CN106236726B - Orazamide coated slow release piece and preparation method thereof - Google Patents
Orazamide coated slow release piece and preparation method thereof Download PDFInfo
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- CN106236726B CN106236726B CN201510324208.3A CN201510324208A CN106236726B CN 106236726 B CN106236726 B CN 106236726B CN 201510324208 A CN201510324208 A CN 201510324208A CN 106236726 B CN106236726 B CN 106236726B
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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 23
- 238000000576 coating method Methods 0.000 claims abstract description 64
- 239000011248 coating agent Substances 0.000 claims abstract description 62
- 239000013563 matrix tablet Substances 0.000 claims abstract description 27
- 239000003814 drug Substances 0.000 claims abstract description 25
- 229940079593 drug Drugs 0.000 claims abstract description 22
- 238000013268 sustained release Methods 0.000 claims abstract description 18
- 239000012730 sustained-release form Substances 0.000 claims abstract description 18
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims abstract description 8
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims abstract description 8
- -1 experiment proves Substances 0.000 claims abstract description 4
- 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 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 17
- 239000007921 spray Substances 0.000 claims description 16
- 238000001035 drying Methods 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 11
- 235000019359 magnesium stearate Nutrition 0.000 claims description 10
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 9
- 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
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 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
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 8
- 239000007939 sustained release tablet Substances 0.000 claims description 8
- 238000007599 discharging Methods 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 6
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 6
- 235000020985 whole grains Nutrition 0.000 claims description 6
- 239000002023 wood Substances 0.000 claims description 6
- RCEAADKTGXTDOA-UHFFFAOYSA-N OS(O)(=O)=O.CCCCCCCCCCCC[Na] Chemical compound OS(O)(=O)=O.CCCCCCCCCCCC[Na] RCEAADKTGXTDOA-UHFFFAOYSA-N 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
- 239000008117 stearic acid Substances 0.000 claims description 5
- 239000004744 fabric Substances 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 239000002245 particle Substances 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 3
- 229920002678 cellulose Polymers 0.000 claims description 2
- 239000001913 cellulose Substances 0.000 claims description 2
- 238000005469 granulation Methods 0.000 claims 2
- 230000003179 granulation Effects 0.000 claims 2
- 238000001816 cooling Methods 0.000 claims 1
- 239000003826 tablet Substances 0.000 abstract description 15
- 239000000463 material Substances 0.000 abstract description 6
- 239000008280 blood Substances 0.000 abstract description 5
- 210000004369 blood Anatomy 0.000 abstract description 5
- 239000011159 matrix material Substances 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 2
- 238000004090 dissolution Methods 0.000 description 8
- 208000006454 hepatitis Diseases 0.000 description 6
- 208000019423 liver disease Diseases 0.000 description 5
- 238000009825 accumulation Methods 0.000 description 4
- 210000004185 liver Anatomy 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
- 239000007788 liquid Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 206010008909 Chronic Hepatitis Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 239000003405 delayed action preparation Substances 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- 231100000283 hepatitis Toxicity 0.000 description 2
- 238000000338 in vitro Methods 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
- DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 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
- 206010019708 Hepatic steatosis Diseases 0.000 description 1
- 206010019728 Hepatitis alcoholic Diseases 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 231100000354 acute hepatitis Toxicity 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 208000002353 alcoholic hepatitis Diseases 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 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
- 230000000857 drug effect Effects 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
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 230000017074 necrotic cell death Effects 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
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 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
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
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Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention discloses a kind of Orazamide coated slow release piece and preparation method thereof, the Orazamide coated slow release piece, 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 using HPMC as main material, outer layer is the coating using Utech EPO as main material, experiment proves, sustained-release matrix tablets with Utech EPO materials after being coated, coatings not only play the role of to delay insoluble drug release to sustained-release matrix tablets, and also have and maintain blood concentration, make blood concentration even running in human body, improve the effect of clinical efficacy.
Description
Technical field
The present invention relates to Orazamide preparation.
