CN102406626B - Pramipexole hydrochloride slow release tablet and preparation method thereof - Google Patents
Pramipexole hydrochloride slow release tablet and preparation method thereof Download PDFInfo
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- CN102406626B CN102406626B CN 201110396061 CN201110396061A CN102406626B CN 102406626 B CN102406626 B CN 102406626B CN 201110396061 CN201110396061 CN 201110396061 CN 201110396061 A CN201110396061 A CN 201110396061A CN 102406626 B CN102406626 B CN 102406626B
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- releasing tablet
- pramipexole
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Abstract
The invention discloses a component formula and a preparation method of a pramipexole hydrochloride slow release tablet. The pramipexole hydrochloride slow release tablet can be continuously and stably released in vivo, is free from influence of pH value change of gastrointestinal tract environment, and only needs to be taken once every day. The preparation method is simple and is suitable for industrial production.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, be specifically related to a kind of body of Pramipexole dihydrochloride tablet and production technology thereof.
Technical background
Oral sustained-release preparation can make blood drug level steady, can reduce the peak valley wave phenomenon, is conducive to reduce the toxic and side effects of medicine, particularly for the narrow medicine for the treatment of window, can guarantee its safety and effectiveness; Make blood drug level maintain effective smelting in a long time and treat in the concentration range, for short medicine of half-life, can reduce administration frequency.
Body of Pramipexole dihydrochloride refers to that pramipexole contains the monohydrate of two salt acid molecules, and chemical formula is C
10H
17N
3S2HClH
2O, molecular weight is 211.32, is used for the treatment of the parkinson disease (Parkinson ' s disease) that are common in the old people, parkinson disease belong to central nervous system degenerative disease, the patient many at 60 years old with sequela.It is slow mainly to show as patient motion, the trembling of the other parts of trick or health, and health has lost flexibility and harmony.The method of at present should disease still not having thorough healing needs Drug therapy long-term, that continue, suppresses disease progression.Therefore, for such patient, need a kind ofly to be easy to take, side effect is little, stable curative effect, toleration and the good medicine of compliance.At present common anti-Parkinson medicine all needs repeatedly take medicine every day on the market, and for example the normal release tablet formulations of pramipexole needs every day and takes 3 times, and this is very inconvenient concerning handicapped Parkinson's disease patients, is difficult to guarantee taking medicine of rule.
Patent CN03817831.1 discloses a kind of dosage form once a day of pramipexole, and it comprises pramipexole and pharmaceutically useful salt thereof, 40%～70% starch, 30%～60% hydroxypropyl emthylcellulose (HPMC) and at least a pharmaceutically acceptable excipient.Said preparation adopts controlled release coat film blocking medicine to discharge, but its preparation technology is very complicated, and also very high to the working condition requirement, there are many difficulties in industrialization, causes product cost high, and seldom has producer to produce.This preparation is under the release in vitro condition, and 24 hours stripping percentage rate is about 90%.Patent CN03817873.7 discloses a kind of slow releasing tablet of composition of pramipexole, and there are identical defective in its technical characterictic and CN03817831.1 basically identical.Patent CN200610136550.1 discloses a kind of slow releasing tablet of composition of pramipexole, and there are identical defective equally in its technical characterictic and CN03817831.1 basically identical.Patent CN200580027635.X discloses a kind of prolongation release tablet that comprises pramipexole or its officinal salt, this right to patent belong to the commercially available slow releasing tablet of pramipexole commodity famous medicine holder all, belong to same holder with the applying right of patent CN03817831.1, patent CN03817873.7 and patent CN200610136550.1.Patent CN200580027635.X has changed the formulation and technology of pramipexole slow releasing tablet, abandoned the structure that the control of controlled release coat film discharges, patent CN03817831.1, patent CN03817873.7 and patent CN200610136550.1 are carried out self-denial, confirmed the technological deficiency about these three patents well.In new patent (CN200580027635.X), adopt gel skeleton substrate to control the release of medicine.The described tablet of this patent can be finished 24 hours slow release preferably and discharge in the simulated gastric fluid of pH1.2.But, in pH4.5 buffer and pH6.8 buffer, discharging and significantly slow down, the stripping percentage rate was about 80% in 24 hours, discharged percentile lower limit for FDA slow releasing preparation guideline is final.And the pH6.8 environment is the main release environment of slow releasing tablet just, i.e. therefore the little intestinal segment of Duodeno-, only reaches in the Gastric pH environment of pH1.2 that to discharge fully be insignificant.And slow releasing tablet is influenced by the gastrointestinal tract emptying, and the time did not in vivo often reach 24 hours, and therefore, this patent is described to be difficult in vivo reach and to discharge fully and absorb, and also is difficult to reach and regular pharmaceutics oral 3 secondary pollutant equivalences in a day, influences therapeutic effect.In addition, the described slow releasing tablet of this patent contains a kind of anionic polymer, for example carbomer.So just increased the complexity of prescription, manufacturing cost has raise.And the described slow releasing tablet of this patent, its activity becomes to peg-grinds, and has increased the complexity of technology, has further improved manufacturing cost.
