CN106236726A - Orazamide coated slow release sheet and preparation method thereof - Google Patents
Orazamide coated slow release sheet and preparation method thereof Download PDFInfo
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- CN106236726A CN106236726A CN201510324208.3A CN201510324208A CN106236726A CN 106236726 A CN106236726 A CN 106236726A CN 201510324208 A CN201510324208 A CN 201510324208A CN 106236726 A CN106236726 A CN 106236726A
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- orazamide
- slow release
- release sheet
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- DVNYTAVYBRSTGK-UHFFFAOYSA-N 5-aminoimidazole-4-carboxamide Chemical compound NC(=O)C=1N=CNC=1N DVNYTAVYBRSTGK-UHFFFAOYSA-N 0.000 title claims abstract description 50
- 229950010911 orazamide Drugs 0.000 title claims abstract description 50
- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- 238000000576 coating method Methods 0.000 claims abstract description 71
- 239000011248 coating agent Substances 0.000 claims abstract description 68
- 239000013563 matrix tablet Substances 0.000 claims abstract description 28
- 239000003826 tablet Substances 0.000 claims abstract description 26
- 239000003814 drug Substances 0.000 claims abstract description 19
- 229940079593 drug Drugs 0.000 claims abstract description 16
- 238000013268 sustained release Methods 0.000 claims abstract description 15
- 239000012730 sustained-release form Substances 0.000 claims abstract description 15
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims abstract description 8
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims abstract description 8
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims abstract description 8
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000006185 dispersion Substances 0.000 claims description 24
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- 239000007921 spray Substances 0.000 claims description 18
- 238000003756 stirring Methods 0.000 claims description 17
- 239000008187 granular material Substances 0.000 claims description 13
- 238000001035 drying Methods 0.000 claims description 11
- 235000019359 magnesium stearate Nutrition 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- 239000001856 Ethyl cellulose Substances 0.000 claims description 9
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 9
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 9
- 238000007599 discharging Methods 0.000 claims description 9
- 229920001249 ethyl cellulose Polymers 0.000 claims description 9
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 9
- 239000008101 lactose Substances 0.000 claims description 9
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 9
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 9
- 238000002156 mixing Methods 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 6
- 239000002023 wood Substances 0.000 claims description 6
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 5
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 5
- 235000021355 Stearic acid Nutrition 0.000 claims description 5
- 238000013019 agitation Methods 0.000 claims description 5
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 5
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 5
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 5
- 239000008117 stearic acid Substances 0.000 claims description 5
- KRQUFUKTQHISJB-YYADALCUSA-N 2-[(E)-N-[2-(4-chlorophenoxy)propoxy]-C-propylcarbonimidoyl]-3-hydroxy-5-(thian-3-yl)cyclohex-2-en-1-one Chemical compound CCC\C(=N/OCC(C)OC1=CC=C(Cl)C=C1)C1=C(O)CC(CC1=O)C1CCCSC1 KRQUFUKTQHISJB-YYADALCUSA-N 0.000 claims description 3
- 235000007164 Oryza sativa Nutrition 0.000 claims description 3
- 239000004744 fabric Substances 0.000 claims description 3
- 235000009566 rice Nutrition 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- 235000010981 methylcellulose Nutrition 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims 2
- 240000007594 Oryza sativa Species 0.000 claims 1
- 239000007788 liquid Substances 0.000 claims 1
- 239000000463 material Substances 0.000 abstract description 6
- 239000008280 blood Substances 0.000 abstract description 5
- 210000004369 blood Anatomy 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 4
- 239000011159 matrix material Substances 0.000 abstract description 4
- -1 test proves Substances 0.000 abstract description 2
- 238000004090 dissolution Methods 0.000 description 9
- 208000019423 liver disease Diseases 0.000 description 5
- 238000009825 accumulation Methods 0.000 description 4
- 208000006454 hepatitis Diseases 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000001514 detection method Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 206010008909 Chronic Hepatitis Diseases 0.000 description 2
- 241000209094 Oryza Species 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 208000019425 cirrhosis of liver Diseases 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000009492 tablet coating Methods 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 208000008964 Chemical and Drug Induced Liver Injury Diseases 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 206010072268 Drug-induced liver injury Diseases 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- 208000004930 Fatty Liver Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 108010044091 Globulins Proteins 0.000 description 1
