CN103893192A - Cardiovascular disease treatment sustained-release tablets and preparation method thereof - Google Patents
Cardiovascular disease treatment sustained-release tablets and preparation method thereof Download PDFInfo
- Publication number
- CN103893192A CN103893192A CN201210570914.2A CN201210570914A CN103893192A CN 103893192 A CN103893192 A CN 103893192A CN 201210570914 A CN201210570914 A CN 201210570914A CN 103893192 A CN103893192 A CN 103893192A
- Authority
- CN
- China
- Prior art keywords
- aspirin
- dipyridamole
- mix
- sealing coat
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention discloses aspirin dipyridamole sustained-release tablets and a preparation method thereof, wherein the aspirin dipyridamole sustained-release tablets comprise an aspirin tablet core, an isolation layer coating, dipyridamole total mixing particles, and a protection layer coating. According to the present invention, the isolation layer is arranged between the dipyridamole layer and the aspirin layer so as to prevent production of the aspirin degradation product salicylic acid due to contact of the aspirin and the dipyridamole; the dry mixing method is adopted when the aspirin total mixing particles are prepared so as to avoid production of salicylic acid due to direct contact of the aspirin and water; and the tableting process of the preparation method of the present invention only requires the one core coating tableting equipment, and other processes can be achieved through the conventional equipment, such that the cost of the aspirin dipyridamole sustained-release tablets is not added while the aspirin stability can be ensured.
Description
Invention field
The present invention relates to slow releasing tablet of a kind of Cardiovarscular and preparation method thereof, particularly a kind of aspirin dipyridamole slow-release tablet and preparation method thereof.
Background technology
Along with aged tendency of population process is accelerated, cardiovascular and cerebrovascular disease sickness rate improves rapidly, and antiplatelet aggregation is the important step for the treatment of cardiovascular and cerebrovascular disease.Aspirin (Aspirin, be called for short ASP) and dipyridamole (Dipyridamole, be called for short DP) be widely used clinically as medicament for resisting platelet aggregation, be mainly used in antithrombotic, the diseases such as arteriosclerosis and scheming infarction.In recent years, the compound solid preparation of aspirin-dipyridomole existing application clinically.This medicine is antithrombotic choice drug by world health organisation recommendations; Be to be the optimal drug that prevents myocardial infarction by antiplatelet experimenter association of the U.S., famous PARISI experimental verification.
First Boehinger Ingelheim company of Germany develops aspirin phenacetin caffeine dipyridamole sustained-release capsules, trade name
within 1999, obtain U.S. FDA approval listing, sell and use in multiple countries such as France of Britain at present.
be the capsule for oral administration, in capsule, formed by the sugar coated tablet of aspirin and the slow-release micro-pill of dipyridamole.But aspirin phenacetin caffeine dipyridamole sustained-release capsules preparation technology needs corresponding Special capsule equipment, and wherein aspirin carries out sugar-coat coating, and dipyridamole carries out slow-release micro-pill preparation, therefore the production technology cycle is long and complicated.
Patent CN2798942Y discloses a kind of utility model of aspirin dipyridamole slow-release tablet agent, this utility model is for being made up of three layers of aspirin lamella, blank adjuvant sealing coat and dipyridamoles, on three laminate machines, suppress the last coating of three-layer tablet, this technique needs three laminate machines, in operating process, inevitable aspirin contacts with dipyridamole simultaneously, causes aspirin degraded.
Patent CN1480144A and patent CN102210693A first prepare dipyridamole extended-release label by tabletting; wrap successively again sealing coat, aspirin release layer and protective layer; but after need being mixed with coating solution to aspirin release layer, dipyridamole layer is carried out to coating; aspirin is very easily hydrolysis in coating solution, and aspirin is easily hydrolyzed in coating process.
Patent CN200310115323.7 suppresses double-layer tablet after granulation respectively by aspirin and dipyridamole, and the made double-layer tablet of this method has contact surface between aspirin layer and dipyridamole layer, thereby can accelerate the degraded of aspirin.
Patent CN201010587095.3 makes aspirin after label enteric coatedly, and dipyridamole carries out coating to aspirin enteric-coated garment piece core after making coating solution, and above two steps all can have facilitation to aspirin degraded.
Patent CN201110052131.0 discloses aspirin-dipyridomole floating in stomach piece preparation method, this method is by tabletting after aspirin, dipyridamole and other adjuvant mixing granulation, aspirin and dipyridamole are not isolated, dipyridamole can accelerate the degraded of aspirin.
Aspirin easily decomposes and produces free salicylic acid under alkalescence or weak basic condition, dipyridamole is again alkalescent medicine, produce free salicylic acid with accelerating aspirin decomposition after aspirin mixed pressuring plate, be difficult to reach the quality control standard of free salicylic acid in aspirin.
Summary of the invention
The object of the present invention is to provide a kind of slow releasing tablet of Cardiovarscular, another object of the present invention is to provide the preparation method of this slow releasing tablet.
The object of the invention is to be achieved through the following technical solutions:
The slow releasing tablet of Cardiovarscular of the present invention, by aspirin label, sealing coat coating, dipyridamole, always mixed granule, protective layer coating form;
Wherein aspirin label is made up of following supplementary material:
Wherein sealing coat coating is made up of following supplementary material:
Coating materials 1-10 weight portion
Alcoholic solution 10-60 weight portion
Wherein dipyridamole always mixed granule made by following supplementary material:
Wherein protective layer coating is made up of following supplementary material:
Coating materials 4-20 weight portion
Alcoholic solution 50-300 weight portion
Wherein the acidity regulator described in aspirin label supplementary material is selected from one or more in tartaric acid, citric acid, malic acid, lactic acid, adipic acid and fumaric acid, preferably tartaric acid; Described disintegrating agent is selected from one or more of pregelatinized Starch, low-substituted hydroxypropyl cellulose, cross linked polyvinyl pyrrolidone, cross-linking sodium carboxymethyl cellulose and carboxymethyl starch sodium, preferably pregelatinized Starch; Described filler is selected from one or more in lactose, starch, sucrose, dextrin, mannitol, microcrystalline Cellulose, preferably lactose and microcrystalline Cellulose; Described lubricant is selected from one or more in stearic acid, magnesium stearate, sodium laurylsulfate, polyethylene glycol 6000, Macrogol 4000, preferably stearic acid;
Wherein coating materials described in sealing coat coating is selected from one or more in Opadry, preferably Opadry 80W620004Yellow; The preferred 10%-30% alcoholic solution of described alcoholic solution;
Wherein dipyridamole always slow-release material described in mixed granular raw adjuvant be selected from one or more in hypromellose, methylcellulose, hydroxyethyl-cellulose, hydroxypropyl cellulose, Carboxymethyl cellulose sodium, pectin, carbomer and chitosan, preferably hypromellose; Described filler is selected from one or more in lactose, starch, sucrose, dextrin, mannitol, microcrystalline Cellulose, preferably lactose; The preferred 20%-40% alcoholic solution of described alcoholic solution; Described lubricant is selected from one or more in stearic acid, magnesium stearate, sodium laurylsulfate, polyethylene glycol 6000, Macrogol 4000, preferably stearic acid.