Summary of the invention
At above deficiency, the object of the present invention is to provide a kind of body of Pramipexole dihydrochloride slow releasing tablet that is better than existing product, described slow releasing tablet can be supported the method for administration of administration every day 1 time well, and absorbs in the body of medicine and blood drug level is not subjected to the influence of gastrointestinal tract emptying and pH variation.
The present invention realizes above purpose by a kind of body of Pramipexole dihydrochloride slow releasing tablet is provided, and specifically comprises following component: by weight
Wherein, the viscosity scope of described HPMC is at 3000Cps～12000Cps.The viscosity scope of preferred HPMC is 6000Cps～11000Cps, and preferred HPMC viscosity scope is 8000Cps～10000Cps.
Wherein, the hardness of the slow releasing tablet of described body of Pramipexole dihydrochloride is at 2kg/cm
2～20kg/cm
2Between.Preferred tablet hardness is at 4kg/cm
2～14kg/cm
2Between, preferred tablet hardness is at 6kg/cm
2～12kg/cm
2Between.
The advantage of the slow releasing tablet of a kind of body of Pramipexole dihydrochloride of the present invention is that its drug release curve is not influenced by pH in pH1.2 to pH6.8 scope, therefore be not subject to the influence that gastrointestinal tract physiology pH value changes in vivo, can remain stable release, and 24 hours stripping percentage rate is greater than 90%, can satisfy the needs of administration every day 1 time.The regular pharmaceutics oral 3 times with respect to every day reduced the difficulty of clinical application greatly, reduced the peak valley wave phenomenon of blood drug level, is conducive to improve therapeutic effect and reduces untoward reaction.
Another object of the present invention provides a kind of preparation method of body of Pramipexole dihydrochloride slow releasing tablet, may further comprise the steps:
(1) 100 mesh sieves is crossed in body of Pramipexole dihydrochloride and ethyl cellulose, hydroxypropyl emthylcellulose (HPMC), pregelatinized Starch respectively and carried out pretreatment;
(2) body of Pramipexole dihydrochloride and the ethyl cellulose that step (1) is obtained carries out premixing, gets premix I;
(3) the premix I that step (2) is obtained mixes back adding magnesium stearate mixing in order with hydroxypropyl emthylcellulose (HPMC), the pregelatinized Starch that step (1) obtains, and gets total mixture II;
(4) the total mixture II that obtains in the step (3) is compressed to tablet, the hardness of wherein said tablet is 2kg/cm
2～20kg/cm
2
Further, described body of Pramipexole dihydrochloride can be at first and ethyl cellulose, pregelatinized Starch and HPMC premixing, always mixes with all the other adjuvants then; Perhaps with body of Pramipexole dihydrochloride at first with ethyl cellulose and pregelatinized Starch premixing, always mix with all the other adjuvants then; Or body of Pramipexole dihydrochloride at first with the pregelatinized Starch premixing, always mix with all the other adjuvants then.
