CN103211795A - Cefaclor film-controlled slow-release pellet capsule - Google Patents
Cefaclor film-controlled slow-release pellet capsule Download PDFInfo
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- CN103211795A CN103211795A CN2012100162666A CN201210016266A CN103211795A CN 103211795 A CN103211795 A CN 103211795A CN 2012100162666 A CN2012100162666 A CN 2012100162666A CN 201210016266 A CN201210016266 A CN 201210016266A CN 103211795 A CN103211795 A CN 103211795A
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Abstract
The invention relates to a cefaclor film-controlled slow-release pellet capsule. A slow-release film of the cefaclor film-controlled slow-release pellet utilizes a mixture of aqueous dispersion Eurdragit RL 30D and Eurdragit RS 30D as a film-formation material, wherein a weight ratio of Eurdragit RL 30D to Eurdragit RS 30D in the mixture is 4: 1. A pellet core of the cefaclor film-controlled slow-release pellet contains sodium carboxymethyl starch having high expansibility, and also contains pharmaceutically-acceptable common excipients for the slow-release pellet, wherein preferably, the excipients comprise microcrystalline cellulose and lactose, and the pellet core comprises 5 to 20wt% of the sodium carboxymethyl starch. The slow-release film comprises the mixture of Eurdragit RL 30D and Eurdragit RS 30D, triethyl citrate as a plasticizer, and talcum powder as an antiplastering aid, wherein preferably, a ratio of Eurdragit RL 30D to Eurdragit RS 30D to triethyl citrate to talcum powder is 24: 6: 2: 4 and a film weight increasing ratio is in a range of 23 to 40%. The cefaclor film-controlled slow-release pellet comprises the pellet core containing sodium carboxymethyl starch having high water expansibility and thus after absorbing water, the cefaclor film-controlled slow-release pellet obviously expands so that the slow-release film is stretched; the thickness of the slow-release film is reduced; the water-permeable micropore size is increased; and permeability is improved and the permeability reduction caused by film aging is counteracted. Therefore, in middle and later stages, the cefaclor film-controlled slow-release pellet release rate is basically constant; in the last stage, residues are less; and stable release performances can be kept in the period of validity.
Description
Technical field
The present invention relates to a kind of cefaclor film-controlled slow-release pellet capsule, specifically, relate to the cefaclor film-controlled slow-release pellet capsule that a kind of ball core contains carboxymethyl starch sodium, belong to field of pharmaceutical preparations.
Background technology
Cefaclor is a cephalosporins, by suppressing the synthetic performance antibacterial action of bacteria cell wall, has microbe killing properties.Can be under low concentration sterilization rapidly, be used for respiratory system, urinary system, department of otorhinolaryngology and skin, soft tissue infection etc. due to the sensitive organism.
Cefaclor is slightly soluble in water, and Shang Shi ordinary preparation need be taken 3 times every day the earliest, and blood concentration fluctuation is big, and peak concentration is too high, and untoward reaction is serious.
The cefaclor slow releasing tablet that gift lists a company (trade name: Cefaclor) be gel skeleton type slow releasing tablet,, often be the first-rate release because the release area of skeleton in continuous variation, discharges so be difficult to keep zero level.Its drug release process is the comprehensive effect process of bulk erosion-drug diffusion-stripping, and often release is inhomogeneous, and discharge too fast early stage, and the later stage discharges incomplete again.
Slow-release micro-pill is that medicine is made multiunit slow release medicine-releasing system, and 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.