Wherein coating materials described in protective layer coating is selected from one or more in Opadry, preferably Opadry 295K 620010Yellow; The alcoholic solution of the preferred 60%-95% of described alcoholic solution.
The slow releasing tablet of Cardiovarscular of the present invention, by aspirin label, sealing coat coated tablet, dipyridamole always mixed granule, protective layer coating form, be preferably:
Wherein aspirin label is made up of following supplementary material:
Wherein sealing coat coating is made up of following supplementary material:
Opadry 80W 620004Yellow 2-4 weight portion
10%-30% alcoholic solution 20-35 weight portion
Wherein dipyridamole always mixed granule made by following supplementary material:
Wherein protective layer coating is made up of following supplementary material:
Opadry 295K 620010Yellow 6-10 weight portion
60%-95% alcoholic solution 100-150 weight portion
The slow releasing tablet of Cardiovarscular of the present invention, by aspirin label, sealing coat coating, dipyridamole always mixed granule, protective layer coating form, more preferably:
Wherein aspirin label is made up of following supplementary material:
Wherein sealing coat coating is made up of following supplementary material:
Opadry 80W 620004Yellow 3 weight portions
20% alcoholic solution 28 weight portions
Wherein dipyridamole always mixed granule made by following supplementary material:
Wherein protective layer coating is made up of following supplementary material:
Opadry 295K 620010Yellow 8 weight portions
80% alcoholic solution 126 weight portions
Or
Wherein aspirin label is made up of following supplementary material:
Wherein sealing coat coating is made up of following supplementary material:
Opadry 80W 620004Yellow 4 weight portions
10% alcoholic solution 35 weight portions
Wherein dipyridamole always mixed granule made by following supplementary material:
Wherein protective layer coating is made up of following supplementary material:
Opadry 295K 620010Yellow 10 weight portions
95% alcoholic solution 150 weight portions
Or
Wherein aspirin label is made up of following supplementary material:
Wherein sealing coat coating is made up of following supplementary material:
Opadry 80W 620004Yellow 2 weight portions
30% alcoholic solution 20 weight portions
Wherein dipyridamole always mixed granule made by following supplementary material:
Wherein protective layer coating is made up of following supplementary material:
Opadry 295K 620010Yellow 6 weight portions
60% alcoholic solution 100 weight portions
The preparation method of the slow releasing tablet of Cardiovarscular of the present invention is:
(1) preparation of aspirin sealing coat coated cores:
Aspirin and L-TARTARIC ACID are pulverized and sieved respectively, pregelatinized Starch, spray-dried lactose, stearic acid sieving for standby respectively; Take aspirin by recipe quantity and mix with L-TARTARIC ACID, then add pregelatinized Starch to mix, then take spray-dried lactose by recipe quantity and mix, then add microcrystalline Cellulose PH101 to mix, finally add stearic acid, mix homogeneously, tabletting; The weightening finish of sealing coat coating, as aspirin sealing coat coated cores;
(2) the always preparation of mixed granule of dipyridamole
Take dipyridamole, slow-release material, filler by recipe quantity, be placed in wet granulator, adopt alcoholic solution soft material processed, granulate, dry, granulate, additional lubricant, mix homogeneously, as always mixed granule of dipyridamole;
(3) preparation of aspirin-dipyridomole slow release clad sheet
Using aspirin sealing coat coated cores as internal layer, dipyridamole, always mixed granule is as skin, and cored tablet machine is suppressed double-deck clad sheet;
(4) protective layer coating weightening finish, to obtain final product.
The preparation method of the slow releasing tablet of Cardiovarscular of the present invention is preferably:
(1) preparation of aspirin sealing coat coated cores
By aspirin pulverized 20-40 mesh sieve, L-TARTARIC ACID was pulverized 70-90 mesh sieve, pregelatinized Starch, spray-dried lactose are crossed 10-30 mesh sieve respectively, stearic acid is crossed 10-30 mesh sieve, for subsequent use; Take aspirin by recipe quantity and mix with L-TARTARIC ACID, then add pregelatinized Starch to mix, then add spray-dried lactose to mix, then add microcrystalline Cellulose PH101 to mix, finally add stearic acid, mix homogeneously, adopts Φ=9.5mm scrobicula drift tabletting; Opadry 80W 620004Yellow sealing coat coating increases weight to 1%-5%, as aspirin label;
(2) the always preparation of mixed granule of dipyridamole
Take dipyridamole, HPMC K4M, lactose by recipe quantity, put successively in wet granulator, adopt 20-40% ethanol soft material processed, 10-30 mesh sieve is granulated, and temperature of charge is no more than 35 DEG C-60 DEG C, is dried to LOD≤3.5%, 10-20 mesh sieve granulate, additional stearic acid, mix homogeneously, as always mixed granule of dipyridamole;
(3) preparation of aspirin-dipyridomole slow release clad sheet
Using aspirin sealing coat coated cores as internal layer, dipyridamole, always mixed granule is as skin, and employing Φ=12mm scrobicula drift is suppressed the double-deck plain sheet of cored;
(4) Opadry 295K 620010Yellow protective layer coating increases weight to 1%-5%, to obtain final product.
