CN105708818A - Lamivudine tablet composition, and preparation method thereof - Google Patents
Lamivudine tablet composition, and preparation method thereof Download PDFInfo
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- CN105708818A CN105708818A CN201410716703.4A CN201410716703A CN105708818A CN 105708818 A CN105708818 A CN 105708818A CN 201410716703 A CN201410716703 A CN 201410716703A CN 105708818 A CN105708818 A CN 105708818A
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Abstract
The invention relates to a lamivudine tablet composition, and a preparation method thereof. The tablet core of the lamivudine tablet composition is prepared from 80 to 120 parts of lamivudine, 90 to 150 parts of microcrystalline cellulose, 4 to 20 parts of carboxymethyl starch sodium, 1 to 6 parts of silicon dioxide, and 0.5 to 4 parts of magnesium stearate. The preparation method comprises following steps: the raw materials are sieved; lamivudine, microcrystalline cellulose, carboxymethyl starch sodium, silicon dioxide, and magnesium stearate are weighed, and are uniformly mixed; the content of an obtained mixed powder is measured; when the content is qualified, a tablet weight is calculated, and direct tabletting is carried out; coating is carried out; and full inspection and packaging are carried out after drying so as to obtain a finished product.
Description
Technical field
The present invention relates to field of medicaments, be specifically related to a kind of lamivudine tablet composition and method of making the same.
Background technology
Lamivudine (Lamivudine) is a kind of deoxycytidine analog, and chemical name is (2R, 5S)-4-amino-1-(2-methylol-1,3-oxathiolane-5-base)-(1H)-pyrimid-2-one.
Its molecular structural formula is as follows:
Molecular formula: C8H11N3O3S
Hepatitis B is that a kind of sickness rate is high, appeal is strong, the epidemic infectious diseases of serious harm human health, is a global public health problem.China has more than 300,000 people to die from hepatitis B related complication every year, wherein 5 years case fatality rate respectively 0%-2%, 14%-20% and 70%-86% of chronic viral hepatitis B, compensatory phase and decompensated liver cirrhosis.The annual total cost for treating hepatitis B of China is more than 100,000,000,000, and chronic viral hepatitis B and complication thereof, while bring very big Disease Spectrum to patient, also bring heavy financial burden for society and individual.
Lamivudine is antiviral agents, belong to efabirenz, developed by BiochemPharma company of Canada the earliest, after by GlaxoWellcome company of Britain in nineteen ninety-five first the U.S. list, for treating HBV infection, within 1996, list in Britain, within 1999, obtain import registration approval in China.
Hepatitis B virus (HBV) in external and experimental infection animal body is had stronger inhibitory action by lamivudine.Lamivudine can generate lamivudine triphosphate at HBV infection cell and normal cell intracellular metabolite, and it is the activity form of lamivudine, is the inhibitor of HBV polymerase, is also the substrate of this polymerase.Lamivudine on DNA in mammalian cells content almost without impact.Lamivudine to mitochondrial structure, DNA content and function without obvious toxicity.The serum HBV DNA testing result of most of hepatitis B patients is shown, lamivudine energy inhibition HBV replication rapidly, its inhibitory action continues at whole therapeutic process.Making serum transaminase be down to normally, prolonged application can significantly improve the struvite change of hepatic necrosis and alleviate or stop the progress of hepatic fibrosis simultaneously.
Domestic and international random contrast clinical trial shows, every day, oral 100mg can substantially suppress HBVDNA level, HBeAg Virus mutation rate extends with treatment time and improves, and HbeAg positive patient was treated after 1,2,3,4 and 5 years HBeAg frequence of seroconversion respectively 22%, 29%, 40%, 47% and 50%；Horizontal the higher person of ALT before treatment, general HBeAg Virus mutation rate is also higher.Long-term treatment can reduce inflammation, and reduces the incidence rate of hepatic fibrosis and liver cirrhosis.Random contrast clinical trial shows, this medicine can reduce liver function and lose compensatory and HCC(hepatocarcinoma) incidence rate.Also can improve liver function at Decompensated Cirrhosis Patients, extend life cycle.Foreign study result shows, the curative effect of lamivudine therapy Chronic Hepatitis B in Children is similar to adult, and safety is good.To hepatitis B liver-transplantation patients, before transplanting, use lamivudine；After transplanting, lamivudine and HBIG coupling, after can obviously reduce liver transplantation, HBV infects again, and can reduce HBIG dosage.
