CN101816637B - Leflunomide tablet preparation and preparation method thereof - Google Patents
Leflunomide tablet preparation and preparation method thereof Download PDFInfo
- Publication number
- CN101816637B CN101816637B CN 200910025145 CN200910025145A CN101816637B CN 101816637 B CN101816637 B CN 101816637B CN 200910025145 CN200910025145 CN 200910025145 CN 200910025145 A CN200910025145 A CN 200910025145A CN 101816637 B CN101816637 B CN 101816637B
- Authority
- CN
- China
- Prior art keywords
- preparation
- leflunomide
- dissolution
- add
- tablet
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention relates to a leflunomide tablet preparation and a preparation method thereof. The solid dispersion method is adopted for improving the dissolution rate of a drug, thereby improving the bioavailability of the drug. The in vitro dissolution experiment shows that the dissolution rate of leflunomide tablets prepared by the method can be more than 90% at 45min under the condition of taking water as a dissolution medium.
Description
Technical field
The present invention relates to a kind of leflunomide tablet preparation and preparation method thereof, belong to field of pharmaceutical preparations.
Background technology
Leflunomide (leflunomide) is the new drug that first that ratify in recent ten years is specifically designed to the treatment rheumatoid arthritis.This product has immunosuppressant and antiinflammatory action, its mechanism of action is novel, and it suppresses the activity of cell adhesion and acid kinase, affects the Information Conduction of cytokine, suppress the activity of dihydroorate dehydrogenase, thereby suppressed the active Proliferation of lymphocytes relevant with the rheumatoid arthritis morbidity.Zoopery and clinical effectiveness show, leflunomide suppresses local inflammation and connective tissue proliferation and arthritic general reaction, it is effective medicine of this chronic disease progress of first rheumatoid arthritis that can slow down, it not only can lower various indications and the symptom of Patients With Rheumatoid Arthritis, and the structure that can stop rheumatoid arthritis to cause is downright bad.X-ray result shows, rotten to the corn and the joint space aspect such as narrow down all is significantly improved in the joint to use this product, this is different from existing resisting rheumatoid disease arthritis drug and comprises methotrexate and willow sulfoamide pyridine etc., being first shows medicine of definite curative effect in objective indicator, but and have rapid-action, use the characteristics such as safety, toleration are good, patient's long-term taking.
The leflunomide poorly water-soluble adopts conventional tablet prescription and preparation method, is difficult to improve its dissolution, also affects thus its bioavailability and curative effect.Given this, in the leflunomide tablet quality standard that State Food and Drug Administration promulgates, adopted extreme dissolution medium to detect its drug dissolution, for example adopting 30% alcoholic solution (containing 0.5% sodium lauryl sulphate) 900ml is dissolution medium.
Summary of the invention
The object of the present invention is to provide prescription of leflunomide tablet preparation and preparation method thereof.The present invention adopts the method for solid dispersion with the dissolution rate of raising medicine, thereby improves the bioavailability of medicine.
The present invention implements by following method:
Leflunomide tablet preparation provided by the present invention, its active constituents of medicine are leflunomide, and pharmaceutic adjuvant is filler, disintegrating agent, solid dispersion carrier, lubricant.Filler can be selected one or more in lactose, microcrystalline Cellulose, starch, pregelatinized Starch, the dextrin.Disintegrating agent can be selected one or more in carboxymethyl starch sodium, hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, the polyvinylpolypyrrolidone.The solid dispersion carrier can be selected one or more in polyethylene glycols, PLURONICS F87, polyvidone class, carbamide, citric acid, tartaric acid, succinic acid, cholic acid, deoxycholic acid, chitosan, dextrose, galactose, sucrose, mannitol, xylitol, the sorbitol.The preferred Macrogol 4000 of polyethylene glycols solid dispersion carrier, polyethylene glycol 6000.The preferred 30 POVIDONE K 30 BP/USP of polyvidone class solid dispersion carrier
30Lubricant can be selected one or both in magnesium stearate, the Pulvis Talci.The weight ratio of leflunomide and adjuvant is 1: 1～80, and preferred weight ratio is 1: 5～15.The weight ratio of leflunomide and solid dispersion carrier is 1: 0.1～60, and preferred weight ratio is 1: 3～5.
The preparation method of leflunomide tablet preparation provided by the present invention has following three kinds: (1) is first with solid dispersion carrier heating and melting, add while stirring leflunomide, obtain fused solution or the suspension of leflunomide, be cooled to rapidly solid, dry, pulverize, add by a certain percentage other adjuvants after, pelletizing press sheet or direct compression.(2) solid dispersion carrier and leflunomide are dissolved in the organic solvent, boil off organic solvent after, drying is pulverized, and adds by a certain percentage other adjuvants and granulates tabletting.Can select methanol, dehydrated alcohol, acetone, ethyl acetate etc. in organic solvent, preferred dehydrated alcohol and acetone.(3) with the solid dispersion carrier with after leflunomide mixes, the powerful lasting certain hour that grinds adds by a certain percentage other adjuvants and granulates tabletting.