The preparation method of the slow releasing tablet of Cardiovarscular of the present invention is more preferably:
(1) preparation of aspirin sealing coat coated cores:
By aspirin pulverized 30 mesh sieves, L-TARTARIC ACID was pulverized 80 mesh sieves, pregelatinized Starch, spray-dried lactose are crossed respectively 18 mesh sieves, stearic acid and are crossed 20 mesh sieves, for subsequent use; Take aspirin by recipe quantity and mix with L-TARTARIC ACID, then add pregelatinized Starch to mix, then add spray-dried lactose to mix, then add microcrystalline Cellulose PH101 to mix, finally add stearic acid, mix homogeneously, adopts Φ=9.5mm scrobicula drift tabletting; Opadry 80W 620004Ye1low sealing coat coating increases weight to 3%, as aspirin sealing coat coated cores;
(2) the always preparation of mixed granule of dipyridamole
Take dipyridamole, HPMC K4M, lactose by recipe quantity, put successively in wet granulator, adopt 30% ethanol soft material processed, 18 mesh sieves are granulated, and temperature of charge is no more than 45 DEG C and is dried to LOD≤2.0%, 10 mesh sieve granulate; Additional stearic acid, mix homogeneously, as always mixed granule of dipyridamole;
(3) preparation of aspirin-dipyridomole slow release clad sheet
Using dipyridamole extended-release label as internal layer, aspirin always mixed granule as skin, adopt Φ=12mm scrobicula drift compacting cored double-layer tablet;
(4) Opadry 295K 620010Yellow protective layer coating increases weight to 3%, to obtain final product.
The present invention has sealing coat at aspirin and dipyridamole between two-layer, can stop both to be in contact with one another and cause the salicylic generation of aspirin catabolite; Simultaneously adopt when always mixed and be dry mixed method preparation preparing aspirin, avoided aspirin and water directly to contact and caused salicylic acid generation; In addition, preparation method tabletting process of the present invention only needs a cored sheeting equipment, and other are conventional equipment and can realize, and can ensure that aspirin is stable so aspirin dipyridamole slow-release tablet cost of the present invention does not increase.
Following experimental example and embodiment are used for further illustrating the present invention, but are not limited to the present invention.
Experimental example 1: formulation optimization experiment
1.1 aspirin prescriptions are selected
1.1.1 the selection of diluent
Because aspirin is easily hydrolyzed, therefore in order to reduce the generation of hydrolyzate, aspirin layer adopts direct compression, the adjuvant that selective flow is good is particularly important, respectively using microcrystalline Cellulose, lactose, starch as diluent tabletting, investigate result table 1 as index using mobility, outward appearance, hardness.
Table 1 aspirin prescription is selected
| Diluent | Outward appearance | Hardness | Mobility |
| Microcrystalline Cellulose | Well | Larger | Good |
| Spray-dried lactose | Well | Greatly | Well |
| Starch | Well | Larger | Poor |
Can be found out by the above results, using starch as diluent, always mixed logistics is moving differs, consider, select microcrystalline Cellulose and spray-dried lactose as diluent, L-TARTARIC ACID can reduce the hydrolysis of aspirin simultaneously, therefore the diluent of aspirin layer is selected microcrystalline Cellulose-spray-dried lactose-L-TARTARIC ACID.
1.1.2, the selection of disintegrating agent
Microcrystalline Cellulose itself has the function of disintegrating agent concurrently, but after granule processed, disintegrate effect is undesirable, therefore choose a small amount of disintegrating agent.Pregelatinized Starch is the more adjuvant of recent foreign applications, can make filler, has good mobility, compressibility, self-lubricity and cohesive, and has good disintegration, still choose pregelatinized Starch as disintegrating agent.
1.1.3, the selection of disintegrating agent consumption
When aspirin tablet is clad sheet internal layer, in order to make aspirin Fast Stripping, pregelatinized Starch amount should be skin than aspirin time is large, to addition 30%, 33%, 37% investigates, result shows in the time that pregelatinized Starch is 37%, disintegration is only 0.5min, is enough to meet the requirement of the quick disintegrate of aspirin layer and stripping, the results are shown in Table 2.
The impact of the different disintegrate dosage of table 2 on disintegration
| Disintegrate dosage (%) | 30 | 33 | 37 |
| Disintegration min | 1.5 | 1.2 | 0.5 |
1.1.4, the selection of lubricant quantity
Stearic acid is the degraded that a kind of effective lubricant can suppress aspirin simultaneously, therefore preferably stearic acid is as lubricant, consumption is generally 1%-3%.
The selection of 1.2 dipyridamole prescriptions
1.2.1 the selection of hypromellose HPMC type
Because this prescription dipyridamole requires 12 hours slow release, with reference to related documents, should select high viscosity HPMC, therefore select K4M, the HPMC of K15M investigates viscosity to the impact (dipyridamole: HPMC is 1: 1) discharging, and the results are shown in Table 3.
The impact of table 3 different viscosities HPMC on dipyridamole release
| Release (%) | 1hr | 3hr | 5hr | 7hr | 12hr |
| HPMC(4M) | 10.3％ | 35.2％ | 44.7％ | 56.5％ | 79.0％ |
| HPMC(15M) | 3.6％ | 9.2％ | 15.6％ | 22.4％ | 34.1％ |
The HPMC that can be found out different viscosities by upper table result has different impacts to discharging, and viscosity is high to be discharged slowly, discharges but HPMC K15M can control dipyridamole strongly, and the variation of consumption has considerable influence to the stability of prescription, therefore select HPMC K4M.
1.2.2 filler is selected
Investigate different diluent to discharging impact (dipyridamole: HPMC is 200: 100), selecting respectively lactose, starch or sucrose is diluent, after the sheet of compacting same rigidity, measures the release of 12 hours, starch release is incomplete, within 12 hours, discharge approximately 80%, and the release ratio of lactose and sucrose is more approaching, discharges completely, all be greater than 90%, but the easy moisture absorption of cane sugar powder, thus accelerate the degraded of aspirin, therefore select lactose as diluent.