Further, the tablet hardness that obtains according to a kind of method of producing the body of Pramipexole dihydrochloride slow releasing tablet of the present invention is at 2kg/cm
2～20kg/cm
2Between, preferred tablet hardness is at 4kg/cm
2～14kg/cm
2Between, preferred tablet hardness is at 6kg/cm
2～12kg/cm
2Between.
Simple and the easy operating of the preparation method of body of Pramipexole dihydrochloride slow releasing tablet of the present invention is fit to large-scale industrial production and popularization.
Description of drawings
Fig. 1 is the drug release curve of slow releasing tablet (embodiment 1) in different pH medium of body of Pramipexole dihydrochloride of the present invention.
Fig. 2 is the drug release curve of slow releasing tablet (embodiment 2) in different pH medium of body of Pramipexole dihydrochloride of the present invention.
Fig. 3 is the drug release curve of slow releasing tablet (embodiment 3) in different pH medium of body of Pramipexole dihydrochloride of the present invention.
The specific embodiment
Each component source among the embodiment: body of Pramipexole dihydrochloride (Shenzhen Haiwang Pharmaceutical Co., Ltd, lot number 2011001), ethyl cellulose (Shanghai Ka Lekang, lot number SH312566), HPMC (model K100M, Shanghai Ka Lekang, lot number PD315496), pregelatinized Starch (Japanese Asahi Chemical Industry, lot number 6013), silica sol (Huzhou Zhanwang Pharmaceutical Co., Ltd., lot number 1011003), magnesium stearate (Hunan Er-kang Pharmaceutical Co., Ltd., lot number 1100018).
The prescription of the slow releasing tablet of [embodiment 1] a kind of body of Pramipexole dihydrochloride is formed
The prescription that the slow releasing tablet of [embodiment 2] a kind of body of Pramipexole dihydrochloride is optimized is formed
The prescription that the slow releasing tablet of [embodiment 3] a kind of body of Pramipexole dihydrochloride is optimized is formed
The slow releasing tablet preparation technology of [embodiment 4] body of Pramipexole dihydrochloride
(1) pretreatment: active component, ethyl cellulose, pregelatinized Starch and HPMC cross 100 mesh sieves respectively, and be standby; (2) premixing: active component adds the ethyl cellulose mix homogeneously of equivalent, progressively adds all the other ethyl celluloses and mixing by the equivalent method of progressively increasing; (3) the total mixing: said mixture progressively adds pregelatinized Starch, silica sol, HPMC mix homogeneously, adds the magnesium stearate mixing at last; (4) tabletting: it is 6kg/cm that tablet machine is pressed into hardness
2～12kg/cm
2Between tablet.
The slow releasing tablet release profiles of the body of Pramipexole dihydrochloride that [embodiment 5] are optimized
Pressing Chinese Pharmacopoeia version dissolution method first method in 2010 measures, dissolution medium is pH1.2 hydrochloric acid solution or pH6.8 phosphate buffer 500mL, rotating speed is 100rpm, solution temperature is 37 ℃, release profiles is shown in Fig. 1～3, the result shows that the slow releasing tablet of the body of Pramipexole dihydrochloride of optimization has 24 hours sustained releasing character, and is not subjected to the pH variable effect.