Background technology
Orazamide category hepatopathy medication, it is purine and pyrimidine derivatives precursor, nucleic acid metabolism can be balanced, prevent that liver is thin
Born of the same parents' necrosis, Fibrosis parameters, and can cell cultured supernatant regeneration, activation hepatic parenchymal cells, improvement albumin and globulin and serum
The level of total protein.Clinically it is usually used in acute hepatitis, chronic hepatitis, icteric hepatitis, chronic hepatitis liver cirrhosis, fatty liver and alcoholic liver
Etc. the treatment of hepatopathy.Particularly suitable for the treatment of Non-viral liver disease, as alcoholic hepatitis, drug hepatitis, hepatic sclerosis, liver are fine
Dimensionization etc., it is combined with anti-hepatitis virus medicament, virus hepatitis can be treated well, is rare in current anti-drug for liver disease
The medication of first-line treatment hepatopathy and liver protecting medicine.Because the formulation of current clinical practice is ordinary tablet, its day takes often
(taking day 3 times), bioavilability is relatively low, therefore is changed to sustained release coating piece.
The content of the invention
It is an object of the invention to provide a kind of Orazamide coated slow release piece and preparation method thereof, to overcome prior art to deposit
The defects of.
Described Orazamide coated slow release piece is made up of matrix tablet and the coating being wrapped in outside described matrix tablet；
Described matrix tablet includes the component of following percentage by weight：
The percentage sum of each component is 100%；
Preferably, described matrix tablet includes the component of following percentage by weight：
The described component for including following percentage by weight：
The percentage sum of each component is 100%；
Preferably, the described component for including following percentage by weight：
Wherein, it is coated for 0.8mg/cm2(equivalent to coating 2.08mg/ pieces)~1.5mg/cm2(equivalent to coating 3.9mg/
Piece)；
The preparation method of described Orazamide coated slow release piece, comprises the following steps：
(1) preparation of matrix tablet：Orazamide bulk drug is ground into fine powders more than 80 mesh, crosses 80 mesh sieves, then will
After HPMC, ethyl cellulose, PVP and lactose mixing, shake 10~20 minutes, preferably 15 minutes, add body
Product concentration is 65~75%, and preferred volume concentration is 70% ethanol, and moist wood processed, the addition weight of described ethanol is hydroxypropyl first
Base cellulose, ethyl cellulose, the 15--20% of PVP and lactose gross weight；Pelletized with 15~25 eye mesh screens, preferably 20 mesh
Screen cloth.When aeration-drying to the moisture content of particle is less than 3% (weight) at 60~70 DEG C, discharging, with 15~25 eye mesh screen whole grains,
It is preferred that 20 eye mesh screens.Magnesium stearate is added, shakes more than 5 minutes, preferably 15 minutes, mixes to do before Orazamide tabletting
Grain.
Then method well known in the art is used, tabletting, obtains described matrix tablet, also referred to as sustained release tablets plain piece, plain piece
Hardness is 5~7kg；
(2) preparation of coating dispersion：Under agitation, lauryl sodium sulfate is added to the water, after dissolving, added stearic
Acid, low whipping speed are under 3000~4000rpm, EPO are added under preferably 3500rpm, at room temperature stirring 10~30 minutes, preferably
20 minutes, magnesium stearate is added, low whipping speed is under 5000~6000rpm, under preferably 5500rpm, is stirred 5~15 minutes,
It is preferred that 10 minutes, 30~50 mesh are then crossed, preferably 40 eye mesh screens, obtain coating dispersion；
The weight consumption of water is the 80~90% of coating dispersion gross weight；
(3) matrix tablet of step (1) is added into coating pan, in the case where temperature is 30~40 DEG C, at preferably 35 DEG C, sprays into coating
Dispersion liquid, coating dispersion is stirred in spray.Spray is finished, by the coated slow release piece temperature raising of acquisition to 55~65 DEG C, at preferably 60 DEG C,
Hot blast drying, 30~40 DEG C, preferably 35 DEG C are as cold as, discharged, i.e., what acquisition was described obtains Orazamide sustained release coating piece；
The Orazamide sustained release coating piece that the present invention obtains, generally takes 1 time, 3 tablets once, and serious patient is every daily
It can take 2 times, and total quantity is 0.3 gram -- 0.6 gram/day, it can specifically be determined by doctor, in favor of increasing its bioavilability, and dimension
Relatively stable blood concentration is held to extend drug effect, reduces administration number of times, strengthens clinical efficacy, reduces adverse reaction.