- 206010019668 Hepatic fibrosis Diseases 0.000 description 1
- 206010019708 Hepatic steatosis Diseases 0.000 description 1
- 206010019728 Hepatitis alcoholic Diseases 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 231100000354 acute hepatitis Toxicity 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 208000002353 alcoholic hepatitis Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 201000008865 drug-induced hepatitis Diseases 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 208000010706 fatty liver disease Diseases 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 206010019692 hepatic necrosis Diseases 0.000 description 1
- 230000007866 hepatic necrosis Effects 0.000 description 1
- 230000002443 hepatoprotective effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 210000004738 parenchymal cell Anatomy 0.000 description 1
- 229940083251 peripheral vasodilators purine derivative Drugs 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 231100000240 steatosis hepatitis Toxicity 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000002700 tablet coating Substances 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention discloses a kind of orazamide coated slow release sheet and preparation method thereof, described orazamide coated slow release sheet, it is characterised in that be made up of matrix tablet and the coating being wrapped in outside described matrix tablet.Internal layer of the present invention is the matrix tablet with hydroxypropyl methylcellulose as main material, outer layer is with the especially strange EPO coating as main material, test proves, sustained-release matrix tablets is with after especially strange EPO material coating, coatings not only has the effect delaying drug release to sustained-release matrix tablets, and also maintain blood drug level, make blood drug level even running in human body, improve the effect of clinical efficacy.
Description
Technical field
The present invention relates to orazamide preparation.
Background technology
Orazamide belongs to hepatopathy medication, for purine and pyrimidine derivatives precursor, nucleic acid metabolism can be made to balance,
Prevent hepatic necrosis, Fibrosis parameters, and can cell cultured supernatant regenerate, activate hepatic parenchymal cells,
Improve albumin and globulin and the level of total serum protein.Be usually used in clinically acute hepatitis, chronic hepatitis,
The treatment of the hepatopathys such as icterohepatitis, chronic hepatitis liver cirrhosis, fatty liver and alcoholic liver.It is particularly suitable for
In the treatment of Non-viral liver disease, such as alcoholic hepatitis, drug induced hepatitis, liver cirrhosis, hepatic fibrosis
Etc., it is combined with anti-hepatitis virus medicament, can well treat viral hepatitis, be current anti-hepatopathy
First-line treatment hepatopathy medication rare in medicine and hepatoprotective medicine.Due to current clinical practice
Dosage form is ordinary tablet, its day clothes (take 3 day) often, bioavailability is relatively low, is therefore changed
For sustained release coating sheet.
Summary of the invention
It is an object of the invention to provide a kind of orazamide coated slow release sheet and preparation method thereof, to overcome
The defect that prior art exists.
Described orazamide coated slow release sheet is by matrix tablet and the coating being wrapped in outside described matrix tablet
Constitute；
Described matrix tablet includes the component of following percentage by weight:
The percentage ratio sum of each component is 100%；
Preferably, described matrix tablet includes the component of following percentage by weight:
Described coating includes the component of following percentage by weight:
The percentage ratio sum of each component is 100%；
Preferably, described coating includes the component of following percentage by weight:
Wherein, coating is 0.8mg/cm2(being equivalent to coating 2.08mg/ sheet)～1.5mg/cm2(quite
In coating 3.9mg/ sheet)；
The preparation method of described orazamide coated slow release sheet, comprises the steps:
(1) preparation of matrix tablet: orazamide crude drug is ground into the fine powder of more than 80 mesh, mistake
80 mesh sieves, after then hydroxypropyl methylcellulose, ethyl cellulose, polyvidone and lactose being mixed, shake
Shaking 10～20 minutes, preferably 15 minutes, adding volumetric concentration was 65～75%, and preferred volume concentration is
The ethanol of 70%, moist wood processed, the addition weight of described ethanol is hydroxypropyl methylcellulose, ethyl cellulose
Element, polyvidone and the 15--20% of lactose gross weight；Pelletize with 15～25 eye mesh screens, preferably 20 mesh sieves
Net.At 60～70 DEG C aeration-drying to granule moisture content less than 3% (weight) time, discharging, with 15～25
Eye mesh screen granulate, preferably 20 eye mesh screens.Add magnesium stearate, shake more than 5 minutes, preferably 15
Minute, mix to obtain dry granule before orazamide tabletting.