Claims (9)
1. body of Pramipexole dihydrochloride slow releasing tablet is characterized in that being made up of following component by weight:
2. body of Pramipexole dihydrochloride slow releasing tablet is characterized in that being made up of following component by weight:
3. body of Pramipexole dihydrochloride slow releasing tablet is characterized in that being made up of following component by weight:
4. the described body of Pramipexole dihydrochloride slow releasing tablet of any one of claim 1～3, the tablet hardness that it is characterized in that described slow releasing tablet is 2kg/cm
2～20kg/cm
2
5. the described body of Pramipexole dihydrochloride slow releasing tablet of claim 4, the tablet hardness that it is characterized in that described slow releasing tablet is 4kg/cm
2～14kg/cm
2
6. the described body of Pramipexole dihydrochloride slow releasing tablet of claim 5, the tablet hardness that it is characterized in that described slow releasing tablet is 6kg/cm
2～12kg/cm
2
7. prepare the method for any one described body of Pramipexole dihydrochloride slow releasing tablet of claim 1～3, may further comprise the steps:
(1) 100 mesh sieves are crossed in body of Pramipexole dihydrochloride and ethyl cellulose, hydroxypropyl emthylcellulose, pregelatinized Starch respectively and carried out pretreatment, the viscosity scope of wherein said hydroxypropyl emthylcellulose is 3000Cps～12000Cps;
(2) body of Pramipexole dihydrochloride and the ethyl cellulose that step (1) pretreatment is obtained carries out premixing, gets premix I;
(3) the premix I that step (2) is obtained mixes back adding magnesium stearate mixing in order with hydroxypropyl emthylcellulose, the pregelatinized Starch that step (1) obtains, and gets total mixture II;
(4) the total mixture II that obtains in the step (3) is compressed to tablet, the hardness of wherein said tablet is 2kg/cm
2～20kg/cm
2
8. the described method of claim 7, wherein hydroxypropyl emthylcellulose viscosity scope is 6000Cps～11000Cps; Tablet hardness is at 4kg/cm
2～14kg/cm
2Between.
9. the described method of claim 8, wherein hydroxypropyl emthylcellulose viscosity scope is 8000Cps～10000Cps; Tablet hardness is at 6kg/cm
2～12kg/cm
2Between.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 201110396061 CN102406626B (en) | 2011-12-02 | 2011-12-02 | Pramipexole hydrochloride slow release tablet and preparation method thereof |
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| CN 201110396061 CN102406626B (en) | 2011-12-02 | 2011-12-02 | Pramipexole hydrochloride slow release tablet and preparation method thereof |
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| CN102406626B true CN102406626B (en) | 2013-08-28 |
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Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104146979A (en) * | 2013-05-14 | 2014-11-19 | 上海星泰医药科技有限公司 | Pramipexole dihydrochloride sustained release tablet and preparation method thereof |
| CN104161735A (en) * | 2013-05-19 | 2014-11-26 | 成都康弘药业集团股份有限公司 | Sustained-release preparation containing pramipexole hydrochloride and preparation method thereof |
| CN103520128B (en) | 2013-10-12 | 2018-08-21 | 石家庄杏林锐步医药科技股份有限公司 | A kind of sustained-release tablet of Pramipexole, preparation method and its usage |
| CN105456216B (en) * | 2014-08-18 | 2019-11-05 | 江苏神龙药业股份有限公司 | Pramipexole hydrochloride slow release tablet composition and preparation method thereof |
| CN104606162B (en) * | 2015-01-07 | 2017-03-29 | 海南康虹医药科技开发有限公司 | A kind of body of Pramipexole dihydrochloride slow releasing preparation and preparation method thereof |
| CN109316466B (en) * | 2017-07-31 | 2022-04-05 | 深圳翰宇药业股份有限公司 | Pramipexole dihydrochloride sustained-release preparation and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1671381A (en) * | 2002-07-25 | 2005-09-21 | 法马西亚公司 | Pramipexole once-daily dosage form |
| CN101884626A (en) * | 2004-08-13 | 2010-11-17 | 贝林格尔.英格海姆国际有限公司 | The prolongation release tablet, the Preparation Method And The Use that comprise pramipexole or its officinal salt |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006046256A1 (en) * | 2004-10-27 | 2006-05-04 | Alembic Limited | Extended release formulation of pramipexole dihydrochloride |
| EP2575780A1 (en) * | 2010-05-24 | 2013-04-10 | Lupin Limited | Extended release formulation of pramipexole |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1671381A (en) * | 2002-07-25 | 2005-09-21 | 法马西亚公司 | Pramipexole once-daily dosage form |
| CN101884626A (en) * | 2004-08-13 | 2010-11-17 | 贝林格尔.英格海姆国际有限公司 | The prolongation release tablet, the Preparation Method And The Use that comprise pramipexole or its officinal salt |
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