CN102258497B - Lamivudine tablet composition and preparation method thereof - Google Patents
Lamivudine tablet composition and preparation method thereof Download PDFInfo
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- CN102258497B CN102258497B CN 201110237281 CN201110237281A CN102258497B CN 102258497 B CN102258497 B CN 102258497B CN 201110237281 CN201110237281 CN 201110237281 CN 201110237281 A CN201110237281 A CN 201110237281A CN 102258497 B CN102258497 B CN 102258497B
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- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 title claims abstract description 87
- 229960001627 lamivudine Drugs 0.000 title claims abstract description 86
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- 239000007916 tablet composition Substances 0.000 title claims abstract description 11
- 229920002472 Starch Polymers 0.000 claims abstract description 99
- 239000008107 starch Substances 0.000 claims abstract description 99
- 235000019698 starch Nutrition 0.000 claims abstract description 99
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims abstract description 72
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 68
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 68
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 claims abstract description 48
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims abstract description 48
- 239000011734 sodium Substances 0.000 claims abstract description 45
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 45
- 238000003756 stirring Methods 0.000 claims abstract description 41
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 34
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 34
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 34
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 34
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 34
- 239000000377 silicon dioxide Substances 0.000 claims abstract description 34
- 235000012239 silicon dioxide Nutrition 0.000 claims abstract description 34
- 238000000576 coating method Methods 0.000 claims abstract description 24
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000004408 titanium dioxide Substances 0.000 claims abstract description 24
- 239000011248 coating agent Substances 0.000 claims abstract description 23
- IFNWPVOGRPXDCH-UHFFFAOYSA-N (3,5-dichloro-2,4-difluorophenyl)urea Chemical compound NC(=O)NC1=CC(Cl)=C(F)C(Cl)=C1F IFNWPVOGRPXDCH-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000001035 drying Methods 0.000 claims abstract description 11
- 238000007873 sieving Methods 0.000 claims abstract description 11
- 239000008187 granular material Substances 0.000 claims description 60
- 239000012530 fluid Substances 0.000 claims description 50
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 44
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 44
- NDLPOXTZKUMGOV-UHFFFAOYSA-N oxo(oxoferriooxy)iron hydrate Chemical compound O.O=[Fe]O[Fe]=O NDLPOXTZKUMGOV-UHFFFAOYSA-N 0.000 claims description 32
- 239000011230 binding agent Substances 0.000 claims description 30
- 239000000725 suspension Substances 0.000 claims description 30
- -1 Hydroxypropyl Chemical group 0.000 claims description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- 239000000203 mixture Substances 0.000 claims description 13
- 238000001816 cooling Methods 0.000 claims description 10
- 239000004744 fabric Substances 0.000 claims description 10
- 239000012467 final product Substances 0.000 claims description 10
- 238000010438 heat treatment Methods 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 10
- 239000000314 lubricant Substances 0.000 claims description 10
- 235000011837 pasties Nutrition 0.000 claims description 10
- 229920000573 polyethylene Polymers 0.000 claims description 10
- 239000007921 spray Substances 0.000 claims description 10
- 238000005507 spraying Methods 0.000 claims description 10
- 238000012546 transfer Methods 0.000 claims description 10
- 238000005303 weighing Methods 0.000 claims description 10
- 239000002994 raw material Substances 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 3
- 239000001678 brown HT Substances 0.000 claims description 2
- 239000000463 material Substances 0.000 abstract 2
- 239000000853 adhesive Substances 0.000 abstract 1
- 230000001070 adhesive effect Effects 0.000 abstract 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 abstract 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 abstract 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 abstract 1
- 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 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- LDHBWEYLDHLIBQ-UHFFFAOYSA-M iron(3+);oxygen(2-);hydroxide;hydrate Chemical compound O.[OH-].[O-2].[Fe+3] LDHBWEYLDHLIBQ-UHFFFAOYSA-M 0.000 abstract 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 abstract 1
- 230000001050 lubricating effect Effects 0.000 abstract 1
- 229940083542 sodium Drugs 0.000 abstract 1
- 238000002474 experimental method Methods 0.000 description 11
- 238000012360 testing method Methods 0.000 description 9
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 7
- 239000012535 impurity Substances 0.000 description 7
- 241000700721 Hepatitis B virus Species 0.000 description 6
- YLEQMGZZMCJKCN-NKWVEPMBSA-N [[(2r,5s)-5-(4-amino-2-oxopyrimidin-1-yl)-1,3-oxathiolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)SC1 YLEQMGZZMCJKCN-NKWVEPMBSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 208000002672 hepatitis B Diseases 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000005286 illumination Methods 0.000 description 3
- 208000030507 AIDS Diseases 0.000 description 2
- 108010017384 Blood Proteins Proteins 0.000 description 2
- 102000004506 Blood Proteins Human genes 0.000 description 2
- 208000000419 Chronic Hepatitis B Diseases 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000011287 therapeutic dose Methods 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 1
- 206010008909 Chronic Hepatitis Diseases 0.000 description 1
- 108010023321 Factor VII Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 108091006764 Organic cation transporters Proteins 0.000 description 1
- 241000282577 Pan troglodytes Species 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000006652 catabolic pathway Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 230000024924 glomerular filtration Effects 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 230000010224 hepatic metabolism Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 229940098312 lamivudine 100 mg Drugs 0.000 description 1
- 229940080431 lamivudine 150 mg Drugs 0.000 description 1
- 229940029101 lamivudine 300 mg Drugs 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 125000003835 nucleoside group Chemical class 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003463 sulfur Chemical class 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
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- Medicinal Preparation (AREA)
Abstract
The invention discloses a lamivudine tablet composition and a preparation method thereof. The tablet is prepared from the following materials: lamivudine, microcrystalline cellulose, sodium carboxymethyl starch, starch, silicon dioxide, magnesium stearate, hydroxypropyl methylcellulose E-15, talcum powder, titanium dioxide, red iron oxide, yellow iron oxide and propylene glycol. The preparation method comprises the following steps of: sieving raw and subsidiary materials respectively, preparing an adhesive, stirring, palletizing, drying, granulating, lubricating, tabletting, coating and obtaining the lamivudine tablet composition. The lamivudine tablet composition has the advantages of fast dissolving-out speed, moderate hardness and good stability, and is suitable for industrial production.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition and preparation method thereof, particularly a kind of lamivudine tablet and preparation method thereof.