Through the clinical verification in more than 10 years, lamivudine is the progress being proved at present and can delaying hepatitis cirrhosis, and few side effects spends few medicine.
Patent application 200910116030.8 discloses following a kind of lamivudine tablet and preparation, and described lamivudine tablet is made up of the raw material of following weight portion: lamivudine 100 parts, microcrystalline Cellulose 90～110 parts, carboxymethyl starch sodium 15～25 parts, hypromellose 1～5 part, magnesium stearate 1～5 part, 50% ethanol 90～110 parts.100 mesh sieves are crossed in its preparation respectively for lamivudine, microcrystalline Cellulose, carboxymethylstach sodium, microcrystalline Cellulose and lamivudine mixing, take 50% ethanol hypromellose mixing, add soft material processed in above-mentioned compound, cross 20 mesh sieves to granulate, dry, cross 20 mesh sieve granulate, adding magnesium stearate, carboxymethylstach sodium mixing, tabletting both obtained.
But in practice, it has been found that its disintegrate effect of above-mentioned preparation is unsatisfactory.In order to find the more rapid effective lamivudine preparation of a kind of disintegrate, the special proposition present invention.
Summary of the invention
Lamivudine is conventional tablet, dissolution test is the emphasis of preparation research, the leading indicator being recipe development with the dissolution of medicine, found by prescription screening test, be mixed and made into preparation as major auxiliary burden and lamivudine using microcrystalline Cellulose, carboxymethyl starch sodium, magnesium stearate, silicon dioxide there is good disintegrative and dissolution.
The technical solution realizing above-mentioned purpose is as follows:
A kind of lamivudine tablet compositions, described lamivudine tablet compositions label is prepared from by following composition: lamivudine 80～120 parts, microcrystalline Cellulose 90～150 parts, carboxymethylstach sodium 4～20 parts, silica 1～6 part, magnesium stearate 0.5～4 part.
According to foregoing lamivudine tablet compositions, described lamivudine tablet compositions label is prepared from by following composition: lamivudine 90～110 parts, microcrystalline Cellulose 110～130 parts, carboxymethylstach sodium 8～15 parts, silicon dioxide 2～5 parts, magnesium stearate 1～4 part.
According to foregoing lamivudine tablet compositions, described lamivudine tablet compositions label is prepared from by following composition: lamivudine 100 parts, microcrystalline Cellulose 120 parts, carboxymethylstach sodium 10 parts, silicon dioxide 3 parts, magnesium stearate 2 parts.
Lamivudine tablet compositions according to above any one, outside described tablet composition label, also there is coatings, described coatings be hypromellose, polyoxyethylene sorbitan monoleate, Macrogol 4000, titanium dioxide 70% alcoholic solution make, described coatings weight is the 1%～6% of label weight, it is preferred to 2%～4%.
The above preparation method of lamivudine tablet compositions described in any one, described tablet composition preparation method is:
(1) sieve: lamivudine, microcrystalline Cellulose, carboxymethylstach sodium, magnesium stearate, silicon dioxide are sieved respectively；
(2) mixing: weigh recipe quantity lamivudine, microcrystalline Cellulose, carboxymethyl starch sodium, silicon dioxide and magnesium stearate, mix homogeneously；
(3) measure mixing intermediates content, calculate after qualified and answer tabletting weight；
(4) tabletting: choose suitable ellipse punch die direct compression, obtain label；
(5) coating solution: hypromellose, polyoxyethylene sorbitan monoleate, Macrogol 4000, titanium dioxide 70% alcoholic solution；
(6) coating operations: take lamivudine label, puts in coating pan, carries out coating, and coated tablet drying obtains Lamy stationary slice finished product after solidifying；
(7) after full inspection, packaging and get final product.