Then method well known in the art, tabletting are used, it is thus achieved that described matrix tablet, also referred to as slow release
Sheet element sheet, element sheet hardness is 5～7kg；
(2) preparation of coating dispersion: under agitation, sodium lauryl sulphate is added to the water, molten
Xie Hou, adds stearic acid, and low whipping speed is under 3000～4000rpm, adds under preferably 3500rpm
EPO, stirs under room temperature 10～30 minutes, preferably 20 minutes, adds magnesium stearate, low whipping speed
It is under 5000～6000rpm, under preferably 5500rpm, stirs 5～15 minutes, preferably 10 minutes, so
Rear mistake 30～50 mesh, preferably 40 eye mesh screens, it is thus achieved that coating dispersion；
The weight consumption of water is the 80～90% of coating dispersion gross weight；
(3) matrix tablet of step (1) is added coating pan, at temperature is 30～40 DEG C, preferably
At 35 DEG C, spray into coating dispersion, spray limit, limit stirring coating dispersion.Spray is finished, the coating that will obtain
Slow releasing tablet temperature raising to 55～65 DEG C, at preferably 60 DEG C, hot blast drying, it is as cold as 30～40 DEG C, preferably 35 DEG C,
Discharging, i.e. obtain described in orazamide sustained release coating sheet；
The orazamide sustained release coating sheet that the present invention obtains, takes 1 time, each 3 usual every day,
The person of being in a bad way can take 2 times every day, and total quantity is 0.3 gram--0.6 gram/day, specifically can be determined by doctor,
It is beneficial to increase its bioavailability, maintains more stable blood drug level to extend drug effect, reduce and be administered
Number of times, strengthens clinical efficacy, reduces untoward reaction.
Orazamide coated slow release sheet of the present invention, is made up of two parts, and internal layer is with hydroxypropyl first
Base cellulose is the matrix tablet of main material, and outer layer is with the especially strange EPO coating as main material, real
Verifying bright, sustained-release matrix tablets is with after especially strange EPO material coating, and coatings is not only to sustained-release matrix
Sheet has the effect delaying drug release, and also maintains blood drug level, makes blood drug level in human body
Even running, improves the effect of clinical efficacy.
Detailed description of the invention
Embodiment 1
Prescription: (1) matrix tablet (tablet weight 0.37g, tablet total surface area 2.6cm2):
(2) coating:
Preparation method:
(1) preparation of matrix tablet: orazamide crude drug is ground into the fine powder of more than 80 mesh, mistake
80 mesh sieves, after then hydroxypropyl methylcellulose, ethyl cellulose, polyvidone and lactose being mixed, shake
Shaking 15 minutes, adding volumetric concentration is the ethanol of 70%, moist wood processed, the addition weight of described ethanol
For hydroxypropyl methylcellulose, ethyl cellulose, polyvidone and the 20% of lactose gross weight；Cross 20 mesh sieves
Net pelletize, at 60 DEG C aeration-drying to granule moisture content less than 3% (weight) time, discharging, with 20
Eye mesh screen granulate, is subsequently adding magnesium stearate, stirs 5 minutes, mixing；
Then using method well known in the art, tabletting, it is thus achieved that described matrix tablet, hardness is 5kg；
(2) preparation of coating dispersion: under agitation, sodium lauryl sulphate is added to the water, molten
Xie Hou, adds stearic acid, and low whipping speed is addition EPO under 3500rpm, stirs 20 points under room temperature
Clock, adds magnesium stearate, and low whipping speed is under 6000rpm, stirs 10 minutes, then crosses 40
Eye mesh screen, it is thus achieved that coating dispersion；The weight consumption of water is the 84% of coating dispersion gross weight；