Cefaclor 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 NE30D and Aquacoat Aquacoat and Surelease, yet we find: the cefaclor film controlling type slow-release micro-pill 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 cefaclor film controlling type slow-release micro-pill that solves aqueous dispersion coating preparation, the invention provides a kind of film controlling type cefaclor sustained-release micro-pill capsules that can remain stable release performance before the deadline, characteristics are to contain in the ball core of micropill has the carboxymethyl starch sodium 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 coating material commonly used at present, for example Eurdragit RL 30D or EurdragitRS 30D, the macromolecule of coating material itself is also water insoluble, but be dispersed in the water with particulate form, with make the aqueous dispersion coating solution after the mixing such as plasticizer, antiplastering aid, 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 cefaclor sustained-release micro-pill capsules, 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 cefaclor film controlling type slow-release micro-pill of aqueous dispersion coating adopts the ball core of the carboxymethyl starch sodium that contains high-expansion, because the carboxymethyl starch sodium suction is inflatable to 300% of original volume, can obviously expand behind the ball wicking absorbent, 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 cefaclor film-controlled slow-release micropill of aqueous dispersion coating so greatly.Because the high-expansion of carboxymethyl starch sodium in the ball core, expansive force is very big, along with increase 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, cefaclor film-controlled slow-release pellet capsule of the present invention, the carboxymethyl starch sodium that contains high-expansion in the ball core, and the excipient used of pharmaceutically acceptable slow-release micro-pill, excipient preferably microcrystalline cellulose and lactose, wherein, the percentage ratio that carboxymethyl starch sodium accounts for ball core weight in the ball core is 5～20%.It is Eurdragit RL 30D that the extended release coatings film of micropill adopts weight ratio: Eurdragit RS 30D=4: the mixture of 1 aqueous dispersion is as filmogen, preferred extended release coatings film comprises Eurdragit RL30D: Eurdragit RS 30D=4: 1 mixture, plasticizer triethyl citrate and antiplastering aid Pulvis Talci, its ratio is preferably Eurdragit RL 30D: Eurdragit RS 30D: triethyl citrate: Pulvis Talci=24: 6: 2: 4, and the coating weightening finish is preferably 23～40%.
As one of preferred implementation of the present invention, the micropill of cefaclor film-controlled slow-release micropill 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 23～40%.
The present invention provides a kind of method of improving the cefaclor film-controlled slow-release micropill ageing resistace of aqueous dispersion coating simultaneously, it is Eurdragit RL 30D that the extended release coatings film of its micropill adopts weight ratio: Eurdragit RS 30D=4: 1 mixture is as filmogen, the carboxymethyl starch sodium that contains high-expansion in the ball core, and the excipient used of other pharmaceutically acceptable slow-release micro-pill, described excipient preferably microcrystalline cellulose and lactose; Wherein, the percentage ratio that carboxymethyl starch sodium accounts for ball core weight in the ball core is 5～20%.As preferably, the extended release coatings film comprises Eurdragit RL 30D: Eurdragit RS 30D=4: 1 mixture, plasticizer triethyl citrate and antiplastering aid Pulvis Talci, its ratio is preferably Eurdragit RL 30D: Eurdragit RS 30D: triethyl citrate: Pulvis Talci=24: 6: 2: 4, and the coating weightening finish is preferably 23～40%.Said method preferred is in 1000, and described micropill has following prescription:
One, ball core prescription (1000 meters)
Two, extended release coatings film prescription
The weightening finish of extended release coatings film coating is 23～40%.
The preparation method of film controlling type cefaclor sustained-release micro-pill capsules 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, comprise batch mixing, pill core, the slow clothing film of bag etc., preferred employing is extruded spheronization and is prepared the ball core.With the slow-release micro-pill that the makes common stomach dissolution type gelatine capsule of 00el (promptly No. 00 lengthening) of packing into, promptly obtain cefaclor film-controlled slow-release pellet capsule.
Film controlling type cefaclor sustained-release micro-pill capsules 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+Eurdragit RS 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 carboxymethyl starch sodium 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 carboxymethyl starch sodium, 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 cefaclor sustained-release micro-pill capsules of embodiment 1 common ball core
One, prescription
1, ball core prescription (1000)
2, extended release coatings film coating fluid prescription
3, the common stomach dissolution type gelatine capsule shell of 00el is 1000
Two, preparation technology:
1, ball core preparation technology:
(1) cefaclor is crossed 60 mesh sieves.
(2) take by weighing cefaclor, microcrystalline Cellulose PH101, the lactose 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 30D, Eurdragit RS 30D at last, stirs, 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 16.4%.
4, heat treatment:
With the micropill of wrapping extended release coatings in fluid bed, heat treatment under 40 ℃/2h condition.
5, micropill is filled:
With the coated micropill filling capsule, promptly get the cefaclor sustained-release micro-pill capsules.