1.2.3 the selection of binding agent
We have selected respectively I%HPMC, water, 30% ethanol is binding agent, and the former two's viscosity is too strong, and the soft material of making becomes agglomerate, therefore employing alcoholic solution is wetting agent.
1.2.4 the selection of lubricant
In order to reduce the degraded of aspirin, preferably stearic acid is lubricant.
The 1.3 dipyridamoles always prescription of mixed granule are preferred
1.3.1 the preferred best prescription of orthogonal design
Taking HPMC K4M, lactose, binding agent and stearic consumption as four factors, adopt three levels below:
HPMC K4M consumption: 75mg; 80mg; 85mg
Binder dosage (inside adding the % of material): 30%; 35%; 40%
Lactose consumption: 90mg; 100mg; 110mg
Stearic acid dosage: 3mg; 5mg; 8mg
Table 4 factor and level
| ? | A (HPMC consumption) | B (binder dosage) | C (lactose consumption) | D (stearic acid dosage) |
| 1 | 75 | 30％ | 90 | 3 |
| 2 | 80 | 35％ | 100 | 5 |
| 3 | 85 | 40％ | 110 | 8 |
1.3.2 experimental establishment
Select the orthogonal design L of four factor three levels
9(3
4) prepare always mixed granule of dipyridamole, tabletting, measures the vitro release of each prescription, taking the drug release rate of main time point as evaluation criterion, selected optimum prescription.To the accumulative releasing degree of 1 hour, 3 hours, 7 hours three time points of release high spot reviews, with 1h:33%; 3h:68%; 7h:95% standard compares.Adopt comprehensive P=30/|100 × P
1hr sample (two)-33|+40/|100 × P
3hr sample (two)-68|+30/|100 × P
7hr sample (two)-95|, P value is larger, and score is higher, shows with selected standard trend more approachingly, the results are shown in Table 5.
Can find out from intuitive analysis and variance analysis, influence factor's the order that affects on score value is: A > C > D > B, optimum prescription is: A
2b
1c
3d
3, that is:
Table 5 dipyridamole is the orthogonal array of mixed granule always
The selection of 1.4 aspirin tablet sealing coat coating materials
Select self-control coating powder (2%HPMC, titanium dioxide, Oleum Ricini, color lake), Opadry (color company), three kinds of coating materials of LE film coating agent (Tianjin Aileyi Medicine Materials Co., Ltd.) to aspirin coating tablets, coated tablet (label) and always mixed granule compacting clad sheet of dipyridamole, respectively 60 DEG C 5 days, within 10 days, measure salicylic acid content, the results are shown in Table 6.
The different coating material salicylic acid of table 6 measurement result
Can be found out by upper table result, three kinds of coating materials are on the salicylic significant difference that affects.Opadry 80W620004 to the isolation effect of dipyridamole extended-release coating tablets significantly better than self-control coating material and LE film coating agent, therefore select Opadry 80W620004 to carry out sealing coat coating to dipyridamole extended-release sheet.
The selection of 1.5 aspirin dipyridamole slow-release tablet coating materials
Selected self-control coating powder (2%HPMC, titanium dioxide, Oleum Ricini, color lake), Opadry (color company), (aspirin tablet is label to aspirin dipyridamole slow-release tablet easily to release beautiful (Tianjin Aileyi Medicine Materials Co., Ltd.) three kinds of coating materials, dipyridamole always mixed granule is outer) coating, respectively at 25 DEG C, under RH 90% ± 5% condition, place 10 days, in the 5th day, within 10 days, measure salicylic acid content, the results are shown in Table 7.
The different coating material salicylic acid of table 7 measurement result
Can be found out by upper table result, Opadry 295K620010 and easily to release the humidity resistance of beautiful GMI best, self-control coating material humidity resistance is bad and repeatability is poor, therefore Opadry 295K620010 and easily release beautiful GMI and all aspirin is had to better moisture protection effect.
By above the effects, determine the preparation technology of aspirin (internal layer)/dipyridamole (skin) slow releasing tablet:
By aspirin pulverized 30 mesh sieves, L-TARTARIC ACID was pulverized 80 mesh sieves, pregelatinized Starch, spray-dried lactose are crossed respectively 18 mesh sieves, stearic acid and are crossed 20 mesh sieves, for subsequent use; Take aspirin by recipe quantity and mix with L-TARTARIC ACID, then add pregelatinized Starch to mix, then add spray-dried lactose to mix, add again microcrystalline Cellulose PH101 to mix, finally add stearic acid, mix homogeneously, adopt Φ=9.5mm scrobicula drift tabletting, as aspirin tablet; Opadry 80W 620004Yellow sealing coat coating increases weight to 3%, as aspirin sealing coat coated cores; Take dipyridamole, HPMC K4M, lactose by recipe quantity, put successively in wet granulator, adopt 30% ethanol soft material processed, 18 mesh sieves are granulated, and temperature of charge is no more than 45 DEG C and is dried to LOD≤2.0%, 10 mesh sieve granulate; Additional stearic acid, mix homogeneously, as always mixed granule of dipyridamole; Using aspirin sealing coat coated cores as internal layer, dipyridamole, always mixed granule is as skin, and employing Φ=12mm scrobicula drift is suppressed the double-deck plain sheet of cored; Opadry 295K 620010Yellow protective layer coating increases weight to 3%, to obtain final product.
The repeatability of 1.6 prescriptions and production technology is investigated
Prepare three batch samples by prescription and production technology (embodiment 1 method) after determining, it is detected, thereby the repeatability of investigation prescription and production technology the results are shown in Table 8.
Table 8 aspirin sustained release dipyridamole clad sheet testing result
Better from this prescription of detection data declaration and the production technology repeatability of upper table.
1.7 study on the stability
Get three batch samples, under temperature is 40 DEG C ± 2 DEG C, the condition of RH75% ± 5%, in 1,2, March sampling and measuring, and with result comparison in 0 month, the results are shown in Table 9.