Background technology
It is to cause acute, chronic hepatitis, the reason of liver cirrhosis and constitutional cell carcinoma that hepatitis B virus (HBV) infects.Lamivudine is used to treat the inflammation that copies and cause that chronic viral hepatitis B virus infects the hepatitis B virus of following, and is the most economical effective medicine of current treatment chronic hepatitis B.The therapeutical effect of lamivudine does not rely on the pretreat feature, and in addition, lamivudine also shows effectively the invalid patient population of a-interferon therapy.
Lamivudine is nucleoside analog, can become lamivudine triphosphate (L-TP) in the endocellular phosphorus acidify, and be embedded in the viral DNA by hepatitis B virus (HBV) polymerase with ring gland glycosides phosphoric acid, causes the synthetic termination of DNA chain.The lamivudine triphosphate is the weak inhibitor of mammal α, β and γ-DNA polymerase.In experiment in vitro, the half-life of lamivudine triphosphate in hepatocyte is 17～19 hours.
Lamivudine is a kind of antiviral agents, all shows the inhibitory action to hepatitis B virus on kinds of experiments cell line and infected animal model.But wherein there is the serum dna level that occurs respectively hepatitis B virus in after stopping this product treatment 4 and 14 days of two kinds of animal models (duckling and chimpanzee) to go up.
Lamivudine can be by the gastrointestinal tract good absorption, and becoming under normal circumstances human oral lamivudine artifact availability is 80～85%.Behind the oral administration, the average out to peak time (Tmax) of maximum plasma concentration (Cmax) is about 1 hour.With every day 1 time, the therapeutic dose of each 100mg gives lamivudine, its maximum plasma concentration (Cmax) is about 1.1～1.5 μ g/ml (4.8～6.5 μ mol/L), and valley blood drug level is 0.015～0.020 μ g/ml (0.065～0.087 μ mol/L).
Lamivudine and food are taken simultaneously and can be postponed Tmax and reduce Cmax (maximum to 47%), but can not change its bioavailability (press area under the drug-time curve calculating), therefore, and ante cibum and all can taking after meal.
The intravenously administrable result of study shows that it is 1.3L/kg that lamivudine is evenly distributed volume, linear pharmacokinetics in the therapeutic dose scope, and with albuminous plasma protein binding rate lower (＜36%).Limited data shows that lamivudine can pass through the central nervous system, enters in the cerebrospinal fluid (CSF), and oral lamivudine is after 2～4 hours, and the average of relatives of cerebrospinal fluid/serum Chinese medicine concentration is about 0.12.
Metabolism is the minor path that lamivudine is removed, and the unique known metabolite of lamivudine in human body is to turn the sulfur metabolite.Because the liver metabolism degree low (5～10%) of lamivudine, and plasma protein binding rate is low, so it is very little that interactional probability occurs between lamivudine and its metabolite.
Lamivudine mainly with original shape through glomerular filtration and secretion (organic cation transporter system), certainly drain in the urine, kidney remove account for its total remove 70%, the average system clearance rate is 0.3L/h/kg, removing the half-life is 5～7 hours.But present lamivudine tablet quality is unstable.
Summary of the invention
The object of the invention is to provide a kind of lamivudine tablet, and another purpose of the present invention is to provide the preparation method of this pharmaceutical composition.
The present invention seeks to be achieved through the following technical solutions
The raw material of lamivudine tablet of the present invention consists of:
Lamivudine 100～300 weight portion microcrystalline Cellulose 100～300 weight portions
Carboxymethyl starch sodium 44～132 weight portion starch 50～150 weight portions
Silicon dioxide 3～9 weight portion magnesium stearate 3～9 weight portions
Hydroxypropyl emthylcellulose E-154.758～14.274 weight portion Pulvis Talci, 1.589～4.767 weight portions
Titanium dioxide 1.589～4.767 weight portion red ferric oxide 0.159～0.477 weight portion
Yellow ferric oxide 0.316～0.948 weight portion propylene glycol 1.589～4.767 weight portions.
Above-mentioned raw materials preferred weight proportioning is as follows:
Lamivudine 100 weight portion microcrystalline Cellulose 100 weight portion carboxymethyl starch sodium 20+24 weight portions
Starch 45+5 weight portion silicon dioxide 3 weight portion magnesium stearate 3 weight portions
Hydroxypropyl emthylcellulose E-156.187 weight portion Pulvis Talci 2.067 weight portions
Titanium dioxide 2.067 weight portion red ferric oxide 0.207 weight portion yellow ferric oxide 0.412 weight portion
Propylene glycol 2.067 weight portions.
Above-mentioned raw materials preferred weight proportioning is as follows:
Lamivudine 150 weight portion microcrystalline Cellulose 250 weight portion carboxymethyl starch sodium 50 weight portions
Starch 140 weight portion silicon dioxide 4 weight portion magnesium stearate 8 weight portions
Hydroxypropyl emthylcellulose E-155 weight portion Pulvis Talci 4.6 weight portions
Titanium dioxide 1.6 weight portion red ferric oxide 0.4 weight portion yellow ferric oxide 0.4 weight portion
Propylene glycol 4.7 weight portions.