Orazamide coated slow release piece of the present invention, is made up of two parts, and internal layer is with HPMC
For the matrix tablet of main material, outer layer is the coating using Utech EPO as main material, it is demonstrated experimentally that sustained-release matrix tablets are with outstanding
After special strange EPO materials coating, coatings not only play the role of to delay insoluble drug release to sustained-release matrix tablets, and also have and maintain blood medicine
Concentration, make blood concentration even running in human body, improve the effect of clinical efficacy.
Embodiment
Embodiment 1
Prescription：(1) matrix tablet (piece weight 0.37g, tablet total surface area 2.6cm2)：
(2) it is coated：
Preparation method：
(1) preparation of matrix tablet：Orazamide bulk drug is ground into fine powders more than 80 mesh, crosses 80 mesh sieves, then will
After HPMC, ethyl cellulose, PVP and lactose mixing, shake 15 minutes, it is 70% to add volumetric concentration
Ethanol, moist wood processed, the addition weight of described ethanol is HPMC, ethyl cellulose, PVP and lactose gross weight
The 20% of amount；20 eye mesh screens are crossed to pelletize, when aeration-drying to the moisture content of particle is less than 3% (weight) at 60 DEG C, discharging, with 20 mesh
Screen cloth whole grain, magnesium stearate is then added, stirred 5 minutes, mixed；
Then method well known in the art is used, tabletting, obtains described matrix tablet, hardness 5kg；
(2) preparation of coating dispersion：Under agitation, lauryl sodium sulfate is added to the water, after dissolving, added stearic
Acid, low whipping speed are to add EPO under 3500rpm, stir 20 minutes at room temperature, add magnesium stearate, low whipping speed is
Under 6000rpm, stir 10 minutes, then cross 40 eye mesh screens, obtain coating dispersion；The weight consumption of water is that coating dispersion is total
The 84% of weight；
(3) preparation of sustained release coating piece：The matrix tablet of step (1) is added into coating pan, in the case where temperature is 35 DEG C, sprays into bag
Ginning outturn dispersion liquid, coating dispersion is stirred in spray, spray is finished, and by the coated slow release piece of acquisition at 60 DEG C, hot blast drying, is as cold as 35
DEG C, discharging, that is, obtain described Orazamide sustained release coating piece；
Using dissolution detection method under Chinese Pharmacopoeia tablet item in 2010, respectively at 2.4.8.12.16.20.24 hours
After take Orazamide sustained release tablets plain piece measure release (being defined by Ah card's content, the 4- aminooimidazoles -5- formamides of Ah card-i.e.).
3 batches of products are continuously prepared with above-mentioned matrix tablet technology, lot number is：150301；150302；150303.Made sustained release tablets
Plain piece vitro release the results are shown in Table (1)：
Table (1) Orazamide sustained release preparation plain piece Accumulation dissolution
| Time | 2 hours | 4 hours | 8 hours | 12 hours | 16 hours | 20 hours | 24 hours | Lot number |
| Release the drug % | 25.3% | 33.5% | 49.6% | 71.3% | 81.5% | 91% | 100% | 150301 |
| Release the drug % | 26.5% | 35.2% | 52% | 72.9% | 83% | 91.8% | 100% | 150302 |
| Release the drug % | 25.8% | 34.9% | 50.5% | 72.1% | 82.3% | 92% | 100% | 150303 |
Release will be detected after above-mentioned three batches of skeleton coating tablets with above-mentioned sustained release coating piece preparation technology, the results are shown in Table (2)：
The vitro release of table (2) Orazamide sustained release coating piece
| Time | 2 hours | 4 hours | 8 hours | 12 hours | 16 hours | 20 hours | 24 hours | Lot number |
| Release the drug % | 18.2 | 25.5 | 40.9 | 53.6 | 65.7 | 77.1 | 84.8 | 150301 |
| Release the drug % | 16.8 | 23.3 | 38.5 | 50.9 | 63.3 | 74.6 | 82.3 | 150302 |
| Release the drug % | 15.6 | 22.8 | 37.1 | 49.6 | 62.2 | 73.1 | 80.9 | 150303 |
Wherein, 150301 crowdes of coating 0.8mg/cm2(equivalent to coating 2.08mg/ pieces)；150302 crowdes of coating 1.2mg/cm2
(equivalent to coating 3.12mg/ pieces)；150303 crowdes of coating 1.5mg/cm2(equivalent to coating 3.9mg/ pieces).