Table 9 aspirin sustained release dipyridamole clad sheet Detection of Stability result
Can find out from upper table data, aspirin dipyridamole slow-release tablet stability is better, therefore show this practical process.
Detailed description of the invention
Embodiment 1: aspirin dipyridamole slow-release tablet
Aspirin tablet:
Sealing coat coating:
Opadry 80W 620004Yellow 3kg
20% alcoholic solution 28kg
Dipyridamole is mixed granule always:
Protective layer coating:
Opadry 295K 620010Yellow 8kg
80% alcoholic solution 126kg
By aspirin pulverized 30 mesh sieves, L-TARTARIC ACID was pulverized 80 mesh sieves, pregelatinized Starch, spray-dried lactose are crossed respectively 18 mesh sieves, stearic acid and are crossed 20 mesh sieves, for subsequent use; Take aspirin by recipe quantity and mix with L-TARTARIC ACID, then add pregelatinized Starch to mix, then add spray-dried lactose to mix, then add microcrystalline Cellulose PH101 to mix, finally add stearic acid, mix homogeneously, adopts Φ=9.5mm scrobicula drift tabletting; Opadry 80W 620004Yellow sealing coat coating increases weight to 3%, as aspirin sealing coat coated cores; Take dipyridamole, HPMC K4M, lactose by recipe quantity, put successively in wet granulator, adopt 30% ethanol soft material processed, 18 mesh sieves are granulated, and temperature of charge is no more than 45 DEG C and is dried to LOD≤2.0%, 10 mesh sieve granulate; Additional stearic acid, mix homogeneously, as always mixed granule of dipyridamole; Using aspirin sealing coat coated cores as internal layer, dipyridamole, always mixed granule is as skin, and employing Φ=12mm scrobicula drift is suppressed the double-deck plain sheet of cored; Opadry 295K 620010Yellow protective layer coating increases weight to 3% and get final product.
Embodiment 2: aspirin dipyridamole slow-release tablet
Aspirin tablet:
Sealing coat coating:
Opadry 80W 620004Yellow 4kg
10% alcoholic solution 35kg
Dipyridamole is mixed granule always:
Protective layer coating:
Opadry 295K 620010Yellow 10kg
95% alcoholic solution 150kg
By aspirin pulverized 40 mesh sieves, L-TARTARIC ACID was pulverized 70 mesh sieves, pregelatinized Starch, spray-dried lactose are crossed respectively 10 mesh sieves, stearic acid and are crossed 30 mesh sieves, for subsequent use; Take aspirin by recipe quantity and mix with L-TARTARIC ACID, then add pregelatinized Starch to mix, then add spray-dried lactose to mix, then add microcrystalline Cellulose PH101 to mix, finally add stearic acid, mix homogeneously, adopts Φ=9.5mm scrobicula drift tabletting; Opadry 80W 620004Yellow sealing coat coating increases weight to 3%, as aspirin sealing coat coated cores; Take dipyridamole, HPMC K4M, lactose by recipe quantity, put successively in wet granulator, adopt 20% ethanol soft material processed, 30 mesh sieves are granulated, and temperature of charge is no more than 50 DEG C, is dried to LOD≤1.0%, 10 mesh sieve granulate; Additional stearic acid, mix homogeneously, as always mixed granule of dipyridamole; Using aspirin sealing coat coated cores as internal layer, dipyridamole, always mixed granule is as skin, and employing Φ=12mm scrobicula drift is suppressed the double-deck plain sheet of cored; Opadry 295K 620010Yellow protective layer coating increases weight to 4% and get final product.
Embodiment 3: aspirin dipyridamole slow-release tablet
Aspirin tablet:
Sealing coat coating:
Opadry 80W 620004Yellow 2kg
30% alcoholic solution 20kg
Dipyridamole is mixed granule always:
Protective layer coating:
Opadry 295K 620010Yellow 6kg
60% alcoholic solution 100kg
By aspirin pulverized 20 mesh sieves, L-TARTARIC ACID was pulverized 90 mesh sieves, pregelatinized Starch, spray-dried lactose are crossed respectively 20 mesh sieves, stearic acid and are crossed 10 mesh sieves, for subsequent use; Take aspirin by recipe quantity and mix with L-TARTARIC ACID, then add pregelatinized Starch to mix, then add spray-dried lactose to mix, then add microcrystalline Cellulose PHl01 to mix, finally add stearic acid, mix homogeneously, adopts Φ=9.5mm scrobicula drift tabletting; Opadry 80W 620004Yellow sealing coat coating increases weight to 2%, as aspirin sealing coat coated cores; Take dipyridamole, HPMC K4M, lactose by recipe quantity, put successively in wet granulator, adopt 40% ethanol soft material processed, 10 mesh sieves are granulated, and temperature of charge is no more than 35 DEG C, is dried to LOD≤3.0%, 20 mesh sieve granulate, additional stearic acid, mix homogeneously, as always mixed granule of dipyridamole; Using aspirin sealing coat coated cores as internal layer, dipyridamole, always mixed granule is as skin, and employing Φ=12mm scrobicula drift is suppressed the double-deck plain sheet of cored; Opadry 295K 620010Yellow protective layer coating increases weight to 2% and get final product.
Claims (15)
1. a slow releasing tablet for Cardiovarscular, it is characterized in that this slow releasing tablet by aspirin label, sealing coat coating, dipyridamole always mixed granule, protective layer coating form,
Wherein aspirin label is made up of following supplementary material:
Wherein sealing coat coating is made up of following supplementary material:
Coating materials 1-10 weight portion
Alcoholic solution 10-60 weight portion
Wherein dipyridamole always mixed granule made by following supplementary material:
Wherein protective layer coating is made up of following supplementary material:
Coating materials 4-20 weight portion
Alcoholic solution 50-300 weight portion.