Dissolution in vitro experiment shows, under the condition take water as dissolution medium, can reach more than 90% with the leflunomide tablet of method preparation provided by the present invention dissolution when the 45min.The assay method of dissolution: get this product, according to dissolution method (two appendix XC the second methods of Chinese Pharmacopoeia version in 2005), take water 900ml as dissolution medium, Revolution Per Minute 75 turns, in accordance with the law operation, in the time of 45 minutes, get solution 10ml, filter, get subsequent filtrate, according to ultraviolet visible spectrophotometry (two appendix IVA of Chinese Pharmacopoeia version in 2005), measure absorbance at the wavelength place of 261nm; It is an amount of that other gets the leflunomide reference substance, accurately weighed, adds dissolve with ethanol, makes the solution that every 1ml contains 10 μ g with the dissolution medium dilution, measures with method, calculates every stripping quantity.
The specific embodiment
Following type reaction is used for illustrating the present invention, all belongs within the technical scheme that the present invention protects in simple replacement that those skilled in the art do the present invention or improvement etc.
Embodiment 1:
Preparation prescription of the present invention is comprised of following component by weight:
Leflunomide 10g
Microcrystalline Cellulose 20g
Lactose 30g
Carboxymethyl starch sodium 10g
PLURONICS F87 30g
Magnesium stearate 1g
Make altogether 1000
Preparation technology: with the PLURONICS F87 heating and melting, add while stirring leflunomide and make into solution, stir, be cooled to rapidly solid, drying was pulverized 80 mesh sieves, added other auxiliary materials and mixing, and 20 mesh sieves are granulated, 55 ℃～60 ℃ oven dry.18 mesh sieve granulate.Add the magnesium stearate mix homogeneously, tabletting.
The leflunomide tablet that according to said method prepares, the dissolution when 45min is greater than 90%.
Embodiment 2:
Preparation prescription of the present invention is comprised of following component by weight:
Leflunomide 10g
Microcrystalline Cellulose 20g
Lactose 30g
Carboxymethyl starch sodium 10g
Polyvidone 50g
Magnesium stearate 1g
Make altogether 1000
Preparation technology: recipe quantity polyvidone and leflunomide are joined in an amount of dehydrated alcohol, stir and make fully dissolving, place on the water-bath and heat, be stirred to mixture and be sticky shape, rapidly cooling, oven dry is pulverized.Add other auxiliary materials and mixing, 20 mesh sieves are granulated, 55 ℃～60 ℃ oven dry, and 18 mesh sieve granulate add the magnesium stearate mix homogeneously, tabletting.
The leflunomide tablet that according to said method prepares, the dissolution when 45min is greater than 90%.
Claims (1)
1. a leflunomide tablet preparation is characterized in that, its prescription and preparation method are as follows:
Preparation technology: recipe quantity polyvidone and leflunomide are joined in an amount of dehydrated alcohol, stir and make fully dissolving, place on the water-bath and heat, be stirred to mixture and be sticky shape, rapidly cooling, oven dry is pulverized, add other auxiliary materials and mixing, 20 mesh sieves are granulated, 55 ℃～60 ℃ oven dry, 18 mesh sieve granulate, add the magnesium stearate mix homogeneously, tabletting.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200910025145 CN101816637B (en) | 2009-02-26 | 2009-02-26 | Leflunomide tablet preparation and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200910025145 CN101816637B (en) | 2009-02-26 | 2009-02-26 | Leflunomide tablet preparation and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101816637A CN101816637A (en) | 2010-09-01 |
| CN101816637B true CN101816637B (en) | 2013-05-01 |
Family
ID=42652018
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200910025145 Active CN101816637B (en) | 2009-02-26 | 2009-02-26 | Leflunomide tablet preparation and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101816637B (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102038660B (en) * | 2011-01-06 | 2012-06-27 | 扬州中宝制药有限公司 | Gastrodine solid dispersible tablet preparation and preparation method thereof |
| CN102406940B (en) * | 2011-11-01 | 2013-07-03 | 温州大学 | Application of nanoscale flaky carboxymethyl starch sodium in solid dispersion |
| CN103006595B (en) * | 2012-12-25 | 2018-04-06 | 江苏亚邦爱普森药业有限公司 | The method for preparing ulipristal acetate |
| CN103989675A (en) * | 2014-05-20 | 2014-08-20 | 王俊国 | Leflunomide tablet and preparation technology thereof |