Above-mentioned raw materials preferred weight proportioning is as follows:
Lamivudine 300 weight portion microcrystalline Cellulose 150 weight portion carboxymethyl starch sodium 130 weight portions
Starch 60 weight portion silicon dioxide 8 weight portion magnesium stearate 4 weight portions
Hydroxypropyl emthylcellulose E-1514 weight portion Pulvis Talci 1.6 weight portions
Titanium dioxide 4.7 weight portion red ferric oxide 0.2 weight portion yellow ferric oxide 0.9 weight portion
Propylene glycol 1.7 weight portions.
The concrete preparation method of lamivudine tablet of the present invention is as follows:
Get respectively above-mentioned lamivudine, microcrystalline Cellulose is crossed 60 mesh sieves, carboxymethyl starch sodium is crossed 80 mesh sieves, starch, silicon dioxide are crossed 200 mesh sieves, magnesium stearate is crossed 100 mesh sieves; The pure water that takes by weighing 100 weight portions places steam kettle, to be steam heated to 90～95 ℃, heating stops the starch of rear adding 5～15 weight portions, constantly stir, form the starch oar, pasty liquid is translucent under constantly stirring in steam kettle, by 40 eye mesh screens, make binding agent, binding agent is placed hermetic container, cooling; Add in order the lamivudine sieved, microcrystalline Cellulose, 20～60 weight portion carboxymethyl starch sodium, 40～135 weight portion starch to fluid bed, be dry mixed 5 minutes, regulate the fluid unit parameter, spraying adds binding agent, until LOD (loss on drying) granulometric range reaches in 3%～5%w/w (weight ratio) scope, turn off fluid unit and heater; To sieving machine, granule is by 20 eye mesh screens with the transfer of granules in the fluid unit, check granule apparent size, place the double-layer seal Polythene Bag; Granule behind the granulate is inserted in the fluid bed, and add equably lubricant 24～72 weight portion carboxymethyl starch sodium, silicon dioxide, continue 5 minutes, when treating that exhaust cap opens 15%, magnesium stearate is added, and further mix, after 2 minutes, pour granule into clean airtight bucket, put screen cloth No. 4 on the bucket top; Machine is set the tabletting order, checks drift and mould, mould and drift is fixed on the machine tabletting; In hermetic container, hydroxypropyl emthylcellulose E-15 and water are mixed with viscosity solution, in above-mentioned viscosity solution, add Pulvis Talci, titanium dioxide and red ferrum oxide and yellow iron oxide, constantly stir, make uniform suspension, then add propylene glycol, stir and cross 100 eye mesh screens after 30 minutes, suspension is placed in batches; Plain sheet is transferred between coating, getting suspension adds in the feeding device, with plain sheet preheating, by the power supply heater blower, open and discharge air in the bed, 2.0～3.0 rev/mins of rotating speeds, inlet temperature are 50～70 ℃, until the bed temperature reaches 40 ℃, coating solution is continued to spray until finish, with coated tablet oven dry 5 minutes, take out coated tablet and be placed in clean double-deck IPC ' the S bag, and get final product.
The concrete preparation method of lamivudine tablet of the present invention is preferably as follows method:
Get respectively above-mentioned lamivudine, microcrystalline Cellulose is crossed 60 mesh sieves, carboxymethyl starch sodium is crossed 80 mesh sieves, starch, silicon dioxide are crossed 200 mesh sieves, magnesium stearate is crossed 100 mesh sieves; The pure water that takes by weighing 100 weight portions places steam kettle, to be steam heated to 90 ℃, heating stops the starch of rear adding 5 weight portions, constantly stir, form the starch oar, pasty liquid is translucent under constantly stirring in steam kettle, by 40 eye mesh screens, make binding agent, binding agent is placed hermetic container, cooling; Add in order the lamivudine sieved, microcrystalline Cellulose, 20 weight portion carboxymethyl starch sodium, 45 weight portion starch to fluid bed, be dry mixed 5 minutes, regulate the fluid unit parameter, spraying adds binding agent, until LOD (loss on drying) granulometric range reaches in 3%～5% (weight ratio) scope, turn off fluid unit and heater; To sieving machine, granule is by 20 eye mesh screens with the transfer of granules in the fluid unit, check granule apparent size, place the double-layer seal Polythene Bag; Granule behind the granulate is inserted in the fluid bed, and add equably lubricant 24 weight portion carboxymethyl starch sodium, silicon dioxide, continue 5 minutes, when treating that exhaust cap opens 15%, magnesium stearate is added, and further mix, after 2 minutes, pour granule into clean airtight bucket, put screen cloth No. 4 on the bucket top; Machine is set the tabletting order, checks drift and mould, mould and drift is fixed on the machine tabletting; In hermetic container, hydroxypropyl emthylcellulose E-15 and water are mixed with viscosity solution, in above-mentioned viscosity solution, add Pulvis Talci, titanium dioxide and red ferrum oxide and yellow iron oxide, constantly stir, make uniform suspension, then add propylene glycol, stir and cross 100 eye mesh screens after 30 minutes, suspension is placed in batches; Plain sheet is transferred between coating, getting suspension adds in the feeding device, with plain sheet preheating, by the power supply heater blower, open and discharge air in the bed, 2.0～3.0 rev/mins of rotating speeds, inlet temperature are 50～70 ℃, until the bed temperature reaches 40 ℃, coating solution is continued to spray until finish, with coated tablet oven dry 5 minutes, take out coated tablet and be placed in clean double-deck IPC ' the S bag, and get final product.
Lamivudine tablet of the present invention is used for the chronic hepatitis B of hepatitis B replication and the auxiliary treatment of acquired immune deficiency syndrome (AIDS).Lamivudine tablet dissolution rate of the present invention is fast, and hardness is moderate, good stability, suitable suitability for industrialized production.Compare with existing lamivudine tablet and to have outstanding feature stable and controllable for quality.Following experimental example and embodiment are used for further specifying but are not limited to the present invention.
Experimental example 1 contrast screening experiment
1.1 with general proportioning and preparation method
Table 1 is with general proportioning and preparation method gained lamivudine tablet experimental data
The result: the disintegration of tablet time limit is higher, and sheet is disintegrate layer by layer, can not fine dispersion, further affect composition final dissolution.
