CN100384411C - Oral carbidopa/levodopa disintegrant tablet - Google Patents
Oral carbidopa/levodopa disintegrant tablet Download PDFInfo
- Publication number
- CN100384411C CN100384411C CNB2006100650518A CN200610065051A CN100384411C CN 100384411 C CN100384411 C CN 100384411C CN B2006100650518 A CNB2006100650518 A CN B2006100650518A CN 200610065051 A CN200610065051 A CN 200610065051A CN 100384411 C CN100384411 C CN 100384411C
- Authority
- CN
- China
- Prior art keywords
- parts
- oral cavity
- microcrystalline cellulose
- cavity disintegration
- disintegration 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
Images
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention discloses an oral carbidopa/levodopa disintegration tablet which uses carbidopa and levodopa as the main medicines. The oral carbidopa/levodopa disintegration tablet also comprises a disintegrating agent and a diluting agent. The oral carbidopa/levodopa disintegration tablet is characterized in that the disintegrating agent is low-substituted hydroxypropyl cellulose, and the diluting agent is prepared from microcrystalline cellulose and mannitol. The present invention also provides a production method of the oral carbidopa/levodopa disintegration tablet. The production method has the advantage of simple and stable technology, and is particularly suitable for industrial production.
Description
Technical field
The present invention relates to a kind of oral carbidopa/levodopa disintegrant tablet and its production method, specifically, relate to a kind of with the oral cavity disintegration tablet and the production method thereof of Carbidopa as principal agent.Described oral carbidopa/levodopa disintegrant tablet can be used for treating parkinson or parkinsonism etc.
Background technology
The maincenter that enters after levodopa is oral changes into dopamine and plays a role, carbidopa is a periphery deacidification enzyme inhibitor, be difficult for entering maincenter, only suppress the periphery levodopa and change into dopamine, make that levodopa content increases in the circulation, thereby the amount that enters the levodopa of maincenter increases also, levodopa is converted into dopamine and brings into play pharmacological action through the dopamine decarboxylation in brain, improve the Parkinsonism symptom, be used for the treatment of parkinson or parkinsonism etc.
Disclose a kind of treatment parkinson medicament among the CN1358090A, its main component is levodopa, carbidopa and entacapone.But disclosed a kind of dispersive composition of L-DOPA ethyl ester among the CN1329487A, wherein comprised carbidopa, disintegrating agent, filler and lubricant.
Summary of the invention
Oral cavity disintegration tablet is the ideal that is difficult to swallow the parkinson of the moderate of full wafer medicine or severe symptom or the parkinsonism patient dosage form of taking medicine.
The present invention selects by prescription screening and adjuvant on the basis of existing technology, is surprised to find that the oral cavity disintegration tablet of Carbidopa by selecting for use suitable disintegrating agent and diluent to be prepared from has excellent tablet effect.Oral carbidopa/levodopa disintegrant tablet of the present invention, preparation are formed and are different from the existing medicament that disperses.
The invention provides a kind of oral cavity disintegration tablet, with Carbidopa as principal agent, wherein the weight ratio of Carbidopa is 1: (4～10), comprise disintegrating agent and diluent, it is characterized in that described disintegrating agent is low-substituted hydroxypropyl cellulose (L-HPC), described diluent is microcrystalline Cellulose (CMCC) and mannitol.
Wherein said microcrystalline Cellulose can be microcrystalline Cellulose pH102, microcrystalline Cellulose pH301 or microcrystalline Cellulose KG802, also can be microcrystalline Cellulose-90 (CMCC 90) or microcrystalline Cellulose-50 (CMCC 50).Wherein, preferably microcrystalline cellulose is microcrystalline Cellulose pH102, microcrystalline Cellulose pH301 or microcrystalline Cellulose KG802.
Wherein, the consumption of microcrystalline Cellulose and mannitol, by weight calculating, can be (1～2): (1～1.5) is preferably 2: 1.