According to foregoing preparation method, sieve as crossing 60～100 mesh sieves described in step (1), it is preferred to 80 mesh sieves.
According to foregoing preparation method, step (4) described tabletting method is direct compression.
According to foregoing preparation method, the described coating solution compound method of step (5) is for taking recipe quantity hypromellose, it is scattered in 700ml alcoholic solution, after swelling, adding water to 1000ml and dissolve completely, add recipe quantity polyoxyethylene sorbitan monoleate and Macrogol 4000, stirring and dissolving is complete, add recipe quantity titanium dioxide dispersed with stirring before coating uniform, obtain coating solution.
Below technical solution of the present invention is elaborated:
The major part of the lamivudine tablet compositions of the present invention is a piece of core segment, and described lamivudine tablet compositions label is prepared from by following composition: lamivudine, microcrystalline Cellulose, carboxymethylstach sodium, magnesium stearate, silicon dioxide.Wherein microcrystalline Cellulose is for filling disintegration, and carboxymethylstach sodium also functions to the effect of disintegrating agent, and magnesium stearate is lubricant, and silicon dioxide is fluidizer.The present invention is by the optimized choice to disintegrating agent and fluidizer kind and consumption so that the Lamy stationary slice disintegration rate of preparation greatly improves.
Preferred for this invention tablet Core formulation proportioning of preparing is: lamivudine 80～120 parts, microcrystalline Cellulose 90～150 parts, carboxymethylstach sodium 4～20 parts, silica 1～6 part, magnesium stearate 0.5～4 part.
Wherein can further be preferably: lamivudine 90～110 parts, microcrystalline Cellulose 110～130 parts, carboxymethylstach sodium 8～15 parts, silicon dioxide 2～5 parts, magnesium stearate 1～4 part.
But can also be much further preferably from: lamivudine 100 parts, microcrystalline Cellulose 120 parts, carboxymethylstach sodium 10 parts, silicon dioxide 3 parts, magnesium stearate 2 parts.
Described label is the major part playing drug effect, but those skilled in the art all know, and generally also can be coated with one layer of coatings outside the sheet core segment of tablet, to improve mouthfeel.The kind of this coatings and preparation are generally conventionally known to one of skill in the art, say, that the realization of the present invention the first goal of the invention, are not limit by the kind of coatings and preparation.
But, the present invention can preferably employ coatings be hypromellose, polyoxyethylene sorbitan monoleate, Macrogol 4000, titanium dioxide 70% alcoholic solution make, described coatings weight is preferably the 1%～6% of label weight, more preferably 2%～4%.
The present invention adopts the hypromellose of certain concentration, polyoxyethylene sorbitan monoleate, Macrogol 4000, titanium dioxide alcoholic solution to prepare coatings, and the tablet appearance of preparation is fine and smooth, smooth, good mouthfeel.Additionally, realize the adjustment to coatings thickness by controlling the weight of coatings so that the not easily moisture absorption of the tablet of preparation, and having certain interception, the stability raising for medicine has benefit.
Detailed description of the invention
By embodiment, technical scheme is further described below; will assist in the advantage to technical scheme; effect has further to be understood, and embodiment does not limit protection scope of the present invention, and protection scope of the present invention is determined by claim.
Embodiment 1
Take supplementary material lamivudine, microcrystalline Cellulose, carboxymethylstach sodium, silicon dioxide, magnesium stearate, cross 80 mesh sieves.Weigh lamivudine 100g, microcrystalline Cellulose 130g, carboxymethylstach sodium 10g, silicon dioxide 2g, magnesium stearate 2g, mix homogeneously respectively, measure the content of mixing intermediate, calculate after qualified and answer tabletting weight, direct compression.Take lamivudine label, put in coating pan, with coating solution (hypromellose, polyoxyethylene sorbitan monoleate, Macrogol 4000, titanium dioxide 70% alcoholic solution) carry out coating, to weightening finish 2%, coated tablet drying obtains Lamy stationary slice finished product after solidifying, after Quan Jian, packaging and get final product.