1.2 by inside and outside increase carboxymethyl starch sodium, improve disintegrate.The results are shown in Table 2.
Table 2 lamivudine tablet experimental data of the present invention (being made by embodiment 1)
Above-mentioned experimental data shows, lamivudine tablet of the present invention good dispersion in dissolution medium evenly expands, and is dispersed into fine particle.
1.3 according to the above ratio, 150,000 of a collection of productions, inventory is as follows:
Table 3 Lamy stationary slice inventory of the present invention (being made by embodiment 1)
# also has loss because of coating in the coating process, so the coating batching exceeds 30%
Lamivudine tablet of the present invention is uniformly dispersed, good fluidity, and disintegration is short, and hardness is moderate, and friability is little.
Experimental example 2 accelerates the contrast experiment
Lamivudine tablet of the present invention (being made by embodiment 1) compares with listing Lamy stationary slice steadiness
2.1 condition of storage
40 ℃ ± 2 ℃ of temperature, place under relative humidity 75% ± 5% condition, respectively at sampling in 0,1,3,6 month, check according to Lamy stationary slice quality standard draft.
2.2 investigation project:
(1) character: range estimation.
(2) dissolution: in the time of 30 minutes, stripping quantity is no less than 80% of labelled amount.
(3) related substance: the carboxylic acid impurity of relative retention time 0.4 is no more than 0.3%; Salicylic acid is no more than 0.1%; The impurity of relative retention time 0.9 is no more than 0.2%; Total impurities is no more than 0.6%.
(4) content: 90%～110%.
The results are shown in following table:
090502 batch of Lamy stationary slice of table 4 the present invention accelerates experimental result
09010054 batch of Lamy stationary slice accelerated test of table 5 listing sample result
Above-mentioned experimental data explanation: lamivudine tablet of the present invention is compared with the listing Lamy stationary slice, and stability is high.Each testing result does not have significant change before and after the Lamy stationary slice experiment of the present invention, all conforms to quality requirements; Total impurities content this shows by the lamivudine tablet ratio listing Lamy stationary slice of formulation and technology preparation of the present invention stable and controllable for quality all above surpassing the limit of impurities (0.6%) after 6 months and listing Lamy stationary slice acceleration experiment is placed.
Experimental example 3 influence factor contrast experiments
This experiment is to carry out under the fiercer condition of experiment than accelerating.Its objective is the inherent stability of inquiring into medicine, understand and affect its stable factor and possible degradation pathway and catabolite, for preparation production technique, packing, storage requirement and the analytical method of setting up catabolite provide scientific basis.
Experiment condition: (4500Lx ± 500Lx) place under the condition, timing sampling are measured indices for high temperature (60 ℃), high humidity (92.5%RH), illumination.
090502 crowd of Lamy stationary slice influence factor of table 6 the present invention result of the test (60 ℃ of high temperature)
090502 crowd of Lamy stationary slice influence factor of table 7 the present invention result of the test (illumination)
090502 crowd of Lamy stationary slice influence factor of table 8 the present invention result of the test high humidity (92.5%)
Table 9 listing sample 09010054 crowd of Lamy stationary slice influence factor result of the test (60 ℃ of high temperature)
The illumination of 09010054 crowd of Lamy stationary slice influence factor of table 10 listing sample result of the test
Table 11 listing sample 09010054 crowd of Lamy stationary slice influence factor result of the test high humidity (92.5%)
Above-mentioned experimental data explanation: lamivudine tablet of the present invention (being made by embodiment 1) is compared with the listing Lamy stationary slice, and stability is high.Each testing result does not have significant change before and after the Lamy stationary slice experiment of the present invention, all conforms to quality requirements; Total impurities content this shows by the lamivudine tablet of formulation and technology preparation of the present invention more stable and controllable for quality than the listing Lamy stationary slice all above surpassing the limit of impurities (0.6%) after 10 days and listing Lamy stationary slice high temperature is placed.
Following embodiment all can realize the described effect of above-mentioned experimental example.
The preparation of embodiment 1 lamivudine tablet
Lamivudine 100g microcrystalline Cellulose 100g carboxymethyl starch sodium 44g starch 50g
Silicon dioxide 3g magnesium stearate 3g hydroxypropyl emthylcellulose E-15 6.187g
Pulvis Talci 2.067g titanium dioxide 2.067g red ferric oxide 0.207g
Yellow ferric oxide 0.412g propylene glycol 2.067g.
Get respectively above-mentioned lamivudine, microcrystalline Cellulose is crossed 60 mesh sieves, carboxymethyl starch sodium is crossed 80 mesh sieves, starch, silicon dioxide are crossed 200 mesh sieves, magnesium stearate is crossed 100 mesh sieves; Take by weighing pure water 100g and place steam kettle, to be steam heated to 90 ℃, heating stops rear adding starch 5g, constantly stirs, form the starch oar, the pasty liquid that is translucent under constantly stirring in steam kettle is by 40 eye mesh screens, make binding agent, binding agent is placed hermetic container, cooling; Add in order the lamivudine sieved, microcrystalline Cellulose, carboxymethyl starch sodium 20g, starch 45g to fluid bed, be dry mixed 5 minutes, regulate the fluid unit parameter, spraying adds binding agent, until LOD (loss on drying) granulometric range reaches in 3%～5% (weight ratio) scope, turn off fluid unit and heater; To sieving machine, granule is by 20 eye mesh screens with the transfer of granules in the fluid unit, check granule apparent size, place the double-layer seal Polythene Bag; Granule behind the granulate is inserted in the fluid bed, and add equably lubricant carboxymethyl starch sodium 24g, silicon dioxide, continue 5 minutes, when treating that exhaust cap opens 15%, magnesium stearate is added, and further mix, after 2 minutes, pour granule into clean airtight bucket, put screen cloth No. 4 on the bucket top; Machine is set the tabletting order, checks drift and mould, mould and drift is fixed on the machine tabletting; In hermetic container, hydroxypropyl emthylcellulose E-15 and water are mixed with viscosity solution, in above-mentioned viscosity solution, add Pulvis Talci, titanium dioxide and red ferrum oxide and yellow iron oxide, constantly stir, make uniform suspension, then add propylene glycol, stir and cross 100 eye mesh screens after 30 minutes, suspension is placed in batches; Plain sheet is transferred between coating, getting suspension adds in the feeding device, with plain sheet preheating, by the power supply heater blower, open and discharge air in the bed, 2.0～3.0 rev/mins of rotating speeds, inlet temperature are 50～70 ℃, until the bed temperature reaches 40 ℃, coating solution is continued to spray until finish, with coated tablet oven dry 5 minutes, take out coated tablet and be placed in clean double-deck IPC ' the S bag, and get final product.Can prepare 1000 of Lamy stationary slices, every contains active component lamivudine 100mg.Taking dose: once a day, each 1.