| 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 |
| CN104523630B (en) * | 2015-01-22 | 2017-08-25 | 山东新时代药业有限公司 | A kind of NVP tablet |
| CN105287420A (en) * | 2015-12-03 | 2016-02-03 | 李正梅 | Leflunomide tablet for treating adult rheumatoid arthritis |
| 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 |
|---|---|---|---|---|
| CN1771941A (en) * | 2005-11-01 | 2006-05-17 | 北京正大绿洲医药科技有限公司 | Leflunomide dripping pill and its prepn |
-
2009
- 2009-02-26 CN CN 200910025145 patent/CN101816637B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1771941A (en) * | 2005-11-01 | 2006-05-17 | 北京正大绿洲医药科技有限公司 | Leflunomide dripping pill and its prepn |
Non-Patent Citations (3)
| Title |
|---|
| 常忆凌.固体分散技术.《药剂学》.中国医药科技出版社,2008,315-319. * |
| 爱若华;王金陵等;《中国新药杂志》;20011231;第10卷(第3期);229-230 * |
| 王金陵等.爱若华.《中国新药杂志》.2001,第10卷(第3期),229-230. |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101816637A (en) | 2010-09-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101816637B (en) | Leflunomide tablet preparation and preparation method thereof | |
| RU2456989C2 (en) | Solid dosage forms containing tadalafil | |
| CN101889987B (en) | Method for preparing novel cefixime tablets and cefixime capsules | |
| CN102764264A (en) | Celecoxib solid composition with high dissolution, preparation method and application | |
| CN109875972B (en) | Olmesartan medoxomil and amlodipine pharmaceutical composition | |
| CN103610677A (en) | Repaglinide troche and preparation method thereof | |
| CN1899277B (en) | Composition of rheinic acid or rheinic acid compounds, its preparing method and its use in preparing medicine for treating diabetic nephrosis | |
| CN101732235B (en) | Method for preparing solid dispersion of tamoxifen citrate | |
| CN100577157C (en) | Dispersant tablet containing hypolipidemic component and preparation method thereof | |
| CN1331470C (en) | Method for preparing high stripping-degree hautriwaic glipizide capsule | |
| CN103127022A (en) | Allopurinol composite type drug release system and preparation method of allopurinol | |
| CN102068415B (en) | Carbazole sulfonamide anti-tumor medicine dispersible tablets and preparation method thereof | |
| CN102038642A (en) | Ginkgolide B solid dispersoid and preparation method thereof | |
| US7326427B2 (en) | Tablet composition containing Kampo medicinal extract and its manufacturing process | |
| CN102552920B (en) | Entecavir-containing medicinal composition and preparation method thereof | |
| CN103505466A (en) | Solid compound preparation containing metformin hydrochloride and glimepiride, preparation method and application thereof | |
| CN110115715A (en) | A kind of composite tablet and preparation method thereof containing Irbesartan | |
| CN101721414B (en) | Composition containing pioglitazone hydrochloride and metformin hydrochloride and preparation thereof | |
| CN106074394A (en) | A kind of pharmaceutical composition preparation method improving insoluble drug Peltatin glucoside dissolution | |
| CN103622970B (en) | A kind of irbesartan and hydrochlorthiazide tablet and preparation method thereof | |
| CN104382859A (en) | SLGT2 inhibitor granule and preparation method thereof | |
| CN104127390B (en) | A kind of Domperidone Tablets and preparation technology thereof | |
| CN104147012B (en) | A kind of oral disintegrated preparation containing ftorafur, Gimeracil and oteracil potassium | |
| JP7080504B2 (en) | Curcumin-containing solid preparation for oral ingestion | |
| CN101780089B (en) | Irbesartan hydrochlorothiazide capsule and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CB03 | Change of inventor or designer information | ||
| CB03 | Change of inventor or designer information |
Inventor after: Zhao Xiaohong Inventor after: Mao Baiyang Inventor after: Chen Zaixin Inventor after: Yin Xueqin Inventor after: Yang Xuyue Inventor after: Ge Yuhong Inventor after: Xie Ruili Inventor after: Sun Haitang Inventor after: Huang Fan Inventor before: Zhao Xiaohong Inventor before: Mao Baiyang Inventor before: Chen Zaixin Inventor before: Yin Xueqin Inventor before: Yang Xuyue Inventor before: Ge Yuhong Inventor before: Xie Ruili Inventor before: Sun Haitang Inventor before: Huang Fan |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20220527 Address after: 224600 Xiangshui Economic Development Zone, Yancheng City, Jiangsu Province Patentee after: JIANGSU YABANG AIPUSEN PHARMACEUTICAL Co.,Ltd. Address before: 224600 Xiangshui Economic Development Zone, Jiangsu Province Patentee before: JIANGSU YABANG AIPUSEN PHARMACEUTICAL Co.,Ltd. Patentee before: Changzhou Yabang Pharmaceutical Research Institute Co., Ltd |