Three, release, assay and result
[drug release determination] gets this product, according to drug release determination method (two appendix X of Chinese Pharmacopoeia version in 2005 D, first method), adopt dissolution method (two appendix X of Chinese Pharmacopoeia version in 2005 C) first subtraction unit, (9 → 1000ml) 900ml are solvent with hydrochloric acid solution, rotating speed is that per minute 100 changes, operation in accordance with the law, in the time of 0.5 hour, 1 hour, 4 hours, getting solution 10ml filters, it is an amount of that precision is measured subsequent filtrate respectively, (9 → 1000ml) are diluted to the solution that contains 25 μ g among every 1ml approximately, as need testing solution to add hydrochloric acid solution; It is an amount of that other gets the cefaclor reference substance, and accurate the title decides, and (solution that contains 25 μ g among every 1ml approximately, product solution are in contrast made in 9 → 1000ml) dissolvings also dilution to add hydrochloric acid solution.Get above-mentioned two kinds of solution,, measure trap respectively, calculate every burst size respectively at different time at the wavelength place of 265nm according to ultraviolet visible spectrophotometry (two appendix IV of Chinese Pharmacopoeia version in 2005 A).Every burst size at 0.5 hour, 1 hour, 4 hours of this product should should be more than 5%～30%, 20%～50% and 80% of labelled amount respectively mutually, all should be up to specification.
[assay] measured according to high performance liquid chromatography (two appendix V of Chinese Pharmacopoeia version in 2005 D).
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; (get potassium dihydrogen phosphate 6.8g, be dissolved in water and be diluted to 1000ml, regulate pH value to 3.4 with phosphoric acid)-acetonitrile (92: 8) is a mobile phase with potassium dihydrogen phosphate; Flow velocity is per minute 1.0ml, and the detection wavelength is 254nm.The while precision takes by weighing the cefaclor reference substance and cefaclor δ-3-isomer reference substance is an amount of, add mobile phase dissolving and dilution and make the mixed solution that contains cefaclor and cefaclor δ-about 0.2mg of 3-isomer among every 1ml respectively, measure 20 μ l and inject chromatograph of liquid, the record chromatogram, the separating degree of cefaclor and cefaclor δ-3-isomer should meet the requirements.Number of theoretical plate calculates by cephalo clo peak should be not less than 1500.
Algoscopy is got 20 of this product, incline and content, the accurate title, decide, porphyrize, and precision takes by weighing in right amount (being equivalent to cefaclor 100mg approximately), add mobile phase dissolving and dilution and make the solution (supersound process in case of necessity) that contains cefaclor 0.2mg among every 1ml approximately, shake up, filter, precision is measured subsequent filtrate 20 μ l, inject chromatograph of liquid, the record chromatogram; It is an amount of that other gets the cefaclor reference substance, adds mobile phase dissolving and dilution and make the solution (supersound process in case of necessity) that contains cefaclor 0.2mg among every 1ml approximately, measures with method.Go out C in the test sample by external standard method with calculated by peak area
15H
14ClN
3O
4The content of S, 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 cefaclor sustained-release micro-pill capsules of high-expansion 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 micropills to be measured, remove softgel shell, 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 softgel shell, micropill in the capsule is inclined to, put respectively in above-mentioned 3 500ml beakers and soak, respectively take out 1 group at 0.5h, 1h, 4h 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 cefaclor sustained-release micro-pill capsules of intumescent 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 cefaclor sustained-release micro-pill capsules of 5% carboxymethyl starch sodium
One, prescription
1, ball core prescription (1000)
2, extended release coatings film coating fluid prescription: with embodiment 1
3, the common stomach dissolution type gelatine capsule shell of 00el is 1000
Two, preparation technology:
1, ball core preparation technology:
(1) cefaclor is crossed 60 mesh sieves;
(2) take by weighing cefaclor, microcrystalline Cellulose PH101, lactose, the carboxymethyl starch sodium 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) put on the spheronizator round as a ballly, 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 22.6%.
4, heat treatment: with embodiment 1
5, micropill is filled: 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 cefaclor sustained-release micro-pill capsules initial release performance of carboxymethyl starch sodium 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 cefaclor sustained-release micro-pill capsules of intumescent material carboxymethyl starch sodium 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 cefaclor sustained-release micro-pill capsules of 10% carboxymethyl starch sodium
One, prescription
1, ball core prescription (1000)
2, extended release coatings film coating fluid prescription: with embodiment 1
3, the common stomach dissolution type gelatine capsule shell of 00el 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 26.5%, 30.7%.