The preparation of embodiment 2 lamivudine tablets
Lamivudine 200g microcrystalline Cellulose 200g carboxymethyl starch sodium 88g starch 100g
Silicon dioxide 6g magnesium stearate 6g hydroxypropyl emthylcellulose E-15 9.516g
Pulvis Talci 3.178g titanium dioxide 3.178g red ferric oxide 0.318g yellow ferric oxide 0.632g
Propylene glycol 3.178g.
Get respectively above-mentioned lamivudine, microcrystalline Cellulose is crossed 60 mesh sieves, carboxymethyl starch sodium is crossed 80 mesh sieves, starch, silicon dioxide are crossed 200 mesh sieves, magnesium stearate is crossed 100 mesh sieves; The pure water that takes by weighing 100g places steam kettle, and to be steam heated to 93 ℃, the starch that heating stops rear adding 10g constantly stirs, form the starch oar, the pasty liquid that is translucent under constantly stirring in steam kettle is by 40 eye mesh screens, make binding agent, binding agent is placed hermetic container, cooling; Add in order the lamivudine sieved, microcrystalline Cellulose, carboxymethyl starch sodium 40g, starch 90g to fluid bed, be dry mixed 5 minutes, regulate the fluid unit parameter, spraying adds binding agent, until LOD (loss on drying) granulometric range reaches in 4% (weight ratio) scope, turn off fluid unit and heater; To sieving machine, granule is by 20 eye mesh screens with the transfer of granules in the fluid unit, check granule apparent size, place the double-layer seal Polythene Bag; Granule behind the granulate is inserted in the fluid bed, and add equably lubricant carboxymethyl starch sodium 48g, silicon dioxide, continue 5 minutes, when treating that exhaust cap opens 15%, magnesium stearate is added, and further mix, after 2 minutes, pour granule into clean airtight bucket, put screen cloth No. 4 on the bucket top; Machine is set the tabletting order, checks drift and mould, mould and drift is fixed on the machine tabletting; In hermetic container, hydroxypropyl emthylcellulose E-15 and water are mixed with viscosity solution, in above-mentioned suspendible viscosity solution, add Pulvis Talci, titanium dioxide and red ferrum oxide and yellow iron oxide, constantly stir, make uniform suspension, then add propylene glycol, stir and cross 100 eye mesh screens after 30 minutes, suspension is placed in batches; Plain sheet is transferred between coating, getting suspension adds in the feeding device, with plain sheet preheating, by the power supply heater blower, open and discharge air in the bed, 2.0～3.0 rev/mins of rotating speeds, inlet temperature are 60 ℃, until the bed temperature reaches 40 ℃, coating solution is continued to spray until finish, with coated tablet oven dry 5 minutes, take out coated tablet and be placed in clean double-deck IPC ' the S bag, and get final product.Can prepare 1000 of Lamy stationary slices, every contains active component lamivudine 200mg.Taking dose: once a day, each 1.
The preparation of embodiment 3 lamivudine tablets
Lamivudine 150g microcrystalline Cellulose 250g carboxymethyl starch sodium 50g starch 140g
Silicon dioxide 4g magnesium stearate 8g hydroxypropyl emthylcellulose E-15 5g
Pulvis Talci 4.6g titanium dioxide 1.6g red ferric oxide 0.4g yellow ferric oxide 0.4g
Propylene glycol 4.7g.
Get respectively above-mentioned lamivudine, microcrystalline Cellulose is crossed 60 mesh sieves, carboxymethyl starch sodium is crossed 80 mesh sieves, starch, silicon dioxide are crossed 200 mesh sieves, magnesium stearate is crossed 100 mesh sieves; The pure water that takes by weighing 100g places steam kettle, to be steam heated to 90～95 ℃, heating stops the starch of rear adding 15g, constantly stir, form the starch oar, pasty liquid is translucent under constantly stirring in steam kettle, by 40 eye mesh screens, make binding agent, binding agent is placed hermetic container, cooling; Add in order the 150g lamivudine sieved, 250g microcrystalline Cellulose, 25g carboxylic carboxymethyl starch sodium, 125g starch to fluid bed, be dry mixed 5 minutes, regulate the fluid unit parameter, spraying adds binding agent, until LOD (loss on drying) granulometric range reaches in 3%～5% (weight ratio) scope, turn off fluid unit and heater; To sieving machine, granule is by 20 eye mesh screens with the transfer of granules in the fluid unit, check granule apparent size, place the double-layer seal Polythene Bag; Granule behind the granulate is inserted in the fluid bed, and add equably lubricant 25g carboxymethyl starch sodium, 4g silicon dioxide, continue 5 minutes, when treating that exhaust cap opens 15%, magnesium stearate is added, and further mix, after 2 minutes, pour granule into clean airtight bucket, put screen cloth No. 4 on the bucket top; Machine is set the tabletting order, checks drift and mould, mould and drift is fixed on the machine tabletting; In hermetic container, hydroxypropyl emthylcellulose E-15 and water are mixed with viscosity solution, in above-mentioned suspendible viscosity solution, add Pulvis Talci, titanium dioxide and red ferrum oxide and yellow iron oxide, constantly stir, make uniform suspension, then add propylene glycol, stir and cross 100 eye mesh screens after 30 minutes, suspension is placed in batches; Plain sheet is transferred between coating, getting suspension adds in the feeding device, with plain sheet preheating, by the power supply heater blower, open and discharge air in the bed, 2.0～3.0 rev/mins of rotating speeds, inlet temperature are 50～70 ℃, until the bed temperature reaches 40 ℃, coating solution is continued to spray until finish, with coated tablet oven dry 5 minutes, take out coated tablet and be placed in clean double-deck IPC ' the S bag, and get final product.Can prepare 1000 of Lamy stationary slices, every contains active component lamivudine 150mg.Taking dose: once a day, each 1.