Embodiment 2
Take supplementary material lamivudine, microcrystalline Cellulose, carboxymethylstach sodium, silicon dioxide, magnesium stearate, cross 90 mesh sieves.Weigh lamivudine 100g, microcrystalline Cellulose 130g, carboxymethylstach sodium 10g, silicon dioxide 2g, magnesium stearate 2g, mix homogeneously respectively, measure the content of mixing intermediate, calculate after qualified and answer tabletting weight, direct compression.Take lamivudine label, put in coating pan, with coating solution (hypromellose, polyoxyethylene sorbitan monoleate, Macrogol 4000, titanium dioxide 70% alcoholic solution) carry out coating, to weightening finish 3%, coated tablet drying obtains Lamy stationary slice finished product after solidifying, after Quan Jian, packaging and get final product.
Embodiment 3
Take supplementary material lamivudine, microcrystalline Cellulose, carboxymethylstach sodium, silicon dioxide, magnesium stearate, cross 100 mesh sieves.Weigh lamivudine 100g, microcrystalline Cellulose 130g, carboxymethylstach sodium 10g, silicon dioxide 2g, magnesium stearate 2g, mix homogeneously respectively, measure the content of mixing intermediate, calculate after qualified and answer tabletting weight, direct compression.Take lamivudine label, put in coating pan, with coating solution (hypromellose, polyoxyethylene sorbitan monoleate, Macrogol 4000, titanium dioxide 70% alcoholic solution) carry out coating, to weightening finish 4%, coated tablet drying obtains Lamy stationary slice finished product after solidifying, after Quan Jian, packaging and get final product.
Embodiment 4
Take supplementary material lamivudine, microcrystalline Cellulose, carboxymethylstach sodium, silicon dioxide, magnesium stearate, cross 80 mesh sieves.Weigh lamivudine 100g, microcrystalline Cellulose 120g, carboxymethylstach sodium 10g, silicon dioxide 3g, magnesium stearate 2g, mix homogeneously respectively, measure the content of mixing intermediate, calculate after qualified and answer tabletting weight, direct compression.Take lamivudine label, put in coating pan, with coating solution (hypromellose, polyoxyethylene sorbitan monoleate, Macrogol 4000, titanium dioxide 70% alcoholic solution) carry out coating, to weightening finish 3%, coated tablet drying obtains Lamy stationary slice finished product after solidifying, after Quan Jian, packaging and get final product.
Embodiment 5
Take supplementary material lamivudine, microcrystalline Cellulose, carboxymethylstach sodium, silicon dioxide, magnesium stearate, cross 80 mesh sieves.Weigh lamivudine 100g, microcrystalline Cellulose 120g, carboxymethylstach sodium 10g, silicon dioxide 4g, magnesium stearate 2g, mix homogeneously respectively, measure the content of mixing intermediate, calculate after qualified and answer tabletting weight, direct compression.Take lamivudine label, put in coating pan, with coating solution (hypromellose, polyoxyethylene sorbitan monoleate, Macrogol 4000, titanium dioxide 70% alcoholic solution) carry out coating, to weightening finish 4%, coated tablet drying obtains Lamy stationary slice finished product after solidifying, after Quan Jian, packaging and get final product.
The present invention also provides for following test example, so that the present invention is further described:
Test example 1
This test example have detected result of extraction provided by the invention, and detection method carries out with reference to " Chinese Pharmacopoeia " 2010 editions the 2nd annex XC dissolution method second method.
With distilled water 900ml for dissolution medium, rotating speed is 50 turns per minute, operate in accordance with the law, when 15min, take solution appropriate, filter, take subsequent filtrate 1ml, it is diluted with water to 10ml as need testing solution, according to ultraviolet visible spectrophotometry (Chinese Pharmacopoeia two annex IV A of version in 2010), measures absorbance at the wavelength place of 272nm；Separately take lamivudine control product appropriate, accurately weighed, it is dissolved in water and quantitatively the solution in every 1ml containing about 10 μ g is made in dilution, be measured in the same method.Calculate the stripping quantity of every.Each batch measures 12 altogether.