Above-mentioned described oral cavity disintegration tablet also comprises fluidizer, lubricant or correctives.Wherein, described fluidizer for example is one or more in micropowder silica gel, Pulvis Talci, Cab-O-sil, Arosil, the hydrated sodium aluminosilicate etc.; Described lubricant for example is one or more in magnesium stearate, calcium stearate, zinc stearate, glyceryl monostearate, Polyethylene Glycol, hydrogenated vegetable oil, sodium stearyl fumarate, polyoxyethylene monostearate, single Laurel sucrose acid ester, sodium laurylsulfate, magnesium laurylsulfate, Stepanol MG and the Pulvis Talci etc.; Described correctives for example is one or more in aspartame, flavoring banana essence, flavoring pineapple essence, vanillin, fragrant citrus essence, flavoring orange essence, Herba Menthae essence, ginseng essence, strawberry essence, citric acid, the citric acid etc.
Preferred oral cavity disintegration tablet of the present invention is: calculate by weight, 10～25 parts of carbidopas, 100 parts of levodopa, 150～200 parts of microcrystalline Cellulose, 100～150 parts in mannitol, 20～30 parts of low-substituted hydroxypropyl celluloses, 2～8 parts of micropowder silica gels, 2～6 parts of magnesium stearate, 0.5～4 part of aspartame, 0.5～2 part in fragrant citrus essence, 0.5～2 part in Herba Menthae essence.
As one of specific embodiments of the present invention, described oral cavity disintegration tablet is: calculate 10 parts of carbidopas by weight, 100 parts of levodopa, 150 parts of microcrystalline Cellulose pH102,50 parts of microcrystalline Cellulose pH301,100 parts in mannitol, 25 parts of low-substituted hydroxypropyl celluloses, 5 parts of micropowder silica gels, 3.6 parts of magnesium stearate, 2 parts of aspartames, 1 part in fragrant citrus essence, 1 part in Herba Menthae essence.
As one of specific embodiments of the present invention, described oral cavity disintegration tablet is: calculate 10 parts of carbidopas, 100 parts of levodopa by weight, 200 parts of microcrystalline Cellulose pH102,100 parts in mannitol, 25 parts of low-substituted hydroxypropyl celluloses, 5 parts of micropowder silica gels, 3.6 parts of magnesium stearate, 2 parts of aspartames, 1 part in fragrant citrus essence, 1 part in Herba Menthae essence.
Oral cavity disintegration tablet of the present invention has suitable hardness, and preferred hardness is between 20～40N (newton).
Above-mentioned described oral cavity disintegration tablet can be used for preparing the medicine of diseases such as treatment parkinson or parkinsonism.
Can adopt direct compression process to prepare oral cavity disintegration tablet of the present invention.The production method of oral cavity disintegration tablet of the present invention, it comprises following steps: crude drug and adjuvant were with proper method (dilution method etc. for example progressively increases) mix homogeneously during (1) will write out a prescription; (2) adjust compression force to suitable sheet hardness (for example 20～40N), carry out tabletting.After the process quality examination was qualified, packing promptly got oral cavity disintegration tablet.
The inventor is with reference to the correlational study of existing oral cavity disintegration tablet, and in conjunction with the own characteristic of Carbidopa, by adjuvant is screened, be surprised to find that, with low-substituted hydroxypropyl cellulose (L-HPC) as disintegrating agent, particularly microcrystalline Cellulose pH102, microcrystalline Cellulose pH301 or microcrystalline Cellulose KG802 and mannitol are as diluent with microcrystalline Cellulose, and the oral cavity disintegration tablet that makes has excellent beneficial effect.Orally disintegrating tablet production method of the present invention, technology is simple, stable, is suitable for commercial production especially.
Description of drawings
The carbidopa stripping curve figure of accompanying drawing 1: embodiment 1 oral cavity disintegration tablet
The levodopa stripping curve figure of accompanying drawing 2: embodiment 1 oral cavity disintegration tablet
The specific embodiment
Come further the present invention to be made an explanation below by embodiment, but be not appreciated that it is that the scope of the invention is construed as limiting.