The preparation of embodiment 4 lamivudine tablets
Lamivudine 250g microcrystalline Cellulose 150g carboxymethyl starch sodium 130g starch 60g
Silicon dioxide 8g magnesium stearate 4g hydroxypropyl emthylcellulose E-15 14g
Pulvis Talci 1.6g titanium dioxide 4.7g red ferric oxide 0.2g yellow ferric oxide 0.9g
Propylene glycol 1.7g.
Get respectively above-mentioned lamivudine, microcrystalline Cellulose is crossed 60 mesh sieves, carboxymethyl starch sodium is crossed 80 mesh sieves, starch, silicon dioxide are crossed 200 mesh sieves, magnesium stearate is crossed 100 mesh sieves; Take by weighing pure water 100g and place steam kettle, to be steam heated to 90 ℃, heating stops rear adding starch 6g, constantly stirs, form the starch oar, the pasty liquid that is translucent under constantly stirring in steam kettle is by 40 eye mesh screens, make binding agent, binding agent is placed hermetic container, cooling; Add in order the lamivudine sieved, microcrystalline Cellulose, carboxymethyl starch sodium 58g, starch 54g to fluid bed, be dry mixed 5 minutes, regulate the fluid unit parameter, spraying adds binding agent, until LOD (loss on drying) granulometric range reaches in 3% (weight ratio) scope, turn off fluid unit and heater; To sieving machine, granule is by 20 eye mesh screens with the transfer of granules in the fluid unit, check granule apparent size, place the double-layer seal Polythene Bag; Granule behind the granulate is inserted in the fluid bed, and add equably lubricant carboxymethyl starch sodium 72g, silicon dioxide, continue 5 minutes, when treating that exhaust cap opens 15%, magnesium stearate is added, and further mix, after 2 minutes, pour granule into clean airtight bucket, put screen cloth No. 4 on the bucket top; Machine is set the tabletting order, checks drift and mould, mould and drift is fixed on the machine tabletting; In hermetic container, hydroxypropyl emthylcellulose E-15 and water are mixed with viscosity solution, in above-mentioned suspendible viscosity solution, add Pulvis Talci, titanium dioxide and red ferrum oxide and yellow iron oxide, constantly stir, make uniform suspension, then add propylene glycol, stir and cross 100 eye mesh screens after 30 minutes, suspension is placed in batches; Plain sheet is transferred between coating, getting suspension adds in the feeding device, with plain sheet preheating, by the power supply heater blower, open and discharge air in the bed, 2.0～3.0 rev/mins of rotating speeds, inlet temperature are 50～70 ℃, until the bed temperature reaches 40 ℃, coating solution is continued to spray until finish, with coated tablet oven dry 5 minutes, take out coated tablet and be placed in clean double-deck IPC ' the S bag, and get final product.Can prepare 1000 of Lamy stationary slices, every contains active component lamivudine 250mg.Taking dose: once a day, each 1.
The preparation of embodiment 5 lamivudine tablets
Lamivudine 300g microcrystalline Cellulose 150g carboxymethyl starch sodium 130g
Starch 60g silicon dioxide 8g magnesium stearate 4g
Hydroxypropyl emthylcellulose E-1514g Pulvis Talci 1.6g
Titanium dioxide 4.7g red ferric oxide 0.2g yellow ferric oxide 0.9g propylene glycol 1.7g.
Get respectively above-mentioned lamivudine, microcrystalline Cellulose is crossed 60 mesh sieves, carboxymethyl starch sodium is crossed 80 mesh sieves, starch, silicon dioxide are crossed 200 mesh sieves, magnesium stearate is crossed 100 mesh sieves; Take by weighing pure water 100g and place steam kettle, to be steam heated to 90 ℃, heating stops rear adding starch 6g, constantly stirs, form the starch oar, the pasty liquid that is translucent under constantly stirring in steam kettle is by 40 eye mesh screens, make binding agent, binding agent is placed hermetic container, cooling; Add in order the lamivudine sieved, microcrystalline Cellulose, carboxymethyl starch sodium 58g, starch 54g to fluid bed, be dry mixed 5 minutes, regulate the fluid unit parameter, spraying adds binding agent, until LOD (loss on drying) granulometric range reaches in 3% (weight ratio) scope, turn off fluid unit and heater; To sieving machine, granule is by 20 eye mesh screens with the transfer of granules in the fluid unit, check granule apparent size, place the double-layer seal Polythene Bag; Granule behind the granulate is inserted in the fluid bed, and add equably lubricant carboxymethyl starch sodium 72g, silicon dioxide, continue 5 minutes, when treating that exhaust cap opens 15%, magnesium stearate is added, and further mix, after 2 minutes, pour granule into clean airtight bucket, put screen cloth No. 4 on the bucket top; Machine is set the tabletting order, checks drift and mould, mould and drift is fixed on the machine tabletting; In hermetic container, hydroxypropyl emthylcellulose E-15 and water are mixed with viscosity solution, in above-mentioned suspendible viscosity solution, add Pulvis Talci, titanium dioxide and red ferrum oxide and yellow iron oxide, constantly stir, make uniform suspension, then add propylene glycol, stir and cross 100 eye mesh screens after 30 minutes, suspension is placed in batches; Plain sheet is transferred between coating, getting suspension adds in the feeding device, with plain sheet preheating, by the power supply heater blower, open and discharge air in the bed, 2.0～3.0 rev/mins of rotating speeds, inlet temperature are 50～70 ℃, until the bed temperature reaches 40 ℃, coating solution is continued to spray until finish, with coated tablet oven dry 5 minutes, take out coated tablet and be placed in clean double-deck IPC ' the S bag, and get final product.Can prepare 1000 of Lamy stationary slices, every contains active component lamivudine 300mg.Taking dose: once a day, each 1.