The different sample dissolution of table 1
Wherein sample 1 is the embodiment of the present invention 1 product, and 2 is embodiment 2 product, and 3 is embodiment 3 product.4 is embodiment 4 product, and 5 is embodiment 5 product.
By table 1 data, it is possible to find that the dissolution of the inventive method was all higher than 85% when 15 minutes.It is significantly larger than the Lamy stationary slice adopting common prior art method to prepare.
And the form of medication being administered orally is taked according to lamivudine tablet, this Lamy stationary slice provided by the present invention is more favorable for the performance of this medicine effect, greatly strengthen its bioavailability.
Claims (8)
1. a lamivudine tablet compositions, it is characterized in that, described lamivudine tablet compositions label is prepared from by following composition: lamivudine 80～120 parts, microcrystalline Cellulose 90～150 parts, carboxymethylstach sodium 4～20 parts, silica 1～6 part, magnesium stearate 0.5～4 part.
2. lamivudine tablet compositions according to claim 1, it is characterized in that, described lamivudine tablet compositions label is prepared from by following composition: lamivudine 90～110 parts, microcrystalline Cellulose 110～130 parts, carboxymethylstach sodium 8～15 parts, silicon dioxide 2～5 parts, magnesium stearate 1～4 part.
3. lamivudine tablet compositions according to claim 2, it is characterized in that, described lamivudine tablet compositions label is prepared from by following composition: lamivudine 100 parts, microcrystalline Cellulose 120 parts, carboxymethylstach sodium 10 parts, silicon dioxide 3 parts, magnesium stearate 2 parts.
4. the lamivudine tablet compositions according to claims 1 to 3 any one, it is characterized in that, outside described tablet composition label, also there is coatings, described coatings be hypromellose, polyoxyethylene sorbitan monoleate, Macrogol 4000, titanium dioxide 70% alcoholic solution make, described coatings weight is the 1%～6% of label weight, it is preferred to 2%～4%.
5. the preparation method of lamivudine tablet compositions described in Claims 1 to 4 any one, it is characterised in that described tablet composition preparation method is:
(1) sieve: lamivudine, microcrystalline Cellulose, carboxymethylstach sodium, magnesium stearate, silicon dioxide are sieved respectively；
(2) mixing: weigh recipe quantity lamivudine, microcrystalline Cellulose, carboxymethyl starch sodium, silicon dioxide and magnesium stearate, mix homogeneously；
(3) measure mixing intermediates content, calculate after qualified and answer tabletting weight；
(4) tabletting: choose suitable ellipse punch die direct compression, obtain label；
(5) coating solution: hypromellose, polyoxyethylene sorbitan monoleate, Macrogol 4000, titanium dioxide 70% alcoholic solution；
(6) coating operations: take lamivudine label, puts in coating pan, carries out coating, and coated tablet drying obtains Lamy stationary slice finished product after solidifying；
(7) after full inspection, packaging and get final product.
6. preparation method according to claim 5, sieves as crossing 60～100 mesh sieves, it is preferred to 80 mesh sieves described in step (1).
7. preparation method according to claim 5, according to foregoing preparation method, step (4) described tabletting method is direct compression.
8. according to foregoing preparation method, the described coating solution compound method of step (5) is for taking recipe quantity hypromellose, it is scattered in 700ml alcoholic solution, after swelling, adding water to 1000ml and dissolve completely, add recipe quantity polyoxyethylene sorbitan monoleate and Macrogol 4000, stirring and dissolving is complete, add recipe quantity titanium dioxide dispersed with stirring before coating uniform, obtain coating solution.
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| CN201410716703.4A CN105708818A (en) | 2014-12-02 | 2014-12-02 | Lamivudine tablet composition, and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN113030307A (en) * | 2021-03-02 | 2021-06-25 | 天地恒一制药股份有限公司 | Method for determining content of auxiliary materials in lamivudine tablet |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113030307A (en) * | 2021-03-02 | 2021-06-25 | 天地恒一制药股份有限公司 | Method for determining content of auxiliary materials in lamivudine tablet |
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Application publication date: 20160629 |
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