Embodiment 1: preparation embodiment
Embodiment 2: preparation embodiment
Embodiment 3: preparation embodiment
Carbidopa 25 grams, levodopa 100 grams, microcrystalline Cellulose pH102 150 grams, microcrystalline Cellulose KG80250 gram, mannitol 100 grams, low-substituted hydroxypropyl cellulose 30 grams, micropowder silica gel 5 grams, magnesium stearate 3.6 grams, aspartame 2 grams, fragrant citrus essence 1 gram, Herba Menthae essence 1 gram.Make 1000 according to embodiment 1 described method.
Embodiment 4: contrast test
Embodiment 4a: with the low-substituted hydroxypropyl cellulose in the cross-linking sodium carboxymethyl cellulose 25 gram alternative embodiments 1, all the other all are same as embodiment 1.Make 1000 according to embodiment 1 described method.
Embodiment 4b: with the low-substituted hydroxypropyl cellulose in the polyvinylpolypyrrolidone 25 gram alternative embodiments 1, all the other all are same as embodiment 1.Make 1000 according to embodiment 1 described method.
Embodiment 4c: with the mannitol in the erithritol 100 gram alternative embodiments 1, all the other all are same as embodiment 1.Make 1000 according to embodiment 1 described method.
Key property to the oral cavity disintegration tablet of embodiment 1～4 is investigated.The results are shown in Table 1.
Wherein the disintegration time mensuration method is:
Method 1: small beaker method: get 1 5ml small beaker, add 2ml water, sheet is placed in one, the disintegration time of record tablet.
Method 2: instrument test method: for the lifting frequency that solves the disintegration tester that uses in the existing disintegration time mensuration method of Chinese Pharmacopoeia is fixed this shortcoming, with reference to some disintegration time mensuration methods of mentioning in the external oral cavity disintegration tablet patent, the present invention utilizes the hanging basket of 2000 editions two dissolution test systems of existing Chinese Pharmacopoeia and lift disintegration tester simultaneously.The former can regulate rotating speed.
Check: 37 degrees centigrade of waters bath with thermostatic control that the beaker that digestion instrument is equipped with at random places dissolution test system, inject 750 ml waters, hanging basket is installed on the dissolution test system by the basket axle, hanging basket is immersed in the water, make at the bottom of the hanging basket apart from the bottom of the beaker 5 centimetres; get this product, place the glass tubing of hanging basket.Start rotating shaft timing simultaneously, rotating speed is that per minute 50 or 80 changes, and tablet and powder is a disintegration time by the time of screen cloth all, the record disintegration time.The results are shown in Table 1
Table 1 oral carbidopa/levodopa disintegrant tablet prescription key property is investigated the result
Measurement result shows, oral carbidopa/levodopa disintegrant tablet of the present invention is a disintegrating agent with low-substituted hydroxypropyl cellulose, and microcrystalline Cellulose and mannitol are as diluent, and the oral cavity disintegration tablet of making has excellent galenic pharmacy effect.
Embodiment 5: dissolution is investigated test
Algoscopy: get this product, according to dissolution method (two appendix XC first methods of Chinese Pharmacopoeia version in 2000), with 750ml 0.1N hydrochloric acid solvent, rotating speed is that per minute 50 changes, operation in accordance with the law, in the time of 30 minutes, it is an amount of to get solution, filters, get subsequent filtrate, carry out assay, calculate dissolution
Embodiment 1 is carried out dissolution investigate, stripping curve is drawn in sampling in the time of 2,5,10,20,30 minutes.Stripping curve is seen Fig. 1 and 2.
Oral cavity disintegration tablet of the present invention (getting embodiment 1 sample), according to the medicine stability test guideline, (investigate 10 under 45001x ± 5001x), high temperature (60 degrees centigrade), high humidity (relative humidity is 90% ± 5%) condition, investigate its stability at strong illumination respectively.Result of the test shows that product stability is good, and related substance and content all meet the requirements.