(3) preparation of sustained release coating sheet: the matrix tablet of step (1) is added coating pan, in temperature
Being at 35 DEG C, spray into coating dispersion, spray limit, limit stirring coating dispersion, spray is finished, the bag that will obtain
Clothing slow releasing tablet at 60 DEG C, hot blast drying, be as cold as 35 DEG C, discharging, i.e. obtain described orazamide
Sustained release coating sheet；
Use dissolution detection method under Chinese Pharmacopoeia tablet item in 2010, respectively at
2.4.8.12.16.20.24 take orazamide slow releasing tablet element sheet mensuration release after hour (with Ah card's content it is
Standard, Ah Ka is 4-aminooimidazole-5-Methanamide).3 batches are prepared continuously by above-mentioned matrix tablet Technology
Product, lot number is: 150301；150302；150303.Made slow releasing tablet element sheet vitro release
The results are shown in Table (1):
Table (1) orazamide slow releasing preparation element sheet Accumulation dissolution
| Time | 2 hours | 4 hours | 8 hours | 12 hours | 16 hours | 20 hours | 24 hours | Lot number |
| Release % | 25.3% | 33.5% | 49.6% | 71.3% | 81.5% | 91% | 100% | 150301 |
| Release % | 26.5% | 35.2% | 52% | 72.9% | 83% | 91.8% | 100% | 150302 |
| Release % | 25.8% | 34.9% | 50.5% | 72.1% | 82.3% | 92% | 100% | 150303 |
To detect release after above-mentioned three batches of matrix tablet coatings by above-mentioned sustained release coating sheet preparation technology, result is shown in
Table (2):
The vitro release of table (2) orazamide sustained release coating sheet
| Time | 2 hours | 4 hours | 8 hours | 12 hours | 16 hours | 20 hours | 24 hours | Lot number |
| Release % | 18.2 | 25.5 | 40.9 | 53.6 | 65.7 | 77.1 | 84.8 | 150301 |
| Release % | 16.8 | 23.3 | 38.5 | 50.9 | 63.3 | 74.6 | 82.3 | 150302 |
| Release % | 15.6 | 22.8 | 37.1 | 49.6 | 62.2 | 73.1 | 80.9 | 150303 |
Wherein, 150301 crowdes of coating 0.8mg/cm2(being equivalent to coating 2.08mg/ sheet)；150302 batches of coatings
1.2mg/cm2(being equivalent to coating 3.12mg/ sheet)；150303 crowdes of coating 1.5mg/cm2(be equivalent to bag
Clothing 3.9mg/ sheet).
Embodiment 2
Prescription:
(1) matrix tablet (tablet weight 0.4g, tablet total surface area 2.8cm2):
(2) coating:
Preparation method:
(1) preparation of matrix tablet: orazamide crude drug is ground into the fine powder of 80 mesh, crosses 80 mesh
Sieve, after then hydroxypropyl methylcellulose, ethyl cellulose, polyvidone and lactose being mixed, shakes 10
Minute, adding the ethanol that volumetric concentration is 65～75%, moist wood processed, the addition weight of described ethanol is hydroxyl
Third methylcellulose, ethyl cellulose, polyvidone and the 20% of lactose gross weight；Cross 20 eye mesh screen systems
Grain, at 60 DEG C aeration-drying to granule moisture content less than 3% (weight) time, discharging, use 20 mesh sieves
Net granulate, is subsequently adding magnesium stearate, shakes 30 minutes, mixing；
Then method well known in the art, tabletting are used, it is thus achieved that described matrix tablet, i.e. orazamide
Slow releasing tablet element sheet, element sheet hardness is 7kg；
(2) preparation of coating dispersion: under agitation, sodium lauryl sulphate is added to the water, molten
Xie Hou, adds stearic acid, and low whipping speed is addition EPO under 3000rpm, stirs 10 points under room temperature
Clock, adds magnesium stearate, and low whipping speed is under 6000rpm, stirs 5 minutes, then crosses 40 mesh
Screen cloth, it is thus achieved that coating dispersion；The weight consumption of water is the 86% of coating dispersion gross weight；
(3) preparation of sustained release coating sheet: the matrix tablet of step (1) is added coating pan, in temperature
Being at 40 DEG C, spray into coating dispersion, spray limit, limit stirring coating dispersion, spray is finished, the bag that will obtain