2. slow releasing tablet as claimed in claim 1, it is characterized in that wherein the acidity regulator described in aspirin label supplementary material is selected from tartaric acid, citric acid, malic acid, lactic acid, one or more in adipic acid and fumaric acid, described disintegrating agent is selected from pregelatinized Starch, low-substituted hydroxypropyl cellulose, cross linked polyvinyl pyrrolidone, one or more of cross-linking sodium carboxymethyl cellulose and carboxymethyl starch sodium, described filler is selected from lactose, starch, sucrose, dextrin, mannitol, one or more in microcrystalline Cellulose, described lubricant is selected from stearic acid, magnesium stearate, sodium laurylsulfate, polyethylene glycol 6000, one or more in Macrogol 4000.
3. slow releasing tablet as claimed in claim 1, is characterized in that coating materials described in sealing coat coating is wherein selected from one or more in Opadry, the preferred 10%-30% alcoholic solution of described alcoholic solution.
4. slow releasing tablet as claimed in claim 1, it is characterized in that wherein dipyridamole always slow-release material described in mixed granular raw adjuvant be selected from hypromellose, methylcellulose, hydroxyethyl-cellulose, hydroxypropyl cellulose, Carboxymethyl cellulose sodium, pectin, one or more in carbomer and chitosan, described filler is selected from lactose, starch, sucrose, dextrin, mannitol, one or more in microcrystalline Cellulose, the preferred 20%-40% alcoholic solution of described alcoholic solution, described lubricant is selected from stearic acid, magnesium stearate, sodium laurylsulfate, polyethylene glycol 6000, one or more in Macrogol 4000.
5. slow releasing tablet as claimed in claim 1, is characterized in that coating materials described in protective layer coating is wherein selected from one or more in Opadry, the alcoholic solution of the preferred 60%-95% of described alcoholic solution.
6. the slow releasing tablet as described in as arbitrary in claim 1-5, is characterized in that:
Wherein aspirin label is made up of following supplementary material:
Wherein sealing coat coating is made up of following supplementary material:
Opadry 80W 620004Yellow 2-4 weight portion
10%-30% alcoholic solution 20-35 weight portion
Wherein dipyridamole always mixed granule made by following supplementary material:
Wherein protective layer coating is made up of following supplementary material:
Opadry 295K 620010Yellow 6-10 weight portion
60%-95% alcoholic solution 100-150 weight portion.
7. the slow releasing tablet as described in as arbitrary in claim 1-6, is characterized in that:
Wherein aspirin label is made up of following supplementary material:
Wherein sealing coat coating is made up of following supplementary material:
Opadry 80W 620004Yellow 3 weight portions
20% alcoholic solution 28 weight portions
Wherein dipyridamole always mixed granule made by following supplementary material:
Wherein protective layer coating is made up of following supplementary material:
Opadry 295K 620010Yellow 8 weight portions
80% alcoholic solution 126 weight portions.
8. the slow releasing tablet as described in as arbitrary in claim 1-6, is characterized in that:
Wherein aspirin label is made up of following supplementary material:
Wherein sealing coat coating is made up of following supplementary material:
Opadry 80W 620004Yellow 4 weight portions
10% alcoholic solution 35 weight portions
Wherein dipyridamole always mixed granule made by following supplementary material:
Wherein protective layer coating is made up of following supplementary material:
Opadry 295K 620010Yellow 10 weight portions
95% alcoholic solution 150 weight portions.
9. the slow releasing tablet as described in as arbitrary in claim 1-6, is characterized in that:
Wherein aspirin label is made up of following supplementary material:
Wherein sealing coat coating is made up of following supplementary material:
Opadry 80W 620004Yellow 2 weight portions
30% alcoholic solution 20 weight portions
Wherein dipyridamole always mixed granule made by following supplementary material:
Wherein protective layer coating is made up of following supplementary material:
Opadry 295K 620010Yellow 6 weight portions
60% alcoholic solution 100 weight portions.
10. the slow releasing tablet as described in as arbitrary in claim 1-9, is characterized in that this slow releasing tablet prepared by the following method:
(1) preparation of aspirin sealing coat coated cores
Aspirin and L-TARTARIC ACID are pulverized and sieved respectively, pregelatinized Starch, spray-dried lactose, stearic acid sieving for standby respectively; Take aspirin by recipe quantity and mix with L-TARTARIC ACID, then add pregelatinized Starch to mix, then take spray-dried lactose by recipe quantity and mix, then add microcrystalline Cellulose PH101 to mix, finally add stearic acid, mix homogeneously, tabletting; The weightening finish of sealing coat coating, as aspirin sealing coat coated cores;
(2) the always preparation of mixed granule of dipyridamole
Take dipyridamole, slow-release material, filler by recipe quantity, be placed in wet granulator, adopt alcoholic solution soft material processed, granulate, dry, granulate, additional lubricant, mix homogeneously, as always mixed granule of dipyridamole;
(3) preparation of aspirin-dipyridomole slow release clad sheet
Using aspirin sealing coat coated cores as internal layer, dipyridamole, always mixed granule is as skin, and cored tablet machine is suppressed double-deck clad sheet;
(4) protective layer coating weightening finish, to obtain final product.
11. slow releasing tablet as claimed in claim 10, is characterized in that this slow releasing tablet prepared by the following method:
(1) preparation of aspirin sealing coat coated cores
By aspirin pulverized 20-40 mesh sieve, L-TARTARIC ACID was pulverized 70-90 mesh sieve, pregelatinized Starch, spray-dried lactose are crossed 10-30 mesh sieve respectively, stearic acid is crossed 10-30 mesh sieve, for subsequent use; Take aspirin by recipe quantity and mix with L-TARTARIC ACID, then add pregelatinized Starch to mix, then add spray-dried lactose to mix, then add microcrystalline Cellulose PH101 to mix, finally add stearic acid, mix homogeneously, adopts Φ=9.5mm scrobicula drift tabletting; Opadry 80W 620004Yellow sealing coat coating increases weight to 1%-5%, as aspirin label;
(2) the always preparation of mixed granule of dipyridamole
Take dipyridamole, HPMC K4M, lactose by recipe quantity, put successively in wet granulator, adopt 20-40% ethanol soft material processed, 10-30 mesh sieve is granulated, and temperature of charge is no more than 35 DEG C-60 DEG C, is dried to LOD≤3.5%, 10-20 mesh sieve granulate, additional stearic acid, mix homogeneously, as always mixed granule of dipyridamole;
(3) preparation of aspirin-dipyridomole slow release clad sheet
Using aspirin sealing coat coated cores as internal layer, dipyridamole, always mixed granule is as skin, and employing Φ=12mm scrobicula drift is suppressed the double-deck plain sheet of cored;
(4) Opadry 295K 620010Yellow protective layer coating increases weight to 1%-5%, to obtain final product.