Embodiment 2
Prescription：
(1) matrix tablet (piece weight 0.4g, tablet total surface area 2.8cm2)：
(2) it is coated：
Preparation method：
(1) preparation of matrix tablet：Orazamide bulk drug is ground into 80 targeted fine powders, 80 mesh sieves are crossed, then by hydroxypropyl
After methylcellulose, ethyl cellulose, PVP and lactose mixing, shake 10 minutes, it is 65~75% to add volumetric concentration
Ethanol, moist wood processed, the addition weight of the ethanol is HPMC, ethyl cellulose, PVP and lactose gross weight
20%；20 eye mesh screens are crossed to pelletize, when aeration-drying to the moisture content of particle is less than 3% (weight) at 60 DEG C, discharging, with 20 mesh sieves
Net whole grain, magnesium stearate is then added, shaken 30 minutes, mixed；
Then method well known in the art is used, tabletting, obtains described matrix tablet, i.e. Orazamide sustained release tablets plain piece,
Plain piece hardness is 7kg；
(2) preparation of coating dispersion：Under agitation, lauryl sodium sulfate is added to the water, after dissolving, added stearic
Acid, low whipping speed are to add EPO under 3000rpm, stir 10 minutes at room temperature, add magnesium stearate, low whipping speed is
Under 6000rpm, stir 5 minutes, then cross 40 eye mesh screens, obtain coating dispersion；The weight consumption of water is that coating dispersion is total
The 86% of weight；
(3) preparation of sustained release coating piece：The matrix tablet of step (1) is added into coating pan, in the case where temperature is 40 DEG C, sprays into bag
Ginning outturn dispersion liquid, coating dispersion is stirred in spray, and spray is finished, by the coated slow release piece temperature raising of acquisition to 65 DEG C, hot blast drying, is as cold as
30 DEG C, discharging, that is, obtain described Orazamide sustained release coating piece；
Using dissolution detection method under Chinese Pharmacopoeia tablet item in 2010, respectively at 2.4.8.12.16.20.24 hours
After take Orazamide sustained release tablets plain piece measure release (being defined by Ah card's content, the 4- aminooimidazoles -5- formamides of Ah card-i.e.),
Made sustained release tablets plain piece vitro release the results are shown in Table (3) above：
The substantially square sustained release preparation plain piece Accumulation dissolution of table (3) Orazamide
| Hour time | 2 | 4 | 8 | 12 | 16 | 20 | 24 |
| Drug release | 20.8% | 30.5% | 45% | 61.3% | 75.5% | 88.2% | 95.3% |
The vitro release of prepared Orazamide sustained release coating piece the results are shown in Table (4)
The substantially square coated slow release piece accumulative dissolution rate in vitro of table (4) Orazamide
| Time | 2 | 4 | 8 | 12 | 16 | 20 | 24 |
| Drug release | 18.5.5% | 25.8% | 41.7% | 55.6% | 68.8% | 78.4% | 85.5% |
Comparative example 1 (preparation of Orazamide normal packet garment piece)
1. prepared by Orazamide ordinary tablet plain piece：Formula：
1000, piece weight 0.17g are made altogether, Φ 7mm punch die tablettings.
Experimental implementation：
Above-mentioned Orazamide, starch, dextrin are added in blender, is sufficiently mixed uniformly, is slowly added into hot starch slurry, side
Edged stirs, and moist wood is made.Pelletized to obtain Orazamide wet granular with 20 eye mesh screens, in 65-75 DEG C of normal pressure aeration-drying.Dry
Finish, with 20 eye mesh screen whole grains, sampling surveys moisture content ＜ 5% and obtains the qualified dry particl of Orazamide.By Orazamide dry particl and tristearin
Sour magnesium is well mixed, and Orazamide ordinary tablet plain piece is obtained with Φ 7mm punch die tablettings.
2. the common coating tablets of Orazamide：
40ml purified waters are added in heater, 80 DEG C is heated to, it is (soluble in the stomach that film-coating coating powder is slowly added under stirring
Type) 6g, obtain Orazamide coating solution within 45 minutes in 80 DEG C or so quick stirrings.
