CN103989675A - Leflunomide tablet and preparation technology thereof - Google Patents
Leflunomide tablet and preparation technology thereof Download PDFInfo
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- CN103989675A CN103989675A CN201410212557.1A CN201410212557A CN103989675A CN 103989675 A CN103989675 A CN 103989675A CN 201410212557 A CN201410212557 A CN 201410212557A CN 103989675 A CN103989675 A CN 103989675A
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- leflunomide
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- pregelatinized starch
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Abstract
The invention discloses a leflunomide tablet and a preparation technology and use thereof. The product is prepared from leflunomide, milk sugar, pregelatinized starch, hydroxypropyl methyl cellulose, carboxymethyl starch sodium, polysorbate-80, 12% slushing pregelatinized starch, magnesium stearate and a gastric soluble film coating premix. The production method comprises the steps of fabricating tablets and coatings, and the like. The leflunomide tablet disclosed by the invention is high in dissolution rate, good in stability, good in anti-inflammatory analgesic effect, and small in effect on erythrocyte sedimentation rate, and the total effective rate is 85%. The drug disclosed by the invention has the characteristics of being fewer in medication administration times, stable in plasma concentration, long in lasting time and the like.
Description
Invention field
The present invention relates to a kind of pharmaceutical preparation for the treatment of rheumatoid arthritis and preparation method thereof, belong to the medication of orthopaedics class disease, be specifically related to a kind of leflunomide tablet and preparation method thereof.
Background of invention
Arthritis is a kind of commonly encountered diseases, chronic disease, wherein take osteoarthritis and rheumatoid arthritis as principal mode.It is reported, China approximately has 18% people to suffer from the arthritis of certain form, and number of the infected surpasses 200,000,000.The mankind's health in arthritis serious threat, has influence on patient's live and work, some patient be can't take care of oneself, disability.Some patient's activity is restricted, arthroncus, stiff and pain, and severe patient joint permanent deformation, is the major reason that old people is disabled, and therefore needs treatment in time.
Leflunomide (Leflunomide) is the synthetic depressant of a kind of pyrimidine, be widely used in recently treating rheumatoid arthritis, respond well, mainly by suppressing to promote the synthetic dihydro lactic acid dehydrogenase activity of pyrimidine to suppress the synthetic of pyrimidine nucleotide in DNA building-up process, suppress tyrosine phosphorylation simultaneously, suppressing the startup of interleukin (IL)-2 gene transcribes, thereby suppress the generation of (IL)-2, hypertrophy and the cell cycle progress of blocking-up activated lymphocyte, reduce antibody and generate.The inhibitor that the NF-kB of leflunomide or a kind of effective various inflammatory stimulus inductions activates, can inflammation-inhibiting and immunocompetence, by suppressing Thl effector lymphocyte's activation and regulating Thl lymphocyte to produce the lymphoproliferative inhibitory action to T to the lymphocytic differentiation of Th2.The effect that laboratory observation leflunomide has stronger inhibition anti-dsDNA antibody to produce to MRL/Ipr Mus, and can obviously alleviate brightic pathological manifestations, reduce the deposition of IgG immune complex in glomerule.Another Ju report, leflunomide is in organ transplantation, and there is the data of more successfully applying in the fields such as lupus erythematosus.Leflunomide (Leflunomide), to treatment rheumatoid arthritis with remarkable effect, only has leflunomide tablet in the market.
, at aspects such as curative effects, there is undesirable part in the medicine of existing treatment rheumatoid arthritis, painful osteoarthritis (arthrosis, osteoarthritis).The object of the present invention is to provide a kind of rheumatoid arthritis, effective leflunomide tablet and preparation technology thereof of painful osteoarthritis for the treatment of, gained Dissolution of Tablet is high, steady quality, preparation technology is simple to operate, pollute less, with low cost, be applicable to suitability for industrialized production.
Summary of the invention
The object of the present invention is to provide a kind of rheumatoid arthritis, effective leflunomide tablet and preparation technology thereof of painful osteoarthritis for the treatment of, and through repetition test, each component screening is arrived to weight ratio of the present invention, be surprised to find that the tablet quality obtaining is stable, stripping is fast, in body, distribute rapidly, bioavailability is high.