12. slow releasing tablet as described in claim 10 or 11, is characterized in that this slow releasing tablet prepared by the following method:
(1) preparation of aspirin sealing coat coated cores:
By aspirin pulverized 30 mesh sieves, L-TARTARIC ACID was pulverized 80 mesh sieves, pregelatinized Starch, spray-dried lactose are crossed respectively 18 mesh sieves, stearic acid and are crossed 20 mesh sieves, for subsequent use; Take aspirin by recipe quantity and mix with L-TARTARIC ACID, then add pregelatinized Starch to mix, then add spray-dried lactose to mix, then add microcrystalline Cellulose PH101 to mix, finally add stearic acid, mix homogeneously, adopts Φ=9.5mm scrobicula drift tabletting; Opadry 80W 620004Yellow sealing coat coating increases weight to 3%, as aspirin sealing coat coated cores;
(2) the always preparation of mixed granule of dipyridamole
Take dipyridamole, HPMC K4M, lactose by recipe quantity, put successively in wet granulator, adopt 30% ethanol soft material processed, 18 mesh sieves are granulated, and temperature of charge is no more than 45 DEG C and is dried to LOD≤2.0%, 10 mesh sieve granulate; Additional stearic acid, mix homogeneously, as always mixed granule of dipyridamole;
(3) preparation of aspirin-dipyridomole slow release clad sheet
Using dipyridamole extended-release label as internal layer, aspirin always mixed granule as skin, adopt Φ=12mm scrobicula drift compacting cored double-layer tablet;
(4) Opadry 295K 620010Yellow protective layer coating increases weight to 3%, to obtain final product.
The preparation method of 13. slow releasing tablet as described in as arbitrary in claim 1-12, is characterized in that the method comprises the steps:
(1) preparation of aspirin sealing coat coated cores:
Aspirin and L-TARTARIC ACID are pulverized and sieved respectively, pregelatinized Starch, spray-dried lactose, stearic acid sieving for standby respectively; Take aspirin by recipe quantity and mix with L-TARTARIC ACID, then add pregelatinized Starch to mix, then take spray-dried lactose by recipe quantity and mix, then add microcrystalline Cellulose PH101 to mix, finally add stearic acid, mix homogeneously, tabletting; The weightening finish of sealing coat coating, as aspirin sealing coat coated cores;
(2) the always preparation of mixed granule of dipyridamole
Take dipyridamole, slow-release material, filler by recipe quantity, be placed in wet granulator, adopt alcoholic solution soft material processed, granulate, dry, granulate, additional lubricant, mix homogeneously, as always mixed granule of dipyridamole;
(3) preparation of aspirin-dipyridomole slow release clad sheet
Using aspirin sealing coat coated cores as internal layer, dipyridamole, always mixed granule is as skin, and cored tablet machine is suppressed double-deck clad sheet;
(4) protective layer coating weightening finish, to obtain final product.
14. the preparation method of slow releasing tablet as claimed in claim 13, is characterized in that the method comprises the steps:
(1) preparation of aspirin sealing coat coated cores
By aspirin pulverized 20-40 mesh sieve, L-TARTARIC ACID was pulverized 70-90 mesh sieve, pregelatinized Starch, spray-dried lactose are crossed 10-30 mesh sieve respectively, stearic acid is crossed 10-30 mesh sieve, for subsequent use; Take aspirin by recipe quantity and mix with L-TARTARIC ACID, then add pregelatinized Starch to mix, then add spray-dried lactose to mix, then add microcrystalline Cellulose PH101 to mix, finally add stearic acid, mix homogeneously, adopts Φ=9.5mm scrobicula drift tabletting; Opadry 80W 620004Yellow sealing coat coating increases weight to 1%-5%, as aspirin label;
(2) the always preparation of mixed granule of dipyridamole
Take dipyridamole, HPMC K4M, lactose by recipe quantity, put successively in wet granulator, adopt 20-40% ethanol soft material processed, 10-30 mesh sieve is granulated, and temperature of charge is no more than 35 DEG C-60 DEG C, is dried to LOD≤3.5%, 10-20 mesh sieve granulate, additional stearic acid, mix homogeneously, as always mixed granule of dipyridamole;
(3) preparation of aspirin-dipyridomole slow release clad sheet
Using aspirin sealing coat coated cores as internal layer, dipyridamole, always mixed granule is as skin, and employing Φ=12mm scrobicula drift is suppressed the double-deck plain sheet of cored;
(4) Opadry 295K 620010Yellow protective layer coating increases weight to 1%-5%, to obtain final product.