Clothing slow releasing tablet temperature raising to 65 DEG C, hot blast drying, it is as cold as 30 DEG C, discharging, i.e. obtain described Aura rice
Special sustained release coating sheet；
Use dissolution detection method under Chinese Pharmacopoeia tablet item in 2010, respectively at
2.4.8.12.16.20.24 take orazamide slow releasing tablet element sheet mensuration release after hour (with Ah card's content it is
Standard, Ah Ka is 4-aminooimidazole-5-Methanamide), above made slow releasing tablet element sheet vitro release knot
Fruit is shown in Table (3):
Table (3) orazamide side's slow releasing preparation element sheet Accumulation dissolution substantially
| Time hour | 2 | 4 | 8 | 12 | 16 | 20 | 24 |
| Release | 20.8% | 30.5% | 45% | 61.3% | 75.5% | 88.2% | 95.3% |
The vitro release of prepared orazamide sustained release coating sheet the results are shown in Table (4)
Table (4) orazamide side's coated slow release sheet accumulative dissolution rate in vitro substantially
| Time | 2 | 4 | 8 | 12 | 16 | 20 | 24 |
| Release | 18.5.5% | 25.8% | 41.7% | 55.6% | 68.8% | 78.4% | 85.5% |
Comparative example 1 (prepared by orazamide normal packet garment piece)
1. prepared by orazamide ordinary tablet element sheet: formula:
Make 1000 altogether, tablet weight 0.17g, Φ 7mm punch die tabletting.
Experimental implementation:
Above-mentioned orazamide, starch, dextrin are added in blender, is sufficiently mixed uniformly, slowly adds
Enter hot starch slurry, stirring while adding, make moist wood.Pelletize to obtain orazamide wet granular with 20 eye mesh screens,
In 65-75 DEG C of normal pressure aeration-drying.Being dried and finish, with 20 eye mesh screen granulate, sampling is surveyed moisture content ＜ 5% and is obtained
The qualified dry granule of orazamide.Dry for orazamide granule is mixed homogeneously with magnesium stearate, uses Φ 7mm
Punch die tabletting obtains orazamide ordinary tablet element sheet.
2. orazamide ordinary tablet coating:
In heater, add 40ml purified water, be heated under 80 DEG C, stirring be slowly added into film-coat coating powder
(stomach dissolution type) 6g, quickly stirs 45 minutes to obtain orazamide coating solution in about 80 DEG C.
Starting coating pan, add the orazamide element sheet of above-mentioned preparation, slowly heating orazamide element sheet arrives
45 DEG C, control between coating pan rotating speed 4-10 rev/min, between 40-50 DEG C, slowly spray into coating solution (control
Spray gun pressure 4-6kg/cm processed2).Spray is finished, and with about 50 DEG C hot blast dryings, lets cool to obtain product Aura rice
Mortopl leads to coated tablet.Sampling detection accumulative dissolution rate in vitro, the results are shown in Table (5).
Table (5) orazamide normal packet garment piece Accumulation dissolution
| Time | 2 | 4 | 6 | 8 | 10 | 12 | 14 |
| Release % | 25.3 | 45.6 | 78.5 | 95.4 |
Shown by above-mentioned table (3), table (4), table (5) Accumulation dissolution data, orazamide slow release
Coated tablet drug release time is longer than orazamide slow release element sheet, and orazamide slow release element sheet drug release time is the biggest
It is longer than greatly orazamide ordinary tablet, illustrates that orazamide slow releasing tablet has good slow releasing function.
Claims (9)
1. orazamide coated slow release sheet, it is characterised in that by matrix tablet and be wrapped in described skeleton
The coating of off-chip is constituted.
2. orazamide coated slow release sheet, it is characterised in that by matrix tablet and be wrapped in described skeleton
The coating of off-chip is constituted, and described matrix tablet includes the component of following percentage by weight:
The percentage ratio sum of each component is 100%；
Described coating includes the component of following percentage by weight:
The percentage ratio sum of each component is 100%.