The present invention is described according to preferred embodiment.Should be understood that the description of front and embodiment are just to illustrating the present invention.Under prerequisite without departing from the spirit and scope of the present invention, those skilled in the art can design multiple alternative of the present invention and improvement project, and it all should be understood to be within protection scope of the present invention.
Claims (10)
1. oral cavity disintegration tablet, with Carbidopa as principal agent, wherein the weight ratio of Carbidopa is 1: (4～10), comprise disintegrating agent and diluent, it is characterized in that described disintegrating agent is a low-substituted hydroxypropyl cellulose, described diluent is microcrystalline Cellulose and mannitol, and the weight ratio of microcrystalline Cellulose and mannitol is 2: 1.
2. oral cavity disintegration tablet according to claim 1, wherein said microcrystalline Cellulose are selected microcrystalline Cellulose pH102, microcrystalline Cellulose pH301 or microcrystalline Cellulose KG802 for use.
3. according to claim 1 or 2 described oral cavity disintegration tablets, wherein also comprise fluidizer, lubricant or correctives.
4. oral cavity disintegration tablet according to claim 3 is characterized in that: calculate 10 parts of carbidopas by weight, 100 parts of levodopa, microcrystalline Cellulose pH102150 part, microcrystalline Cellulose pH30150 part, 100 parts in mannitol, 25 parts of low-substituted hydroxypropyl celluloses, 5 parts of micropowder silica gels, 3.6 parts of magnesium stearate, 2 parts of aspartames, 1 part in fragrant citrus essence, 1 part in Herba Menthae essence.
5. oral cavity disintegration tablet according to claim 3, it is characterized in that: calculate 10 parts of carbidopas, 100 parts of levodopa by weight, microcrystalline Cellulose pH102200 part, 100 parts in mannitol, 25 parts of low-substituted hydroxypropyl celluloses, 5 parts of micropowder silica gels, 3.6 parts of magnesium stearate, 2 parts of aspartames, 1 part in fragrant citrus essence, 1 part in Herba Menthae essence.
6. according to claim 1 or 2 described oral cavity disintegration tablets, the hardness that it is characterized in that sheet is between 20～40 newton.
7. oral cavity disintegration tablet according to claim 3, the hardness that it is characterized in that sheet is between 20～40 newton.
8. according to claim 4 or 5 described oral cavity disintegration tablets, the hardness that it is characterized in that sheet is between 20～40 newton.
9. each described oral cavity disintegration tablet of claim 1-8 is used for the treatment of purposes in parkinson or the parkinsonism medicine in preparation.
10. the production method of each described oral cavity disintegration tablet of claim 1-8 is characterized in that comprising following steps:
(1) will write out a prescription in crude drug and adjuvant proper method mix homogeneously;
(2) adjustment compression force to 20～40 newton's sheet hardness is carried out tabletting.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100650518A CN100384411C (en) | 2006-03-17 | 2006-03-17 | Oral carbidopa/levodopa disintegrant tablet |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100650518A CN100384411C (en) | 2006-03-17 | 2006-03-17 | Oral carbidopa/levodopa disintegrant tablet |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1857245A CN1857245A (en) | 2006-11-08 |
| CN100384411C true CN100384411C (en) | 2008-04-30 |
Family
ID=37296233
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2006100650518A Active CN100384411C (en) | 2006-03-17 | 2006-03-17 | Oral carbidopa/levodopa disintegrant tablet |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100384411C (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101797244B (en) * | 2010-04-01 | 2012-07-04 | 青岛科技大学 | Levodopa/benserazide orally disintegrating tablet |