Claims (6)
1. lamivudine tablet compositions is characterized in that this tablet makes by the following method:
Get supplementary material:
Lamivudine 100 ~ 300 weight portion microcrystalline Cellulose 100 ~ 300 weight portions
Carboxymethyl starch sodium 44 ~ 132 weight portion starch 50 ~ 150 weight portions
Silicon dioxide 3 ~ 9 weight portion magnesium stearate 3 ~ 9 weight portions
Hydroxypropyl emthylcellulose E-15 4.758 ~ 14.274 weight portion Pulvis Talci 1.589 ~ 4.767 weight portions
Titanium dioxide 1.589 ~ 4.767 weight portion red ferric oxide 0.159 ~ 0.477 weight portion
Yellow ferric oxide 0.316 ~ 0.948 weight portion propylene glycol 1.589 ~ 4.767 weight portions;
Get respectively lamivudine, microcrystalline Cellulose is crossed 60 mesh sieves, carboxymethyl starch sodium is crossed 80 mesh sieves, starch, silicon dioxide are crossed 200 mesh sieves, magnesium stearate is crossed 100 mesh sieves; The pure water that takes by weighing 100 weight portions places steam kettle, to be steam heated to 90 ~ 95 ° of C, heating stops the starch of rear adding 15 weight portions, constantly stir, form the starch oar, pasty liquid is translucent under constantly stirring in steam kettle, by 40 eye mesh screens, make binding agent, binding agent is placed hermetic container, cooling; Add in order the lamivudine sieved, microcrystalline Cellulose, 20 ~ 60 weight portion carboxymethyl starch sodium, 40 ~ 135 weight portion starch to fluid bed, be dry mixed 5 minutes, regulate the fluid unit parameter, spraying adds binding agent, until LOD loss on drying granulometric range reaches in 3% ~ 5% weight ratio scope, turn off fluid unit and heater; To sieving machine, granule is by 20 eye mesh screens with the transfer of granules in the fluid unit, check granule apparent size, place the double-layer seal Polythene Bag; Granule behind the granulate is inserted in the fluid bed, and add equably lubricant 24 ~ 72 weight portion carboxymethyl starch sodium, silicon dioxide, continue 5 minutes, when treating that exhaust cap opens 15%, magnesium stearate is added, and further mix, after 2 minutes, pour granule into clean airtight bucket, put screen cloth No. 4 on the bucket top; Machine is set the tabletting order, checks drift and mould, mould and drift is fixed on the machine tabletting; In hermetic container, hydroxypropyl emthylcellulose E-15 and water are mixed with viscosity solution, in above-mentioned viscosity solution, add Pulvis Talci, titanium dioxide and red ferric oxide and yellow ferric oxide, constantly stir, make uniform suspension, then add propylene glycol, stir and cross 100 eye mesh screens after 30 minutes, suspension is placed in batches; Plain sheet is transferred between coating, getting suspension adds in the feeding device, with plain sheet preheating, by the power supply heater blower, open and discharge air in the bed, 2.0 ~ 3.0 rev/mins of rotating speeds, inlet temperature are 50 ~ 70 ° of C, until the bed temperature reaches 40 ° of C, coating solution is continued to spray until finish, with coated tablet oven dry 5 minutes, take out coated tablet and be placed in clean double-deck IPC ' the S bag, and get final product.
2. lamivudine tablet compositions as claimed in claim 1 is characterized in that the raw material of this tablet consists of:
Lamivudine 100 weight portion microcrystalline Cellulose 100 weight portion carboxymethyl starch sodium 44 weight portions
Starch 50 weight portion silicon dioxide 3 weight portion magnesium stearate 3 weight portions
Hydroxypropyl emthylcellulose E-15 6.187 weight portion Pulvis Talci 2.067 weight portions
Titanium dioxide 2.067 weight portion red ferric oxide 0.207 weight portion yellow ferric oxide 0.412 weight portion
Propylene glycol 2.067 weight portions.
3. lamivudine tablet compositions as claimed in claim 1 is characterized in that the raw material of this tablet consists of:
Lamivudine 150 weight portion microcrystalline Cellulose 250 weight portion carboxymethyl starch sodium 50 weight portions
Starch 140 weight portion silicon dioxide 4 weight portion magnesium stearate 8 weight portions
Hydroxypropyl emthylcellulose E-155 weight portion Pulvis Talci 4.6 weight portions
Titanium dioxide 1.6 weight portion red ferric oxide 0.4 weight portion yellow ferric oxide 0.4 weight portion
Propylene glycol 4.7 weight portions.
4. lamivudine tablet compositions as claimed in claim 1 is characterized in that the raw material of this tablet consists of:
Lamivudine 300 weight portion microcrystalline Cellulose 150 weight portion carboxymethyl starch sodium 130 weight portions
Starch 60 weight portion silicon dioxide 8 weight portion magnesium stearate 4 weight portions
Hydroxypropyl emthylcellulose E-15 14 weight portion Pulvis Talci 1.6 weight portions
Titanium dioxide 4.7 weight portion red ferric oxide 0.2 weight portion yellow ferric oxide 0.9 weight portion
Propylene glycol 1.7 weight portions.