Orazamide coated slow release sheet the most according to claim 2, it is characterised in that described
Matrix tablet includes the component of following percentage by weight:
Orazamide coated slow release sheet the most according to claim 3, it is characterised in that
Preferably, described coating includes the component of following percentage by weight:
5. according to the orazamide coated slow release sheet described in any one of Claims 1 to 4, it is characterised in that
Wherein, coating is 0.8mg/cm2～1.5mg/cm2。
6. according to the preparation method of the orazamide coated slow release sheet described in any one of claim 2～5,
It is characterized in that, comprise the steps:
(1) preparation of matrix tablet: by orazamide crude drug, hydroxypropyl methylcellulose, ethyl cellulose
After element, polyvidone and lactose mixing, shaking, add ethanol, moist wood processed, cross screen cloth and pelletize, ventilate
It is dried, discharging, granulate, is subsequently adding magnesium stearate, shaking mixing, then tabletting, it is thus achieved that described
Slow releasing tablet element sheet；
(2) preparation of coating dispersion: under agitation, sodium lauryl sulphate is added to the water, molten
Xie Hou, adds stearic acid, adds EPO, stirs under room temperature, add magnesium stearate under low whipping speed,
Stirring, then crosses screen cloth, it is thus achieved that coating dispersion；
(3) matrix tablet of step (1) being added coating pan, spray into coating dispersion, spray limit, limit is stirred
Mixing coating dispersion, spray is finished, the coated slow release sheet hot blast drying that will obtain, and cooling discharging i.e. obtains
Described obtains orazamide sustained release coating sheet.
Method the most according to claim 6, it is characterised in that in step (1), by Aura rice
After special crude drug, hydroxypropyl methylcellulose, ethyl cellulose, polyvidone and lactose mixing, shake 10～20
Minute, adding volumetric concentration is 65～75% ethanol, and moist wood processed, the addition weight of described ethanol is hydroxyl
Third methylcellulose, ethyl cellulose, polyvidone and the 15--20% of lactose gross weight, cross 20 mesh sieves
Net pelletize, at 60～70 DEG C aeration-drying to granule moisture content less than 3% (weight) time, discharging, use
20 eye mesh screen granulate, are subsequently adding magnesium stearate, shake mixing in more than 5 minutes.
Method the most according to claim 6, it is characterised in that in step (2), coating dispersion
The preparation of liquid: under agitation, is added to the water sodium lauryl sulphate, after dissolving, adds stearic acid,
Low whipping speed is under 3000～4000rpm, lower addition EPO, stirs 10～30 minutes, add under room temperature
Entering magnesium stearate, low whipping speed is under 5000～6000rpm, stirs 5～15 minutes, then crosses 40
Eye mesh screen, it is thus achieved that coating dispersion；
The weight consumption of water is the 80～90% of coating dispersion gross weight.
Method the most according to claim 6, it is characterised in that in step (3), step (1)
Matrix tablet add coating pan, at temperature is 30～40 DEG C, spray into coating dispersion, spray limit, limit is stirred
Coating dispersion, spray is complete, the coated slow release sheet temperature raising to 55～65 DEG C that will obtain, hot blast drying, cooling
To 30～40 DEG C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510324208.3A CN106236726B (en) | 2015-06-12 | 2015-06-12 | Orazamide coated slow release piece and preparation method thereof |
Applications Claiming Priority (1)
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1425373A (en) * | 2003-01-08 | 2003-06-25 | 江苏正大天晴药业股份有限公司 | Slow-releasing kurarinol preparation and its preparing method |
| CN1650877A (en) * | 2004-12-09 | 2005-08-10 | 中国药科大学 | Slow release preparation of diammonium glycyrrhizate |
| CN102065847A (en) * | 2008-04-29 | 2011-05-18 | 韩诺生物制约株式会社 | Pharmaceutical formulation containing angiotensin-II receptor blocker |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1425373A (en) * | 2003-01-08 | 2003-06-25 | 江苏正大天晴药业股份有限公司 | Slow-releasing kurarinol preparation and its preparing method |
| CN1650877A (en) * | 2004-12-09 | 2005-08-10 | 中国药科大学 | Slow release preparation of diammonium glycyrrhizate |
| CN102065847A (en) * | 2008-04-29 | 2011-05-18 | 韩诺生物制约株式会社 | Pharmaceutical formulation containing angiotensin-II receptor blocker |
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| CN106236726B (en) | 2018-03-20 |
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