| CN104523671A (en) * | 2014-11-20 | 2015-04-22 | 美吉斯制药（厦门）有限公司 | Sinemet orally disintegrating tablet, and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1168440C (en) * | 1999-06-30 | 2004-09-29 | 欧里恩公司 | Pharmaceutical formulation of levodopa/carbidopa/entacapone |
| US20050147670A1 (en) * | 2002-05-29 | 2005-07-07 | Impax Laboratories Inc. | Oral disintegrating dosage forms |
| CN1739514A (en) * | 2005-09-12 | 2006-03-01 | 重庆康刻尔制药有限公司 | Oral loratadine disintegrating tablet and its prepn |
-
2006
- 2006-03-17 CN CNB2006100650518A patent/CN100384411C/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1168440C (en) * | 1999-06-30 | 2004-09-29 | 欧里恩公司 | Pharmaceutical formulation of levodopa/carbidopa/entacapone |
| US20050147670A1 (en) * | 2002-05-29 | 2005-07-07 | Impax Laboratories Inc. | Oral disintegrating dosage forms |
| CN1739514A (en) * | 2005-09-12 | 2006-03-01 | 重庆康刻尔制药有限公司 | Oral loratadine disintegrating tablet and its prepn |
Non-Patent Citations (2)
| Title |
|---|
| 口腔崩解片的研制进展. 柳松.中国药业，第14卷第11期. 2005 |
| 口腔崩解片的研制进展. 柳松.中国药业，第14卷第11期. 2005 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1857245A (en) | 2006-11-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Pawar et al. | Development and evaluation of orodispersible tablets using a natural polysaccharide isolated from Cassia tora seeds | |
| WO2010045788A1 (en) | A orally disintegrating tablet of donepezil hydrochloride and the preparation method thereof | |
| Gandhi et al. | Comparative study on effect of natural and synthetic superdisintegrants in the formulation of orodispersible tablets | |
| CN101411715B (en) | Pharmaceutical composition containing acarbose | |
| CN101461788B (en) | Phloroglucine orally disintegrating tablet and preparation method thereof | |
| CN101209249A (en) | Spaston orally disintegrating tablets and preparation thereof | |
| CN102631329A (en) | Oral paroxetine disintegrating tablet and preparation process thereof | |
| CN101336904B (en) | Acarbose chewable tablets and preparation method thereof | |
| CN100384411C (en) | Oral carbidopa/levodopa disintegrant tablet | |
| CN102440973B (en) | Diphenhydramine citrate orally disintegrating tablet and preparation method thereof | |
| CN104706605B (en) | A kind of preparation method and resulting product of memantine oral solid tablet | |
| CN101991559B (en) | Stable Agomelatine capsule medicine composition | |
| CN113384549A (en) | Acetaminophen vitamin C effervescent tablet and preparation method thereof | |
| CN101361720A (en) | Nebivolol hydrochloric acid orally disintegrating tablet and preparation method thereof | |
| CN105476971A (en) | Medical composition for treating cold and preparation method of medical composition | |
| CN105853382B (en) | A kind of Li Gelieting oral disintegrating tablet and preparation method thereof | |
| CN101401796A (en) | Pramipexole orally disintegrating tablets and preparation method thereof | |
| CN113274365B (en) | Ramelteon quick-release slow-release double-release preparation and preparation method thereof | |
| EP2726063A1 (en) | Ibuprofen chewable tablet | |
| CN101467985B (en) | Bisoprolol fumarate dispersible tablet and preparation method thereof | |
| CN1927301A (en) | Tongmai Jiangzhi dispersant tablet and method for making same | |
| CN106727371B (en) | Donepezil hydrochloride pharmaceutical composition and preparation method thereof | |
| JP2020066610A (en) | Estradiol production promoting pharmaceutical composition and food composition | |
| CN105434378B (en) | Mei Suoshuli dispersible tablets and preparation method thereof | |
| JP2007039337A (en) | Health functional food tablet |
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 | ||
| C56 | Change in the name or address of the patentee | ||
| CP02 | Change in the address of a patent holder |
Address after: 100083 Haidian District, Xueyuan Road, No. 30, A building, room No. 15, room, room 15 Patentee after: Beijing Kexin Bicheng Medicine Science & Technology Developing Co., Ltd. Address before: 100080, room 1410, satellite building, No. 63, Zhichun Road, Beijing, Haidian District Patentee before: Beijing Kexin Bicheng Medicine Science & Technology Developing Co., Ltd. |