5. the preparation method of lamivudine tablet compositions as claimed in claim 1 is characterized in that the preparation method of this tablet is:
Get respectively lamivudine, microcrystalline Cellulose is crossed 60 mesh sieves, carboxymethyl starch sodium is crossed 80 mesh sieves, starch, silicon dioxide are crossed 200 mesh sieves, magnesium stearate is crossed 100 mesh sieves; The pure water that takes by weighing 100 weight portions places steam kettle, to be steam heated to 90 ~ 95 ° of C, heating stops the starch of rear adding 15 weight portions, constantly stir, form the starch oar, pasty liquid is translucent under constantly stirring in steam kettle, by 40 eye mesh screens, make binding agent, binding agent is placed hermetic container, cooling; Add in order the lamivudine sieved, microcrystalline Cellulose, 20 ~ 60 weight portion carboxymethyl starch sodium, 40 ~ 135 weight portion starch to fluid bed, be dry mixed 5 minutes, regulate the fluid unit parameter, spraying adds binding agent, until LOD loss on drying granulometric range reaches in 3% ~ 5% weight ratio scope, turn off fluid unit and heater; To sieving machine, granule is by 20 eye mesh screens with the transfer of granules in the fluid unit, check granule apparent size, place the double-layer seal Polythene Bag; Granule behind the granulate is inserted in the fluid bed, and add equably lubricant 24 ~ 72 weight portion carboxymethyl starch sodium, silicon dioxide, continue 5 minutes, when treating that exhaust cap opens 15%, magnesium stearate is added, and further mix, after 2 minutes, pour granule into clean airtight bucket, put screen cloth No. 4 on the bucket top; Machine is set the tabletting order, checks drift and mould, mould and drift is fixed on the machine tabletting; In hermetic container, hydroxypropyl emthylcellulose E-15 and water are mixed with viscosity solution, in above-mentioned viscosity solution, add Pulvis Talci, titanium dioxide and red ferric oxide and yellow ferric oxide, constantly stir, make uniform suspension, then add propylene glycol, stir and cross 100 eye mesh screens after 30 minutes, suspension is placed in batches; Plain sheet is transferred between coating, getting suspension adds in the feeding device, with plain sheet preheating, by the power supply heater blower, open and discharge air in the bed, 2.0 ~ 3.0 rev/mins of rotating speeds, inlet temperature are 50 ~ 70 ° of C, until the bed temperature reaches 40 ° of C, coating solution is continued to spray until finish, with coated tablet oven dry 5 minutes, take out coated tablet and be placed in clean double-deck IPC ' the S bag, and get final product.
6. the preparation method of lamivudine tablet compositions as claimed in claim 5 is characterized in that the preparation method of this tablet is:
Get respectively lamivudine, microcrystalline Cellulose is crossed 60 mesh sieves, carboxymethyl starch sodium is crossed 80 mesh sieves, starch, silicon dioxide are crossed 200 mesh sieves, magnesium stearate is crossed 100 mesh sieves; The pure water that takes by weighing 100 weight portions places steam kettle, to be steam heated to 90 ° of C, heating stops the starch of rear adding 5 weight portions, constantly stir, form the starch oar, pasty liquid is translucent under constantly stirring in steam kettle, by 40 eye mesh screens, make binding agent, binding agent is placed hermetic container, cooling; Add in order the lamivudine sieved, microcrystalline Cellulose, 20 weight portion carboxymethyl starch sodium, 45 weight portion starch to fluid bed, be dry mixed 5 minutes, regulate the fluid unit parameter, spraying adds binding agent, until LOD loss on drying granulometric range reaches in 3% ~ 5% weight ratio scope, turn off fluid unit and heater; To sieving machine, granule is by 20 eye mesh screens with the transfer of granules in the fluid unit, check granule apparent size, place the double-layer seal Polythene Bag; Granule behind the granulate is inserted in the fluid bed, and add equably lubricant 24 weight portion carboxymethyl starch sodium, silicon dioxide, continue 5 minutes, when treating that exhaust cap opens 15%, magnesium stearate is added, and further mix, after 2 minutes, pour granule into clean airtight bucket, put screen cloth No. 4 on the bucket top; Machine is set the tabletting order, checks drift and mould, mould and drift is fixed on the machine tabletting; In hermetic container, hydroxypropyl emthylcellulose E-15 and water are mixed with viscosity solution, in above-mentioned viscosity solution, add Pulvis Talci, titanium dioxide and red ferric oxide and yellow ferric oxide, constantly stir, make uniform suspension, then add propylene glycol, stir and cross 100 eye mesh screens after 30 minutes, suspension is placed in batches; Plain sheet is transferred between coating, getting suspension adds in the feeding device, with plain sheet preheating, by the power supply heater blower, open and discharge air in the bed, 2.0 ~ 3.0 rev/mins of rotating speeds, inlet temperature are 50 ~ 70 ° of C, until the bed temperature reaches 40 ° of C, coating solution is continued to spray until finish, with coated tablet oven dry 5 minutes, take out coated tablet and be placed in clean double-deck IPC ' the S bag, and get final product.
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| CN104473896B (en) * | 2014-12-01 | 2017-04-19 | 东莞市金美济药业有限公司 | Rapidly-disintegrating lamivudine tablets and preparation process thereof |
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| CN101732316A (en) * | 2008-11-17 | 2010-06-16 | 上海迪赛诺医药发展有限公司 | Lamivudine preparation and preparation method thereof |
| CN101461790B (en) * | 2009-01-09 | 2011-04-20 | 安徽贝克生物制药有限公司 | Lamivudine tablet and preparation method |
| CN102144984B (en) * | 2011-04-06 | 2012-11-28 | 福建广生堂药业股份有限公司 | Easy-dissolution lamivudine tablet and preparation method thereof |
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