The preparation method of 15. slow releasing tablet as described in claim 13 or 14, is characterized in that the method comprises the steps:
(1) preparation of aspirin sealing coat coated cores:
By aspirin pulverized 30 mesh sieves, L-TARTARIC ACID was pulverized 80 mesh sieves, pregelatinized Starch, spray-dried lactose are crossed respectively 18 mesh sieves, stearic acid and are crossed 20 mesh sieves, for subsequent use; Take aspirin by recipe quantity and mix with L-TARTARIC ACID, then add pregelatinized Starch to mix, then add spray-dried lactose to mix, then add microcrystalline Cellulose PH101 to mix, finally add stearic acid, mix homogeneously, adopts Φ=9.5mm scrobicula drift tabletting; Opadry 80W 620004Yellow sealing coat coating increases weight to 3%, as aspirin sealing coat coated cores;
(2) the always preparation of mixed granule of dipyridamole
Take dipyridamole, HPMC K4M, lactose by recipe quantity, put successively in wet granulator, adopt 30% ethanol soft material processed, 18 mesh sieves are granulated, and temperature of charge is no more than 45 DEG C and is dried to LOD≤2.0%, 10 mesh sieve granulate; Additional stearic acid, mix homogeneously, as always mixed granule of dipyridamole;
(3) preparation of aspirin-dipyridomole slow release clad sheet
Using dipyridamole extended-release label as internal layer, aspirin always mixed granule as skin, adopt Φ=12mm scrobicula drift compacting cored double-layer tablet;
(4) Opadry 295K 620010Yellow protective layer coating increases weight to 3%, to obtain final product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210570914.2A CN103893192B (en) | 2012-12-26 | 2012-12-26 | A kind of slow releasing tablet treating cardiovascular disease and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210570914.2A CN103893192B (en) | 2012-12-26 | 2012-12-26 | A kind of slow releasing tablet treating cardiovascular disease and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103893192A true CN103893192A (en) | 2014-07-02 |
| CN103893192B CN103893192B (en) | 2016-09-14 |
Family
ID=50984980
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210570914.2A Active CN103893192B (en) | 2012-12-26 | 2012-12-26 | A kind of slow releasing tablet treating cardiovascular disease and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103893192B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105030719A (en) * | 2015-08-20 | 2015-11-11 | 杭州成邦医药科技有限公司 | Composition containing alogliptin and pioglitazone |
| CN112618554A (en) * | 2021-01-11 | 2021-04-09 | 重庆康刻尔制药股份有限公司 | Compound tablet for treating hypertension complicated with coronary heart disease and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1111985A (en) * | 1994-05-06 | 1995-11-22 | 王志刚 | Method for preparing laminated compound tablet of aspirin and persantine |
| CN102198147A (en) * | 2010-03-24 | 2011-09-28 | 济南瑞安药业发展有限公司 | New preparation method for aspirin-containing compound preparation |
| CN102210693A (en) * | 2010-04-10 | 2011-10-12 | 山东新华制药股份有限公司 | Method for preparing aspirin and dipyridamole multilayer tablets |
-
2012
- 2012-12-26 CN CN201210570914.2A patent/CN103893192B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1111985A (en) * | 1994-05-06 | 1995-11-22 | 王志刚 | Method for preparing laminated compound tablet of aspirin and persantine |
| CN102198147A (en) * | 2010-03-24 | 2011-09-28 | 济南瑞安药业发展有限公司 | New preparation method for aspirin-containing compound preparation |
| CN102210693A (en) * | 2010-04-10 | 2011-10-12 | 山东新华制药股份有限公司 | Method for preparing aspirin and dipyridamole multilayer tablets |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105030719A (en) * | 2015-08-20 | 2015-11-11 | 杭州成邦医药科技有限公司 | Composition containing alogliptin and pioglitazone |
| CN105030719B (en) * | 2015-08-20 | 2018-07-20 | 杭州成邦医药科技有限公司 | A kind of composition containing Egelieting and Pioglitazone |
| CN112618554A (en) * | 2021-01-11 | 2021-04-09 | 重庆康刻尔制药股份有限公司 | Compound tablet for treating hypertension complicated with coronary heart disease and preparation method thereof |
| CN112618554B (en) * | 2021-01-11 | 2022-03-22 | 重庆康刻尔制药股份有限公司 | Compound tablet for treating hypertension complicated with coronary heart disease and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103893192B (en) | 2016-09-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102058554B (en) | Method for preparing sustained-release tablets through granulating by adopting bonding agents in atomizing states | |
| CN106389360A (en) | Directly-compressed tablet of dapoxetine hydrochloride and preparation method thereof | |
| CN103301084B (en) | Berberine hydrochloride tablet and preparation method thereof | |
| CN101658505A (en) | Sustained-release preparation of uloric and preparation method thereof | |
| AU2011247642C1 (en) | Orally disintegrating tablet containing acarbose | |
| CN101632647A (en) | Preparation method for compound preparation comprising aspirin and alkaline drugs | |
| CN103006649A (en) | Compound preparation of valsartan amlodipine tablet (I) and preparation method thereof | |
| CN106389369A (en) | Ferrous fumarate folic acid compound film coated tablet preparation method | |
| CN100488515C (en) | Ground erythromycin enteric micropill and its preparation method | |
| CN109157522A (en) | Pharmaceutical composition and its preparation method and application comprising Xi Gelieting or its officinal salt | |
| CN102114005B (en) | Tracleer capsule and preparation method thereof | |
| CN101804056A (en) | Compound tablet of pioglitazone hydrochloride, glimepiride and preparation method thereof | |
| CN101347413B (en) | Quetiapine sustained release tablets and method of preparing the same | |
| CN102526748B (en) | Oral tablet containing Valsartan, Hydrochioro and Amlodipine Besylate Tablet | |
| CN103893192A (en) | Cardiovascular disease treatment sustained-release tablets and preparation method thereof | |
| CN103893193A (en) | Cardiovascular disease treatment sustained-release tablets and preparation method thereof | |
| CN104644598A (en) | Tenofovir disoproxil fumarate tablets | |
| CN105362243B (en) | Bisulfate clopidogrel oral solid drug composition and preparation method thereof | |
| CN203107745U (en) | Aspirin dipyridamole slow-release structure | |
| CN101711753A (en) | Preparation method of lansoprazole solid preparation | |
| CN103271886B (en) | Pirfenidone tablet and preparation method thereof | |
| CN104367562A (en) | Pramipexole dihydrochloride slow-release tablets and preparation method thereof | |
| CN101756971A (en) | Oral solid drug composition of metformin hydrochloride repaglinide | |
| KR101817714B1 (en) | Oral solid composite comprising valsartan | |
| CN111012750A (en) | Paracetamol tablet and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20140702 Assignee: Shanxi Pharmaceutical Group Co., Ltd. Ya Bao Assignor: YABAO PHARMACEUTICAL CO. LTD. BEIJING? Contract record no.: 2016990000514 Denomination of invention: Sustained release tablet for treating cardiovascular diseases and preparation method thereof Granted publication date: 20160914 License type: Common License Record date: 20161221 |
|
| LICC | Enforcement, change and cancellation of record of contracts on the licence for exploitation of a patent or utility model |