4, heat treatment: with embodiment 1
5, micropill is filled: 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 cefaclor sustained-release micro-pill capsules initial release performance of carboxymethyl starch sodium 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 cefaclor sustained-release micro-pill capsules of carboxymethyl starch sodium 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 cefaclor sustained-release micro-pill capsules of 15% carboxymethyl starch sodium
One, prescription
1, ball core prescription (1000)
2, extended release coatings film coating fluid prescription: with embodiment 1.
3, the common stomach dissolution type gelatine capsule shell of 00el 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 33.3%.
4, heat treatment: with embodiment 1
5, micropill is filled: 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 cefaclor sustained-release micro-pill capsules initial release performance of carboxymethyl starch sodium 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 cefaclor sustained-release micro-pill capsules of carboxymethyl starch sodium 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 cefaclor sustained-release micro-pill capsules of 20% carboxymethyl starch sodium
One, prescription
1, ball core prescription (1000)
2, extended release coatings film coating fluid prescription: with embodiment 1;
3, the common stomach dissolution type gelatine capsule shell of 00el 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 39.7%.
4, heat treatment: with embodiment 1
5, micropill is filled: 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 cefaclor sustained-release micro-pill capsules initial release performance of carboxymethyl starch sodium 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 cefaclor sustained-release micro-pill capsules of carboxymethyl starch sodium 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. cefaclor film-controlled slow-release pellet capsule, the extended release coatings film that it is characterized in that micropill adopts weight ratio Eurdragit RL 30D: Eurdragit RS 30D=4: 1 mixture is as filmogen, and the ball core contains the excipient that carboxymethyl starch sodium and other pharmaceutically acceptable slow-release micro-pill are used.
2. cefaclor film-controlled slow-release pellet capsule according to claim 1, feature is that the excipient that described pharmaceutically acceptable slow-release micro-pill is used is microcrystalline Cellulose and lactose.
3. cefaclor film-controlled slow-release pellet capsule as claimed in claim 1 or 2 is characterized in that the percentage ratio that carboxymethyl starch sodium in the ball core of micropill accounts for ball core weight is 5-20%.
4. as cefaclor 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 aqueous dispersion filmogen Eurdragit RL 30D: Eurdragit RS 30D=4: the mixture of 1 weight ratio, plasticizer triethyl citrate and antiplastering aid Pulvis Talci.
5. as cefaclor 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: Eurdragit RS 30D: triethyl citrate: Pulvis Talci=24: 6: 2: 4, and the coating weightening finish is 23～40%.
6. cefaclor 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:
Wherein the weightening finish of extended release coatings film coating is 23～40%.
7. method of improving the cefaclor 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 aqueous dispersion Eurdragit RL 30D: Eurdragit RS 30D=4: the mixture of 1 weight ratio is as filmogen, and the ball core of micropill contains the excipient that carboxymethyl starch sodium and 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 pharmaceutically acceptable slow-release micro-pill is used is microcrystalline Cellulose and lactose.
9. as method as described in claim 7 or 8, it is characterized in that the percentage ratio that carboxymethyl starch sodium in the ball core of micropill accounts for ball core weight is 5-20%, the extended release coatings film of micropill comprises aqueous dispersion filmogen Eurdragit RL 30D: Eurdragit RS 30D=4: the mixture of 1 weight ratio, plasticizer triethyl citrate and antiplastering aid Pulvis Talci and weight ratio are Eurdragit RL 30D: Eurdragit RS30D: triethyl citrate: Pulvis Talci=24: 6: 2: 4, and the coating weightening finish is 23～40%.
10. as method as described in the claim 9, its feature is according to 1000 capsules meters, and described micropill adopts following prescription:
Ball core prescription:
Extended release coatings film prescription:
Wherein the weightening finish of extended release coatings film coating is 23～40%.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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| CN112137984A (en) * | 2020-10-30 | 2020-12-29 | 四川制药制剂有限公司 | Cefaclor capsule and preparation process thereof |
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| CN104940207A (en) * | 2015-05-26 | 2015-09-30 | 青岛海之星生物科技有限公司 | Cefalexin and probenecid compound sustained-release capsule and preparation method thereof |
| CN112137984A (en) * | 2020-10-30 | 2020-12-29 | 四川制药制剂有限公司 | Cefaclor capsule and preparation process thereof |
| CN112137984B (en) * | 2020-10-30 | 2023-02-03 | 四川制药制剂有限公司 | Cefaclor capsule and preparation process thereof |
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| Publication number | Publication date |
|---|---|
| CN103211795B (en) | 2017-07-11 |
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