preparation technology: with embodiment 2.
2, extended release coatings film coating solution preparation technology: with embodiment 1.
3, coating (extended release coatings film):
The ball core is placed the fluid bed coating, the weightening finish of control clothing film, the coating weightening finish is 23.5%, 28.4%.
4, heat treatment: with embodiment 1.
5, filled capsules: with embodiment 1.
Three, release, assay and result
Assay method:, the results are shown in Table 5 with embodiment 1:
Table 5 embodiment 3 discharges the result
The result shows, the ball core contains that the Nifedipine sustained-release pellet capsule initial release performance of cross-linking sodium carboxymethyl cellulose 10% is all good, and along with increase standing time, releasing effect is still fine, and the end point discharges residual all very little.
Four, expansion rate experiment
Experimental technique:, the results are shown in Table 6 with embodiment 1:
Expansion rate result after the long-term placement of table 6 room temperature
Experimental result shows that the ball core contains the Nifedipine sustained-release pellet capsule of cross-linking sodium carboxymethyl cellulose 10%, and the micropill expansion rate is bigger, and room temperature is long-term places down, and expansion rate remains unchanged, and has offset the aging of extended release coatings film.
Embodiment 4 contains the Nifedipine sustained-release pellet capsule of 15% cross-linking sodium carboxymethyl cellulose
One, prescription
1. ball core prescription (1000)
2. extended release coatings film coating fluid prescription: with embodiment 1.
3.0 1000 of number stomach dissolution type gelatine capsule shell.
Two, preparation technology
1, ball core preparation technology: with embodiment 2.
2, extended release coatings film coating solution preparation technology: with embodiment 1.
3, coating (extended release coatings film):
The ball core is placed the fluid bed coating, the weightening finish of control clothing film, the coating weightening finish is 32.3%.
4, heat treatment: with embodiment 1.
5, filled capsules: with embodiment 1.
Three, release, assay and result
Assay method:, the results are shown in Table 7 with embodiment 1:
Table 7 embodiment 4 discharges the result
The result shows, the ball core contains that the Nifedipine sustained-release pellet capsule initial release performance of cross-linking sodium carboxymethyl cellulose 15% is all good, and along with increase standing time, releasing effect is still fine, and the end point discharges residual all very little.
Four, expansion rate experiment
Experimental technique:, the results are shown in Table 8 with embodiment 1:
Expansion rate after the long-term placement of table 8 room temperature
The result shows that the ball core contains the Nifedipine sustained-release pellet capsule of cross-linking sodium carboxymethyl cellulose 15%, and the micropill expansion rate is bigger, and room temperature is long-term places down, and expansion rate remains unchanged, and has offset the aging of extended release coatings film.
Embodiment 5 contains the Nifedipine sustained-release pellet capsule of 20% cross-linking sodium carboxymethyl cellulose
One, prescription
1. ball core prescription (1000)
2. extended release coatings film coating fluid prescription: with embodiment 1
3.0 1000 of number stomach dissolution type gelatine capsule shell.
Two, preparation technology
1, ball core preparation technology: with embodiment 2.
2, extended release coatings film coating solution preparation technology: with embodiment 1.
3, coating (extended release coatings film):
The ball core is placed the fluid bed coating, the weightening finish of control clothing film, the coating weightening finish is 35.2%.
4, heat treatment: with embodiment 1.
5, filled capsules: with embodiment 1.
Three, release, assay and result
Assay method:, the results are shown in Table 9 with embodiment 1:
Table 9 embodiment 5 discharges the result
The result shows, the ball core contains that the Nifedipine sustained-release pellet capsule initial release performance of cross-linking sodium carboxymethyl cellulose 20% is all good, and along with increase standing time, releasing effect is still fine, and the end point discharges residual all very little.
Four, expansion rate experiment
Experimental technique:, the results are shown in Table 10 with embodiment 1:
Expansion rate after the long-term placement of table 10 room temperature
The result shows that the ball core contains the Nifedipine sustained-release pellet capsule of cross-linking sodium carboxymethyl cellulose 20%, and the micropill expansion rate is bigger, and room temperature is long-term places down, and expansion rate remains unchanged, and has offset the aging of extended release coatings film.
Claims (10)
1. nifedipine film-controlled slow-release pellet capsule is characterized in that the extended release coatings film of micropill adopts Eurdragit RL 30D as filmogen, and the ball core contains the excipient that cross-linking sodium carboxymethyl cellulose and other pharmaceutically acceptable slow-release micro-pill are used.
2. nifedipine film-controlled slow-release pellet capsule according to claim 1, feature is that the excipient that described other pharmaceutically acceptable slow-release micro-pill are used is filler microcrystalline Cellulose, lactose and solubilizing agent PEG 4000.
3. nifedipine film-controlled slow-release pellet capsule as claimed in claim 1 or 2 is characterized in that the percentage ratio that cross-linking sodium carboxymethyl cellulose in the ball core of micropill accounts for ball core weight is 5～20%.
4. as nifedipine film-controlled slow-release pellet capsule as described in the claim 3, it is characterized in that the extended release coatings film of micropill comprises Eurdragit RL30D, plasticizer triethyl citrate and antiplastering aid Pulvis Talci.
5. as nifedipine film-controlled slow-release pellet capsule as described in the claim 4, the composition weight ratio that it is characterized in that the extended release coatings film of micropill is Eurdragit RL 30D: triethyl citrate: Pulvis Talci=30: 3: 4, the coating weightening finish is 21～35%.
6. nifedipine film-controlled slow-release pellet capsule is characterized in that by 1000 capsules, described micropill has following prescription:
Ball core prescription:
Extended release coatings film prescription:
The weightening finish of extended release coatings film coating is 21～35%.
7. method of improving the nifedipine film-controlled slow-release pellet capsule ageing resistace of aqueous dispersion coating, the extended release coatings film that it is characterized in that micropill adopts Eurdragit RL 30D as filmogen, and the ball core of micropill contains the excipient that cross-linking sodium carboxymethyl cellulose and other pharmaceutically acceptable slow-release micro-pill are used.
8. as method as described in the claim 7, it is characterized in that the excipient that described other pharmaceutically acceptable slow-release micro-pill are used is filler microcrystalline Cellulose, lactose and solubilizing agent PEG 4000.
9. as method as described in claim 7 or 8, it is characterized in that the percentage ratio that cross-linking sodium carboxymethyl cellulose in the ball core of micropill accounts for ball core weight is 5～20%, the extended release coatings film of micropill comprises Eurdragit RL 30D, plasticizer triethyl citrate and antiplastering aid Pulvis Talci and weight ratio is Eurdragit RL 30D: triethyl citrate: Pulvis Talci=30: 3: 4, the coating weightening finish is 21～35%.
10. as method as described in the claim 9, it is characterized in that by 1000 capsules, described micropill adopts following prescription:
Ball core prescription:
Extended release coatings film prescription:
The weightening finish of extended release coatings film coating is 21～35%.
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| CN112075445A (en) * | 2020-09-15 | 2020-12-15 | 湖北工程学院 | Cross-linked sodium carboxymethylcellulose suspension seed coating agent and preparation method thereof |
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| 刘彦生，等: "硝苯地平缓释微丸的制备", 《中国新药杂志》 * |
| 王立，等: "流化床包衣法制备硝苯地平缓释微丸", 《中国药学杂志》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112075445A (en) * | 2020-09-15 | 2020-12-15 | 湖北工程学院 | Cross-linked sodium carboxymethylcellulose suspension seed coating agent and preparation method thereof |
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| CN103211788B (en) | 2017-07-18 |
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