Coating pan is started, adds the Orazamide plain piece of above-mentioned preparation, slowly heats Orazamide plain piece to 45 DEG C, control
Between 4-10 revs/min of coating pan rotating speed, coating solution (control spray gun pressure 4-6kg/cm is slowly sprayed between 40-50 DEG C2).Spray
Finish, with 50 DEG C or so hot blast dryings, let cool to obtain product Orazamide normal packet garment piece.Sampling detection accumulative dissolution rate in vitro, knot
Fruit is shown in Table (5).
Table (5) Orazamide normal packet garment piece Accumulation dissolution
| Time | 2 | 4 | 6 | 8 | 10 | 12 | 14 |
| Release the drug % | 25.3 | 45.6 | 78.5 | 95.4 |
By above-mentioned table (3), table (4), table (5) Accumulation dissolution as shown by data, Orazamide sustained release coating piece drug release time
It is longer than Orazamide sustained release plain piece, Orazamide sustained release plain piece drug release time is significantly longer than Orazamide ordinary tablet, illustrates Austria again
Rummy spy's sustained release tablets have good slow releasing function.
Claims (7)
1. Orazamide coated slow release piece, it is characterised in that it is made up of matrix tablet and the coating being wrapped in outside described matrix tablet,
Described matrix tablet is made up of the component of following percentage by weight：
The percentage sum of each component is 100%；
Described coating is made up of the component of following percentage by weight：
The percentage sum of each component is 100%.
2. Orazamide coated slow release piece according to claim 1, it is characterised in that described matrix tablet is by following weight
The component composition of percentage：
Described coating is made up of the component of following percentage by weight：
3. the Orazamide coated slow release piece according to any one of claim 1~2, it is characterised in that wherein, be coated and be
0.8mg/cm2~1.5mg/cm2。
4. the preparation method of the Orazamide coated slow release piece according to any one of claims 1 to 3, it is characterised in that step
It is rapid as follows：
(1) preparation of matrix tablet：Orazamide bulk drug, HPMC, ethyl cellulose, PVP and lactose are mixed
After conjunction, shaking, ethanol is added, moist wood processed, screen cloth granulation is crossed, aeration-drying, discharging, whole grain, then adds magnesium stearate, shake
Mix, then tabletting, obtain described sustained release tablets plain piece；
(2) preparation of coating dispersion：Under agitation, lauryl sodium sulfate is added to the water, after dissolving, adds stearic acid,
EPO is added under low whipping speed, is stirred at room temperature, magnesium stearate is added, stirring, then crosses screen cloth, obtain coating dispersion；
(3) matrix tablet of step (1) being added into coating pan, sprays into coating dispersion, coating dispersion is stirred in spray, spray is finished,
By the coated slow release piece hot blast drying of acquisition, cooling discharging, that is, described Orazamide sustained release coating piece is obtained.
5. according to the method for claim 4, it is characterised in that in step (1), by Orazamide bulk drug, hydroxypropyl
After cellulose, ethyl cellulose, PVP and lactose mixing, shake 10~20 minutes, addition volumetric concentration is 65~75% second
Alcohol, moist wood processed, the addition weight of described ethanol is HPMC, ethyl cellulose, PVP and lactose gross weight
15--20%, cross the granulation of 20 eye mesh screens, when aeration-drying to the moisture content of particle be less than 3% (weight) at 60~70 DEG C, discharge,
With 20 eye mesh screen whole grains, magnesium stearate is then added, shaking mixes for more than 5 minutes.
6. according to the method for claim 5, it is characterised in that in step (2), the preparation of coating dispersion：Under agitation,
Lauryl sodium sulfate is added to the water, after dissolving, adds stearic acid, low whipping speed is under 3000~4000rpm, is added
EPO, stir 10~30 minutes at room temperature, add magnesium stearate, low whipping speed is under 5000~6000rpm, stirs 5~15 points
Clock, 40 eye mesh screens are then crossed, obtain coating dispersion；
The weight consumption of water is the 80~90% of coating dispersion gross weight.
7. according to the method for claim 4, it is characterised in that in step (3), the matrix tablet of step (1) adds coating pan,
In the case where temperature is 30~40 DEG C, coating dispersion is sprayed into, coating dispersion is stirred in spray, spray is finished, by the coated slow release of acquisition
Piece temperature raising hot blast drying, is cooled to 30~40 DEG C to 55~65 DEG C.
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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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