On the one hand, the invention provides a kind of leflunomide tablet, wherein every 1000 are comprised of following weight item:
Some embodiments therein, leflunomide tablet of the present invention, wherein every 1000 are comprised of following weight item:
On the other hand, the invention provides a kind of preparation technology of leflunomide tablet, it comprises the following steps:
(1) make label: leflunomide, lactose, pregelatinized Starch, hydroxypropyl methylcellulose, carboxymethylstach sodium are crossed to 100 mesh sieves, by equivalent incremental method, join mix homogeneously in wet mixing pelletizer, obtain mixed powder; Tween-80, magnesium stearate are dissolved in 30～50 times of ethanol, join in above-mentioned mixed powder, mix, again 12% concentration punching slurry is joined in mixed powder with pregelatinized Starch, make 18～40 order granules, 60～70 ℃ dry, 24 mesh sieve granulate, rewinding when moisture is 1.0～3.0%, makes label standby;
(2) coating: stomach dissolved film coating pre-mix dose is mixed with to 11% outstanding mixed liquid with 80% ethanol, be uniformly mixed 60 minutes standby; Label is poured in coating pan, coating pan adjustment of rotational speed is 2～3 revs/min, spray gun distance is adjusted to from sheet bed 30～40cm, start preheating label, ℃ left and right, label temperature to 40～50, atomisation pressure, at 0.5～0.6MPa, starts coating to 3.0%, 30～40 ℃ of sheet weightening finishes and within dry 12 hours, obtains product;
The consumption of above-mentioned each component, every 1000 are comprised of following ingredients:
Leflunomide tablet of the present invention is applied to preparation treatment rheumatoid arthritis, painful osteoarthritis medicine.
The specific embodiment
Below in conjunction with embodiment, further explain the present invention, but embodiment does not limit in any form to the present invention.
(1) make label: leflunomide, lactose, pregelatinized Starch, hydroxypropyl methylcellulose, carboxymethylstach sodium are crossed to 100 mesh sieves, by equivalent incremental method, join in wet mixing pelletizer and mix equal Uniform, obtain mixed powder; Tween-80, magnesium stearate are dissolved in 30～50 times of ethanol, join in above-mentioned mixed powder, mix, again 12% concentration punching slurry is joined in mixed powder with pregelatinized Starch, make 18～40 order granules, 60～70 ℃ dry, 24 mesh sieve granulate, rewinding when moisture is 1.0～3.0%, makes label standby;
(2) coating: stomach dissolved film coating pre-mix dose is mixed with to 11% outstanding mixed liquid with 80% ethanol, be uniformly mixed 60 minutes standby; Label is poured in coating pan, coating pan adjustment of rotational speed is 2～3 revs/min, spray gun distance is adjusted to from sheet bed 30～40cm, start preheating label, ℃ left and right, label temperature to 40～50, atomisation pressure, at 0.5～0.6MPa, starts coating to 3.0%, 30～40 ℃ of sheet weightening finishes and within dry 12 hours, obtains product;
The consumption of above-mentioned each component, every 1000 are comprised of following ingredients:
Leflunomide tablet of the present invention is applied to preparation treatment rheumatoid arthritis, painful osteoarthritis medicine.
Biological test
Comparative Study on Dissolution
This test example has detected result of extraction provided by the invention, and detection method is carried out with reference to 2005 editions the 2nd appendix XC dissolution method the second method of < < Chinese Pharmacopoeia > >.
Take distilled water as dissolution medium, rotating speed 50rpm, 30min sampling, injection liquid chromatography, records chromatogram, and gets reference substance solution injection liquid chromatography, records chromatogram.With external standard method, calculate leflunomide stripping quantity in test sample.Each sample carries out under the same conditions, and the same terms repeats 50 calculating mean values.
Wherein sample 1 is the embodiment of the present invention 1 product, reference reagent: the special commercially available ordinary tablet reference substance (ordinary tablet, specification: 10mg, Wansui Pharmaceutical Co Ltd, Hebei Prov.) of fluorine rice.
The different sample dissolutions of table 1
| Sample | 5min | 10min | 15min | 30min | 45min |
| Embodiment 1 | 78.4 | 90.9 | 96.7 | 99.6 | 100.25 |
| Marketed tablet | 50.3 | 79.6 | 88.2 | 93.8 | 99.45 |
By table 1 data, can find that the inventive method prepares tablet and more can improve the dissolution of product than commercially available ordinary tablet.And the prescription of the embodiment of the present invention 1, make dissolution reach optimum.
This test is for fear of error effect, special each sample respectively got to 10 batches, and every batch of duplicate detection 10 times, averages.Learn and calculate by statistics, P < 0.05, this test has statistical significance.
And take oral form of medication according to leflunomide tablet, this leflunomide tablet provided by the present invention is beneficial to the performance of this medicine effect more, has greatly strengthened its bioavailability.
Accelerate 6 months stability tests
The leflunomide tablet of blister package (embodiment 1) is put under the condition of 40 ℃ ± 2 ℃ of temperature, relative humidity 75% ± 5% and placed six months, outcome quality is stable, and indices is as shown in table 2.
Six months accelerated test testing results of table 2 leflunomide tablet
| Inspection batch | Outward appearance | Related substance % | Dissolution % | Content % |
| Batch 1 | White is smooth | 0.19 | 100.25 | 100.20 |
| Batches 2 | White is smooth | 0.21 | 100.18 | 100.12 |
| Batches 3 | White is smooth | 0.20 | 100.23 | 100.18 |
Claims (3)
1. a leflunomide tablet, wherein every 1000 are comprised of following weight item:
2. leflunomide tablet according to claim 1, wherein every 1000 are comprised of following weight item:
3. a preparation technology for leflunomide tablet, it comprises the following steps:
(1) make label: leflunomide, lactose, pregelatinized Starch, hydroxypropyl methylcellulose, carboxymethylstach sodium are crossed to 100 mesh sieves, by equivalent incremental method, join mix homogeneously in wet mixing pelletizer, obtain mixed powder; Tween-80, magnesium stearate are dissolved in 30～50 times of ethanol, join in above-mentioned mixed powder, mix, again 12% concentration punching slurry is joined in mixed powder with pregelatinized Starch, make 18～40 order granules, 60～70 ℃ dry, 24 mesh sieve granulate, rewinding when moisture is 1.0～3.0%, makes label standby;
(2) coating: stomach dissolved film coating pre-mix dose is mixed with to 11% outstanding mixed liquid with 80% ethanol, be uniformly mixed 60 minutes standby; Label is poured in coating pan, coating pan adjustment of rotational speed is 2～3 revs/min, spray gun distance is adjusted to from sheet bed 30～40cm, start preheating label, ℃ left and right, label temperature to 40～50, atomisation pressure, at 0.5～0.6MPa, starts coating to 3.0%, 30～40 ℃ of sheet weightening finishes and within dry 12 hours, obtains product;
The consumption of above-mentioned each component, every 1000 are comprised of following ingredients:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201410212557.1A CN103989675A (en) | 2014-05-20 | 2014-05-20 | Leflunomide tablet and preparation technology thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410212557.1A CN103989675A (en) | 2014-05-20 | 2014-05-20 | Leflunomide tablet and preparation technology thereof |
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| CN103989675A true CN103989675A (en) | 2014-08-20 |
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| CN201410212557.1A Pending CN103989675A (en) | 2014-05-20 | 2014-05-20 | Leflunomide tablet and preparation technology thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104490758A (en) * | 2014-12-05 | 2015-04-08 | 海南卫康制药(潜山)有限公司 | Leflunomide composition freeze-dried tablets and preparation method thereof |
| CN105287420A (en) * | 2015-12-03 | 2016-02-03 | 李正梅 | Leflunomide tablet for treating adult rheumatoid arthritis |
| CN106924713A (en) * | 2017-04-14 | 2017-07-07 | 福建汇天生物药业有限公司 | A kind of leflunomide tablet of high bioavilability and preparation method thereof |
| CN108014081A (en) * | 2017-12-28 | 2018-05-11 | 福建汇天生物药业有限公司 | A kind of leflunomide tablet of stability and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101816637A (en) * | 2009-02-26 | 2010-09-01 | 江苏亚邦爱普森药业有限公司 | Leflunomide tablet preparation and preparation method thereof |
-
2014
- 2014-05-20 CN CN201410212557.1A patent/CN103989675A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101816637A (en) * | 2009-02-26 | 2010-09-01 | 江苏亚邦爱普森药业有限公司 | Leflunomide tablet preparation and preparation method thereof |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104490758A (en) * | 2014-12-05 | 2015-04-08 | 海南卫康制药(潜山)有限公司 | Leflunomide composition freeze-dried tablets and preparation method thereof |
| CN105287420A (en) * | 2015-12-03 | 2016-02-03 | 李正梅 | Leflunomide tablet for treating adult rheumatoid arthritis |
| CN106924713A (en) * | 2017-04-14 | 2017-07-07 | 福建汇天生物药业有限公司 | A kind of leflunomide tablet of high bioavilability and preparation method thereof |
| CN108014081A (en) * | 2017-12-28 | 2018-05-11 | 福建汇天生物药业有限公司 | A kind of leflunomide tablet of stability and preparation method thereof |
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Application publication date: 20140820 |